abstracts - 31. Deutscher Krebskongress 2014
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abstracts - 31. Deutscher Krebskongress 2014
Oncol Res Treat 37(suppl 1) VI–145 (2014) 37 | S1 | 14 print online ISSN 2296–5270 e-ISSN 2296–5262 e-ISBN 978-3-318-02610-8 Formerly Band 37, Supplement 1, Februar 2014 31. Deutscher Krebskongress ABSTRACTS Berlin, 19.–22. Februar 2014 KON – ntelligente Konzepte in der Onkologie Herausgeber Michael Hallek, Köln S. Karger Medical and Scientific Publishers Basel . Freiburg . Paris . London . New York . Chennai . New Delhi . Bangkok . Beijing . Shanghai . Tokyo . Kuala Lumpur . Singapore . Sydney www.karger.com/ort Band 37, Supplement 1, Februar 2014 Offizielles Organ von DGHO– Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie ÖGHO– Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie DFaG – Deutsche Fatigue Gesellschaft AIO – Arbeitsgemeinschaft Internistische Onkologie in der Deutschen Krebsgesellschaft e.V. Mitglied der Deutschen Krebsgesellschaft e.V. Editors Editor-in-Chief Associate Editors M. Hallek, Köln S. Al-Batran, Frankfurt/M. C. Berking, München C. Bokemeyer, Hamburg M. Borner, Bern T. Cerny, St. Gallen H. T. Eich, Münster A. Engert, Köln M. Fassnacht, München B. Groner, Frankfurt/M. V. Heinemann, München M. Hentrich, München R. D. Issels, München W. Janni, Ulm U. R. Kleeberg, Hamburg H. Lang, Mainz M. Moehler, Mainz M. Schuler, Essen R. Stupp, Zürich M. Theobald, Mainz R. Thomas, Köln U. Wedding, Jena J. A. Werner, Marburg A. Heidenreich, Aachen U. Herrlinger, Bonn A. Hochhaus, Jena R.-D. Hofheinz, Mannheim F. Honecker, St. Gallen V. Jacobs, Salzburg K. Jordan, Halle U. Keilholz, Berlin J. P. Klussmann, Gießen H. Kölbl, Wien W. Kuhn, Bonn H.-J. Lenz, Los Angeles P. Mallmann, Köln H. Moch, Zürich K. Possinger, Berlin P. Reichardt, Bad Saarow S. Reske, Ulm I. Runnebaum, Jena P. Schöffski, Leuven C. Spitzweg, München I. Strohscheer, St. Peter-Ording S. Ugurel, Graz R. Voltz, Köln M. Weller, Zürich Editorial Board P. Albers, Düsseldorf C. Bausewein, München L. Bergmann, Frankfurt/M. J. Boos, Münster P. Brossart, Bonn W. Budach, Düsseldorf R. Büttner, Bonn E. Dippel, Ludwigshafen A. Du Bois, Essen T. Fehm, Düsseldorf F. Geiser, Bonn N. Harbeck, München Editorial Office S. Karger GmbH Attn. Dr. Steffi Hentzelt P.O. Box D-79095 Freiburg E-mail [email protected] Basel · Freiburg · Paris · London · New York · Chennai · New Delhi · Bangkok · Beijing · Shanghai · Tokyo · Kuala Lumpur · Singapore · Sydney Disclosure Statement XXX Imprint ISSN Print Edition: 2296–5270 ISSN Online Edition: 2296–5262 Journal Homepage: http://www.karger.com/ort Publication Data: Volume 37, 2014 of ‘Oncology Research and Treatment’ appears with 12 issues. Copyright: © 2014 by S. Karger Verlag für Medizin und Naturwissenschaften GmbH, Freiburg (Germany). All rights reserved. No part of the journal may be reproduced in any form without the written permission of the publisher. 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Februar 2014 ABSTRACTS Herausgeber Michael Hallek, Köln Basel · Freiburg · Paris · London · New York · Chennai · New Delhi · Bangkok · Beijing · Shanghai · Tokyo · Kuala Lumpur · Singapore · Sydney Oncol Res Treat 2014;37(suppl 1):IV Programmkomitee Albers, P. (Düsseldorf ), Bartsch, H.H. (Freiburg), Baumann, F. (Köln), Becker, J. (Graz), Bergmann, L. (Frankfurt/M), Bokemeyer, C. (Hamburg), Bruns, J. (Berlin), Büttner, R. (Köln), Cursiefen, C. (Köln), Dietel, M. (Berlin), Dietz, A. (Leipzig), Domagk, K. (Hamburg), Dunst, J. (Lübeck), Eggert, A. (Berlin), Engers, R. (Düsseldorf ), Enghofer, E. (Leverkusen), Fehm, T. (Düsseldorf ), Feyer, P. (Berlin), Fietkau, R. (Erlangen), Graeven, U. (Mönchengladbach), Gschwend, J. (München), Gutzmer, R. (Hannover), Hallek, M. (Köln), Hartmann, J. (Kiel), Hasch, G. (Darmstadt), Hegewisch-Becker. (Hamburg), Helbig, U. (Berlin), Hochhaus, A. (Jena), Hölscher, A. (Köln), Hübner, J. (Berlin), Issels, R. (München), Jackisch, C. (Offenbach), Katalinic, A. (Lübeck), Kerschgens, C. (Berlin), Kleeberg, U. (Hamburg), Klinkhammer-Schalke, M. (Regensburg), Kohlhuber, F. (Bonn), Kotzerke, J. (Dresden), Krege, S. (Krefeld), Kusch, M. (Köln), Lang, H. (Mainz), Lordick, F. (Leipzig), Mallmann, P. (Köln), Meier, K. (Soltau), Nettekoven, G. (Bonn), Neugebauer, E. (Witten), Ortmann, O. (Regensburg), Paradies, K. (Hamburg), Pfaff, H. (Köln), Reif, K. (Bochum), Retz, M. (München), Riemann, J.F. (Ludwigshafen), Röcken, C. (Kiel), Rüffer, J.U. (Köln), Schadendorf, D. (Essen), Schirren, J. (Wiesbaden), Schlag, P. (Berlin), Schmidberger, H. (Mainz), Schmutzler, R. (Köln), Singer, S. (Mainz), Souchon, R. (Tübingen), Stadler, R. (Minden), Steiner, T. (Erfurt), Stummer, W. (Münster), Sturm, D. (Chemnitz), Thomas, M. (Heidelberg), Thomas, R. (Köln), van, Oorschot. (Würzburg), Voltz, R. (Köln), vom, Hagen, U. (Berlin), Wallwiener, D. (Tübingen), Walther, J. (Heidelberg), Walter, S. (Bonn), Weisse, I. (Stuttgart), Wiedenmann, B. (Berlin), Wiegel, T. (Ulm), Wiestler, O. (Heidelberg), Wittekind, C. (Leipzig), Wolf, J. (Köln), Zander, T. (Köln) Gutachter lbers, P. (Düsseldorf ), Albus, C. (Köln), Arnold, D. (Freiburg), Bahra, M. (Berlin), A Bamberg, M. (Tübingen), Beckmann, M.W. (Erlangen), Benzing, T. (Köln), Berdel, W.E. (Münster), Berthold, F. (Köln), Beuth, J. (Köln), Biersack, H.J. (Bonn), Bloch, W. (Köln), Bokemeyer, C. (Hamburg), Bootz, F. (Bonn), Brossart, P. (Bonn), Brüning, J. (Köln), Budach, W. (Düsseldorf ), Cornely, O. (Köln), Debatin, K.M. (Ulm), Deckert, M. (Köln), Domagk, K. (Stadt), Emons, G. (Göttingen), Engenhart-Cabillic, R. (Marburg), Engers, R. (Neuss), Feyer, P. (Berlin), Fietkau, R. (Erlangen), Frank, K. (Köln), Friedel, G. (Gerlingen), Gabbert, H. (Düsseldorf ), Gathof, B. (Köln), Geiser, F. (Bonn), Graeven, U. (Mönchengladbach), Harbeck, N. (München), Hartmann, G. (Bonn), Hegewisch-Becker, S. (Hamburg), Hellmich, M. (Köln), Henne-Bruns, D. (Ulm), Herden, J. (Köln), Herschbach, P. (München), Hertenstein, B. (Bremen), Heukamp, L. (Köln), Höffken, K. (Jena), Hohenberger, W. (Erlangen), Hölscher, A. (Köln), Hopt, U.T. (Freiburg), Howaldt, H.P. (Gießen), Hübner, J. (Berlin), Jonat, W. (Kiel), Kalff, J. (Bonn), Keller, M. (Heidelberg), Kiechle, M. (München), Klaschik, E. (Alfter), Klingebiel, T. (Frankfurt/M.), Koch, U. (Hamburg), Kortmann, R.D. (Leipzig), Krieg, T. (Köln), Kuhn, W. (Bonn), Lang, H. (Mainz), Lehmacher, W. (Köln), Liekweg, A. (Köln), Lutz, M. (Saarbrücken), Maintz, D. (Köln), Mallmann, P. (Köln), Malter, W. (Köln), Meier, K. (Soltau), Meyer, H.J. (Berlin), Molls, M. (München), Müller, S. (Bonn), Perner, S. (Bonn), Possinger, K. (Egling), Radbruch, L. (Bonn), Reif, K. (Bochum), Reinacher-Schick, A. (Bochum), Riemann, J.F. (Ludwigshafen), Rödel, C. (Frankfurt/M.), Scheid, C. (Stadt), Scheulen, M. (Essen), Schild, H. (Bonn), Schirren, J. (Wiesbaden), Schlegel, U. (Bochum), Schmidt-Wolf, I. (Bonn), Schmoll, H.J. (Halle/S.), Schmutzler, R. (Köln), Schuler, M. (Essen), Schulz, R.J. (Köln), Schütte, W. (Halle/S.), Seehofer, D. (Berlin), Seufferlein, T. (Ulm), Sterner-Kock, A. (Köln), Stürzl, M. (Erlangen), Stuschke, M. (Essen), Tannapfel, A. (Bochum), Thiel, E. (Berlin), Thomas, R. (Köln), Trümper, L. (Göttingen), Ukena, D. (Bremen), Unger, C. (Freiburg), Vanhoefer, U. (Hamburg), Vatter, H. (Bonn), Voltz, R. (Köln), vom, Hagen, U. (Berlin), Wahl, G. (Bonn), Wahlers, T. (Köln), Wallwiener, D. (Tübingen), Weis, J. (Freiburg), Welt, A, (Essen), Wenz, F, (Mannheim), Wiestler, O, (Heidelberg), Wittekind, C, (Leipzig), Zander, T, (Köln) © 2014 S. Karger GmbH, Freiburg Fax +49 761 4 52 07 14 [email protected] www.karger.com Accessible online at: www.karger.com/ort Inhalt Oncol Res Treat 2014;37(suppl 1):V © 2014 S. Karger GmbH, Freiburg Fax +49 761 4 52 07 14 [email protected] www.karger.com Accessible online at: www.karger.com/ort Antiangiogenic or Antimetastatic Agents 1 Biomarkers 2 Breast Cancer – Adjuvant Therapy 10 Breast Cancer – Local-Regional Therapy 15 Breast Cancer – Metastatic Breast Cancer 17 Cancer Prevention 21 Cell Cycle, Apoptosis, Angiogenesis 22 Cell-Based Therapy 23 Central Nervous System Tumors 24 Clinical Trial Design 27 Developmental Therapeutics: Immunotherapy 29 Developmental Therapeutics: Molecular Therapeutics 31 Economy 32 Epidemiology 33 Functional Imaging 38 Gastrointestinal (Colorectal) Cancer (including liver metastases) 39 Gastrointestinal (Noncolorectal) Cancer 50 Gastrointestinal Stromal Tumors 57 Genitourinary Cancer including Prostate Cancer 58 Gynecologic Cancer 65 Head and Neck Cancer 76 Health Services Research 79 Leukemia, Myelodysplasia, and Transplantation 84 Lung Cancer – Adjuvant Therapy 86 Lung Cancer – Local-Regional Therapy 86 Lung Cancer – Metastatic Lung Cancer 87 Lymphoma and Plasma Cell Disorders 92 Miscellaneous 92 Molecular Pathology 95 Molecular Targets 96 Oncological Pharmacy 100 Paediatric Cancer 101 Palliative Care 101 Patient Care 102 Phase I Studies 105 Psychooncology 106 Quality-of-Life Management 111 Radiation Biology 114 Inhalt Oncol Res Treat 2014;37(suppl 1):VI Sarcoma 115 Skin Cancer including Melanoma 118 Stem Cells in Cancer 119 Supportive Care 120 Surgical Oncology 124 Tumor and Cell Biology 127 Tyrosine Kinase Inhibitors 131 Pflegerische Beiträge 132 Autorenindex 134 Imprint © 2014 S. Karger GmbH, Freiburg Fax +49 761 4 52 07 14 [email protected] www.karger.com Accessible online at: www.karger.com/ort II Inhalt Index Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 Antiangiogenic or Antimetastatic Agents ID 285 Dimethylfumarate suppresses prostate cancer cell proliferation and fortifies chemotherapeutic action I. Hrgovic1, E. Valesky1, R. Rustemeyer1, T. Hailemariam-Jahn1, F. Roos2, A. Pinter1, R. Kaufmann1, M. Meissner1 Universitätsklinik Frankfurt, Klinik für Dermatologie, Venerologie und Allergologie, Frankfurt, Deutschland 2 Universitätsklinik Mainz, Klinik für Urologie, Mainz, Deutschland 1 Recent evidence suggests, that Dimethylfumarate (DMF), known as a highly potent anti-psoriatic agent, might have anti-tumorigenic properties. To analyze, the effects of DMF on prostate carcinoma cell lines, we first performed cytotoxicity assays with the androgen dependent cell line LNCAP and the androgen independent cell line PC-3. No LDH release could be demonstrated. In further analysis we could show, that DMF suppresses prostate carcinoma cell proliferation in a concentration dependent manner. These effect could be paralleled with reduced prostate specific antigen (PSA) expression. In functional tumor invasion assays we could demonstrate that DMF treatment reduces prostate cancer cell invasion almost as effective as the first-line chemotherapeutic Docetaxel. To examine whether these effects are conveyed by apoptotic mechanisms we performed apoptosis assays. There was no significant apoptosis induced by DMF in both cell lines. Therefore, we performed cell cycle analysis. DMF induced an G0/G1 arrest in both prostate carcinoma cell lines. Interestingly, in LNCAP DMF induced p53, p21 and p27 whereas in PC-3, which harbors a p53 mutation, only p21 and p27 were induced. In further experiments, possible additive effects of DMF treatment combined with Docetaxel, were evaluated. Here, it could be demonstrated, that the combination of both agents is more effective than the chemotherapeutic agent alone. These data provide first evidence, that DMF inhibits prostate cancer proliferation by reinduction of important cell cycle inhibitors. The combination of Docetaxel and DMF provides additive anti-cancer effects. Hence, DMF might be an interesting agent in the treatment of prostate cancer and is worth for further in vivo analysis. ID 424 2-Methoxyestradiol impairs lymphangiogenesis through G2/M cell cycle arrest and apoptosis I. Hrgovic, M. Doll, A. Pinter, S. Kippenberger, E. Valesky, R. Kaufmann, M. Meissner Klinikum der Johann Wolfgang Goethe-Universität, Klinik für Dermatologie, Venerologie und Allergologie, Frankfurt am Main, Deutschland Question: Lymphangiogenesis is a crucial step in the progression of cancer. Formation of new lymphatic vessels provides an additional route for tumor cells to metastasize. Therefore, inhibiting lymphangiogenesis represents an interesting target in cancer therapy. 2-Methoxyestradiol (2-ME) is a physiological metabolite of estradiol with low cytotoxicity. As 2-ME promotes anti-angiogenic effects on endothelial cells, we hypothesized that 2-ME may have impact on lymphangiogenesis. Methods: Human lymphatic endothelial cells (LEC) were cultured in vitro and treated with or without 2-ME. Effects of 2-ME on proliferation, cell cycle progress and apoptosis were analyzed mainly by Bromdesoxy- © 2014 S. Karger GmbH, Freiburg Fax +49 761 4 52 07 14 [email protected] www.karger.com Accessible online at: www.karger.com/ort uridin assay, flow cytometry and immunoblotting. In vitro angiogenesis was investigated using the Matrigel tube formation assay. Results: We found that 2-ME inhibited cell proliferation in a concentration-dependent manner. Furthermore, we demonstrate that 2-ME induced both G2/M arrest and apoptosis in LEC. Cell cycle arrest was accompanied by up-regulation of p53 and p21, as well as down-regulation of Cyclin B1, Cdc25c and cdc2. In addition, 2-ME induced apoptosis by cytochrome c release, activating Caspase-9, -7, and -3 and cleavage of poly-(ADP-ribose) polymerase and up-regulation of the pro-apoptotic Protein Bim, whereas cleavage of Caspase 8 was unaffected by higher concentrations of 2-ME. Moreover, 2-ME induced in a time-dependent manner an activation of ERK1/2 and JNK in LEC. Inhibition of JNK- and ERK1/2-pathway reduced 2-ME-induced apoptosis of LEC. In further analysis, we could demonstrate an inhibition of the formation of capillary like structures by 2-ME treatment. Conclusion: Our results demonstrated that 2-ME has distinct anti-lymphangiogenic effects by arresting cell cycle in G2/M phase and activating the intrinsic apoptotic pathway. ID 426 HDAC inhibitors decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p53/p21-dependent pathways I. Hrgovic, M. Doll, A. Pinter, S. Kippenberger, E. Valesky, R. Kaufmann, M. Meissner Klinikum der Johann Wolfgang Goethe-Universität, Klinik für Dermatologie, Venerologie und Allergologie, Frankfurt am Main, Deutschland Question: Lymphangiogenesis is a crucial step in the progression of cancer. Formation of new lymphatic vessels provides an additional route for tumor cells to metastasize. Therefore, inhibiting lymphangiogenesis represents an interesting target in cancer therapy. Recent evidence suggests that histone deacetylase inhibitors (HDACi) may mediate part of their antitumor effects by interfering with angiogenesis. We therefore examined the potential impact of three different HDACi, trichostatin A (TSA), sodium butyrate (NaB) and valproic acid (VPA) on cell proliferation in primary human lymphatic endothelial cells (LEC). Methods: Human lymphatic endothelial cells (LEC) were cultured in vitro and treated with or without HDACi. Effects of HDACi on proliferation, cell cycle progress and apoptosis were analyzed mainly by BrdU-Assay, flow cytometry and immunoblotting. Results: HDACi inhibited cell proliferation in a concentration-dependent manner. We found that TSA induced G0/G1 arrest in LEC. Cell cycle arrest was accompanied by up-regulation of p53 and p21. Moreover, we found that p21 mRNA was significantly up-regulated by TSA, while the protein and mRNA half-life remains largely unaffected. The promoter activity of p21 was enhanced by TSA indicating a transcriptional mechanism. Subsequent EMSA analyses showed increased constitutive Sp1/3-dependent DNA binding in response to HDAC inhibition. We demonstrated that p53 was required for TSA induced p21 expression. Interestingly, siRNA-mediated p21 depletion reduced the antiproliferative effects of TSA in LEC. In addition, TSA induced apoptosis by cytochrome c release, activating Caspase-9/-7 and down-regulating the anti-apoptotic proteins cIAP-1/-2. Conclusion: In conclusion, we demonstrate that HDACi have distinct anti-lymphangiogenic effects by activating the intrinsic apoptotic pathway and cell cycle arrest via p53/p21-dependent pathways. Inhalt Index Biomarkers ID 017 Osteopontin, vascular endothelial growth factor and carbonic anhydrase 9 as potential biomarkers in the radiochemotherapy of non small-cell lung cancer C. Ostheimer1, M. Bache1, A. Güttler1, M. Kotzsch2, D. Vordermark1 Martin-Luther-Universität Halle-Wittenberg, Klinik für Strahlentherapie, Halle, Deutschland 2 Technische Universität Dresden, Institut für Pathologie, Dresden, Deutschland 1 Background: Prognosis and therapeutic outcome of advanced stage non small-cell lung cancer (NSCLC) remains poor and combined radiochemotherapy often is the definite treatment. However, hypoxic radioresistance limits the response to radiotherapy. This prospective study evaluated the inter-relationship and prognostic quality of hypoxia-related proteins in NSCLC patients treated by radiochemotherapy. Material and Methods: Pre-treatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase 9 (CA 9) plasma levels were determined by ELISA in 55 NSCLC (M0) patients. Treatment consisted of a 66-Gy curative-intended radiotherapy ± chemotherapy. Biomarker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was assessed. Results: All biomarkers linearly correlated and were linked to different clinical parameters including weight loss (OPN), gross tumor volume (VEGF) and T stage (CA 9). Single marker plasma levels of OPN (p = 0.03), VEGF (p = 0.02) and CA 9 (p = 0.04) significantly predicted overall survival. Biomarker combination correlated additively with prognosis and increased the risk of death by a factor 2. The effect was most pronounced with the triple combination OPN/VEGF/CA 9, yielding a 6-fold risk of death (p = 0.009). Combined plasma levels of OPN/VEGF/CA 9 were independent predictors of survival in a multivariate analysis (p = 0.03). Conclusions: These results suggest that a biomarker co-detection augments the prognostic value of single markers. The studied proteins should be considered for a hypoxic biomarker profile which might help identifying patients with hypoxic and radioresistant tumors. ID 050 Comparison of the prognostic significance of immunoglobulin kappa C, CD4 and CD8 in node-negative breast cancer M. Schmidt1, B. Hellwig2, I. Sicking1,2, M. Battista1, S. Gebhard1, A. Lebrecht1, M. Gehrmann3, R. Wirtz3,4, G. Hoffmann1, C. Solbach1, J. Rahnenführer1,2, J. Hengstler1,2,5 Universitätsmedizin Mainz, Frauenklinik, Mainz, Deutschland Technische Universität, Institut für Statistik, Dortmund, Deutschland 3 Bayer GmbH, Leverkusen, Deutschland 4 Stratifyer, Köln, Deutschland 5 Technische Universität, Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Deutschland 1 2 Background: The prognostic significance of tumor-infiltrating lymphocytes in breast cancer is well accepted. We compared the prognostic relevance of immunoglobulin kappa C (IGKC), CD4 and CD8 in node-negative breast cancer using mRNA expression. Methods: Microarray based gene-expression data for IGKC (214669_x_ at), CD4 (203547_at) and CD8 (205758_at) were analyzed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n = 824). The prognostic significance for metastasis-free survival (MFS) was compared using a likelihood-ratio-test in the whole cohort as well as in different molecular subtypes (luminal A, luminal B, basal-like, HER2+). Results: IGKC (p < 0.001) had the strongest independent association with MFS in the whole cohort of node-negative breast cancer patients. 2 Oncol Res Treat 2014;37(suppl 1):1–133 CD4 (p < 0.05) and CD8 (p < 0.05) showed only a significant association with MFS in univariate analysis. In luminal A breast cancer, neither IGKC nor CD4 nor CD8 were associated with MFS. In luminal B tumors, only IGKC retained independent prognostic significance (p < 0.001). IGKC showed univariate significance in basal-like breast cancer (p < 0.05) and retained the significance when included in the model as second variable after CD4. In HER2+ breast cancer, IGKC (p < 0.001) as well as CD4 (p < 0.05) and CD8 (p < 0.05) displayed univariate significance but only IGKC maintained independent relevance (p < 0.05). Conclusion: IGKC as marker of the humoral immune system showed the strongest association with MFS in node-negative breast cancer as compared to CD4 or CD8. There were marked differences in the prognostic relevance between different molecular breast cancer subtypes. ID 079 Immunological parameters as predictive and prognostic biomarkers for chemoradioimmunotherapy of patients with pancreatic adenocarcinoma A. Bazhin, J. Werner, S. Karakhanova Chirurgische Uniklinik Heidelberg, Heidelberg, Deutschland Pancreatic adenocarcinoma (PDAC) has a particularly poor prognosis with a median survival of 6 months. Nowadays the standard treatment today is surgical resection and subsequent adjuvant chemotherapy. This is possible in about 20% of all patients, and results in a median survival of over 20 months. Chemoradioimmunotherapy of patients with pancreatic adenocarcinoma (CapRitrial) did not show benefit of interferon-α adding to 5-fluorouracil based treatment protocol. However, the clinical outcome represented the best ever reported survival for patients with resected pancreatic cancer in adjuvant setting. The aim of the present work was to identify immunological parameters in a group of patients treated with chemoradioimmunotherapy, which could be useful for predictive and/ or prognostic purpose.Here we provide evidence that high lymphocyte number before the therapy correlates positive with better disease-free and overall survivals. An increase in effector cytotoxic T cells or a high increase in effector memory CD8+ T cells after interferon-α injection have a positive correlation with the patients’ outcome during the therapy. Moreover a decrease in CD4 cells expressing immunosuppressive molecule CD152 is associated with better disease-free survival. Thus, tmmunological parameters, identified in this trial as possible surrogate blood markers, may be of interest and importance in context of the personalized medicine for improvement of PDAC patients’ treatment, after a validation in a prospective setting. ID 085 WTZ-Tumorprofil – A preemptive biomarker profiling program in relation to personalized clinical drug development at a large German Comprehensive Cancer Center: Two years’ experience. M. Wiesweg1, S. Ting2, H. Reis2, K. Worm2, S. Kasper1, S. Bauer1, T.C. Gauler1, A. Welt1, H. Richly1, M. Tewes1, J. Meiler1, J. Hense1, W.E. Eberhardt1, C. Derks1, D. Cortes-Incio1, S. Skottky2, J. Wohlschläger2, F. Breitenbücher1, L. Freitag3, G. Stamatis3, K.W. Schmid2, M. Schuler1,3 Universität Duisburg-Essen, Westdeutsches Tumorzentrum, Innere Klinik (Tumorforschung), Essen, Deutschland 2 Universität Duisburg-Essen, Westdeutsches Tumorzentrum, Institut für Pathologie und Neuropathologie, Essen, Deutschland 3 Universität Duisburg-Essen, Westdeutsches Lungenzentrum, Ruhrlandklinik, Essen, Deutschland 1 Background: Biomarker-guided treatment of metastatic lung cancer, GIST or melanoma has set unprecedented examples for effective targeted therapies. Multiple investigational drugs are explored in patient populations defined by specific biomarkers of low prevalence, demanding a novel process of patient identification for early clinical trials. Here we Abstracts Inhalt Index describe a biomarker program linked to the standard diagnostic algorithm which has been initiated at the West German Cancer Center, one of 12 German Oncology Centers of Excellence. Methods: In addition to standard diagnostic procedures, profiling is offered to all patients with advanced lung or colorectal cancer, who meet generic study inclusion criteria. Biomarkers comprise oncogenic ‘driver’ mutations (KRAS, NRAS, EGFR, BRAF, PIK3CA, DDR2), gene amplifications and translocations (HER2, ALK, FGFR, PIK3CA, ROS1), and PTEN loss, following prespecified algorithms. The clinical course of ‘profiled’ patients is closely monitored offering trial participation whenever applicable. Results: 410 patients (301 NSCLC, 109 CRC) have been profiled in 20 months. The most prevalent biomarkers were KRAS mutations (29%) for adeno NSCLC, FGFR1 amplification (25%) for squamous NSCLC, and KRAS (38%) and BRAF (6%) mutations for CRC. 21 patients have entered biomarker-guided clinical trials, while therapeutic decisions for approved drugs were guided in 68 patients. Conclusion: Preemptive biomarker profiling was established as part of the diagnostic algorithm of a large Comprehensive Cancer Center, enabling the prospective identification of patients eligible for biomarker-guided trials. High patient numbers and substantial investments are mandatory. ID 094 The detection of excision repair cross-complementing rodent repair deficiency, complementation group 1-positive circulating tumor cells in the blood of ovarian cancer patients as a predictive biomarker for platinum-resistance J.D. Kuhlmann1, P. Wimberger1, A. Bankfalvi2, T. Keller3, S. Schöler2, B. Aktas4, P. Buderath4, S. Hauch5, R. Kimmig4, S. Kasimir-Bauer4 Universitätsklinikum Dresden, Klinik für Frauenheilkunde und Geburtshilfe, Dresden, Deutschland 2 Universitätsklinikum Essen, Institut für Pathologie und Neuropathologie, Essen, Deutschland 3 Acomed Statistics, Leipzig, Deutschland 4 Universitätsklinikum Essen, Klinik für Frauenheilkunde und Geburtshilfe, Essen, Deutschland 5 Adnagen AG, Langenhagen, Deutschland 1 Platinum-resistance constitutes one of the most recognized clinical challenges for ovarian cancer. Primary tumor-based ERCC1-detection by immunhistochemistry was recently shown to be inaccurate for the prediction of platinum-resistance. Considering our previous finding that circulating tumor cells (CTC) in the blood of ovarian cancer patients are prognostically significant and hypothesizing that negative prognostic impact of CTC may arise from a cellular phenotype, being associated with platinum-resistance, we now inquired, whether ERCC1-expression in CTC may be a suitable biomarker for stratifying response to platinum-based chemotherapy. In total, 245 patients were studied. The presence of CTC was analyzed by immunomagnetic CTC-enrichment, targeting the epithelial epitopes GA 73.3 (EpCAM) and MUC-1, followed by multiplex RT-PCR to detect the transcripts GA733-2 (EpCAM), MUC-1 and Ca 125, including ERCC1 in a separate approach. ERCC1-expression in the primary tumor was assessed by immunhistochemistry (antibody 8F1). At primary diagnosis ERCC1+CTC were observed in 8% of patients and associated with decreased progression-free survival (PFS) and overall survival (OS) (p = 0.037, p = 0.035, respectively). Moreover, multivariate analysis revealed ERCC1+CTC to be an independent predictor for a poor PFS (p = 0.007). Most interestingly, the presence of ERCC1+CTC at primary diagnosis was an independent predictor for platinum-resistance (p < 0.007), whereas ERCC1-expression in corresponding primary tumor tissue predicted neither platinum-resistance, nor prognosis. This is the first report, suggesting a blood-based assay for predicting platinum-resistance at primary diagnosis of ovarian cancer. Abstracts ID 099 Validation of plasma proneurotensin as a novel biomarker for the prediction of incident breast cancer O. Melander1, M. Belting2, P. Almgren1, J. Manjer1, B. Hedblad1, G. Engström1, J. Struck3, U. Kilger3, P. Nilsson1, A. Bergmann3, M. Orho-Melander 1 Skåne University Hospital, Malm, Clinical Research Center, Ent 72, bldg 91, floor 12, Malmö, Schweden 2 Lund University, Section of Oncology, Lund, Schweden 3 Sphingotec GmbH, Hennigsdorf, Deutschland 1 Context: Experimental settings have indicated that Neurotensin regulates both satiety and breast cancer growth. In a first study (Malmö Diet and Cancer Study) increasing fasting plasma Proneurotensin 1-117, a stable peptide derived from the same precursor as Neurotensin, was significantly associated with the development of breast cancer. Objective: To validate in an independent second study the initial finding of proneurotensin being a risk prediction marker for the development of breast cancer. Design, Setting, and Participants: The Malmö Preventive Project (MPP) is a general population study and comprised 18,200 subjects at the timepoint of first re-examination (2002–2006). Of these subjects 1569 women including all women of the entire re-examination cohort who developed breast cancer until 2012 were randomly selected for baseline plasma proneurotensin assessment. The mean age of the women at baseline was 70.0±4.4 years, and all women were free from breast cancer at baseline. Proneurotensin was measured in samples from these fasting women and related to the risk of later breast cancer development, which had occurred until 2012 (130 incident breast cancer events), using multivariate Cox proportional hazards models. Results: In the women of the MPP study, Proneurotensin (hazard ratio [HR] per SD increment of log-transformed proneurotensin) was related to incident breast cancer (130 events; HR, 2.07; 95% CI, 1.77–2.42; P < .001; adjusted for age, BMI and smoking). This Hazard ratio was even stronger than initially observed in the Malmö Diet and Cancer Study (123 events; HR, 1.44; 95% CI, 1.21–1.71; P < .001). The women investigated in the MPP study were about 10 years (mean) older than in the Malmö Diet and Cancer Study. Conclusion: Proneurotensin has been validated in a second cohort as a novel risk stratification marker for the development of breast cancer. ID 100 A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells M. Grimm1, P. Teriete2, S. Schmitt3, T. Biegner4, A. Stenzl5, J. Hennenlotter5, H.-J. Muhs6, A. Munz1, T. Nadtotschi1, K. König7, J. Sänger8, O. Feyen9, H. Hofmann9, S. Reinert1, J.F. Coy9 University Hospital Tuebingen, Department of Oral and Maxillofacial Surgery, Tuebingen, Deutschland 2 Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA, Vereinigte Staaten von Amerika 3 University Hospital Heidelberg, German Cancer Research Center (DKFZ) Flow Cytometry Core Facility, Heidelberg, Deutschland 4 University Hospital Tuebingen, Department of Pathology, Tuebingen, Deutschland 5 University Hospital Tuebingen, Department of Urology, Tuebingen, Deutschland 6 Clemenshospital Muenster, Department of Gynecology, Muenster, Deutschland 7 University Hospital Tuebingen, Department of Anaesthesiology and Intensive Care Medicine, Tuebingen, Deutschland 8 Institute of Pathology, Bad Berka, Deutschland 9 TAVARLIN AG, Pfungstadt, Deutschland 1 Background: Biomarkers allowing the characterization of malignancy and therapy response of oral squamous cell carcinomas (OSCC) or other types of carcinomas are still outstanding. The biochemical suicide mole- Oncol Res Treat 2014;37(suppl 1):1–133 3 Inhalt Index cule endonuclease DNaseX (DNaseI-like 1) has been used to identify the Apo10 protein epitope that marks tumour cells with abnormal apoptosis and proliferation. The transketolase-like protein 1 (TKTL1) represents the enzymatic basis for an anaerobic glucose metabolism even in the presence of oxygen (aerobic glycolysis/Warburg effect), which is concomitant with a more malignant phenotype due to invasive growth/metastasis and resistance to radical and apoptosis inducing therapies. Methods: Expression of Apo10 and TKTL1 was analysed retrospectively in OSCC specimen (n = 161) by immunohistochemistry. Both markers represent independent markers for poor survival. Furthermore Apo10 and TKTL1 have been used prospectively EDIM-blood test in patients with OSCC (n = 50), breast cancer (n = 48), prostate cancer (n = 115), and blood donors/controls (n = 74). Results: Positive Apo10 and TKTL1 expression were associated with recurrence of the tumor. Multivariate analysis demonstrated Apo10 and TKTL1 expression as an independent prognostic factor for reduced tumor-specific survival. Apo10+/TKTL1+ subgroup showed the worst disease-free survival rate in OSCC. EDIM-Apo10 and EDIM-TKTL1 blood tests allowed a sensitive and specific detection of patients with OSCC, breast cancer and prostate cancer before surgery and in after care. A combined score of Apo10+/TKTL1+ led to a sensitivity of 95.8% and a specificity of 97.3% for the detection of carcinomas independent of the tumor entity. Conclusions: The combined detection of two independent fundamental biophysical processes by the two biomarkers Apo10 and TKTL1 allow a sensitive and specific detection of neoplasia in a noninvasive and cost-effective way. ID 101 Plasma Pro-Enkephalin, a stable peptide of the precursor to the endogenous opioid Enkephalin, predicts breast cancer risk O. Melander1, M. Orho-Melander1, P. Almgren1, J. Manjer1, B. Hedblad1, G. Engström1, J. Struck2, P. Nilsson1, A. Bergmann2, M. Belting1 Skåne University Hospital, Malm, Clinical Research Center, Ent 72, bldg 91, floor 12, Malmö, Schweden 2 Sphingotec GmbH, Hennigsdorf, Deutschland 1 Context: Opioid peptides may negatively regulate carcinogenesis and the growth of breast tumors by various mechanisms. Little is known about their role in the development of breast cancer in humans. Pro-Enkephalin A 119-159 (pro-ENK), a peptide derived from the same precursor as Enkephalin, has been developed as a reliable surrogate plasma marker for the unstable Enkephalin. Objective: To test if fasting plasma levels of pro-ENK are associated with development of incident breast cancer. Design, Setting, and Participants: We measured pro-ENK in fasting plasma from 2554 women (mean age 58±5.9 years) of the population based Malmö Diet and Cancer Study (MDCS) free from breast cancer prior to the baseline exam in 1991–1994. pro-ENK was related to first breast cancer events (n = 154) during a median of 14.8 years of follow-up. For replication, we related pro-ENK to risk of later breast cancer development (130 incident events) in an independent sample from the Malmö Preventive Project (MPP) consisting of 1569 women (mean age 70.0±4.4 years), all free from breast cancer at baseline. Results: In the MDCS, pro-ENK was inversely related to risk of incident breast cancer [HR 0.76 (0.65–0.89), P = 0.001)]. Women belonging to quartiles 3, 2 and 1 compared to women belonging to the 4th quartile of plasma pro-ENK had hazard ratios of 1.32 (0.75–2.30), 2.05 (1.23–3.42) and 2.58 (1.56–4.25) (P < 0.001). In the MPP, the odds ratio was 0.63 (0.52–0.75) (P<0.001). As compared to women belonging to the 4th quartile of plasma pro-ENK, women belonging to quartiles 3, 2 and 1 had odds ratios for breast cancer of 2.45 (1.23–4.88), 2.93 (1.49–5.74) and 4.79 (2.51–9.12) (P<0.001). 4 Oncol Res Treat 2014;37(suppl 1):1–133 Conclusion: In two large general population studies low fasting plasma concentration of pro-ENK is strongly associated with increased risk of future breast cancer development in middle aged and post-menopausal women. ID 163 Specific miRNA signatures characterize distant metastases of clear cell renal cell carcinoma at different sites J. Heinzelmann1,2, U. Wickmann2, S. Baumgart1,2, F. Stolzenbach1, R. Schneeweiss1, M. Gajda3, M. Stöckle1, K. Junker1 Universitätsklinikum des Saarlandes, Klinik für Urologie, Homburg, Deutschland 2 Universitätsklinikum Jena, Klinik für Urologie, Jena, Deutschland 3 Universitätsklinikum Jena, Institut für Pathologie, Jena, Deutschland 1 Background: miRNAs are regulators of gene expression in tumorigenesis and progression. To identify miRNAs associated with metastases miRNA expression in distant metastases was compared to primary ccRCC. Material and Methods: Total RNA of 27 primary ccRCC samples and 25 distant metastases (lung, bone and brain) was isolated from formalin-fixed paraffin-embedded (FFPE) samples Microarray analyses were performed for a global miRNA expression profiling. Results were validated by qPCR. Results: We identified 9 miRNAs (including miR-30c and miR-126) with a similar expression in metastatic primary ccRCC and distant metastases from different metastatic sites compared to non-metastatic primary ccRCC. 11 miRNAs (including miR-10b and miR-204) were differently expressed in distant metastases compared to primary ccRCC. Furthermore, each metastatic site is characterized by a specific miRNA signature. Results were verified on selected miRNAs using qPCR. Ongoing in vitro studies are investigating the functional role of miRNAs in metastatic processes of ccRCC. Discussion: These data suggest that miRNAs play an important role in metastatic processes of ccRCC. Furthermore, our results regarding different metastatic sites suggest to two important statements: Specific miRNAs characterize distant metastases in general. On the other hand, miRNA expression is associated with specific conditions at different metastatic sites. Thus, the data presented in this study give the base for a better understanding of the involvement of miRNAs as regulators of metastasis which opens new possibilities for new targeted therapy options. ID 177 A new diagnostic test for monitoring of breast cancer patients A.-R. Rotmann Praxis für Gynäkologie, Rodgau-Nieder-Roden, Deutschland Background: Impaired glucose metabolism and elevated blood glucose levels have been linked with increased cancer risk and cancer mortality. New therapies have been established addressing new targets controlling glucose metabolism in breast cancer patients. Recently it has been shown that the detection of the biomarker transketolase-like-1 (TKTL1) in monocytes allows the detection of upregulated glucose metabolism in cancer patients. The epitope detection in monocytes (EDIM) has been established as a new technology for a non-invasive biomarker based detection and characterization of tumors as well as early detection of recurrence and/or metastasis. The biomarker Apo10 is highly specifically expressed in tumor cells irrespective of the tumor entity and is accumulated in due to blocked apoptosis. Thus, the combined use of the biomarkers Apo10 and TKTL1 offers the possibility to detect abnormal cell proliferation and up-regulated glucose metabolism, indicating neoplasias and the degree of malignancy. This new technology also could be used to identify breast cancer patients that will benefit from existing and new therapeutic approaches. Just re- Abstracts Inhalt Index cently the mTOR inhibitor everolimus has been approved and Metformin has been shown to reduce the incidence of invasive breast cancer. Methods: In a routine gynecological practice we use the test for early detection, for monitoring of patients during treatment and in aftercare. Conclusion: Our data from more than 100 patients with breast cancer for a period up to 4 years are promising results worth to be further validated. This new diagnostic test could be a useful tool to identify and monitor cancer patients and the use of new therapies. ID 182 Expression of progesterone receptor membrane component 1 (PGRMC1) in tissues of breast cancer patients I. Wurster1, C. Meisner1, H. Seeger2, U. Vogel3, H. Schneck4, C. Blassl4, S. Schultz4, T. Fehm4, H. Neubauer4 University of Tuebingen, Institute for Clinical Epidemiology and Applied Biometry, Tuebingen, Deutschland 2 University of Tuebingen, Department of Obstetrics and Gynaecology, Tuebingen, Deutschland 3 University of Tuebingen, Institute of Pathology, Tuebingen, Deutschland 4 Heinrich Heine University of Duesseldorf, Department of Obstetrics and Gynaecology, Duesseldorf, Deutschland 1 Objectives: Progesterone receptor membrane component 1 (PGRMC1) may be important in tumorigenesis and may thus increase the risk for developing breast cancer under certain circumstances e.g. during hormone therapy. The main purpose of this study was to investigate the expression of PGRMC1 in benign and malignant tissues of breast cancer patients. Methods: Matching ‘baseline’ tissue biopsies of 69 breast cancer patients undergoing pre-surgery therapy were analyzed by immunohistochemistry for expression levels of PGRMC1 and its phosphorylated version at serine 180 (pPGRMC1). Associations with clinicopathological parameters, e.g. tumour grading and receptor expression, and patient’s characteristics such as the patient’s age were calculated. Results: PGRMC1 and pPGRMC1 are expressed in breast cancer tissue as well as in connective tissue and are co-expressed with estrogen receptors, but not with progesterone receptor. Every breats cancer specimen showed expression of PGRMC1 and pPGRMC1 with a very strong expression in the cytoplasm of tumour cells. A much weaker signal was detected in connective tissue surrounding the actual carcinoma tissue (p < 0.001). No correlation was observed forthe expression of PGRMC1 and pPGRMC1 with histopathological status, menopausal status, tumour grading or the patient’s age. However, the expression of PGRMC1 and pPGRMC1 appears to be correlated with the expression of certain hormone receptors, especially in the age group of 60–69 years. Stratification for age revealed that pPGRMC1 is significantly higher expressed in elderly patients > 70 years than in the age groups 50–59 and 60–69 years. Conclusion: PGRMC1 is highly expressed in breast tumour tissues and thus may play a decisive role in breast cancer development. Further studies are necessary to reveal how PGRMC1 may be involved in breast carcinogenesis probably triggered by hormone therapy. ID 183 Medroxyprogesterone acetate-driven increase in breast cancer risk might be mediated via cross-talk with growth factors in the presence of progesterone receptor membrane component-1 H. Neubauer1, H. Seeger2, H. Schneck1, A. Mueck2, T. Fehm1 possible carcinogenic effect of MPA remains unclear so far. Progesterone receptor membrane component-1 (PGRMC1) may be important in tumorigenesis and thus may increase breast cancer risk. We investigated the influence of MPA alone and in combination with growth factors on breast cancer cells overexpressing PGRMC1. Methods: MCF-7 cells were stably transfected with PGRMC1 expression plasmid (WT-12 cells). Cells transfected only with the vector were used as control cells (EVC-cells). Medroxyprogesterone acetate (MPA), norethisterone (NET) and progesterone (P) were tested alone and in combination with a mixture of growth factors. Cell proliferation was measured by MTT assay. Results: The growth factor mixture (GF) was able to induce cell proliferation in both cell types, however, the effect was much higher in the WT12 cells. In WT-12 cells both MPA and NET alone significantly increased cell proliferation with values of 40% and 97%, respectively. Progesterone, however, had no effect. In combination with GF MPA significantly further enhanced cell proliferation as compared to the effect of MPA alone and GF alone in both cell lines. NET showed no further increase as compared to NET alone and P had no effect. Conclusions: We could demonstrate a significant proliferative effect of MPA when combined with high concentrations of growth factors. This effect was more pronounced in breast cancer cells overexpressing PGRMC1. These results may be of clinical relevance since in the combined WHI trial an increased breast cancer risk was found during treatment with conjugated equine estrogens plus MPA. ID 190 Analysing the mutational status of PIK3CA in circulating tumor cells from metastatic breast cancer patients F. Meier-Stiegen1, H. Schneck1, C. Blassl1, R. Pedro Neves2, W. Janni3, T. Fehm1, H. Neubauer1 Universitäts-Frauenklinik Düsseldorf, Forschungslabor Life Science Center, Düsseldorf, Deutschland 2 Heinrich-Heine Universität Düsseldorf, Düsseldorf, Deutschland 3 Universitäts-Frauenklinik Ulm, Ulm, Deutschland 1 The frequently altered phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway is involved in the regulation of cellular processes required for breast carcinogenesis. The aim of the project was to develop a method to identify hotspot mutations in the PIK3CA gene in circulating tumor cells (CTCs) of metastatic breast cancer (metBC) patients. From 44 enrolled CTC-positive metBC patients a total number of 57 peripheral blood samples were analysed by CellSearch. Genomic DNA of enriched CTCs was isolated, amplified and analyzed for PIK3CA mutations in exons 9 and 20 which lead to E542K, E545K or H1047R amino acid changes and result in increased PI3K activity. The mutations were detected by using SNaPshot-methodology comprising PCR amplification and single nucleotide primer extension. SNaPshot analysis was established using genomic DNA from different breast cancer cell lines and then successfully transferred to investigate blood samples and single cells. Overall, twelve hotspot mutations in either exon 9/E545K (6/12, 50%) or exon 20/H1047R (6/12, 50%) could be determined within 9 out of 57 (15.8%) blood samples from 7 out of 44 (15.9%) patients; CTC counts ranged from 1 to 9748. PIK3CA variants E542K, E545G and E545A were not detected. Analysing the PIK3CA genotype of CTCs has clinical relevance with respect to drug resistance, e.g. against HER2-targeted therapy. The herein described approach including SNaPshot technology provides a simple method to characterize hotspot mutations within CTCs. Heinrich Heine University of Duesseldorf, Department of Obstetrics and Gynaecology, Duesseldorf, Deutschland 2 University of Tuebingen, Department of Obstetrics and Gynaecology, Tuebingen, Deutschland 1 Background: The WHI trial suggests an increase of breast cancer in postmenopausal women probably according to the progestogenic compound, i.e. medroxyprogesterone acetate (MPA). However, the mechanism for a Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 5 Inhalt Index ID 195 CTCtrap – Circulating Tumor Cells TheRapeutic APheresis: A novel biotechnology enabling personalized therapy for all cancer patients N. Kasprowicz1, F. Farace2, G. Attard3, B. Rack4, C. Vizler5, R. Zamarchi6, M. Scholz7, A. Aaspõllu8, A. Ventola9, L. Terstappen10, T. Fehm1 Heinrich Heine University of Duesseldorf, Department of Obstetrics and Gynaecology, Duesseldorf, Deutschland 2 Institut de Cancérologie Gustave Roussy, Villejuif, Frankreich 3 Institute of Cancer Research, Großbritannien 4 Ludwig-Maximilians University München, Munich, Deutschland 5 Biological Research Centre – Hungarian Academy of Science (BRC), Ungarn 6 Oncology Institute of Veneto IRCCS, Italien 7 LEUKOCARE AG, Munich, Deutschland 8 Asper Biotech Ltd, Estland 9 Aquamarijn Micro Filtration BV, The Netherlands 10 Twente University, Medical Cell Biophysics, Faculty of Science and Technology, The Netherlands 1 Chemotherapy is slowly being supplemented by a new generation of drugs that recognize specific targets in or on cancer cells and has proven to be more effective with markedly fewer side effects. As a consequence renewed tumor analysis is required to redefine the optimal treatment regiment. However a biopsy can frequently not be obtained without risk and or discomfort to the patient. Circulating tumor cells (CTC) may circumvent this problem. CTC refer to cells that detach from a primary tumor or metastatic site, circulate in the peripheral blood and may form metastasis. CTC represent a ‘liquid biopsy’ that can be used to tailor treatment for individual patients. CTC are however rare and can only be obtained for further characterization in a small fraction of patients. In the CTCtrap consortium universities, research institutions and SMEs are linked in a common effort, starting from the simple, but innovative view of using Therapeutic Apheresis (TA), as a way to collect CTC from peripheral blood in cancer patients. A new TA column will be developed to capture CTC and then reintroduce the blood devoid of tumor cells back into the body with the promise to obtain CTC in all patients at risk for recurrence or diagnosed with metastatic disease. The molecular characterization of these CTC is expected to gather new knowledge on metastasis’ mechanism, provide a risk assessment and the optimal therapy choice during the course of the disease of cancer patients. The new knowledge on CTC heterogeneity within cancer type and within individuals will allow for the tuning of CTCapheresis to specific cancer types. Prospective pilot studies will be setup to investigate the feasibility of the CTCapheresis in the clinic and their potential therapeutic benefit. Success of CTCapheresis will lead to a radical change in the diagnosis and treatment of solid tumors. ID 228 Plasma Pro-Enkephalin adds value to Proneurotensin for the risk prediction of incident breast cancer O. Melander1, M. Orho-Melander1, P. Almgren1, J. Manjer1, B. Hedblad1, G. Engström1, J. Struck2, P. Nilsson1, A. Bergmann2, M. Belting3 Skåne University Hospital, Malm, Clinical Research Center, Malmö, Schweden 2 Sphingotec GmbH, Hennigsdorf, Deutschland 3 Lund University, Section of Oncology, Malmö, Schweden 1 Context: Neurotensin regulates breast cancer growth, and plasma Proneurotensin 1-117 (pro-NT), a stable peptide derived from the Neurotensin precursor, is associated with the development of breast cancer. Enkephalin may negatively regulate carcinogenesis and the growth of breast tumors and can be assessed in plasma by measuring a stable surrogate marker, Pro-Enkephalin A 119-159 (pro-ENK). 6 Oncol Res Treat 2014;37(suppl 1):1–133 Objective: To test if plasma levels of pro-ENK add value to pro-NT for the risk prediction of incident breast cancer. Design, Setting, and Participants: We measured pro-ENK and pro-NT in fasting plasma from 1929 women (mean age 58±5.9 years) of the population based Malmö Diet and Cancer Study (MDCS) free from breast cancer prior to the baseline exam. We used Cox proportional hazards models to relate pro-ENK and pro-NT to first breast cancer events (n = 123) within 15 years of follow-up. Results: Pro-ENK: Women belonging to quartiles 3, 2 and 1 of pro-ENK compared to those of quartile 4 had HRs for breast cancer of 1.41 (0.74– 2.69), 2.3 (1.27–4.14) and 3.19 (1.82–5.62). Pro-NT: As compared to women belonging to the 1st quartile of pro-NT, women belonging to quartiles 2, 3 and 4 of pro-NT had HRs for breast cancer of 1.24 (0.69–2.24), 1.61 (0.92–2.82) and 2.37 (1.4–4.01). Adding pro-ENK to pro-NT provided added predictive value (p < 0.0001), and HR for women with pro-ENK in the 1st quartile and pro-NT in the 4th quartile (high risk group) were 4.17 (2.48–7.03) as compared to women with pro-ENK in quartiles 2–4 and pro-NT in quartiles 1–3 (low risk group). Women with one of the biomarkers in high risk still had a slightly increased risk (HR 1.71 (1.16–2.52)) as compared to the low risk group. Conclusion: Biomarker based risk prediction for the development of breast cancer is significantly improved, when plasma pro-ENK is added to pro-NT. ID 260 Analysis of hypoxia-associated miRNA in oral squamous cell carcinoma M. Kappler1, J. Kotrba1, U. Pabst1, H. Wichmann1, S. Rot1, M. Bache2, H. Taubert3, A.W. Eckert1 Martin-Luther-Universität Halle-Wittenberg, Universitätsklinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie, Halle (Saale), Deutschland 2 Martin-Luther-University Halle-Wittenberg, Department of Radiation Oncology, Halle (Saale), Deutschland 3 Friedrich Alexander University Erlangen, Department of Molecular Urology, Erlangen, Deutschland 1 Introduction: Tumor hypoxia plays a pivotal role in tumor progression. Hypoxic tumors are more insensible to radiation or chemotherapy. The identification of hypoxic tumors can improve the overall and disease free survival of oral squamous cell carcinoma [OSCC] patients. Micro RNA [miRNA] are a class of small non-coding mRNA´s. Out of more than 1600 miRNA´s only miRNA 210 has been described as hypoxia-related in OSCC. The aim of the present investigation was to analyze tumor-specific and hypoxia-related miRNA in OSCC and to compare with the expression level of Hypoxia-inducible factor 1 α [HIF-1 α]. Materials and Methods: All expression profiles were performed at 4 commercially available OSCC cell lines [XF354, Cal33, SAS and FaDu]. All cell lines were incubated under normoxic (21% oxygen) and hypoxic conditions (1% oxygen) over 24 hours. The total amount of HIF-1α protein was analyzed by real time protein managing system. Cell lines were investigated by deep sequencing and specific real-time PCR for each cell line in detail after cultivating under different oxygen pressures. Results: MiRNA 210 was upregulated in all 4 cell lines under hypoxic conditions in comparision to normoxia. We found a 3-fold increase of miRNA 210 (p < 0,001). Two other miRNA (miRNA 193, p = 0,012 and miRNA 34, p = 0,07) were also hypoxia-associated in OSCC cell lines with marginal significance. Conclusion: To our knowledge, this is the first investigation detecting miRNA 193 and miRNA 34 as hypoxia-related miRNA in OSCC. We hypothesize, that OSCC tissues have a unique and specific miRNA profile pattern. The detection of hypoxia-related miRNA may help to stratify the therpeutical options in OSCC. Abstracts Inhalt Index ID 263 Circulating microRNAs to monitor preoperative CRT in rectal cancer patients A. Azizian1, J. Salendo1, P. Jo1, M. Grade1, H. Wolff2, M. Ghadimi1, J. Gaedcke1 Universitätsmedizin Göttingen, Allgemein-, Viszeral- und Kinderchirurgie, Göttingen, Deutschland 2 Universitätsmedizin Göttingen, Strahlentherapie, Göttingen, Deutschland 1 Aim: Preoperative chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer. However tumorresponse is heterogenous. An early estimation of response during CRT is desirable as it could enable a modification of therapy at an early stage. To this day there is no reliable biomarker to monitor therapy response. MicroRNAs represent master regulators of gene expression and may therefore contribute to the diversity of response to CRT. The purpose of this investigation is the evaluation of microRNAs as biomarkers for response monitoring during CRT in patients with locally advanced rectal cancer. Methods: In preliminary work five microRNAs (miR-17, miR-18b, miR-20a, miR-31 and miR-193a_3p) were identified as being differently expressed prior to preoperative CRT compared to healthy controls. MicroRNAs were analyzed in the plasma of patients (n = 43) with locally advanced rectal cancer at four time points, namely: prior to-, during-, and after the CRT, and after the surgical resection. Isolation was carried out using Qiagen RNeasy mini kit columns after adding C. elegans miRNA mimics as spike-ins. Expression levels between these time points were compared and correlated to clinical parameters. Results: miR-31 was excluded due to Ct values beyond 40. The remaining miRNAs showed different expression levels over the time period. The reduction of the expression of miR-18b and miR-20a during CRT correlated significantly with a negative postoperative nodal state (p < 0,05). Conclusion: Circulating microRNAs illustrate the potential to monitor the response to CRT in patients with locally advanced rectal cancer. The development of their expression could predict the nodal state of patients even before surgery. Further genome-wide analyses in a larger patient cohort is necessary. ID 272 DNA Methylation Biomarkers SHOX2 and SEPT9 in Blood for Monitoring Disease Progression in Cancer Patients D. Dietrich1, A. Schröck2, A. Leisse1, F. Bootz2, G. Kristiansen1 Institut für Pathologie, Uniklinikum Bonn, Bonn, Deutschland Klinik und Poliklinik für Hals-, Nasen-, und Ohrenkrankheiten, Uniklinikum Bonn, Bonn, Deutschland 1 2 Diagnostic tests for monitoring the course of malignant diseases are of tremendous value for personalized treatment decisions. The identification of patients who are at increased risk for recurrence might allow subjecting them to an adjuvant treatment, i.e. radio- or chemotherapy. Free-circulating tumor DNA in blood holds great potential to detect postoperative residual tumor and occurrence of local and distant metastases. This study aimed to develop and validate a non-invasive biomarker test, to help monitoring the course of patients suffering from head and neck squamous cell carcinomas (HNSCC). Samples from 55 HNSCC patients (cases) were obtained from patients who underwent clinical work-up for confirmed HNSCC at the University Hospital Bonn, Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn. 61 patients (controls) who underwent clinical work-up for suspected HNSCC without any evidence of presence of any malignancy. The HNSCC patients were followed up for up to one year. A sensitive and accurate qPCR assay was used to quantify methylation levels of the methylation biomarkers SHOX2 and SEPT9 in plasma. Increased copy numbers of free circulating methylated SHOX2 and SEPT9 were found in plasma from patients with HNSCC as compared to patients without malignant diseases. A significant decrease of biomarker level was found 4–10 days after tumor resection. Disease Abstracts recurrence and survival was associated with an increase of SHOX2 and SEPT9 methylation in blood during follow-up. This assay may be used to monitor the disease progression in HNSCC patients and therefore identify patients which might benefit from adjuvant therapy. ID 274 Diagnostic and Prognostic Value of SHOX2 and SEPT9 DNA Methylation and Cytology in Benign, Paramalignant, and Malignant Pleural Effusions M. Jung, D. Dietrich, G. Kristiansen Institut für Pathologie, Uniklinikum Bonn, Bonn, Deutschland Pleural effusions (PE) are a common clinical problem. The discrimination between benign (BPE), malignant (MPE) and paramalignant (PPE) pleural effusions is highly important to trigger the appropriate patients’ treatment. Cytology is the gold standard for diagnosing malignant pleural effusions. However, its sensitivity is limited due to the sometimes low abundance of tumor cells and the challenging assessment of cell morphology in cytological samples. This study aimed to develop and validate a diagnostic test, which allows for the highly specific detection of malignant cells in pleural effusions based on the DNA methylation biomarkers SHOX2 and SEPT9. A quantitative real-time PCR assay was developed which enabled the accurate and sensitive detection of SHOX2 and SEPT9 in PEs In a case control study comprising of 114 patients (58 cases, 56 controls) PEs were analyzed by means of cytology and DNA methylation biomarkers. Cytological analysis as well as SHOX2 and SEPT9 methylation resulted in 100% specificity. The combined analysis of cytology and DNA methylation resulted in an increase of 71% positively classified PEs from cancer patients as compared to cytological analysis alone. Furthermore, DNA methylation analysis in PEs allowed predicting the overall survival in cancer patients (Kaplan-Meier analysis, p = 0.041 (SHOX2), p = 0.007 (SEPT9)). The developed test may be used as a diagnostic and prognostic adjunct to existing clinical and cytopathological investigations in patients with PEs of unclear etiology. ID 294 Assessment of breast volume changes during human pregnancy using a threedimensional surface assessment technique in the prospective CGATE study S.M. Jud1, L. Haeberle1, M.O. Schneider1, J. von Wilucki1, A. Hein1, M.C. Koch1, I. Linde1, C.M. Bayer1, F. Faschingbauer1, E. Raabe1, U. Dammer1, R. Schulz-Wendtland2, M.W. Beckmann1, P.A. Fasching 1 Universitäts-Frauenklinik Erlangen, Erlangen, Deutschland Universität Erlangen, Radiologisches Institut – Gynäkologische Radiologie, Erlangen, Deutschland 1 2 Objectives: Pregnancies and breastfeeding are two important protective factorsconcerning breast cancer risk, especially in younger age.Molecular effect are rarely known.The aim of the present study was todocument changes in breast volume during pregnancy prospectively. Methods: In the prospective Clinical Gravidity Association Trial and Evaluation (CGATE) programme, pregnant women were followed up prospectively from gestational week 12 to birth. Three-dimensional breast surface imaging andsubsequent volume assessments were performed. Factors influencing breast volumeat the end of the pregnancy were assessed using linear regression models. Results: 106 women were prospectivley followed from early pregnancy to birth. Breast volumes averaged 420 ml at the start of pregnancy and 516 ml at the end of pregnancy. The first, second and third quartiles of the volume increase were 41, 95, and 135 ml, respectively. Breast size increased on average by 96 ml, regardless of the initial breast volume. Conclusions: Breast volume measurementduring pregnancyusing 3D-technique is feasible. Breast volume increases during pregnancy, but not all womens’ breastsrespond to pregnancy in the same way. Breast Oncol Res Treat 2014;37(suppl 1):1–133 7 Inhalt Index volume changes during pregnancy arean interesting phenotype that can be easily assessed in further studies to examinebreast cancer risk. ID 307 Ki-67 is a prognostic factor in breast cancer patients – findings of a large population-based cohort of a cancer registry E.C. Inwald1, M. Klinkhammer-Schalke2, F. Hofstädter3, F. Zeman4, M. Koller4, M. Gerstenhauer2, O. Ortmann1 Lehrstuhl für Frauenheilkunde und Geburtshilfe der Universität Regensburg am Caritas-Krankenhaus St. Josef, Regensburg, Deutschland 2 Tumorzentrum Regensburg, An-Institut der Universität Regensburg, Regensburg, Deutschland 3 Institut für Pathologie, Universität Regensburg, Regensburg, Deutschland 4 Zentrum für Klinische Studien, Universität Regensburg, Regensburg, Deutschland 1 Introduction: Beside the conventional established histopathological parameters the assessment of proliferation is an emerging field regarding treatment decisions in breast cancer patients. In this respect, the proliferation marker Ki-67 is intensely discussed. The intention of this population-based study was to evaluate routine use and value of Ki-67 as a prognostic parameter, and to analyze associations between Ki-67 and common histopathological and outcome parameters in routine clinical setting. Methods: This study included data from the clinical cancer registry Regensburg (Bavaria, Germany). Patients with primary, non-metastatic (M0), not neo-adjuvant treated breast cancer were considered. Within the total data pool of 4,692 patients who had been diagnosed between 2005 and 2011, in 3,658 (78%) cases Ki-67 was routinely determined. Results: Ki-67 expression was associated with all common histopathological factors (P < 0.001). Regarding survival analyses, Ki-67 was classified into five categories (reference category Ki-67 ≤15%) due to a non-linear relationship to overall survival (OS). In multivariable analyses, Ki-67 was identified as an independent prognostic parameter both for disease-free survival (DFS) (Ki-67>45%, P = 0.001) and OS (Ki-67: 26–35%, P = 0.017; Ki-67: 36–45%, P = 0.011; Ki-67>45%, P = 0.002) in breast cancer patients. The 5-year DFS (OS) rate was 86.7% (89.3%) in patients with Ki-67 ≤15% in comparison with 75.8% (82.8%) in patients with a Ki-67 value >45%. Conclusion: The current study was able to demonstrate that Ki-67 is already widely applied in routine clinical work. Ki-67 is associated with conventional histopathological parameters and, even more important, is an independent prognostic parameter for DFS and OS in breast cancer patients. ID 327 Detection and clinical relevance of hematogenous tumor cell dissemination in patients with ductal carcinoma in situ N. Krawczyk1, M. Banys2, I. Gruber3, A. Hartkopf3, D. Wallwiener3, A. Staebler4, S. Becker5, T. Fehm1,5 Universität, Frauenklinik, Düsseldorf, Deutschland Marienkrankenhaus, Frauenklinik, Hamburg, Deutschland 3 Universität, Frauenklinik, Tübingen, Deutschland 4 Universität, Pathologie, Tübingen, Deutschland 5 Universität, Frauenklinik, Frankfurt, Deutschland 1 2 Background: Hematogenous tumor cell dissemination is considered a crucial step in systemic disease progression and predicts reduced clinical outcome in breast cancer patients. Only invasive cancers are assumed to shed tumor cells into the bloodstream and infiltrate lymph nodes. However, recent studies have revealed that disseminated tumor cells (DTCs) may be detected in the bone marrow of patients with preinvasive lesions, i.e. in ductal carcinoma in situ (DCIS). The purpose of this analysis was to examine the incidence and clinical value of DTC detection in DCIS patients. 8 Oncol Res Treat 2014;37(suppl 1):1–133 Methods: 404 patients treated for DCIS at the University Hospital Tuebingen, Germany between 2003 and 2012 were included into this analysis. Bone marrow (BM) aspirates were analyzed by immunocytochemistry (pancytokeratin antibody A45-B/B3) according to the ISHAGE evaluation criteria. Sentinel nodes were analyzed in 316 of these patients by extensive step sectioning and hematoxylin-eosin staining. Results: In 63 of 404 patients (16%) DTCs could be detected. No correlation was observed between BM status and tumor size, grading, histology or Van Nuys prognostic index. In two cases metastatic spread into lymph nodes was observed; isolated tumor cells in a sentinel node were found in one patient. A median follow up of 45 months (range: 3–131 months) was obtained for 356 patients. The differences in overall survival (OS) and disease-free survival (DFS) calculated by log-rank test were not statistically significant (OS: p = 0.088, DFS: p = 0.982). Conclusions: Tumor cell dissemination may be detected in patients diagnosed with DCIS. Whether these cells disseminate from real preinvasive mammary lesions or represent the earliest step of microinvasion, remains unclear. A longer follow-up may be necessary to accurately assess clinical value of these cells in DCIS patients. ID 363 The importance of MACC1 in colon cancer stem cells and adult stem cell signaling M. Hardt1,2, C. Lemos1, D. Schumacher3, C. Regenbrecht3, E. Heiden4, U. Stein1,2 Max-Delbrück-Centrum für Molekulare Medizin, AG Prof. Dr. Ulrike Stein, Berlin, Deutschland 2 Charite Universitätsmedizin Berlin, Experimental and Clinical Research Center, Berlin, Deutschland 3 Charite Universitätsmedizin Berlin, Institut für Pathologie, Berlin, Deutschland 4 Charite Comprehensive Cancer Center, Berlin, Deutschland 1 The gene MACC1 (Metastasis-Associated in Colon Cancer 1) has been affirmed as a biomarker for metastasis in colorectal cancer (CRC). Only a subset of cells within a tumor is endowed with the potential to propagate the latter and concomitantly drives metastasis. Following this cancer stem cell hypothesis, MACC1’s role at the level of the stem cell is of crucial importance and investigated herein. We seek to analyze the expression of MACC1 directly in the stem cell population of CRC patient material, cell lines as well as mouse models available in our lab. For this purpose, primary cultures of patient-derived organoids are currently being expanded to allow for efficient fluorescent-activated cell sorting. Likewise, the intestinal stem cell populations of wild type and mouse models with engineered MACC1 expression will be assessed. At the cell line level, we could already show that the sorting of SW620 cells via CD44 enables differential enrichment of the intestinal stem cell marker Lgr5 together with MACC1. In parallel, we aim to elucidate MACC1’s role in stem cell signaling. Of note, we found that MACC1 levels modulate the expression of Oct4 in CRC cell lines. Overexpression of MACC1 in CaCo2 and SW480 cells was related to an increase in Oct4 mRNA and protein expression. Consistently, knockdown of MACC1 in CaCo2 and SW620 cells resulted in decreased levels of Oct4. In conclusion, we provide here the first molecular link between MACC1 and stem cells. Additional studies will help clarify the nature of the MACC1 and Oct4 interaction and its functional relevance. The finding that the expression of MACC1 is indeed focused in cancer stem cells might further increase its prognostic value and accentuate the importance of MACC1 in carcinogenesis. Abstracts Inhalt Index ID 412 Detection of somatic mutations by next-generation sequencing in a clinical setting C. Schroeder1,2, M. Sturm1, S. Junker1, M. Bitzer3, N. Malek3, B. Sipos4, H.-G. Rammensee5, O. Rieß1,2, P. Bauer1,2 Institute of Medical Genetics and Applied Genomics, Tübingen, Deutschland 2 Genes and Therapy, Tübingen, Deutschland 3 University Hospital Tübingen, Department of Internal Medicine I, Tübingen, Deutschland 4 University Hospital Tübingen, Department of Pathology, Tübingen, Deutschland 5 Institute for Cell Biology, Department of Immunology, Tübingen, Deutschland 1 Next-generation-sequencing (NGS) is a key technology for high-throughput identification of genomic biomarkers that are of prognostic or therapeutic relevance. An increasing number of biomarkers, either of prognostic or therapeutic relevance, are reported by case reports and clinical trials. To face these developments, we founded an interdisciplinary clinical-oncogenetic tumor board at our hospital to coordinate sequencing efforts and discuss sequencing results. Specialists involved in this process are pathologists, geneticists and oncologists. Currently, we offer two cancer gene panels (48 genes hotspot panel, 182 genes complete coding sequence) and exome/transcriptome sequencing to selected patients. Up to now, we analyzed 43 tumor samples with our hotspot panel and a total of 11 samples with our 182 cancer gene panel. The analysis included both FFPE material and native tumor tissue from different cancer entities. Our analysis workflow is automated and variants are tracked by our inhouse database. We were able to identify mutations in common cancer genes like KRAS, TP53, CTNNB1, PIK3CA and ERBB2. Each variant was validated to be somatic (comparison to reference sample, e.g. blood) and confirmed by a second independent sequencing method (e.g. Sanger sequencing). Medical reports were generated within four weeks summarizing variants and current literature. Our data suggest that detection of somatic mutations can be highly automated and standardized. Though, clinical interpretation of the majority of somatic mutations remains challenging and functional studies are needed for translation of somatic mutations into therapeutic decisions. ID 435 Changes in the level of plasma microRNAs in rectal cancer patients J. Salendo Universitätsmedizin Göttingen, Klinik für Allgemein Chirurgie, Göttingen, Deutschland Background: The identification of response in locally advanced rectal cancer (RC) to a 5-FU based chemoradiotherapy (CRT) is a crucial step towards an individualization of the therapy. Recently, the impact of microRNAs (miRNAs) on progression or resistance in cancer has been described. Although their expression changes in patients´ blood has recently been described in different cancer types data in rectal cancer are scarce. Materials/Methods: miRNAs were extracted from patient and healthy control plasma. The 30 differentially regulated miRNAs were retrieved from the comparison of rectal cancer and normal tissue based on miRNA microarray analyses. They were analysed in a first plasma set materials of RC patients and gender matched- healthy controls. Furthermore, a subset of miRNAs was further analysed in plasma of 178 individuals, inclusive the expressions before and after the treatment. Results: Eight miRNAs were chosen for further analyses. Subsequently, in the analysis using larger cohort three miRNAs could be further confirmed. Interestingly, all miRNAs that were overexpressed in tumor tend to have lower expressions in the plasma of RC patients than healthy patients. Comparing pre- and post-therapeutical expressions of patients that underwent neoadjuvant CRT all miRNAs were significantly differentially expressed. Abstracts Conclusion: Our study demonstrated changes on the level of circulating miRNA between RC and healthy patients. Furthermore we identified miRNAs responsive to the neoadjuvant CRT, highlighting the potential of plasma miRNA to observe the response in RC patients. The impact of the level changes after treatment on prognosis will be shown in a comprehensive approach. ID 455 Run-in phase of prospective WSG ADAPT HR+/HER2- trial demonstrates feasibility of early endocrine sensitivity prediction by Recurrence Score and conventional parameters in clinical routine. N. Harbeck1, O. Gluz2,3, D. Hofmann2, H.H. Kreipe4, M. Christgen4, C. Svedman5, S. Shak5, S. Kümmel6, B. Nuding7, N. Rezai8, H. Forstbauer9, R. Würstlein2,10, R.E. Kates2, U. Nitz2,3 Universitätsfrauenklinik Großhadern, Brustzentrum der LMU München, München, Deutschland 2 Westdeutsche Studiengruppe GmbH, Mönchengladbach, Deutschland 3 Ev. Bethesda Krankenhaus, Brustzentrum Niederrhein, Mönchengladbach, Deutschland 4 Medizinische Hochschule Hannover, Institut für Pathologie, Hannover, Deutschland 5 Genomic Health, Inc., Redwood City, Deutschland 6 Kliniken Essen-Mitte, Klinik für Senologie/Brustzentrum, Essen, Deutschland 7 Ev. Krankenhaus Bergisch Gladbach, Brustzentrum, Bergisch Gladbach, Deutschland 8 Luisenkrankenhaus Düsseldorf, Brustzentrum, Düsseldorf, Deutschland 9 Praxisnetzwerk Troisdorf, Hämatologie/Intern. Onkologie, Troisdorf, Deutschland 10 Universitätsfrauenklinik Großhadern, Brustzentrum der LMU München, München, Deutschland 1 Background: Endocrine sensitivity by proliferation response to shortterm preoperative endocrine therapy (ET) is currently not included in adjuvant chemotherapy (CTx) decisions in early breast cancer (eBC). Methods: The ADAPT HR+/HER2- trial includes N0-1 eBC patients (pts) being candidates for adjuvant CTx; it aims to spare CTx by combining genomic assessment by Oncotype DX and endocrine sensitivity testing. Pts receive 3-week preoperative ET: aromatase inhibitors (AI) or tamoxifen. Pts with low (0–11) Recurrence Score (RS) or intermediate RS (12–25) and ET response (central Ki-67post<10%) are recommended to forego adjuvant CTx («low-risk»). Results: By 9/2013, 564 pts (median age 54y) from 33 study sites were enrolled. At 1st pre-planned analysis (5/2013; n = 246): RSlow 21.6%, RSintermediate 57.7%, RShigh 20.7%; respective risk group responders (Ki‑67post <10%): 84.1%, 73.9%, 40.0% (p < 0.001 comparing low/intermediate vs. high). Median Ki‑67 level drop (percentage of pre-treatment value) was 25% in pre- (n = 101) vs. 75% in postmenopausal pts (n = 115) (p < 0.001); median drop by RS group was similar: low 61%, intermediate 53%, high 56% (p = 0.81). Ki-67pre, endocrine regimen/menopausal status, and RS were independent predictors for Ki‑67post. Conclusions: The ADAPT Run-In Phase confirms design estimates of RS and proliferation response to induction ET with >70% ET responders with intermediate genomic risk who could potentially be spared CTx. It indicates feasibility of combining static and dynamic biomarker assessment for individualized therapy in eBC. Survival non-inferiority of intermediate RS/responders vs. low RS pts (active control) will be tested in the ADAPT main phase. Oncol Res Treat 2014;37(suppl 1):1–133 9 Inhalt Index Breast Cancer – Adjuvant Therapy ID 078 Endoxifen and fulvestrant regulate gene expression of estrogen receptor alpha and its co-activators DEADbox5 and 17 M. Hirschfeld , V. Neumann , M. Jäger , T. Erbes , E. Stickeler 1 1 1 1 1 Universitätsfrauenklinik Freiburg, Molekulare Onkologie, Freiburg, Deutschland 1 Background: Application of anti-estrogens remains a standard therapy in ERα -positive breast cancer. Endoxifen acts as a selective receptor down-modulator of ERα function, while fulvestrant acts as a selective receptor down-regulator via an increased ERα inhibition and degradation. RNA helicases p68 (DDX5) and p72 (DDX17) act as co-activators of ERα. DDX17 expression correlates with decreased Her2/neu levels, extended relapse-free periods, and an increase in overall survival rates. In contrast, DDX5 expression is associated with increased Her2/neu levels and higher tumor grading, but not correlated with relapse-free or overall survival. This study aimed for the investigation of potential regulatory effects of the anti-estrogens on the expression of ERα, DDX5 and 17. Methods: In vitro application of endoxifen and fulvestrant. Results: Both drugs created a significant decrease of mRNA and protein expression levels of all target genes. DDX5 and 17 expression levels generally decreased, whereat endoxifen treatment triggered a stronger effect than fulvestrant. While both ERα antagonists caused a uniform decrease in ERα protein levels, DDX protein levels were differentially affected. Fulvestrant triggered a uniform downregulation of DDX5 and 17. In contrast, endoxifen stimulation resulted in an up-regulation of DDX5 and 17 protein. Conclusion: Both ERα antagonists show regulatory effects on ERα, DDX5 and 17 expression. The in vitro data might explain individual therapeutic efficacy or the occurrence of resistance against endocrine therapy dependent on cellular context. The elucidation of DDX status might serve as a useful prognostic tool to estimate efficacy of anti-estrogen treatment in breast cancer therapy. ID 110 Chemotherapy in breast cancer patients – predictors of non-adherence to guidelines L. Schwentner1, A. Wöckel1, R. Van Ewijk2, W. Janni1, R. Kreienberg1, M. Blettner2, S. Singer1,2 1 2 Universität Ulm, Frauenheilkunde und Geburtshilfe, Ulm, Deutschland Universität Mainz, IMBEI, Mainz, Deutschland Background: Guideline (GL) adherence in breast cancer is a significant survival predictor. We investigate what patient-related and physician-related factors predict guideline non-adherence. Methods: 642 primary breast cancer patients were followed from hospital admission till systemic treatment beginning. Multi-disciplinary tumorboard chemotherapy (CT) decisions were documented. Patients completed the Patient Health Questionnaire for psychiatric comorbidities, EORTC Quality of Life (QoL) core questionnaire and questions on specific fears of receiving CT. Somatic comorbidity was assessed by ASA score. Potential predictors of a) treatment decision and b) GL non-adherence were tested in multivariate logistic regressions. Results: GL indicated no CT in 8.5% of cases. Tumorboards suggested CT-administration in 49.8%. Reasons for GL deviations were rarely given. 84.5% of patients agreed with CT-decisions. Reasons for patient non-agreement were fear and cost-benefit unbalance. Actual patient treatment was GL-conform in 98.1%: there were 12 cases of under- and 0 of over-treatment. 20.5% of patients had somatic and 21.6% psychiatric comorbidity. 65% reported being very afraid of CT. Tumorboards less often prescribed CT to patients >75 years (OR 0.4), with somatic comorbidities (OR 0.5) or high fear (0.6). Actual treatment more often deviated from GL for >75 years (OR 0.3) and poor QoL (OR 10 Oncol Res Treat 2014;37(suppl 1):1–133 0.7). Neither tumorboard decisions nor actual treatment correlated with education or psychiatric comorbidity. Conclusions: Age, somatic comorbidity, fears regarding CT and QoL are related to CT-decisions. ID 114 Vaginal estriol-lactobacilli combination (Gynoflor®) therapy and sexual quality of life in breast cancer patients on aromatase inhibitors with atrophic vaginitis M. Mögele1, S. Buchholz1, A. Lintermans2, G. Bellen3, V. Prasauskas4, O. Ortmann1, P. Grob4, P. Neven2, G. Donders5 Lehrstuhl für Frauenheilkunde und Geburtshilfe der Universität Regensburg am Caritas Krankenhaus St. Josef, Regensburg, Deutschland 2 University Hospital Gasthuisberg Leuven, Belgium, Leuven, Belgium, Belgien 3 Femicare vzw, Clinical Research for Women, Tienen, Belgium, Belgien 4 Medinova AG, Zurich, Switzerland, Zurich, Deutschland 5 University Antwerp, Belgium, Antwerp, Belgien 1 Besides the pharmacology parameters this clinical study investigated also effect on sexual domain of QOL during the treatment of BC survivors on AI with vaginal ultra-low-dose estriol-lactobacilli combination tablets Gynoflor®. This was an open label bicentric clinical study in 16 postmenopausal BC survivors on AIs suffering from vaginal atrophy induced sexual disorders. Clinical vaginal atrophy symptoms were assessed by scoring with an 11-point estimation scale (0 = not at all, 10 = worst imaginable feeling). Sexuality parameters of QOL and medication compliance were recorded in patient’s diary. Recruited women underwent an initial treatment for 4 weeks (1 vaginal tablet daily) followed by maintenance therapy (3 vaginal tablets weekly) for 8 weeks. Vaginal dryness continuously improved from a median of score 8 at entry to score 4 at the end of initial therapy, and median score 2 at the end of maintenance therapy. Previous normal sexual activity before the BC diagnosis reported 14 (88%) women. During the BC treatment with AIs this number was dramatically decreased, at study entry – only 3 (19%) of women were sexually active, whereas at the end of the study already 7 (31%) women reported sexual intercourse. The FSSEI demonstrated clear trend for improvement of main domains of sexual QOL (desire, arousal, orgasm and satisfaction), whereas the statistically significant result due to a small number of subjects were seen only for few parameters. Local vaginal ultra-low-dose estriol-lactobacilli therapy (Gynoflor®) in postmenopausal breast cancer (BC) survivors on aromatase inhibitors (AIs) with atrophic vaginitis is a safe treatment (presented earlier) with a positive impact on the sexual domain of quality of life (QOL). ID 153 Guideline Adherence in the Therapy of Young Mothers with Breast Cancer in Germany D. Fischer1, M. Hedderich1, A. Heinrich2, K. Baumann1, A. Rody1, A. Waldmann3 Uni Lübeck, Frauenklinik, Lübeck, Deutschland UKE, Hamburg, Deutschland Uni Lübeck, Institut für Sozialmedizin und Epidemiologie (ISE), Lübeck, Deutschland 1 2 3 Background and Objective: The aim of the study is to analyse the guideline adherence in the treatment of young breast cancer patients in an adjuvant setting. Materials and Methods: A retrospective study analyzed the treatment of 1053 young mothers first diagnosed between 2002 and 2011 with primary breast cancer according to the AGO guideline adherence. The patients participated in a resident mother-child program and were compared to age-heterogeneous cohorts. Results: The median age of the young cohort was 39 years. Their tumors were significantly higher in stage and grading than the older group (51% Abstracts Inhalt Index vs. 44% >T1 stage, 47% vs. 36% N+, 45% vs. 29% G3). The biology of the tumors was significantly worse. Therefore young patients got a significantly more aggressive therapy than older women. The percentage of guideline adherence for the therapeutic modalities for BCT, mastectomy, axillary dissection, hormone therapy, chemotherapy and antibody therapy was >95% in the young patients. However, chemotherapy results differ significantly in comparison to the older group. Conclusion: Young breast cancer patients participating in a resident mother-child program are diagnosed in a worse stage and their carcinomas are more aggressive. Their treatment shows a high level of AGO guideline adherence. It remains unclear to what extent the guideline adherence improves overall survival and disease free survival in this group. ID 176 Long-term results of trastuzumab in the adjuvant treatment of breast cancer, with focus on elderly patients P. Dall1, G. Lenzen2, T. Göhler3, G. Feisel-Schwickeradi4, T. Koch5, V. Heilmann6, C. Schindler7, J. Wilke8, H. Tesch9, J. Selbach10, J. Eggert11, A. Hinke12 Städt. Klinikum, Frauenklinik, Lüneburg, Deutschland Practice, Osnabrück, Deutschland 3 Practice, Dresden, Deutschland 4 Klinikum Kassel, Kassel, Deutschland 5 Klinikum Nürnberg Nord, Frauenklinik, Nürnberg, Deutschland 6 Practice, Günzburg, Deutschland 7 Practice, Leipzig, Deutschland 8 Practice, Fürth, Deutschland 9 Onkologie Bethanien, Frankfurt, Deutschland 10 Practice, Duisburg, Deutschland 11 Practice, Moers, Deutschland 12 WiSP, Langenfeld, Deutschland 1 2 Trastuzumab (T) is a standard treatment in patients (pts) with HER2+ early breast cancer in addition to (neo)adjuvant chemotherapy (CT). This German prospective observation study examined the generalizability of the results from pivotal randomized studies, with the focus on benefits and risks for elderly patients (EP) in the present analysis. 4027 pts were enrolled from 2006 to 2012, unselected regarding age or concomitant/sequential adjuvant CT. Among 3940 evaluable pts, 1013 were EP ≥ 65 years (y) of age (26%). This contrasts to the pivotal studies, with only 6% beyond 65 y in the NSABP/NCCTG studies. More than half of the pts had pT≥2, with EP more often presenting with a larger tumor (56 vs. 48%, p < .0001). As expected, performance status was more impaired in EP (ECOG 0: 53 vs 65%, p < .0001). 94% received CT, 78% as adjuvant, 14% as neoadjuvant treatment (in EP only 8%). The proportion without any (neo)adjuvant CT was higher in EP (8 vs. 5%). T was stopped prematurely more often in EP (11 vs 8%, p = .014). After up to a maximum follow-up of 8 y, 370 relapses were reported so far. Recurrence-free survival is 94.7, 89.8 and 82.9% after 2, 3 and 5 y, respectively, in EP only slightly lower with 93.9, 89.3 and 81.6%, not statistically significant (p = .18, HR = 1.17, 95% CI 0.93–1.47). In the EP subgroup the incidence of cardiac events of all grades was only slightly increased (4.6 vs. 3.9% overall). The maturing follow-up data confirm the beneficial results from the randomized studies. Moreover, the data show that a similar anti-tumor efficiency can be achieved in EP, and suggest that minor age-related differences detected with respect to adjuvant treatment duration, aggressiveness and toxicity do not impair the long-term outcome. Abstracts ID 249 Suitable patients for IORT at the Interdisciplinary Breast Cancer Center Mannheim D. Astor1, E. Sperk1, A. Keller1, G. Welzel1, A. Gerhardt2, M. Sütterlin2, F. Wenz1 Medical Center Mannheim, University of Heidelberg, Department of Radiation Oncology, Mannheim, Deutschland 2 Medical Center Mannheim, University of Heidelberg, Department of Obstetrics and Gynecology, Mannheim, Deutschland 1 Background: Recommendations for suitable patients for intraoperative radiotherapy (IORT) alone are available from the ESTRO (European Society for Radiotherapy and Oncology) and ASTRO (American Society for Radiation Oncology). Several TARGIT (TARGeted Intraoperative radiotherapy) trials under guidance of the Interdisciplinary Breast Cancer Center Mannheim (TARGIT E ‘elderly’, TARGIT C ‘consolidation’, TARGIT BQR ‘boost quality registry’) also include patients with other characteristics. Methods: Between 01/03 and 12/09, 1505 cases were treated. Complete data sets for age, stage (T, N, M), histology, hormone receptor status and metastasis were available in 1108 cases. Recommendations are as follows: ESTRO: >50 years, invasive ductal carcinoma/other favourable histology (IDC), T1-2 ( ≥ 3cm), N0, any hormone receptor status, M0; ASTRO: ≥60 years, IDC, T1-2 ( ≥ 2cm), N0, M0; TARGIT E: ≥70 years, IDC, T1, N0, any hormone receptor status, M0; TARGIT C: ≥50 years, IDC, T1-2 ( ≥ 2cm), N0, positive hormone receptor status, M0; TARGIT BQR: every age, every histology, T1-2 ( ≥ 3.5cm), any hormone receptor status, N0/+, M0/+. Results: Out of the 1108 available cases, 379 cases (34.2%) are suitable for IORT regarding the ESTRO and 175 (15.8%) regarding the ASTRO recommendations. 82 (7.4%) patients were suitable for the TARGIT E trial, 258 (23.3%) for TARGIT C and 671 (60.6%) for TARGIT BQR. Conclusion: The TARGIT E and C inclusion criteria for IORT alone are more conservative than the ESTRO recommendations. Nearly two thirds of the treated patients could be allocated to an IORT boost. ID 262 The prognostic relevance of disseminated tumor cells in primary breast cancer patients – results from a large single-center study A. Hartkopf, T. Fehm, M. Wallwiener, M. Hahn, D. Wallwiener, S. Becker, E. Solomayer, F.-A. Taran Universität Tübingen, Tübingen, Deutschland Background: The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of primary breast cancer (PBC) patients is associated with a worsened prognosis. This is the largest single-center study that determines the impact of DTC on disease free (DFS) and overall survival. Methods: BM aspirates were collected from patients that underwent surgery for PBC at Tuebingen University Hospital, Germany, between 01/2001 and 01/2013. DTC were identified by immunocytochemistry (pancytokeratin antibody A45/B3) and cytomorphology. The DTC-status was compared to other prognostic factors by use of the chi-squared test and survival was analyzed in an univariate (log-rank test) and multivariate analysis (cox regression). Results: 3,141 patients were available for this retrospective analysis. Of these 803 (26%) were DTC-positive. DTC-positivity was associated with larger tumors (p < 0.001), positive lymph nodes (p = 0.001), ER-negative (p = 0.022) and PR-negative (p < 0.001) patients. DTC-positive patients were at an increased risk of death (median OS of DTC- vs. DTC+ patients: n. r. (not reached) vs. 115 (95% CI: 113–118) months, p = 0.004) and disease relapse (median DFS was n. r. in either groups, p < 0.001). Independent factors for OS / DFS were DTC-status, menopausal-status, tumor size, nodal-status, ER-status and PR-status / DTC-status, tumor size, nodal-status and ER-status. Oncol Res Treat 2014;37(suppl 1):1–133 11 Inhalt Index Conclusion: This study confirms the strong and independent prognostic value of DTC-determination in primary breast cancer patients. The DTC-status might help to identify patients that are at an increased risk of death or disease relapse and thus in need for an aggressive adjuvant treatment. ID 280 Radiation-induced modulation in the distribution of lymphocytes in breast cancer patients E.K. Sage1, M. Sedelmayr1, M. Gehrmann1, C. Bayer1, D. Schilling1, M.N. Duma1, T.E. Schmid1, H. Geinitz2, G. Multhoff1 Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, München, Deutschland 2 Krankenhaus der Barmherzigen Schwestern, Radio-Onkologie, Linz, Deutschland 1 ID 270 Application of integrative medicine by postmenopausal breast cancer patients in the PreFace Phase IV study – a prospective, longitudinal trial C.C. Hack1, M.W. Beckmann1, A. Hein1, C.M. Bayer1, C. Rauh1, K. Almstedt1, N.B.M. Hüttner1, W. Janni2, T. Fehm3, N. Maass4, A. Rody5, N. Fersis6, D. Wallwiener7, J. Hübner8, P.A. Fasching1,9 Frauenklinik University Hospital Erlangen, Department of Gynecology and Obstetrics, Erlangen, Deutschland 2 University Hospital Ulm, Department of Gynecology and Obstetrics, Ulm, Deutschland 3 University Hospital Düsseldorf, Department of Gynecology and Obstetrics, Düsseldorf, Deutschland 4 University Hospital Aachen, Department of Gynecology and Obstetrics, Aachen, Deutschland 5 University Hospital Schleswig-Holstein, Campus Lübeck, Department of Gynecology and Obstetrics, Lübeck, Deutschland 6 Hospital Chemnitz, Department of Gynecology and Obstetrics, Chemnitz, Deutschland 7 University Hospital Tübingen, Department of Gynecology and Obstetrics, Tübingen, Deutschland 8 German Cancer Society, Berlin, Deutschland 9 University of California at Los Angeles, David Geffen School of Medicine, Department of Medicine, Division of Hematology/Oncology, Los Angeles, CA, USA 1 Aim: It is known, that a relevant number of breast cancer patients applies integrative medicine in addition to conventional cancer therapy. In particular modern cancer therapies as aromatase inhibitors are associated with considerable adverse effects like ostealgia and arthralgia, what could trigger above all the application of integrative medicine to alleviate the pain. Aim of this presented trial is the registration of the usage of integrative medicine in the adjuvant therapy status during the course of treatment. Methods: The PreFace Study is a Phase IV Study, where postmenopausal and hormone-receptor-positive breast cancer patients are medicated with the aromatase inhibitor Letrozol. As part of a patient diary all patients have been asked to document which integrative medicine has been applied at the time before Letrozol therapy (month 0), at month 6 and at month 12 after start of therapy. For this purpose the PRIO questionnaire was used. Results: 2491 patients of 3524 in all gave particulars to the application of integrative medicine within the total study. Respectively 50%, 54% and 53% of the patients have stated to use actively integrative medicine at month 0, 6 and 12. Before start of therapy the motivation at 44% of the users was the promotion of cancer healing and at 61% the improvement of quality of life. During the course of the PreFace study this motivation dwindled significantly. The most frequently documented methods at start of therapy was nutritional supplement (22%), intake of vitamins (21%) and the devotions (19%). Mistletoe therapy was only mentioned from 3–4% of the patients. The frequency of usage of the most integrative methods did not change during the observation period. Conclusion: Integrative medicine is still frequently used by breast cancer patients. Some methods such as the mistletoe therapy are conducted today only in rare cases from postmenopausal breast cancer patients. 12 Oncol Res Treat 2014;37(suppl 1):1–133 Background: Mounting evidence indicates that radiotherapy has a modulating impact on the immune system. We examined immune cells in peripheral blood of breast cancer patients with or without chemotherapy (ChT) before radiotherapy (RT) with respect to percentual distribution. Methods: Blood samples of 40 patients with breast cancer were collected before, at 30 Gy and at the end of RT, as well as six weeks and six months after RT. Eight of these patients received adjuvant chemotherapy before RT. Five healthy volunteers were used as control. Lymphocyte subpopulations were analysed by flow-cytometry. Results: Our results show that ChT affects the lymphocytes’ count more than RT. Particularly B cells are impacted by ChT. Compared to the control (12.8 ± 1.1%) the number of B cells is reduced significantly to 0.8 ± 0.2% by ChT. There was a partial recovery during RT. Regarding patients with RT only, a significant decrease in B cell count from 11.8 ± 0.8% before RT to 8.0 ± 0.7% at the end of RT was observed. Six months after RT the percentage of B cells almost reaches control level (11.0 ± 0.6%). The fraction of Natural killer cells was elevated after ChT (15.8 ± 2.7%) and decreased to normal levels (9.3 ± 1.4%) at the end of RT. During RT there was a transient increase in the amount of regulatory T cells of 14 ± 2% of the initial level, which was more pronounced without previous ChT (43 ± 3%). Conclusion: Our results indicate that B and T cells are differently sensible to RT and ChT. There are also differences in the recovery time of immune cells after chemo- and radiotherapy. A clearer understanding of the impact of radiation and chemotherapeutic agents on immune cells and activation markers could lead towards new innovative therapy concepts combining RT and ChT with immunotherapy. ID 305 Effects of estriol on growth, gene expression and estrogen response element activation in human breast cancer cell lines C. Lattrich, M. Diller, S. Schüler, S. Buchholz, O. Treeck, O. Ortmann Lehrstuhl für Frauenheilkunde und Geburtshilfe der Universität Regensburg am Caritas-Krankenhaus St. Josef, Regensburg, Deutschland Introduction: Local application of estradiol (E2) to treat vulvovaginal atrophy in postmenopausal breast cancer patients receiving aromatase inhibitors is known to elevate serum estradiol levels and thereby might counteract breast cancer therapy. Thus, vaginal application of estriol (E3) has been recommended for these patients. However, it is unclear to what extent E3 stimulates breast cancer cell growth. In this study, we examined the effect of E3 on growth and gene expression of two human breast cancer cell lines. Methods: We used an established in vitro cell culture assay and compared the effect of E2 and E3 on growth of the estrogen receptor alpha-positive breast cancer cell lines MCF-7 and T-47D testing a wide range of hormone concentrations of 10-12 to 10-7 M. E3 effects on gene expression were examined by means of reporter gene assays, RT-qPCR and Western blot analysis. Results: E3 acted as a potent estrogen and exerted a mitogenic effect on T-47D and MCF-7 cells at concentrations of 10-9 M (288 pg/ml) and higher. With regard to activation of an estrogen response element (ERE) in breast cancer cells, effects of E3 were visible at 10-10 M. The same concentrations of E3 activated expression of the estrogen-responsive gene PR and of the proliferation genes cyclin A2, cyclin B1, Ki-67, c-myc and b-myb, providing molecular mechanisms underlying the observed growth increase. Abstracts Inhalt Index Conclusions: Like E2, low levels of E3 were able to trigger an robust estrogenic response in breast cancer cells. Thus, E3 treatment for postmenopausal breast cancer patients with vulvovaginal atrophy has to be indicated with caution. SEPTEMBRA – a pilot study to detect and analyze circulating tumor cells in breast cancer patients had no impact on further outcome (p > 0,05). Statistically significant impact factors for the whole cohort were application of endocrine therapy on local recurrence-free survival (p = 0,026), age > 60 at time of occurence of contralateral breast cancer (p = 0,009) and stage (p < 0,001) on metastasis-free survival, and stage (p < 0,001) on overall survival. Conclusions: Patients with synchronous or metachronous bilateral breast cancer do not differ regarding further outcome. However, age at occurence of contralateral breast cancer has strong impact on metastasis-free survival. N.S. Kasprowicz1, E. Honisch1, S. Mohrmann1, J. Fischer2, D. Niederacher1, N.H. Stoecklein3, T.N. Fehm1 ID 400 ID 332 Universitätsklinikum, Frauenklinik, Düsseldorf, Deutschland 2 Universitätsklinikum, Institut für Transplantationsdiagnostik und Zelltherapeutika, Düsseldorf, Deutschland 3 Universitätsklinikum, Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Düsseldorf, Deutschland 1 Background: Circulating tumor cells (CTC) are promising biomarkers for diagnosis and systemic therapy in breast, colon and prostate cancer. However, their low detection rates – especially in non-metastatic patients – limit currently their clinical use. Leukapheresis may provide a method to increase CTC yields by analyzing an increased blood volume. Methods: To evaluate leukapheresis in non-metastastic breast cancer (BC) patients, we initiated a prospective pilot-study, SEPTEMBRA. Before and after primary surgery of BC, the patients underwent diagnostic leukapheresis (DLA). Simultaneously, 7.5 ml of peripheral blood was drawn to be analyzed by the current gold-standard, the CellSearch-System® (Veridex, USA). We compared DLA products with peripheral blood samples regarding prevalence and quantity of CTC. Statistical analysis was performed with exact Fisher-test and Mann-Withney-U-test. P-value of <0.05 was regarded as significant. Results: So far, we have included 6 patients with non-metastatic breast cancer. Analysis was performed on 21 peripheral blood samples and 11 DLA products. Analysis shows a significant higher prevalence of CTC in DLA products than in the peripheral blood samples (82% versus 19% p < 0.001). Furthermore, the number of CTCs was higher in DLA products (median 5, range 0–20 vs. median 0, range 0–3; p < 0,001). Conclusion: Our results suggest that leukapheresis (DLA) seems to be able to increase both CTC detection rate as well as CTC yields. Thus we believe that leukapheresis will help to exploit the full clinical potential of CTC as biomarkers for diagnosis and systemic therapy. In the future, we plan to extend this study to metastatic patients and those with neoadjuvant treatment. ID 390 Bilateral breast cancer: Risk factors with impact on clinical outcome A. Meyer1,2, A. Köhler2, R. Hermann2,3, H. Christiansen2 Gemeinschaftspraxis für Strahlentherapie, Hildesheim, Deutschland 2 Medizinische Hochschule Hannover, Klinik für Strahlentherapie, Hannover, Deutschland 3 Zentrum für Strahlentherapie und Radioonkologie, Westerstede, Deutschland 1 Introduction: Unilateral breast cancer patients have a 2–3 fold increased risk of the development of contralateral breast cancer. Little is known about the prognostic outlook after treatment of second primary cancer. Patients and Methods: 331 pat. with bilateral metachronous or synchronous breast cancer were treated with radiotherapy of the breast or the thoracic wall between 01/1998 and 12/2008. Median follow-up was 74 months. Synchronous bilateral breast cancer was defined as occurence of second contralateral tumour within 6 months of diagnosis of first tumor. Results: Further outcome after 2 and 5 years regarding overall survival was 82% and 66%, local recurrence-free survival 83% and 73% and metastasis-free survival 77% and 60%. Synchronous or metachronous occurence of contralaeteral breast cancer had no impact on further outcome regarding the above mentioned end points (p > 0,05). In patients with metachronous contralateral breast cancer the interval between the two breast cancer events Abstracts Impact of adjuvant treatment decisions for survival outcomes in very elderly breast cancer patients (≥75 years) J. Bonacker, A. Stachs, S. Hartmann, J. Stubert, M. Dieterich, B. Gerber, T. Reimer Universität Rostock, Gynäkologie, Rostock, Deutschland Background: The optimal management of adjuvant breast cancer in very elderly women is controversial. The lack of data from clinical trials reduces the value of published guidelines. The aim of our study was to evaluate the impact of prognostic factors and therapeutic applications on survival. Methods: This unicentric study included 452 breast cancer patients aged ≥75 years who received adjuvant therapy between 2000 and 2009. Reported treatment modalities were categorized as optimal or suboptimal standard. Factors with impact on survival (disease-free [DFS], breast cancer-specific [BCSS], and overall survival [OS]) were identified by logrank test and Cox regression. Results: Among 452 patients, 37 women (8.2%) refused any surgery. The rates of suboptimal standard treatment were higher for endocrine (12.8%), systemic (30.8%), and radiation therapy (18.8%). Using log-rank test standard radiotherapy, hormone receptor status, grading, tumor size, and nodal status were significantly related with DFS. The corresponding factors with an impact on BCSS were: standard endocrine therapy, hormone receptor, HER2, and nodal status. Age was significantly associated with OS. Various treatment modalities and prognostic factors maintained their statistical impact on OS. The multivariate analysis will be presented at the DKK 2014. Conclusions: Among this selected cohort, 46.7% of patients were treated with suboptimal standard. The general acceptance of published guidelines showed only a marginal effect on BCSS. However, standard radiation (DFS) and endocrine therapy (BCSS) revealed a significant impact on survival outcomes. Both should be considered in treatment decisions with respect to patient’s health status. ID 437 Pathological complete response rates in patients with BRCA1/2-associated breast cancer after neoadjuvant chemotherapy L. Richters1,2, K. Rhiem1, B. Wappenschmidt1, M. Kiechle3, R. Schmutzler1 Universitätsklinkum Köln, Zentrum für Familiären Brust- und Eierstockkrebs, Köln, Deutschland 2 Universitätsklinikum Köln, Klinik und Poliklinik für Gynäkologie und Geburtshilfe, Köln, Deutschland 3 Frauenklinik rechts der Isar, München, Deutschland 1 Purpose: As shown in previous studies, hereditary breast cancer responds differently to diverse chemotherapeutics. Therefore the present paper investigates retrospectively the rate of pathological complete response (pCR: ypT0 ypN0) and overall response (ORR) in Patients with BRCA1/2-associated breast cancer after differing neoadjuvant regimens. Methods: 135 cases of BRCA1/2-associated breast cancer (BRCA1: n = 101; BRCA2: n = 34) treated with neoadjuvant chemotherapy could be identified in our collective between 1996 and 2013. Mainly inva- Oncol Res Treat 2014;37(suppl 1):1–133 13 Inhalt Index sive-ductal (n = 119), triple-negative (n = 75) and high grade (G3, n = 94) carcinomas were described. Regimens containing anthracyclines (A; n = 9), A and taxans (T) (n = 101), A and T in combination with Platin (P) (N=19) and T with P were compared. Because of their her2/neu-status trastuzumab was applicated in 9 cases, in context of clinical studies bevazizumab (n = 5), lapatinib (n = 1) and sorafenib (n = 1) were administered. Results: Overall 51.1% (n = 135; BRCA1: 55.5%; BRCA2: 38.2%) of the cases showed a pCR, the ORR was 94.6%. After a treatment containing P and A pCR was achieved in 68.8% (n = 16, ORR: 100%), therapies without P containing T and A (n = 74) showed a pCR-rate of 52.7% (ORR: 94.4%). Conclusions: BRCA-associated breast cancers show high ORR and pCR rates. Highest rates can be observed after therapies with platin and anthracyclines in BRCA1-mutation carriers. These results coincide with preliminary data. More extensive analyses are required to evaluate the response rates of hereditary breast cancers after different regimens and their correlation to progression-free and overall survival. Through this an optimized therapy for these high risk patients might be enabled in future. ID 449 Prevalence of circulating tumor cells (CTCs) after adjuvant chemotherapy with or without anthracyclines in patients with HER2-negative early breast cancer (EBC) F. Schochter1, U. Andergassen2, J.K. Neugebauer2, T.W. Friedl1, A. Pestka2, J.K. Jückstock2, B. Jäger1, J.C. Salmen1, P.G. Hepp3, G. Heinrich4, O. Camara5, T. Decker6, A. Ober7, T.N. Fehm3, K. Pantel8, P.A. Fasching9, A. Schneeweiss10, M.W. Beckmann9, W. Janni1, B.K. Rack2 University of Ulm, Department of Obstetrics and Gynecology, Ulm, Deutschland 2 Ludwig-Maximilians-University, Department of Obstetrics and Gynecology, Munich, Germany, Deutschland 3 Heinrich Heine University, Department of Obstetrics and Gynecology, Duesseldorf, Deutschland 4 Medical Office of Gynecology, Fürstenwalde, Deutschland 5 Jena University Hospital, Department of Obstetrics and Gynecology, Jena, Deutschland 6 Medical Office of Oncology, Ravensburg, Deutschland 7 St. Vincenz Hospital, Limburg, Deutschland 8 University Medical Center Hamburg-Eppendorf, Institute of Tumor Biology, Hamburg, Deutschland 9 University Erlangen, Department of Obstetrics and Gynecology, Erlangen, Deutschland 10 National Center for Tumor Diseases, Heidelberg, Deutschland 1 Background: Based on data suggesting a limited benefit of anthracycline-based chemotherapy in HER2-negative early breast cancer (EBC), the SUCCESS C study randomly assigned patients with EBC to a chemotherapy regimen with or without anthracyclines. Given the demonstrated prognostic value of circulating tumor cells (CTCs) in EBC, we compared CTC prevalence after chemotherapy between both treatment arms. Methods: The SUCCESS C trial was a randomized, open-label, Phase III study comparing disease-free survival (DFS) in patients with HER2-negative EBC treated with either 3 cycles of epirubicin, 5-fluorouracil and cyclophosphamide followed by 3 cycles of Docetaxel (FEC-DOC), or 6 cycles of an anthracycline-free regimen with docetaxel and cyclophosphamide (DOC-C). The CTC status at chemotherapy cycle 6 was evaluated using the FDA-approved CellSearch -system (Veridex, USA). Results: CTCs were found in 221 of 1766 patients (12.5%; median 1, range 1–18 CTCs). One CTC was detected in 123 (55.7%), two CTCs in 54 (24.4%), three to five CTCs in 37 (16.7%), and more than five CTCs in 7 (3.2%) of these patients. CTC prevalence after chemotherapy did not differ significantly between the two treatment arms (Chi-square test, p = 0.18). CTCs were detected in 11.5% (103 out of 897; median = 1, range 1–18) of patients treated with anthracycline-containing chemotherapy and in 13.6% (118 out of 869; median = 1, range 1–8) of patients treated with anthracycline-free chemotherapy. 14 Oncol Res Treat 2014;37(suppl 1):1–133 Conclusions: The comparable prevalence of CTCs after chemotherapy indicates that anthracycline-free chemotherapy may not be inferior to anthracycline-containing chemotherapy in HER2-negative EBC. This, however, has to be confirmed by survival analyses. ID 454 Quality of life of Young Mothers with Breast Cancer in Germany K. Baumann1, B. Wedel1, C. Benz-Jansen1, A. Waldmann1, A. Rody1, D. Fischer1 Universtitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Frauenheilkunde und Geburtshilfe,Universitäres Brustzentrum, Lübeck, Deutschland 1 Background and Objective: Aim of the study is to analyse the health-related quality of life in young breast cancer patients in comparison to an age-heterogenous breast cancer cohort and to a young general population. Prevalence markers for a reduced quality of life were identified. Materials and Methods: A retrospective study analyzed quality of life of 517 young mothers (at least 1 child < 12 yrs) first diagnosed between 2006 and 2011 with primary breast cancer. The patients participated in a resident mother-child program. The standardized questionnaire focused on medical, clinical and social data and especially on quality of life (EORTC QLQ-C30, -BR23). Results: The median age of the young cohort was 39 years. Inability to work, being unemployed and a higher body mass index were predictors for a globaly reduced quality of life. Unanticipated treatment and clinical issues did not affect quality of life. Young breast cancer patients compared to the older breast cancer cohort showed a reduced quality of life regarding social, emotional and cognitive functioning. In contrast to this physical and sexual functions and stress by hair loss were significant better tolerated by the younger patients. Compared to the young general population the patients showed a serious reduced quality of life. Conclusion: Young breast cancer patients with children under the age of 12 should be carefully observed because of their high risk of reduced quality of life. Our results may lead to the development of interventional procedures to enhance quality of life in the vulnerable group of young breast cancer patients. ID 456 Febrile neutropenia (FN) and infections under adjuvant chemotherapy of breast cancer with 6 x TC vs. 4 x EC – 4 x Doc: Toxicity data of the WSG planB trial O. Gluz1, D. Hofmann1, R. Von Schumann 1,2, R. Kates1, M. Clemens3, M. Salem 4, T. Reimer5, B. Liedtke6, B. Aktas7, A. Stefek8, A. Pollmanns9, F. Lorenz-Salehi 10, C. Uleer11, P. Krabisch12, D. Augustin13, N. Harbeck1,14, U. Nitz1,2 Westdeutsche Studiengruppe GmbH, Mönchengladbach, Deutschland Ev. Bethesda Krankenhaus, Brustzentrum Niederrhein, Mönchengladbach, Deutschland 3 Klinikum Mutterhaus der Borromäerinnen, Hämatologie/Onkologie, Trier, Deutschland 4 Universitätsfrauenklinik Köln, Brustzentrum Köln/Frechen, Köln, Deutschland 5 Klinikum Südstadt, Fachambulanz für Onkologie, Rostock, Deutschland 6 Ev. Krankenhaus Bergisch Gladbach, Brustzentrum, Bergisch Gladbach, Deutschland 7 Universitätsfrauenklinikum Essen, Essen, Deutschland 8 Johanniter Frauenklinik, Gynäkologie, Stendal, Deutschland 9 Ev. Krankenhaus Oberhausen, Brustzentrum, Oberhausen, Deutschland 10 Dr. Horst-Schmidt Kliniken, Wiesbaden, Deutschland 11 Gemeinschaftspraxis, Hildesheim, Deutschland 12 Klinikum Chemnitz, Frauenklinik, Chemnitz, Deutschland 13 Klinikum Deggendorf, Mammazentrum Ostbayern, Deggendorf, Deutschland 14 Universitätsfrauenklinik Großhadern, Brustzentrum der LMU München, München, Deutschland 1 2 Abstracts Inhalt Index Background: FN and infections are the main causes of advanced grade morbity/mortality in adjuvant therapy of BC. Heterogeneous data for TC are available: 3.3–6.6% with G-CSF support and up to 50% without G-CSF prophylaxis. The advantage of primary G-CSF prophylaxis (PP) is therefore uncertain. Methods: Within in the planB trial HER2- high risk patients with pN0/+ BC were randomized to anthracycline-free schedule (6 × T75C600) vs. 4 × E90C600 – 4 × Doc100. PP was recommended in patients with age ≥ 65 and/ or concomitant diseases. Toxicity was documented at every cycle, graded accorded to CTC 3.0 criteria and compared according to Chi-square test. Results: Out of 2449 randomized patients (TC/EC-Doc: 1222/1227), data of 1930 patients (TC/EC-Doc: 982/948; age > 65 years 180/184) with ≥ 1 adverse event were analyzed. FN was observed in 92 patients (TC/EC-Doc: 48 (4.9%)/44 (4.7%), n.s.; age ≥65 years TC/EC-Doc: 6.7%/4.3%, n.s.). PP was documented within the first cycle at the following rates: TC/ECDoc 11.4%/3.3%, p < 0.01. FN in the first cycle (n = 1680): TC/EC-Doc: 2.3%/0.7%, p = 0.004; with PP 1%/0%; without PP: 2.9%/0.9%, p = 0.003) Infections grade 3–5 (n = 110) where documented in 105 patients (TC/ EC-Doc: 68 (6.6%)/37 (3.9%), p = 0.003). Deaths: TC: 5 (4 × infections, especially gastrointestinal infections, 1 pulmonary embolism). EC-Doc: 1 (infection); p = 0.1. Discussion: Despite more frequent PP TC causes significantly more severe infections, FN at the first cycle, and more therapy-related mortality than EC-Doc (n.s.). Nevertheless, the FN rate is lower than published data for TC. It is recommended to add PP to risk groups (gastrointestinal risks, older patients). Breast Cancer – Local-Regional Therapy ID 161 Application ofreirradiation and hyperthermia in recurrent breast cancer: Long-term results and technological opportunities. G. van Rhoon, M. Linthorst, A. van Geel, M. Baaijens, J. van der Zee Erasmus MC Cancer Institute, Radiotherapy, Rotterdam, Niederlande Introduction: Reirradiation combined with hyperthermia is an effective treatment for recurrent breast cancer. Here we report long-term results of patients treated since 1992. Materials and Methods: 198 patients with subclinical and 250 with irresectable disease were treated, including 36 patients with tissue transfers. All patients were treated with 8 fractions of 4 Gy twice weekly, and 8 (until 1996) or 4 one-hour hyperthermia treatments applied after radiotherapy. Approximately half of the patients received radiotherapy in another institute. Results: In subclinical disease the 3- and 5-year local control (LC) was 83% and 78%. In patients with irresectable disease complete response was 70% and 3- and 5-year LC was 40% and 39%. 5- and 10-year overall survival was 60 and 36% for subclinical disease, and 18 and 10% for irresectable disease. Both LC and toxicity in patients with tissue transfers were similar to those in the other patients. Superficially measured temperatures >43° were associated with more hyperthermia toxicity. Patients irradiated elsewhere had a better LC than patients irradiated in the Erasmus MC. For patients with gross disease, the radiating institute was the only significant factor influencing LC in multivariate analysis. At the same time, patients with subclinical disease irradiated elsewhere had significantly less late grade 3–4 toxicity (7% at 5 years) than patients irradiated in Erasmus MC (15%). Conclusions: These results again show that reirradiation with hyperthermia is worthwhile. Patients with tissue transfers can be treated safely. The better results in patients irradiated elsewhere was unexpected. Hyperthermia toxicity may be decreased when superficially measured temperatures are kept below 43 °C. Abstracts ID 251 Cosmetic Differences after Hypofractionated & Normofractionated Intensity Modulated Radiotherapy in Breast Cancer Patients: An Interim Analysis of the Phase II KOSIMA-Trial (ARO 2010-3) A.Y. Aboumadian1,2, O. Aldabbas1, M. Polednik1, G. Welzel1, F. Wenz1 Universitätsmedizin Mannheim, Heidelberg Universität, Klinik für Strahlentherapie und Radioonkologie, Mannheim, Deutschland 2 Cairo University, Department of Clinical Oncology, Cairo, Egypt 1 Purpose: We aim to compare the cosmetic outcome and treatment side effects between a hypofractionated (HF) and a normofractionated (NF) radiotherapy schedules after breast conserving surgery. Methods: Early breast cancer patients >60 years were stratified in two arms, right sided cases to 40/2.67 Gy and left sided to 50/2 Gy using a tangential intensity modulated radiotherapy (tIMRT) technique. A boost dose of 16/2 Gy was added to patients <70 years. Planning was performed according to strict dosimetric limits. CTC-AE v3 & LENT-SOMA scaled side effects were prospectively documented. Here, we report on early adverse effects at 1 and 6 weeks after end of RT for the first serial 96 patients. Results: Minor differences were present in average breast size (1170 cc vs. 1105 cc) and number of patients receiving a boost (54% vs. 50%) for HF and NF arms respectively. Median age was similar with 69 years. Planning quality was preserved in both groups. The peak incidence of acute G2-dermatitis at 1 week was similar in both arms with 10.4%. At 6 weeks only maximum of G1-dermatitis in 16 and 18% was still observed. Hyperpigmentation was persistent during the first 6 weeks with max. G2 hyperpigmentation of 4.1% vs. 10.4%. Breast edema reached a peak at 1 week and tended to be less incident in the HF arm with G1+2 edema in 22.9% vs. 31.2% in the NF arm. Breast retraction was evident in around 10% of patients at baseline. At 6 weeks it increased to 18.7% in the HF group vs. 25% in the NF group. No grade 3 or 4 adverse effects were observed in all previously mentioned outcome points. At week 6, G3 breast pain was observed in 1 patient in each arm with G2 pain being 10.4% and 6.3% which were close to baseline values. Conclusion: Minimal acute adverse effects are associated with breast IMRT. In the early post therapeutic phase, the hypofractionated treatment schedule seemed to be better tolerated and caused relatively less cosmetic changes. ID 373 Single center experiences with intraoperative radiotherapy as a boost during oncoplastic breastconserving surgery W. Malter1,2, V. Kirn1, R. Bongartz2, R. Semrau2, B. Markiefka3, P. Mallmann1, S. Krämer1 Uniklinik Köln, Brustzentrum der Frauenklinik, Köln, Deutschland Uniklinik Köln, ³Klinik und Poliklinik für Strahlentherapie, Köln, Deutschland 3 Uniklinik Köln, Zentrum für Pathologie, Köln, Deutschland 1 2 Background: Breast-conserving surgery (BCS) is performed in an oncoplastic approach with tumor-specific immediate reconstruction of the partial mastectomy defect. In the attempt to further improve local outcome in breast-conserving therapy we introduced intraoperative radiotherapy (IORT) with low-kilovoltage X-rays as a boost during oncoplastic BCS followed by EBRT. Material and Methods: Between February 2010 and July 2012, a total of 149 patients were treated with IORT as a boost during primary oncoplastic breast-conserving surgery, followed by whole-breast radiotherapy. After mobilisation of glandular tissue the segmental resection borders were narrowed to the applicator using purse-string sutures. Resection defects were definitely reconstructed after IORT-boost using the predefined oncoplastic principles to achieve optimal esthetic results after BCS. Oncol Res Treat 2014;37(suppl 1):1–133 15 Inhalt Index Results: Median age was 58 (range 36–86) years. There were T1 and T2 tumours in 117 and 29 patients, respectively, and N0, N1 and N2 disease in 111, 26, and 12 patients, respectively. The used radiation applicator-sizes ranged between 25 and 40 mm in 79% of the patients. The mean radiation time was 21 (range 18–32) minutes. IORT boost radiotherapy was combined with oncoplastic principles for partial mastectomy reconstruction: glandular rotation (n = 109), dermoglandular rotation (n = 29), tumoradapted reduction mammoplasty (n = 11). Conclusion: IORT as a tumour bed boost with low-kilovoltage x-rays is clinically applicable with low toxicity and complication rates. The method supports the close interdisciplinarity between radiation therapy and breast surgery and can be combined with oncoplastic principles in BCS. ID 378 Targeted breast surgery – classification of oncoplastic techniques S. Krämer, W. Malter, N. Lange, C. Fridrich, P. Mallmann Uniklinik Köln, Brustzentrum der Frauenklinik, Köln, Deutschland Background: Most patients presenting with breast cancer are treated by breast-conserving therapy (BCT). Some of these patients present with poor cosmetic results after surgery. To avoid partial defects after BCT a wide spectrum of reconstructive techniques have been published during the last years – a concept termed oncoplastic breast surgery. To improve clinical utility of oncoplastic breast-conserving surgery we developed a classification of oncoplastic techniques with standardization of indications and surgical performance. Material and Methods: We prospectively defined five major principles in oncoplastic breast surgery based on the localization, size of the segmental resection defect, size of the breast and the necessity for skin resection during breast-conserving therapy. These major principles are: BCT-glandular rotation, BCT-dermoglandular rotation, BCT-tumoradapted reduction mammoplasty, BCT-thoracoepigastric flap, BCT-latissimus dorsi flap. Results: Between November 2008 and November 2011 we performed 952 breast-conserving operations in 913 patients. For reconstruction of the partial resection defect during segmental resection the defined five oncoplastic principles were used as follows: glandular rotation (n = 549; 58%), dermoglandular rotation (n = 149; 16%), tumoradapted reduction mammoplasty (n = 135; 14%), thoracoepigastric flap (n = 27; 3%) and latissimus dorsi flap (n = 92; 9%). Partial mastectomy defects could be reconstructed during BCT with these five oncoplastic principles in 97%. The cosmetic results were good or excellent in 95%. Conclusion: The use of five defined oncoplastic principles allows the reconstruction of segmental resection defects during breast-conserving therapy with highest clinical applicability and results in favourable esthetic outcomes. This approach might be useful in extending the indications for breast-conserving therapy. ID 383 Intraoperativeassessment of macroscopic instantaneous sections to prevent re-resection in IORT patients W. Malter1, S. Kapteina1, F. Thangarajah1, B. Markiefka2, R. Bongartz3, R. Semrau3, M. Hellmich4, S. Krämer1, P. Mallmann1 Uniklinik Köln, Brustzentrum der Frauenklinik, Köln, Deutschland Uniklinik Köln, Zentrum für Pathologie, Köln, Deutschland 3 Uniklinik Köln, Klinik und Poliklinik für Strahlentherapie, Köln, Deutschland 4 Universität Köln, Inst. of Medical Statistics, Informatics and Epidemiology, Köln, Deutschland 1 2 Objective: Local breast-conserving surgery combined with intraoperative (boost) radiotherapy of early breast cancer is becoming a new standard in local therapy during the last years. To get the applicated full dose of IORT translated into an increased local control it is important to reduce 16 Oncol Res Treat 2014;37(suppl 1):1–133 the re-resection rate as low as possible after IORT-boost and to achieve tumor-free resection margins before whole-breast irradiation. Methods: Between 2/2010 and 12/2012 intaoperative boost irradiation was performed after breast-conserving surgery of breast cancer using the INTRABEAM System, Carl Zeiss Surgical, Oberkochen, Germany; 20 Gy, 50 KV x-ray). Breast-conserving surgery was performed in an oncoplastic-targeted concept with segmentally formed resection specimens, which was published elsewhere in combination with IORT. The resected specimens were then analyzed by an experienced pathologist with macroscopically analysis to reveal tumor-free resection margins or close margin situations with targeted re-resectioning before IORT. Results: In 141 patients (pts.) intraoperative boost irradiation was performed. In 13% a re-excision (after IORT-boost) was performed to achieve tumor-free resection margins. In 19 out of 22 pts. (NPV 86,4%; 95% CI 66,7 to 95,3%) the final tumor-free margins were as expected during macroscopically section assessment. In 99 out of 119 pts. (PPV 83,2%; 95% CI 75,5 to 88,8%) the intraoperative margin-assessment of the pathologist revealed correctly tumor-free resection margins during macroscopically analysis of the resected specimens. Conclusion: The macroscopic instantaneous section analysis of resection margins during breast-conserving surgery is a reliable and precise method to estimate tumor-free margins before IORT (boost) irradiation. An experienced breast pathologist is able to do these margin examinations fast and economically based. ID 395 Updates from the TARGIT A trial for the German centers: Local recurrence and survival E. Sperk1, J. Vaidya2, M. Bulsara3, M. Sütterlin4, B. Ataseven5, S. Pigorsch6, P. Feyer7, J.U. Blohmer8, M. Kaufmann9, C. Rödel10, K. Friese11, C. Belka12, E.-F. Solomayer13, J. Fleckenstein14, T.-W. Park-Simon15, M. Bremer16, D. Joseph17, J. Tobias18, M. Baum18, F. Wenz1 Universitätsmedizin Mannheim, Strahlentherapie und Radioonkologie, Mannheim, Deutschland 2 University College London, Breast Surgery, London, Großbritannien 3 The University of Western Australia, School of Population Health, Perth, Australien 4 Universitätsmedizin Mannheim, Universitätsfrauenklinik, Mannheim, Deutschland 5 Kliniken Essen-Mitte, Department of Gynecology and Gynecologic Oncology, Essen, Deutschland 6 Klinikum rechts der Isar Klinik, Poliklinik für Strahlentherapie und Radiologische Onkologie, München, Deutschland 7 Vivantes Kliniken Berlin-Neukölln, Klinik für Strahlentherapie und Nuklearmedizin, Berlin, Deutschland 8 St. Gertrauden-Krankenhaus, Frauenklinik, Berlin, Deutschland 9 Universitätsklinikum Frankfurt, Universitätsfrauenklinik, Frankfurt, Deutschland 10 Universitätsklinikum Frankfurt, Klinik für Strahlentherapie, Frankfurt, Deutschland 11 Klinikum der Universität LMU München, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, München, Deutschland 12 Klinikum der Universität LMU München, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, München, Deutschland 13 Universitätsklinikum des Saarlandes, Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin, Homburg, Deutschland 14 Universitätsklinikum des Saarlandes, Klinik für Strahlentherapie und Radioonkologie, Homburg, Deutschland 15 Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe Gynäkologische Onkologie, Hannover, Deutschland 16 Medizinische Hochschule Hannover, Strahlentherapie und Spezielle Onkologie, Hannover, Deutschland 17 Sir Charles Gairdner Hospital, Department of Radiation Oncology, Nedlans, Australien 18 University College London, Department of Oncology, London, Großbritannien 1 Purpose: Updated results from the randomized TARGIT A trial with 3451 patients were presented at the San Antonio Breast Cancer Sympo- Abstracts Inhalt Index sium in 2012. Now the German cohort of patients was analyzed regarding local recurrence and survival. The German cohort was supposed to be more homogeneous than the international cohort (age, treatment, smaller tumours < 2 cm). Methods: 734 patients were randomized either to the TARGIT group (n = 366), where after breast conserving surgergy (BCS) an IORT was added (20 Gy) during the same procedure. External beam radiotherapy (EBRT, 46–50 Gy) was added per protocol if high risk factors (lymphovascular invasion, positive lymph nodes or resection margins, extensive intraductal component, T2) were present. Or patients were randomized to the EBRT group (n = 368), where BCS was followed by EBRT as a standard procedure (56 Gy to the whole breast). Kaplan Meier estimates (5 years) were performed for local relapse and overall survival. Results: After 5 years, 4 local recurrences as primary endpoint were seen in the TARGIT group and 1 in the EBRT group, p = 0.19. As secondary endpoint 6 deaths (3 breast cancer deaths, 3 non breast cancer deaths) were seen in the TARGIT group and 12 deaths (5 breast cancer deaths, 7 non breast cancer deaths) in EBRT group, p = 0.01. Significantly less non breast cancer deaths were reported after IORT compared to the EBRT group, p = 0.04. No difference could be seen for breast cancer deaths, p = 0.45. Conclusion: Patients treated within the TARGIT A trial in Germany have excellent 5 year outcomes regarding local control and overall survival. A significantly better overall survival was seen in the TARGIT group. Breast Cancer – Metastatic Breast Cancer ID 016 HER1, HER2, HER3 and HER4 – clinicopathologic analysis of matched pairs of primary and cerebral metastatic breast cancer C. Bachmann1, G. Brockhoff2, E. Grischke1, A. Staebler3, J. Schittenhelm4, D. Wallwiener1 Universitätsfrauenklinik Tübingen, Tübingen, Deutschland Universität, Frauenklinik, Regensburg, Deutschland 3 Universität, Pathologie, Tübingen, Deutschland 4 Universität, Neuropathologie, Tübingen, Deutschland 1 2 Background and Aim: HER2 overexpression is a prognostic and predictive factor for development of CNS metastases (BM) in primary breast cancer. Studies have shown that the immunophenotype of distant breast cancer metastases may be different from that of primary tumour, leading to inappropriate choice of systemic treatment. A number of studies have demonstrated that HER3 overexpression is associated with poor prognosis and HER4 is more related with a favourable prognosis in breast cancer. Aim is to study if there is receptor change for ER/PR and HER1–4 status in matched pairs of BM and primary. Methods: 24 consecutive patients with surgical resected BM of breast cancer were enrolled. All patients were treated at the Department of Gynecology, University Tübingen, Germany and got first diagnosis of primary breast cancer between 2001 and 2008. Matched pair analysis of primary and BM were performed with IHC staining for ER/PR/HER1–4. HER2 in situ hybridization was done in cases of IHCconversion or IHC showed 2+. Results: Her2 positive breast cancer patients had higher risk getting BM (52%: Her2 positive) compared to Her2 negative patients. There was almost 100% coincidence of HER2 status in BM and primary and a high discordance for ER/PR status. In almost all cases BM showed loss of receptor positivity (ER/PR). The comparison of HER1/3/4 status of primary and BM showed inhomogeneous results. Conclusion: The HER1–4 status of primary and BM showed inhomogenous results. The impact of Her3/4 expression on prognosis has to be investigated in larger studies. Definite conclusions for HER3/4 expression could not yet be drawn. Abstracts ID 067 Serial Enumeration of Circulating Tumor Cells Predicts Treatment Response and Prognosis in Metastatic Breast Cancer M. Wallwiener1, A.D. Hartkopf2, C. Modugno1, S. Riethdorf3, J. Nees1, D. Madhavan4, S. Schott1, C. Domschke1, I. Baccelli1,4, B. Burwinkel4, F. Marmé1, J. Heil1, C. Sohn1, K. Pantel3, A. Trumpp4, A. Schneeweiss1,5 Uni-Frauenklinik Heidelberg, Heidelberg, Deutschland Uni-Frauenklinik Tübingen, Tübingen, Deutschland 3 Universität Hamburg-Eppendorf, Hamburg-Eppendorf, Deutschland 4 DKFZ, Heidelberg, Deutschland 5 NCT, Heidelberg, Deutschland 1 2 Purpose: To prospectively assess circulating tumor cell (CTC) status at baseline (CTCBL) and after one cycle of a new line of systemic therapy (CTC1C) and changes from CTCBL to CTC1C (CTC kinetics, CTCKIN) for their utility in predicting response, progression-free (PFS) and overall survival (OS) in metastatic breast cancer (MBC). Experimental Design: CTCBL and CTC1C status was determined as negative or positive for < 5 or ≥ 5 CTC/7.5 ml blood using CellSearch™ (Veridex). CTCKIN was categorized as favorable (CTC1C negative) or unfavorable (CTC1C positive). Tumor response was assessed every 2–3 months using the Response Evaluation Criteria in Solid Tumors (RECIST). CTC status and kinetics were tested statistically for correlation with outcome. Results: 126/366 (34%) patients enrolled were CTCBL+, and 56/191 (29%) were CTC1C+. Median PFS and OS (months) were significantly reduced in CTCBL+ vs CTCBL− patients (PFS 4.5 [95% confidence interval 3.6–6.0] vs 7.7 [6.1–9.1]; OS 13.9 [9.7–18.9] vs 33.4 [33.4-not available (na)]), and for CTC1C+ vs CTC1C− patients (PFS 4.1 [3.5–6.1] vs 8.2 [6.7–10.2]; OS 13.1 [7.0–23.9] vs 31.8 [28.2-na]. Unfavorable CTCKIN was significantly associated with progressive disease. Multivariate Cox regression analysis revealed CTCBL+ and ≥3rd-line therapy as independent prognostic factors for shorter PFS, and CTCBL+, bone-plus-visceral/ local metastases, and triple-negative receptor status for shorter OS. Conclusions: CTCBL, CTC1C, and CTCKIN are predictive of outcome in MBC. Serial CTC enumeration is a useful tool to tailor systemic treatment in MBC. ID 068 The prognostic impact of circulating tumor cells in subtypesof metastatic breast cancer M. Wallwiener1, A.D. Hartkopf2, I. Baccelli3, S. Riethdorf4, S. Schott1, K. Pantel4, F. Marme5, C. Sohn1, F. Schütz1, A. Trumpp3, B. Rack6, B. Aktas7, E.-F. Solomayer8, V. Müller4, W. Janni9, A. Schneeweiss5, T.N. Fehm10 Uni-Frauenklinik Heidelberg, Heidelberg, Deutschland Universitäts-Frauenklinik, Tübingen, Deutschland 3 DKFZ, HI-STEM, Heidelberg, Deutschland 4 Universität Hamburg-Eppendorf, Hamburg-Eppendorf, Deutschland 5 NCT Heidelberg, Heidelberg, Deutschland 6 LMU München, München, Deutschland 7 Universität Essen, Essen, Deutschland 8 Universität Homburg, Homburg, Deutschland 9 Universität Ulm, Ulm, Deutschland 10 Universität Düsseldorf, Düsseldorf, Deutschland 1 2 The detection of circulating tumor cells (CTCs) in the peripheral blood of metastatic breast cancer (MBC) patients is an independent marker of prognosis. This large prospective multicenter study aimed to assess the impact of CTCs on overall survival (OS) and progression free survival (PFS) in patients with predefined molecular subgroups of MBC. To this end, 468 MBC patients were divided into three subgroups based on immunohistochemical staining of the primary tumor: (1) hormone receptor-positive/HER2-negative (HorR+/HER2-), (2) HER2-positive (HER2+), and (3) HorR-negative/HER2-negative (HorR-/HER2-) patients. CTC status (≥5 CTCs/7.5 ml blood (CTC-positive)) was deter- Oncol Res Treat 2014;37(suppl 1):1–133 17 Inhalt Index mined using the CellCearch/ system before patients started a new line of therapy. At baseline, 205 (42%) patients were CTC-positive.On multivariate analysis, CTC-positivity was an independent prognostic factor for shorter PFS and OS. In HorR+/HER2- patients, median PFS [95% CI] of CTC-negative versus CTC-positive patients was 8.60 [5.93–11.27] versus 4.33 [3.29–5.38] months (pHER2+ patients 7.60 [5.40–9.79] versus 6.60 [4.20–9.00] months (p = 0.477) and in HorR-/HER2- patients 5.83 [5.09–6.78] versus 3.05 [1.81–4.29] months (pversus 18.07 [11.10– 25.05] months (p = 0.001) in the HER2+ subgroup, and not reached versus 8.57 [4.07–13.07] months in the HorR-/HER2- subgroup (p = 0.001). In conclusion, our results strongly confirm the independent prognostic value of CTC enumeration in MBC patients. In contrast to recent reports, there was no association between primary tumor-based molecular subgroups and the impact of CTC status on OS. Hence, CTC status may help to identify patients who require aggressive therapy, especially among those with triple-negative MBC. ID 120 Baseline results from ACT-FASTER, a prospective cohort study exploring treatmentpatterns with fulvestrant and exemestane in postmenopausal patients with advancedhormone-receptor positive breast cancer under real-life conditions in Germany D. Bauerschlag, N. Maass, W. Greiner, K. Possinger, H. Tesch, S. Zaun, P. Klein, H. Ostermann Uniklinik RWTH Aachen, Gynäkologie, Aachen, Deutschland Introduction: Fulvestrant (FUL) is a selective estrogen receptor down-regulator forpostmenopausal (PMP) women with advanced ER+ breast cancer (ABC) after tamoxifen. Atpresent, there is no definitive recommendation on endocrine therapy (ET) sequencing in ABC. ACT-FASTER aims to generate data on use of FUL 500 mg and exemestane (EXE) under real-life conditions with a focus on different treatment lines. Methods: This is a prospective non-interventional cohort study (NCT01171417) in PMP women with HR+ ABC on treatment with FUL 500 mg (1st, 2nd, 3rd line) or EXE. The two coprimary objectives are: For pts on FUL, to compare the time to progression (TTP) as a function of line of treatment (1st / 2nd / 3rd line); for all pts, real-life data on epidemiology and management, incl. tumour characteristics, co-morbidities and treatments received. Secondary endpoints include outcome parameters (TTP, CBR, OS) and healthcare resource use. Results: Across 115 centers, 493 evaluable pts were enrolled. Mean age was 67.4 years; 85.4% had WHO PS 0-1; 72% had concomitant diseases; 99% were ER+; 87% PgR+. 72% had a recurrence after early disease (EBC). In these, primary therapy for EBC included surgery (97%), radiation (71%) and adjuvant systemic therapy (95%). On study, 87% of pts received FUL for ABC (42%, 37% and 21% as 1st, 2nd and 3rd-line), and 13% EXE. 73% of pts had received prior treatment for ABC. ET (62%) was the most frequent prior therapy for ABC; disease progression the most common reason for changing therapy (64%). Conclusions: ACT-FASTER aims to generate real-life information on ET of PMP patients with ER+ ABC. Consistent with current standards of care, ET was the most frequently used therapy for patients with ER+ ABC prior to initiation of FUL or EXE. ID 130 Metastatic breast cancer: Improving survival in routine care by targeted therapies Methods: Retrospective analysis of all patients with metastatic breast cancer who were treated between 06/1995 and 06/2013. Relevant clinical data were transferred from clinical files into a database and analysed statistically using SPSS and SURVSOFT. Results: 716 female patients with a median age of 61 years (31–93) (time of metastasis) were analysed. 80% were postmenopausal, 21% suffered from primary metastatic disease. Sites of metastases were distributed as follows: 47% visceral, 36% bone, 9% lymph nodes, 4% CNS and 4% others. Mean number of metastatic sites was 1.4 (1–4). Median overall survival was 34 months (0–301+), disease specific survival was 36.8 months. Overall survival was significantly correlated with the sites of metastases, number of involved organs, disease-free survival since initial diagnosis and hormone receptor status. Patients with a hormone receptor positive tumour had a median overall survival of 37 months (0–277+) compared to patients with a triple negative tumour, who showed a median overall survival of 13 months (0–116+). Patients with a HER2-positive tumour had a median overall survival of 35 months (0–301+). Conclusions: Survival of patients with metastatic breast cancer with hormone receptor or HER2-positive tumours can be extended significantly by the sequential use of targeted therapies in routine care. ID 135 The conditional knockdown of bone sialoprotein reveals modulation of genes inversely related to breast cancer skeletal metastasis M. Kovacheva1, S. Berger2, M. Berger1 DKFZ, Toxicology and Chemotherapy, Heidelberg, Deutschland Central Institute of Mental Health, Department of Molecular Biology, Mannheim, Deutschland 1 2 Bone metastasis is a serious complication in breast cancer patients and renders the disease virtually incurable. Bone sialoprotein (BSP) is thought to play an important role in lytic skeletal lesions, though the underlying mechanisms are not clear. We established MDA-MB-231 cell subclones with conditional (doxycycline dependent) miRNA mediated inhibition of BSP production. In these cells tetracycline-dependant transactivator (tTA) stimulates the simultaneous expression of a specific miRNA, of RFP and firefly luciferase. Following 6 days of miRNA expression, BSP concentrations were decreased by 22–86% in the respective cell clones. The function of the genes introduced was investigated by fluorescent microscopy and FACS analyses. BSP knockdown was associated with rounded cells and cell fragments as signs of apoptosis. In order to understand the molecular mechanism triggered by diminished BSP levels, which induce apoptosis, an expression profiling analysis was performed and selected proteins confirmed by western blot. A decrease in BSP concentrations for 6 days led to a modulation of 1.3% of all genes, implicating a specific effect of BSP knockdown. Both, ATF3 and CHOP mRNA levels were elevated more than 5fold, and the corresponding protein levels by 2.4fold and more. The increased expression of these transcription factors was associated with cleavage of caspases 8, 9, 3, 7 and of PARP. In conclusion, these data indicate that BSP knockdown causes specific cellular responses associated with ER stress and activation of intrinsic and extrinsic apoptotic pathways. They also confirm the relevance of BSP in breast cancer skeletal metastasis and render the protein a promising target in the clinical treatment of these patients. R. Weide1, S. Feiten2, V. Friesenhahn2, J. Heymanns1, K. Kleboth2, J. Thomalla1, C. van Roye1, H. Köppler1 Praxisklinik für Hämatologie und Onkologie Koblenz, Koblenz, Deutschland Institut für Versorgungsforschung in der Onkologie, Koblenz, Deutschland 1 2 Objectives: Evaluation of routine care in unselected patients with metastatic breast cancer who were treated in an oncology group practice. 18 Oncol Res Treat 2014;37(suppl 1):1–133 Abstracts Inhalt Index ID 136 Preemptive tumor profiling for biomarker-stratified early clinical drug development in metastatic breast cancer patients A. Welt1, S. Kasper1, M. Tewes1, B. Aktas2, O. Hoffmann2, M. Wiesweg1, S. Ting3, H. Reis3, K. Worm3, H. Richly1, J. Hense1, M.R. Palmer4, B.H. Lee4, J. Wendling1, J. Kossow1, M.E. Scheulen1, C. Lehnerdt1, M. Kohl1, C. Derks1, S. Slottky3, U. Haus5, K. Schmid3, R. Kimmig2, M. Schuler1,6 Westdeutsches Tumorzentrum, Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Essen, Deutschland 2 Westdeutsches Tumorzentrum, Universitätsklinikum, Klinik für Frauenheilkunde u. Geburtshilfe, Essen, Deutschland 3 Westdeutsches Tumorzentrum, Universitätsklinikum, Institut für Pathologie, Essen, Deutschland 4 Novartis Instituts for Biomedical Resaerch, Cambridge, MA, USA 5 Novartis Pharma, Nürnberg, Deutschland 6 German Cancer Consortium (DKTK), Heidelberg, Deutschland 1 Introduction: Multiple drug candidates have been developed to modulate molecular targets in breast cancer (BC) besides hormone receptors and Her2 which may associate with specific biomarker profiles. Exploratory biomarkers are increasingly incorporated in early clinical trials. This demands a new process of patient selection. Here we describe the implementation of preemptive, multiplexed biomarker profiling linked to standard diagnostic algorithms for metastatic BC patients treated at the West German Cancer Center. Methods: Profiling for experimental biomarkers was prospectively offered to patients with metastatic BC who met generic clinical trial inclusion criteria. Formalin-fixed, paraffin-embedded tumor samples were retrieved and studied for potentially ‘actionable’ biomarkers related to active clinical trials by immunohistochemistry, amplicon sequencing, and in-situ hybridization. The clinical course of ‘profiled’ patients was monitored to offer trial participation whenever applicable. Results: We report results from the first 131 patients enrolled in this program. PIK3CA mutations (23%) and amplifications (2%), loss of PTEN expression (13%), and FGFR1 amplifications (8%) were detected next to established biomarkers such as estrogen (67%) and progesterone receptor expression (52%), and HER2 overexpression or amplification (23%). So far 16 ‘profiled’ patients (12%) have been enrolled in biomarker-stratified early clinical trials. Conclusion: Preemptive biomarker profiling can be integrated into the diagnostic algorithm of a large Comprehensive Cancer Center. Extensive administrative efforts are required to successfully enroll ‘profiled’ patients in ‘stratified’ early clinical trials. ID 271 microRNA miR-142-3p inhibits breast cancer cell invasiveness by interfering with WASL / N-WASP- and ITGAV-dependent cytoskeletal function A. Schwickert1, E. Weghake1, K. Brüggemann1, A. Engbers1, J. Seggewiß2, B. Kemper3, C. Stock4, C. Riethmüller5, L. Kiesel1, M. Götte1 Universitätsklinikum Münster, Klinik für Frauenheilkunde und Geburtshilfe, Münster, Deutschland 2 University of Münster, IFG, IZKF, Münster, Deutschland 3 University of Münster, Center for Biomedical Optics and Photonics, Münster, Deutschland 4 University of Münster, Institut of Physiology II, Münster, Deutschland 5 Center for Nanotechnology, Serend-ip GmbH, Münster, Deutschland 1 Aim of Study: MicroRNAs are pivotal post-transcriptional regulators of gene expression. Their differential regulation plays an important role in tumorigenesis and cancer progression. miR-142-3p has been found to be dysregulated in several breast cancer subtypes. We aimed at investigating a potential role for miR-142-3p in breast cancer cell invasiveness. Abstracts Methods: MDA-MB-231, MDA-MB-468 and MCF-7 cell lines were transiently transfected with control or miR-142-3p precursors or antimiR-inhibitors. Target gene expression was monitored by Affymetriy gene array, qPCR, Western blotting and 3’UTR luciferase assay. Cell behaviour was monitored by Matrigel invasion assay. Cell morphology was investigated by confocal immunofluorescence microscopy, nanoscale atomic force microscopy and digital holographic microscopy. Results: miR-142-3p upregulation reduced matrigel invasiveness and lead to reduced expression of WASL, Integrin-αV, RAC1, CFL2, ROCK2, IL6ST, KLF4,PGRMC2 and ADCY9. Microscopyrevealed a restructuring of the intracellular actin cytoskeleton as well as a reduction in cell volume and size. A more cortical actin distribution as well as a loss of invadopodia were observed in cells overexpressing miR-142-3p. siRNA-mediated depletion of WASL and ITGAV resulted in a significant reduction of cellular invesiveness, highlighting the contribution of these factors to the miRNA-dependent invasion phenotype. Conclusions: Our data identify WASL and ITGAV as novel invasion-associated targets of miR-142-3p in breast cancer. With its tumor suppressive potential, miR-142-3p is a promising candidate for future approaches of miRNA-based anti-metastatic cancer therapy. ID 403 Preclinicale evaluation of 5-FdU-Alendornat, a new antimetabolite-bisphosphonate against bone metastasis in a breast cancer mice model S. Schott1, R. Towers2, S. Tiwari32, A.- C. Rambow3, P. Kneissl3, C. Busch4, C. Glüer2, C. Sohn1, W. Jonat3, C. Schem3 Universitätsfrauenklnik Heidelberg, Heidelberg, Deutschland Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für diagnostische Radiologie, Sektion für Molekulares Imaging (MOIN CC), Kiel, Deutschland 3 Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Gynäkologie und Geburtshilfe, Klinik für Gynäkologie und Geburtshilfe, Kiel, Deutschland 4 Universitätsklinikum, Dermatologie, Tübingen, Deutschland 1 2 Bone metastasis occurs among 80% of progressed breast cancer patients with limited therapeutic options. In order to optimize the therapeutic strategies for bone metastasis the antimetaboilte 5-FdU was chemically linked to the bisphosphonate alendronate (ale). The obtained 5-FdU-alendronate-conjugate (5-FdU-Ale) enables a bone targeting. The conjugated BSP-part attaches to the bone matrix. The molecule accumulates and locally metabolises. First in vivo data are presented. Material, Methods: The embryotoxicity of 5-FdU-Ale was evaluated in comparison to ale in the chicken embryo assay at concentrations from 0.01 to 500 mM, incubatied for 72 h. The maximum tolerable dose (MTD) was evaluated in analogue to the NCI acute toxicology determination protocol. In each group, 3 BalbC mice obtained either 200, 100, 50 or 25 mg/kg 5-FdU-Ale i.p. An in vivo mice model, established for bone metastasis, provided fist in vivo data on 5-FdU-Ale in comparison to PBS controls. The mice received 5-FdU-Ale (200 mg/kg) q7d for 5 weeks. A longitudinal follow-Up was performed with the NightOWL LB983; Berthold, weekly. The Bioluminescence of the tumors allowed comparison of the number and size. Additionally the bone mineral density and bone volume/tissue ratio was evaluated with the micro-animal CT scan vivaCT40, Sanco Medical. Side effects were monitored by mice appearance and weight loss. Results: In comparison to ale, that was toxic to all chic embryos with 100 mM after 24 h, the 5-FdU-Ale was toxic with 500 mM. The MTD was not reached with 200 mg/kg. The 5-FdU-Ale group showed significant smaller metastases as well as generally less manifestations in comparison to the controls. The weight loss was significant lower in the therapy than in the control group Further studies are recommended. Oncol Res Treat 2014;37(suppl 1):1–133 19 Inhalt Index ID 413 Clinical utility of the CellSearchTM system to predict radiologically confirmed failure of systemic therapy in patients with metastatic breast cancer: A singleinstitution experience C.M. Kurbacher1, J.A. Kurbacher1, S. Dexel2, U. Schween2, J. Lepique1, R. Reichelt2 Medizinisches Zentrum Bonn-Friedensplatz, Zentrum für Gynäkologie und Geburtshilfe, Bonn, Deutschland 2 L.a.n.c.e. mbH, Bonn, Deutschland 1 Background: The occurrence of circulating tumor cells (CTC) in the peripheral blood of patients (pts) with metastatic breast cancer (MBC) determined by the CellSearchTM system (CSS) is now widely recognized as an adverse prognostic factor. We hereby report on our single-institution experience with the routine use of CSS to monitor pts on systemic treatment (Tx) due to MBC. Methods: A total of 35 pts with MBC were included in this non-interventional study. Systemic Tx was as follows: chemotherapy (CTx), n = 8; endocrine Tx (HTx), n = 9; targeted Tx (TTx), n = 1; multimodal combinations of either CTx or HTx and TTx (MTx), n = 17. Baseline investigations including both CTC determination by CCS and the appropriate radiologic technique were performed immediately prior to start of Tx. A second CTC count was scheduled 6 weeks later. For all CTC counts, a value of > 5 CTCs per 7.5 mL venous blood was considered pathological. The first radiologic tumor reevaluation was performed 12 weeks after Tx initiation and repeated every 12 weeks in cases that did not show clear evidence of disease progression (PD). Results: All pts with radiological PD showed either increasing (n = 12) or decreasing, but non-normalized CTC values (n = 3) Four of these pts had moderately increasing CTC counts within the normal range. In pts lacking radiological evidence of PD, remained normal in 12 cases, normalized in 6 cases and decreased without normalization in another 2 instances. Thus, the positive predictive value (PPV) for the CCS for Tx failure was 73.3% with a negative predictive value (NPV) of 90%. Hence, the overall predictive accuracy for radiological Tx failure was 82.9%. Conclusions: Serial CTC counts are able to predict radiological failure of systemic therapy for MBC. Further propspective trials in this setting are thus extremely justified. ID 421 Eribulin 1,23 mg/m² an d1/8 q3w als Therapieoption beim fortgeschrittenen metastasierten Mammakarzinom in der Klinischen Anwendung D. Benndorf, E. Solomayer, I. Juhasz-Böss Universitätsklinikum des Saarlandes, Gynäkologie, Homburg, Deutschland Fragestellung: Beim fortgeschrittenen metastasierten Mammakarzinom sind nach mehreren Vortherapien die Therapieoptionen zum Teil begrenzt. Seit der Zulassung von Eribulin besteht eine neue Therapieoption. Die klinischen Erfahrungen mit Eribulin sind noch unzureichend. Daher werteten wir unser Patientenkollektiv bezüglich Einsatz und Verträglichkeit von Eribulin aus. Methode: Retrospektive Untersuchung aller Patientinnen an der UFK Homburg die bis heute Eribulin 1,23 mg/m² an d1/8 q3w in der Therapie des metastasierten Mammakarzinoms erhalten haben.Ausgewertet wurden der onkologische Verlauf sowie die Eribulin bedingte Verträglichkeit bzw. aufgetretene Nebenwirkungen. Ergebnisse: Insgesamt n = 14 Patientinnen erhielten im Beobachtungszeitraum Eribulin. Eribulin wurde durchschnittlich im metastasierten Stadium als 3,92 Therapielinie (Range 1–7)sowie in der Gesamttherapie als 6,42 Therapielinie eingesetzt (Range 4–9). Die durchschnittliche Therapiedauer beträgt zum aktuellen Beobachtungszeitpunkt 4,5 Zyklen (Range 1–20 Zyklen) bzw. 3,78 Monate (Range 1–20 Monate). 9 Patientinnen erhalten zum Datum der Auswertung immer noch die Medikation. 20 Oncol Res Treat 2014;37(suppl 1):1–133 Als Nebenwirkung wurden angegeben: Leukopenie mit Unterbrechung der Therapie um 1 Woche (1), periphere Polyneuropathie Grad 1 (3×), Fatigue (2×), Hautausschlag perioral ohne weitere Nebenwirkung (1x) sowie milde Übelkeit (2×). Schlussfolgerung: Eribulin ist beim fortgeschrittenen metastasierten Mammakarzinom eine effektive und gut verträgliche Therapieoption. Selbst in der fortgeschrittenen Therapielinie kann der Progress über mehrere Monate bis >1,5 Jahr vermieden werden. ID 425 Macrophage-capping protein (CapG) as a putative oncogen is overexpressed in invasive breast carcinoma cells M. Neumann, R.P. Neves, S. Schulz, H. Neubauer, M. Fleisch, T. Fehm, D. Niederacher Universitäts-Frauenklinik Düsseldorf, Molekulargenetisches Labor, Düsseldorf, Deutschland Objective: The aim of this work was to study the correlation between CapG expression level and clinico-pathological parameter in breast cancer as well as functional characterization of CapG and analysis of CapGtranscriptome in mamma carcinoma cell lines to understand the pathogenic mechanism of CapG up-regulation. Material and Methods: CapG expression level in breast cancer tissue and MaCa-cells were analyzed by qRT-PCR. CapG knockdown was performed using siRNA and stable CapG overexpression was achieved by retroviral vector based transfection. Invasiveness was analysed using the BioCoat™Matrigel™ based invasion assay. Subcellular localization and CapG-protein leve was analyzed by immunoblotting. Microarray expression profiling was performed to identify CapG associated candidate genes and analyzed by gene ontology tools. Co-immunoprecipitation was performed for identification of CapG interacting proteins. Results: CapG over-expression was detected in 28% of breast cancer tissues and significantly associates with metastasis-status (M1) and ER-status (ER-negative) (both p ≤ 0.05). Invasiveness of MaCa-cell lines correlated with CapG-expression level and CapG knockdown or over-expression decrease or increase invasiveness, respectively. Moreover, CapG nuclear-localization was observed in high invasive MaCa- cell lines or after overexpression in CapG transfectants.. Analyzing CapG-transcriptome and co-immunoprecipitation experiments revealed new CapG associated candidate genes / interacting proteins, which might help to understand the role of CapG in the process of metastasis. Conclusion: The results suggest that CapG plays a role in invasiveness and dissemination of breast cancer cells. ID 430 Plakoglobin is a highly significant prognostic factor in breast cancer E. Mahnke1, I. Fuchs2, G. Schaller3, I. Adamietz4, H. Bühler5 Waldkrankenhaus, Frauenklinik, Berlin, Deutschland Zentrum für Pränataldiagnostik und Humangenetik, Berlin, Deutschland 3 Breast Care Institute, München, Deutschland 4 Universitätsklinikum Marienhospital, Klinik für Strahlentherapie und Radio-Onkologie, Herne, Deutschland 5 Universitätsklinikum Marienhospital, Institut für Molekulare Onkologie, Strahlenbiologie und Experimentelle Strahlentherapie, Herne, Deutschland 1 2 Background: The prognosis for breast cancer patients is mainly affected by spreading of the malignant cells. A crucial step in metastasis is the dissociation of cancer cells from the epithelial network. The loss of cellular adhesion proteins in the course of an EMT (epithelial-mesenchymal-transition) is a prerequisite in this context. Well studied is the role of E-cadherin in prognosis but very little is known about plakoglobin, although this protein is exclusively part of both adhesion structures, adherens junctions and desmosomes. Abstracts Inhalt Index Methods: In a retrospective study on 96 breast cancer patients the expression of plakoglobin was determined immunohistochemically and correlated with the outcome of the patients after a period of 16 years. In addition, the plakoglobin expression was detected in 7 human breast cancer cell lines and correlated with the invasiveness of the cells. Results: Plakoglobin was found to be a valid prognostic marker with p < 0.008 in log-rank tests. In the positive cohort 72% of the patients were still alive after 16 years in contrast to 43% in the negative group. Surprisingly the prognosis was most favorable, with only 28% deceased, if plakoglobin was located in the nucleus of the cells (p < 0.0002). In-vitro experiments revealed a close correlation of high plakoglobin with low invasiveness of the cells. Conclusions: Plakoglobin appeared as a highly significant prognostic factor in breast cancer that probably could spare positive patients a stressful cytostatic therapy. The favorable influence of nuclear localization might be due to a competitive displacement of beta-catenin, a malignant transcription factor in the wnt pathway. ID 442 Overall survival in advanced breast cancer is associated with the type of 1st line treatment but not with an objective response to this treatment A. Regierer1, R. Wolters2, I. Novopashenny2, A. Weigel1, J. Fischer1, M. Constantinidou1, J. Eucker1, K. Possinger1, M. Wischnewsky2 Charité, Onkologie, Berlin, Deutschland 2 Universität Bremen, Mathematik u. Informatik, Bremen, Deutschland 1 Introduction: Patient’s expectations to cancer treatment include a high response rate. However, we have previously shown that the type of response to 1st line therapy in advanced breast cancer is not associated with overall survival (OS). Here we analyze the type of 1st line treatment and correlate it with the type of response. Methods: Our clinical cancer registry includes the data of 934 patients with metastatic breast cancer. The influence of the type of response of the 1st line therapy on OS was analyzed. Response was categorized as objective response (OR, comprising of complete and partial response), no change (NC) and progressive disease (PD). The types of 1st line treatment were categorized as endocrine treatment (ET), mono chemotherapy (monoCT), and poly chemotherapy (polyCT). Results: The type of response differs significantly with the type of 1st line treatment. ET resulted in only 15% OR and 49% NC, monoCT in 26% OR and 38% NC, and polyCT in 41% OR and 27% NC. However, this does not translate into a survival benefit, as pat. receiving ET have a significantly longer OS than pat. receiving chemotherapy (CT) (ET vs. monoCT HR 1.45, 95% CI (1.06–2.00), p = 0.021; ET vs. polyCT HR 1.67, 95% CI (1.36–2.05), p < 0.001). Conclusions: Although ET has significantly lower OR-rates it is significantly associated with a longer OS in advanced breast cancer. Therefore, we underline the fact that the type of response to 1st line treatment is not relevant for survival. Cancer Prevention ID 198 20 years of primary skin cancer prevention in Gremany: Expieriences and results M.P. Anders, K. Choudhury, B. Volkmer, R. Greinert, E.W. Breitbart idence that skin cancer is sun-induced. To reduce both the burden of skin cancer and the exposure to ultraviolet radiation (UVR), primary preventive activities are important to generate an impact on people’s health behavior. Since 1989 the Association of Dermatological Prevention (ADP) therefore developed target group specific interventions. Awareness and multilevel educational campaigns and interdisciplinary workshops were conducted nationwide for over 20 years. Methods: To evaluate the primary preventive activities the ADP conducted seven population-based, cross-sectional surveys. Data collections were carried out from 1989 to 2011. The main focus of the surveys was the UVR related behavior like changes in sun protection behaviors and sunbed use. Further outcomes evaluated intermediate steps in the communication process like knowledge. Results: The proportion of interviewees who used sunscreen when they stayed in the sun increased from 34.6% in 1989 to 47.1% in 1993, then decreased again to 45.5% in 2002. 0.6% used sun protection factor higher than 19 in 1989, but in 2002 this proportion increased to 34.9%. Sunbed use in the last 12 month increased from 1989 (12.9% of interviewees) to 28.1% in 2009, but then declined to 10.4% in 2011. Conclusion: UVR related preventive behavior has improved over the last two decades and the use of sunscreen has been established in the population. Indoor tanning had increased enormously in the late 1990s and in the 2000s, but since 2011 it declined. Simultaneously knowledge about skin cancer and skin cancer risk factors has been increased in the population. ID 276 Breast Cancer in young women after radiation therapy of Hodgkin disease in childhood and adolescence – individual therapeutic strategies K. Rhiem1, N. Herold1, R. Bongartz2, G. Schellong3, R. Schmutzler1 Zentrum für Familiären Brust- und Eierstockkrebs, Köln, Deutschland Universitätsklinikum, Klinik und Poliklinik für Strahlentherapie, Köln, Deutschland 3 Universitätsklinikum, Klinik für Kinderheilkunde – Hämatologie und Onkologie, Münster, Deutschland 1 2 Children with Hodgkin disease (HD) showed an over 90% survival rate after effective combined treatment with radio- and chemotherapy but were burdened with a high number of relevant late effects. Secondary breast cancer is the most frequently diagnosed secondary malignancy in young women after supradiaphragmal radiation therapy of HD in childhood and adolescence. Longitudinal follow-up data (HD-78-HD90 between 1978 and 1995) analysed by a working group on HD-therapy associated late effects of the Society of Pediatric Oncology and Hematology (GPOH) identified a 24fold increase of breast cancer in women between 25 and 45 y after HD radiotherapy during puberty compared to age-adjusted women of the general population. The median time of breast cancer diagnosis was 20.7 years after HD therapy between the ages of 9 and 16 years. Due to these data a structured breast cancer screening program was established in cooperation with the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Two women´s decisions on therapeutic strategies after their early breast cancer diagnosis within the screening program illustrate the scope of alternatives: The first patient (39 y, stage pT1b, pN0, HR+, Her2-, G2) underwent BCT and intraoperative radiotherapy. The second patient (39 y, stage pT1c, pN0, HR+, Her2, G2) underwent bilateral (semi-)prophylactic mastectomy with primary heterologous reconstruction. The data and cases demonstrate 1. the necessity to include women after HD radiotherapy during puberty into the structured screening program, 2. the variety of individual therapeutic strategies based on the support of a multidisciplinary team. Association of Dermatological Prevention, Hamburg, Deutschland Background: The burden of skin cancer has been increasing over the last decades worldwide in the light-skinned population. There is mounting ev- Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 21 Inhalt Index ID 380 Are men twice as careless regarding oncological risks as women? I. Belova Ernst Moritz Arndt Universität Greifswald, Lehrstuhl für Allgemeine Betriebswirtschaftslehre und Gesundheitsmanagement, Greifswald, Deutschland Cell Cycle, Apoptosis, Angiogenesis ID 169 The BH3-only protein BimL overrides Bcl-2-mediated apoptosis resistance in melanoma cells M. Plötz, B. Gillissen, S.-A. Quast, A. Berger, P.T. Daniel Introduction: In order to make screening programs successful, they should appeal to the population. This, it is important to check whether there are differences beetween men and women regarding health awareness. Methods: Using skin cancer – which is the most common cancer – this study aims at finding out which gender in Germany and Russia reacts more sensitively to signs of the disease. For the German sample, the participation rates of men and women in the pilot screening project in Schleswig-Holstein from 2003/2004 are compared. In Russia, detection rates of new cases of non-melanoma skin cancers (NMSC) are compared in the year 2008 in Moscow in women and men. They represent the ratio (proportion) of incidence (ASR/World) without screening checkups compared to the incidence (ASR/World) in medical facilities of the Kremlin, which practise a screening program with 100%-participation rate at ca. 70,000 people. This reflect the health awareness of Muscovites. Results: In Schleswig-Holstein, 2.6 times fewer men than women took part in the screening (10.4 vs. 27.2% (1)). In Moscow, suspected cases of skin cancer, men visited a physician 1.8 times less than women. (The new NMSC detection rates were 10% and 32% accordingly (2)). Conclusions: In both countries, men are negligent with regard to their oncological risks. Education campaigns (at least with respect to skin cancer) should thus be be aimed at the male gender in the first place. Charité, Berlin, Deutschland Literature: 1. Katalinic A, et al.: Does skin cancer screening save lives? Cancer 2012; Vol. 118, Issue 21: 5395–5402. 2. Belova I: Comparison of the effectiveness of German and Russian health care management using the example of skin cancer. PhD thesis, University of Greifswald. V. Bucan, A.-L. Gratzke, K. Reimers, P.M. Vogt ID 453 First experiences with the GS Junior 454 in molecular genetic analysis of patients with hereditary breast and ovarian cancer at the Center of Familial Breast and Ovarian Cancer, Cologne B. Blümcke, A. Baasner, J. Hauke, B. Wappenschmidt, E. Hahnen, R. Schmutzler Uniklinik, Zentrum für familiären Brust- und Eierstockkrebs, Köln, Deutschland Mutations in BRCA1 and BRCA2 are linked to the development of hereditary breast and ovarian cancer. In 2012, 74,500 women and 600 men got breast cancer and 7,200 women got ovarian cancer in Germany, while a hereditary predisposition is suspected in about 10% of these cases. Family history and age of onset are the most important inclusion criteria for genetic testing. Since August 2012, we have analysed 237 index patients with hereditary breast and/or ovarian cancer using the GS Junior 454 (Roche) and the BRCA kit (BRCA MasterTM Dx kit, Multiplicom). The BRCA1/2 genes contain many homopolymer stretches of at least 6 bp in length. Since these stretches are difficult to detect with the GS Junior 454 platform, we additionally employed a homopolymer assay fragment analysis (BRCA HP, Multiplicom), which allows rapid detection of small insertions/deletions in approximately 30 of these coding homopolymer stretches in BRCA1/2. In this cohort, 36 out of 237 index patients were tested positive for pathogenic BRCA1/2 mutations. Of those, 10 individuals show disease-causing alterations located in homopolymer stretches that were easily detected by homopolymer assay pre-screening. Thus, our results warrant homopolymer pre-screening prior to costly next generation sequencing analyses. 22 Oncol Res Treat 2014;37(suppl 1):1–133 Melanoma cells are characterized by apoptosis deficiency coinciding with reduced expression of the proapoptotic Bcl-2 protein Bim. An adenoviral vector was constructed with the BimL cDNA controlled by an inducible promoter. Highly efficient apoptosis induction and abrogated cell proliferation was seen in melanoma cells upon BimL overexpression. Loss of mitochondrial membrane potential, release of mitochondrial apoptogenic factors and caspase-9 processing indicated the activation of mitochondrial apoptosis pathways. BimL activated both Bax and Bak, as shown by siRNA knockdown and activation-specific antibodies. Of note, BimL overrode the apoptosis blockade by Bcl-2 overexpression or by Bax/ Bak single knockdown. The high efficacy correlated to BimL interaction with all antiapoptotic Bcl-2 family members in melanoma cells, shown by co-immunoprecipitation analyses for Bcl-2, Bcl-xL, Mcl-1 and Bcl-w. Thus, BimL reveals an outstanding proapoptotic potential in melanoma cells, and strategies for its re-expression appear of interest. These have been reported for B-Raf inhibitors, and their efficacy may be partly attributed to BimL. ID 193 Using the antiapoptotic protein LFG for sensitizing breast cancer cells to chemotherapy Medizinische Hochschule Hannover, Plastische Hand und Wiederherstellungschirurgie, Hannover, Deutschland Introduction: Lifeguard (LFG) is an anti-apoptotic protein that inhibits programmed cell death mediated by Fas in tumour cells. The exact mechanism of action and the molecular function from LFG in the carcinogenesis of human breast cells is not clear. But the expression of LFG mRNA correlates with LEF-1 transcription factor activity. Here we investigated impact of LFG suppression on the cell apoptosis. Methods: RT-PCR and Western blot were used to investigate LFG expression after down regulation by siRNA transfection. To investigate the activation of caspase-3/7 in the breast cancer cells we using the Apo-One Homogeneous Caspase-3/7 Assay. Results: In the present study corroborates the essential role of LFG as well as its regulatory mechanisms and moreover demonstrates here for the first time sensitisation of breast cancer cells to chemotherapeutics, caused by LFG gene suppression. Our results indicate a pivotal role of LFG in the regulation of apoptosis in MCF-7 breast cancer cells. Conclusion: In prospective, our results have to be tested in context with other resistant types of cancer plus different chemotherapeutics and finally proved in preclinical in vivo experiments. ID 287 Dimethylfumarate impairs lymphangiogenesis by cell cycle arrest E. Valesky, I. Hrgovic, M. Doll, R. Kaufmann, M. Meissner Universitätsklinik Frankfurt, Klinik für Dermatologie, Venerologie und Allergologie, Frankfurt, Deutschland Recent evidence suggests, that Dimethylfumarate (DMF), known as a highly potent anti-psoriatic agent, might have anti-tumorigenic properties. In addition, it could be recently demonstrated that DMF has anti-angiogenic properties by suppression of VEGFR-2. We hypothesized that DMF might also have anti-lymphangiogenic qualities. To prove this Abstracts Inhalt Index assumption, we first performed cytotoxicity assays with primary human lymphendothelial cells (LEC). No relevant LDH release could be demonstrated. In further analysis we could show, that DMF suppresses LEC proliferation in a concentration- and time-dependent manner. In functional analysis we could demonstrate a reduced migration rate as well as an inhibition of the formation of capillary like structures. To further elucidate wether this anti-lymphangiogenic action is conveyed by an apoptotic mechanism we studied the amount of apoptotic nucleosomes and the activity of caspase 3/7. There was no significant apoptosis induced by DMF. Therefore, we performed cell cycle analysis demonstrating a pronounced G1 cell cycle arrest. The further evaluation of important cell cycle regulator proteins revealed an increase in p21 and p27 and a suppression of cyclin D1 and A protein expression. Interestingly, the superordinated regulator of p21, the tumor suppressor gene product p53, was induced and phosphorylated by DMF treatment. To further analyse the regulation of p21 we examined it´s mRNA expression. Here we could demonstrate an increase of p21 mRNA expression. This transcriptional way of regulation was enforced by a posttransscriptional and posttranslational mechanism. In conclusion, our results provide for the first time evidence, that DMF has distinct anti-lymphangiogenic effects. ID 349 Die Effekte des AT1-Blockers Telmisartan in humanen Kolonkarzinomzellen L.D. Lee, J. Gröne, H. Seeliger, M.E. Kreis Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Chirurgische Klinik I, Berlin, Deutschland Fragestellung: Telmisartan ist ein AT1-Blocker mit partiellem PPARgamma Agonismus. PPARgamma Aktivierung in Kolonkarzinomzellen inhibiert Zellproliferation und induziert Apoptose. Unsere Studie untersuchte somit mögliche antiproliferative und apoptotische Effekte von Telmisartan in humanen Kolonkarzinomzellen via partieller PPARgamma-Aktivierung. Methoden: Zelllinien HT-29, SW-480, SW-620. Positivkontrolle Pioglitazon, Telmisartan, Negativkontrolle Vehikel DMSO, PPARgamma Blocker GW9662. Konzentrationen 0,2-5,0µM. Inkubationszeit 24 h. Bestimmung Zellviabilität mittels MTT-Assay und des antiproliferativen Effekts mittels Neubauer Zählkammer. Die mRNA-Regulation von PPARgamma und Cystatin A mittels qRT-PCR. Apopostoseinduktion mittels Caspase-3/7-Assay. Statistische Analyse SPSS Version 19 IBM, p < 0,05. Ergebnisse: Der antiproliferative Effekt von Telmisartan war signifikant (p < 0,05) in therapeutischen Serumkonzentrationen. GW9662 blockiert den Effekt von Pioglitazon, aber nicht von Telmisartan. In SW-480 und SW-620 ist die Reduktion der Zellviabilität durch Telmisartan und GW9662 signifikant größer. Der apoptotische Effekt gleicht Pioglitazone. GW9662 zeigt hier keinen Effekt. PPARgamma mRNA wird erwartungsgemäß durch Telmisartan signifikant herunterreguliert (negative Feedback) und Cystatin A hochreguliert. Schlussfolgerung: Telmisartan zeigt eindeutig signifikante Effekte in Inhibition der Zellproliferation, Reduktion der Zellviabilität und Induktion der Apoptose in HT-29, SW-480 und SW-620. Die Effekte sind annähernd des PPARgamma Vollagonisten Pioglitazon und teilweise stärker, insbesondere in Anwesenheit vom PPARgamma Blocker GW9662. Die Effekte lassen sich somit nicht allein durch den bekannten partiellen PPARgamma Agonismus von Telmisartan erklären. Abstracts ID 379 Novel apoptosis inducers overcome IAP-mediated resistance of the renal cell carcinoma cell line ClearCa-2 J. Stevens1, E. Carosati2, G.M. Randazzo2, R. Mannhold1, L.D. Horsch1, A. Schneider1, S. Heikaus1, G. Cruciani2, H.E. Gabbert1, C. Mahotka1 Universitätsklinikum Düsseldorf, Institut für Pathologie, Düsseldorf, Deutschland 2 University of Perugia, Chemometrics and Cheminformatics, Perugia, Italien 1 Objectives: Deregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. IAPs (inhibitor of apoptosis proteins) as main regulators of apoptosis are potent caspase inhibitors, which are regulated by smac. To explore their relevance for the induction of apoptosis in the drug- and TRAIL-resistant renal cell carcinoma (RCC) cell line clearCa-2 (clear cell type), we analysed 31 novel hit candidates selected by virtual screening. Methods: ligand-based virtual screening, RNAi-method, nucleofection, DNA-cloning, Western blotting, proliferation assays, flow cytometry. Results: 1. Endogenous XIAP-expression is different in the TRAIL-sensitive clearCa-6 (low XIAP levels) and TRAIL-resistant clearCa-2 (high XIAP levels) cell line. 2. The XIAP expression level correlates with the sensitivity to TRAIL, whereas a high level of XIAP induces resistance in clearCa-2. 3. Knocking down the endogenous XIAP-expression by RNAi, the resistant cell line clearCa-2 can be sensitised by TRAIL treatment. 4. In contrast, first XIAP overexpression experiments in a TRAIL-sensitive cell line clearCa-6 show that XIAP might also be responsible for TRAIL resistance. 5. Test compounds LBPS-1, -3, and -5 induce apoptosis by (re-)activation of caspases in the resistant cell line ClearCa-2. Conclusions: The obtained results indicate that IAPs – especially XIAP – are essential regulators of apoptosis in renal cell carcinoma and contribute to the resistance to TRAIL-induced cell death. The novel chemotypes, discovered by virtual screening, are able to induce cell death in highly resistant RCC cell line ClearCa-2. These findings may contribute to new therapy options for RCCs. Cell-Based Therapy ID 086 Tumor-derived adenosine enhances generation and suppressive functions of human adaptive regulatory T cells M. Mandapathil, E.K. Jackson, S. Lang, J.A. Werner, T. Whiteside Philipps-Universität Marburg, Klinik für Hals-Nasen-Ohrenheilkunde, Marburg, Deutschland Objectives: Adaptive regulatory T cells (Tr1) are induced in the periphery upon by environmental stimuli. In cancer patients, their frequency in the peripheral blood and local tumor tissue is increased. Expression of the ectonucleotidase CD73 and adenosine production by the tumor may influence Tr1 generation and their immunosuppressive activity. Methods: Tr1 were generated in a previously established co-culture in vitro system of sorted peripheral blood CD4+CD25neg T cells with autologous immature dendritic cells (iDC) and irradiated adenosine-producing CD73+ MDA-MB231 or non-producing CD73neg MCF-7 breast cancer cell lines (TU). Expression of ectonucleotidases and other surface markers on Tr1 was determined by multicolor flow cytometry. Tr1-mediated suppression of proliferation was evaluated in CFSE-based assays. Luciferase-based ATP-detection assays and mass spectrometry were used to measure ATP hydrolysis and adenosine levels, respectively. Cytokine levels were measured by ELISA or Luminex. CD73 expression on tumor cells or T cells in TU tissues was assessed by immunofluorescence. Oncol Res Treat 2014;37(suppl 1):1–133 23 Inhalt Index Results: CD73+ TU induced higher numbers of Tr1 cells than CD73neg TU (p < 0.01). Tr1TUCD73+ hydrolyzed more exogenous ATP, produced more adenosine and mediated higher suppression than Tr1TUCD73neg (all at p < 0.05). ARL67156, an ectonucleotidase inhibitor, and ZM241385, A2A receptor antagonist, reduced suppression of responder cell proliferation mediated by Tr1TUCD73+ cells (p < 0.01). Basal-like breast cancer (BrCa) cells expressing higher levels of ectonucleotidases induced more Tr1 than less aggressive luminal-like BrCa. Conclusion: Tumors producing adenosine (CD73+TU) create a microenvironment favoring the induction of Tr1 which express CD39 and CD73, mediate enzymatic ATP breakdown to adenosine and are thus in part responsible for suppression of anti-tumor immunity. Central Nervous System Tumors ID 024 mTOR-inihibition and interruption of PI3K/Akt signaling leads to proliferation inhibition and induces apoptosis with defective autophagy in human meningioma cells J. Walter, A.S. Krombholz, S. Grube, D. Freitag, C. Ewald, R. Kalff Universitätsklinikum Jena, Klinik für Neurochirurgie, Jena, Deutschland Objective: The PI3K/Akt pathway and its effector mTOR play an important role in regulation of cell growth and have recently been evaluated as a target for the treatment of gliomas. But to date little is known about mTOR in more benign intracranial tumor like meningiomas. This study aims to elucidate the role of the pro-survival PI3K/Akt/mTOR pathway in the proliferation of human meningiomas, and to assess the use of mTOR inhibitors as therapeutic agents. Methods: MTT and BrdU assays of primary human meningioma cell cultures and permanent meningioma cell lines were used to investigate the viability and proliferation inhibitory effects of the mTOR inhibitors Everolimus and Temsirolimus. Apoptosis analysis proceeded by detecting cleavage of caspase-3 and PARP, whereas autophagy was analyzed by detection of cleaved LC3B-II. The levels of proteins were probed by Western blotting. Furthermore, nuclear fragmentation analysis after mTOR-inhibition was conducted by immunofluorescence. Results: Inhibition of mTOR by Everolimus and Temsirolimus led to a significant reduction of viability as well as inhibition of proliferation of human meningioma cells in a time and concentration dependent manner. There was no relevant difference of efficacy of mTOR inhibition concerning primary cell cultures and permanent cell lines. mTOR inhibition in meningioma cells induced apoptosis in a caspase-PARP-dependent manner. Apoptosis was accompanied by defective autophagy, proven by the detection of cleaved LC3B-II. Conclusions: The ability of Everolimus and Temsirolimus to abrogate phos-mTOR activation and by this to interrupt PI3K/Akt signalling in human meningiomas, leading to proliferation inhibition and induction of apoptosis, warrants mTOR to be investigated as a potent target in anti-meningioma therapy. ID 025 Multi tyrosin kinase inhibition in the treatment of human gliomas J. Walter, D. Freitag, S. Grube, C. Ewald, R. Kalff Universitätsklinikum Jena, Klinik für Neurochirurgie, Jena, Deutschland Objective: Axitinib, a multi receptor tyrosine kinase (RTK) receptor inhibitor, specifically targets VEGFRs, PDGFRs and c-Kit. It`s the aim to investigate the effects of axitinib on glioma cell growth in a ex vivo organotypic brain slice cultures of gliomas, primary glioma cell cultures and glioma cell lines. 24 Oncol Res Treat 2014;37(suppl 1):1–133 Methods: Organotypic brain slice cultures of gliomas, treated with Axitinib, allowed quantification of invasion, proliferation and angiogenesis by staining the treated samples for CD31, GFAP, EMA, Iba1, Ki67, and cleaved Caspase 3 as well as PAS and HE. MTT / BrdU assays of primary glioma cultures and permanent cell lines were used to investigate viability and proliferation inhibitory effects of axitinib. Apoptosis analysis proceeded by detecting cleaved caspase-3 and PARP. Autophagy was analyzed by detection of cleaved LC3B-II. Protein levels were probed by Western blotting. Results: Multi RTK inhibition by axitinib led to a decrease in number of proliferative cells and an increase of apoptotic cells as well as necrotic areas in organotypic glioma slice cultures. In primary cell cultures axitinib led to a significant reduction of viability and inhibition of proliferation. There was no difference of efficacy of RTK inhibition concerning primary cell cultures and cell lines. RTK kinase inhibition induced apoptosis in a caspase-dependent manner in gliomas. Apoptosis was accompanied by defective autophagy, demonstrated by the detection of cleaved LC3B-II. Conclusions: Axitinib effectively inhibits tumor progression in an organotypic ex vivo model of human gliomas. Furthermore multi tyrosin kinase inhibition by axitinib leads to proliferation and viability inhibition in gliomas, as well as to an induction of apoptosis in those tumors. These results suggest that axitinib could constitute a therapeutic alternative for the treatment of human gliomas. ID 098 The treatment of newly diagnosed glioblastoma with cilengitide does not alter patterns of progression G. Eisele1, A. Wick2, A.-C. Eisele1, P. Clement3, J. Tonn4, G. Tabatabai5, A. Ochsenbein6, U. Schlegel7, B. Neyns8, D. Krex9, M. Simon10, G. Nikkhah11,12, M. Picard13, R. Stupp14, W. Wick15, M. Weller1 University Hospital Zurich, Department of Neurology, Zurich, Schweiz University Hospital Heidelberg, Department of Neurooncology, Heidelberg, Deutschland 3 KU Leuven, Department of Oncology, Leuven, Belgien 4 LMU Munich, Department of Neurosurgery, Munich, Deutschland 5 University Hospital Tubingen, Department of General Neurology, Tubingen, Deutschland 6 University Hospital Bern, Department of Oncology, Bern, Schweiz 7 University Hospital Bochum, Department of Neurology, Bochum, Deutschland 8 UZ Brussels, Department of Medical Oncology, Brussels, Belgien 9 TU Dresden, Department of Neurosurgery, Dresden, Deutschland 10 University Hospital Bonn, Department of Neurosurgery, Bonn, Deutschland 11 University Hospital Freiburg, Department of Neurosurgery, Freiburg, Deutschland 12 University Hospital Erlangen, Stereotactic and Functional Neurosurgery, Erlangen, Deutschland 13 Merck Serono, Darmstadt, Deutschland 14 University of Lausanne, Multidisciplinary Oncology Department, Lausanne, Schweiz 15 German Cancer Research Center, Clinical Cooperation Unit Neurooncology, Heidelberg, Deutschland 1 2 Most current efforts to improve the outcome in newly diagnosed glioblastoma focus on the addition of anti-angiogenic agents to the standard of care of concomitant chemoradiotherapy with temozolomide. Preclinical data as well as anecdotal clinical observations indicate that anti-angiogenic treatment may result in altered patterns of tumor progression. We have previously developed an analysis tool using MRIcro software to explore whether comparable groups of patients differ in their patterns of progression. The integrin antagonist cilengitide has been explored in a phase 2 trial as an adjunct to standard of care in newly diagnosed glioblastoma. We analyzed patterns of progression on MRI in 21 patients enrolled in this trial. Thirty patients from the experimental treatment arm of the EORTC/NCIC 26981 trial served as a reference. Analysis of recurrence pattern revealed neither a difference in the size of the recurrent tumor nor in the distance of the recurrences from the preoperative tumor location Abstracts Inhalt Index between groups. Overall frequencies of distant recurrences were 20% in the reference group and 19% (4/21 patients) in the cilengitide group. Compared with standard chemoradiotherapy alone, the addition of cilengitide did not alter patterns of progression. This analysis does not support concerns that cilengitide may induce a more aggressive phenotype at progression, however it also provides no evidence for an anti-invasive activity of cilengitide. and ADAM17 specific inhibitors. Soluble ULBP2 levels in GSC culture supernatants were reduced upon blockade of ADAM10 and ADAM17, underscoring the view that these proteases cleave ULBP2 from the surface of GSC. Subsequently, the impairment of ADAM10 and ADAM17 led to enhanced immune recognition of GSC by natural killer cells and enhanced secretion of interferon-γ by these immune effector cells. Therefore, ADAM10 and ADAM17 constitute suitable targets to boost an immune response against GSC. ID 184 Allele-specific real-time RT-PCR for the detection of IDH1 mutations in gliomas: Mutant and wildtype IDH1 are upregulated in human gliomas whereas systemic treatment and tumor relapse do not change IDH1 gene expression L. Dreher, M. Perrech, G. Röhn, R. Goldbrunner, M. Timmer IDH1 mutations (IDH1mut) occur in more than 70% of WHO grade II and III gliomas and secondary glioblastomas (GBM). The most frequent mutation leads to a specific amino acid change at codon 132. The diagnostic of this mutation is so far based on DNA sequencing and immunohistochemistry (IHC), methods limited in terms of sensitivity and ease of use. Recently, measuring the IDH1mut level by real time PCR was introduced as alternative method. A total of 71 tumor samples were obtained intraoperatively from glioma patients. The samples were divided into 7 subgroups (control brain tissue, diffuse glioma, anaplastic glioma, secondary glioblastoma +/– chemotherapy (CTx), primary glioblastoma +/– CTx). Tumor samples were snap frozen and processed for sectioning, RNA and protein isolation. The quantitative expression of IDH1 mRNA was assessed using real-time PCR with specific primers for IDH1mut and -wt; protein expression was verified by Western Blot analysis and IHC. Allele-specific quantitative PCR does work in larger patient cohorts and seems to be an easy and ~10 times more sensitive method for IDH1mut evaluation compared to the ones used so far. Most astrocytomas and sec. GBM bear the mutation (con. 0.13 to 0.2) whereas most prim. GBM do not. The difference between control tissue, prim. GBM and astrocytomas/ sec. GBM was highly significant (p = 0.003). Radio- and/or CTx do also not alter the IDH1mut expression. This assay is able to analyze 100 samples simultaneously in ~1 hour. Recurrent disease and radio-CTx do not alter the general IDH1 status. In summary, this method is highly sensitive, cost-effective and timesaving and may therefore play an important role in IDH1mut analysis in the future. ID 213 ADAM10 and ADAM17 contribute to the immune evasive phenotype of glioblastoma stem cells F. Wolpert , I. Tritschler , A. Steinle , M. Weller , G. Eisele 1 2 1 INTRAGO – Intraoperative Radiotherapy for Glioblastoma – a phase I/II study F.A. Giordano1, S. Brehmer2, F. Schneider1, S. Clausen1, G. Welzel1, M. Seitz-Rosenhagen2, P. Schmiedek2, Y. Abo-Madyan1,3, F. Wenz1 Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Klinik für Strahlentherapie und Radioonkologie, Mannheim, Deutschland 2 Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Neurochirurgische Klinik, Mannheim, Deutschland 3 Department of Clinical Oncology and Nuclear Medicine (NEMROCK), Cairo University, Kairo, Ägypten 1 Uniklinik Köln, Allgemeine Neurochirurgie, Köln, Deutschland 1 ID 248 1 Universitätsspital Zürich, Klinik für Neurologie, Zürich, Schweiz Goethe-Universität Frankfurt am Main, Institut für Molekulare Medizin, Frankfurt am Main, Deutschland 1 Glioblastoma multiforme (GBM), the most common primary malignant brain tumor, is still associated with a poor prognosis. Despite surgical resection and radiochemotherapy, most tumors recur locally and even a broad variety of salvage therapies (including re-resection, re-irradiation or molecular therapies) can rarely prevent subsequent clinical deterioration with lethal complications. One possible underlying cause of the high rate of local recurrences may be that even after fluorescence- and neuronavigation-guided tumor resection, microscopically persistent tumor cells can rapidly re-colonize until radiochemotherapy is initiated. We therefore hypothesize that intraoperative radiotherapy (IORT) may arrest or eradicate persistent tumor cells and thereby bridge the therapeutical gap between surgery and radiochemotherapy. A novel approach to achieve high degrees of target volume coverage even in complexly shaped tumor cavities might be the use of spherically irradiating sources, such as provided with applicators of the Intrabeam-system (Carl Zeiss Meditec, Oberkochen). We therefore designed a phase I/II dose escalation study termed ‘INTRAGO – INTraoperative RAdiotherapy for GliOblastoma’, which is presented here. Within the study, we will apply spherical IORT after gross tumor resection of primary supratentorial GBMs in patients ≥ 50 years of age with a Karnofsky index of at least 50%. Primary end points are feasibility and definition of the maximum tolerated dose which shall be evaluated in a classical 3+3 design. Secondary end points are efficiency and impact on survival and on quality of life. ID 320 microRNAs in acquired chemoresistance of malignant gliomas 2 C. Happold1, N. Stojceva1, G. Schechtmann2, G. Reifenberger2, M. Weller1 The treatment of glioblastoma remains a challenge in neuro-oncology. In recent years, glioblastoma stem cells (GSC) have been identified as a putative target for immunotherapy of glioblastoma. However, an immune inhibitory phenotype of GSC might counteract immunotherapeutic approaches. The family of a disintegrin and metalloproteinases (ADAM) are involved in the maintenance of themalignant phenotype of glioblastomas. Here, we investigated a possible role of ADAM proteases in the immune evasion of GSC. ADAM10 and ADAM17 were expressed in a panel of GSC lines. The cell surface expression of UL-16 binding protein (ULBP) 2, a ligand for the activating immunoreceptor NKG2D, was enhanced upon blocking ADAM10 and ADAM17 using small interfering RNA or ADAM10 1 Abstracts UniversitätsSpital Zürich,Klinik für Neurologie, Labor für Molekulare Neuro-Onkologie, Zürich, Schweiz 2 Heinrich-Heine-Universität Düsseldorf, Institut für Neuropathologie, Düsseldorf, Deutschland Glioblastomas are the most malignant primary brain tumors. Despite multimodal therapy including surgery, irradiation and chemotherapy, the median survival of remains in the range of 12 months on a population level. Even patients with tumors with a methylated O6-methylguanine DNA methyltransferase (MGMT) promotor, which derive most benefit from standard chemoradiotherapy using temozolomide (TMZ/RT→TMZ), are prone to progress as a result of acquired resistance. Here, we investigate whether selected microRNAs (miRNAs), short, noncoding, Oncol Res Treat 2014;37(suppl 1):1–133 25 Inhalt Index single-stranded RNA molecules involved in the post-transcriptional regulation of gene expression, play a role in the development of acquired resistance in human glioma cell lines. We have generated glioma cell lines with acquired TMZ resistance by repetitive TMZ exposure and verified the stable resistance phenotype by clonogenic growth assays. Next, we performed miRNA expression chip arrays on both parental and resistant cell lines and identified several deregulated miRNAs in a comparative analysis. We validated the selected miRNA by PCR and explored their impact on the development of resistance pattern in functional assays. We demonstrate that miRNA can sustain resistance phenotypes in parental cell lines, therefore representing new investigative targets for future experimental approaches to overcome acquired resistance. ID 324 CD317 Immunotoxin Therapy for Glioblastoma D. Gramatzki1,2, M. Peipp3, K. Frei4, M. Staudinger3, M. Gramatzki3, M. Weller1,2 University Hospital Zurich, Laboratory for Molecular Neuro-Oncology, Department of Neurology, Zurich, Schweiz 2 University of Zurich, Neuroscience Center Zurich, Zurich, Schweiz 3 Christian-Albrechts-University of Kiel, Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Kiel, Deutschland 4 University Hospital Zurich, Department of Neurosurgery, Zurich, Schweiz 1 Targeted immunotoxins are recombinant molecules, consisting of a specific antibody fragment coupled to a protein toxin. In the present proposal, we aim at targeting the cell surface antigen CD317, also known as HM1.24 protein. This antigen is preferentially found on mature cells of B-lineage such as multiple myeloma cells, but was recently found to be overexpressed on some solid cancer types too. Analysis of the glioblastoma database of the Cancer Genome Atlas network demonstrates, that CD317 mRNA levels are up-regulated in human glioblastoma in vivo. Interestingly, enhanced CD317 expression significantly correlates with a reduced probability of survival in this patient group. CD317 protein expression levels, analyzed by immunohistochemistry analysis on a tissue micro array demonstrate, that this protein is up-regulated in human glioblastoma. Moreover, CD317 protein level correlates directly with the malignant phenotype of gliomas. CD317 is expressed heterogeneously in human glioma- initiating and human longterm glioma cell lines on mRNA and protein levels in vitro. The immunotoxin HM1.24-ETA’ is a fusion protein of a humanized, CD317 specific single-chain Fv fragment combined with a truncated version of Pseudomonas exotoxin A. This immunoconjugate induces acute cytotoxicity in CD317-positive glioblastoma cells in a concentration-dependent manner. Target cell cytotoxicity in the human glioma cells in vitro occurred via caspase 3 activity, underlining apoptosis as the mode of cell death induced by HM1.24-ETA’. Interestingly, interferon-β induces CD317 mRNA and protein levels on the cell surface of glioblastoma cells and therefore enhances the cytotoxic effect of HM1.24-ETA’ in vitro. These results underline, that HM1.24-ETA’ may have the potential to provide a novel approach of immunotherapy for glioblastoma patients. ID 351 Sphingosine kinase isoforms and receptors S1PR1, 2, 3 and 5 and their inhibitor Fingolimod in human glioblastomas K. Malgorzata1, M. Ocker2, D. Neureiter3, K. Quint2, H. Strik4 Universität Gießen, Neurochirurgie, Gießen, Deutschland Universität Marburg, Chirurgische Forschung, Marburg, Deutschland 3 Universität Salzburg, Pathologie, Salzburg, Österreich 4 Universität Marburg, Neurologie, Marburg, Deutschland 1 2 Here, the expression of SphKs and their receptors was investigated in human glioblastoma samples and the effect of Fingolimod, a pharmacological SphK1 inhibitor, on human glioma cell lines was tested. Methods: Samples from 59 primary (n = 35), recurrent (n = 18) and secondary (n = 6) glioblastomas were analyzed using quantitative real-time PCR and immunohistochemistry for SphK1 and 2 and S1PR1, 2, 3 and 5. Expression was correlated with patient survival. The effect of Fingolimod on A172, G28 and U118 glioma cell growth was tested with the xCELLigence system (Roche Molecular Diagnostics), measuring impedance as a surrogate marker for proliferation and toxicity. Effects on cell cycle and death were tested with flow cytometry. Results: as compared to normal brain, SphK2, S1PR1 and 5 were significantly upregulated in glioma tissue. In recurrent glioblastomas, S1PR2, 3, and 5 were significantly lower than in untreated primary tumors. Expression in secondary gliomas was not significantly different from controls. Impedance was reduced in a dose-dependent manner at concentrations > 5 µM in G28 and A172 and > 10 µM in U87, respectively. Flow cytometry showed that 10 µM Fingolimod induced a significant increase in sub-diploid events in U87 (78.9 ± 6.0%), G28 (36.4 ± 6.1%) and A172 cells (20.3 ± 1.7%). Conclusion: Sphingosine kinases and their receptors are highly expressed in human gliomas. SPK inhibition with Fingolimod exerts a strong influence on the glioma cell cycle and inhibits efficiently glioma cell growth. This indicates that SphKs and their receptors are promising targets to treat malignant gliomas. ID 406 miRNA fingerprints in the blood as prognostic biomarkers in PCNSL patients P. Roth1, A. Keller2, J. Hoheisel3, P. Codo1, A. Bauer3, C. Backes2, P. Leidinger2, E. Meese2, E. Thiel4, A. Korfel4, M. Weller1 UniversitätsSpital Zürich, Klinik für Neurologie, Zürich, Schweiz Universität des Saarlands, Homburg, Deutschland 3 DKFZ, Heidelberg, Deutschland 4 Charite, Berlin, Deutschland 1 2 Primary CNS lymphoma (PCNSL) is an uncommon variant of extranodal non-Hodgkin lymphoma. Higher age and low Karnofsky Performance Status (KPS) are associated with reduced overall survival (OS). microRNA (miRNA) are small RNA molecules involved in the posttranscriptional gene regulation. They may also be useful as blood-derived biomarkers in various tumor entities. Here, we aimed at characterizing miRNA expression profiles in the blood of PCNSL short- (STS) and long-term survivors (LTS) to determine their potential as novel prognostic markers. All blood samples were obtained at the time of enrolment in the G-PCNSLSG1 trial, a large randomized phase III study which assessed the role of consolidating whole brain radiation therapy (WBRT) in PCNSL patients. We examined 2 cohorts of 20 patients with STS patients having a median OS of 3 months compared to 55 months for the LTS group. Both cohorts were balanced for median age and KPS: 64 years and 70% for STS compared to 62 years and 70% for LTS. miRNA was extracted from blood samples and analyzed using Next Generation Sequencing. The biostatistical analysis revealed a differential regulation of several miRNAs in the 2 cohorts. An in silico enrichment analysis demonstrated that 9 deregulated miRNAs are known to be onco-miRNAs representing a significant enrichment for these markers (p < 0.001). Real-time PCR was used to confirm the differential regulation of the most promising candidate miRNAs as well as novel short RNA molecules with putative miRNA function not known before. Based on these results, blood-derived miRNA patterns warrant further exploration as prognostic biomarkers in PCNSL patients. Objective: Sphingosine-1-phosphate (S1P), the corresponding kinases SphK1 and 2 and receptors S1PR1, 2, 3, and 5 are involved in cell survival, growth, migration and angiogenesis. Previous studies demonstrated that the expression of SphK1 influenced survival of glioblastoma patients. 26 Oncol Res Treat 2014;37(suppl 1):1–133 Abstracts Inhalt Index ID 433 Validation of reference genes for quantitative real-time polymerase chain reaction in surgical specimens of human meningiomas F. Rapp1, S. Grube, D. Freitag, R. Kalff, J. Walter Universitätsklinikum Jena, AG Neuroonkologie, Jena, Deutschland In meningiomas quantitative real-time reverse transcriptase polymerase chain reaction can be used as a sensitive technique for accurate quantitative analysis of specific gene expression levels. To compare mRNA transcripts across different tumor samples, various appropriate reference genes are required to be selected for internal standardisation. So far, such a validation of candidate reference genes of surgical specimens of meningiomas varying in WHO grades has not yet been reported. At first, total RNA was extracted from eight surgical specimens of different human meningiomas of all three WHO grades, before beeing transcripted into cDNA for providing the starting material for the following qPCR. Eight candidate reference genes (B2M, GAPDH, HPRT, HMBS, YWHAZ, UBC, TBP, SDHA) have been chosen for beeing qantitatively measured by running every single one of them with each of the eight cDNA samples. Afterwards, using BestKeeper software, the different expression levels of these reference genes were analyzed and ranked according to the criteria of standard deviation, correlation coefficient, p-Value and the Power of HKG (regression analysis of housekeeping genes versus BestKeeper). The final results identify GAPDH, HPRT and YWHAZ as the three genes showing the highest expression stability wherefore they are the optimal ones for normalisation of target genes in a larger panel of meningioma specimens. ID 440 Validation of Reference Genes for qPCR in Human Glioblastoma Tissue T. Goettig1,2, A. Vestergaard1,2 1 2 Friedrich-Schiller-Universität Jena, Neurochirurgie, Jena, Deutschland Universität, Neurochirurgie, Jena, Deutschland Objective: Our study targets specific tumor signaling pathways in human glioblastoma, which might be of importance for cell proliferation and inducing apoptosis. For the quantitative analysis of the gene expressions by qPCR, we evaluated the best matching reference genes (housekeeping genes) among B2M, GAPDH, HMBS, HPRT, SDHA, TBP, UBC and YWHAZ. Methods: To identify suitable reference genes in human glioblastoma tissue in quantitative RT-PCR we isolated the required RNA surgically obtained cryoconserved human glioblastoma tissue specimina. We chose samples with a RNA-concentration >100 ng/µl to synthesize the cDNA through Reverse-Transcriptase-PCR to optimize the amount of cDNA-product. The eight formally mentioned reference genes were then each tested on 13 various randomly chosen patient cDNA samples. Results: While especially the B2M melting analysis showed unspecific products and was therefore excluded of the BestKeeper analysis, YWHAZ, HMBS and HPRT stood out with the best coefficient of correlation (p = 0,001), standard deviation and power of HKG, implying the highest stability. Conclusions: We found YWHAZ, HMBS and HPRT as the most stable reference genes. As a result they are used for the expression analysis of specific target genes for cell proliferation on a larger population of glioblastoma samples. Abstracts Clinical Trial Design ID 003 Randomized controlled study for the prevention of peritoneal carcinosis in gastric carcinoma D. Zieker, S. Müller, I. Königsrainer, S. Beckert, A. Königsrainer, J. Glatzle Uni Tübingen, Allgemeine Chirurgie, Tübingen, Deutschland Gastric carcinoma is one of the world’s most prevalent tumors. In more than 30% of these tumors the disease spreads to the peritoneum. This is known as peritoneal carcinomatosis (PC) and is associated with a five-year survival rate of less than 2%. The current therapy regime for gastric carcinomas includes a diagnostic laparoscopy with peritoneal wash cytology before commencement of neoadjuvant treatment in order to exclude PC. Patients with PC are deemed incurable and given palliative chemotherapy. Patients with no PC are considered treatable and undergo neoadjuvant chemotherapy according to medical guidelines with subsequent gastrectomy. Problematic is the finding of a small number of tumor cells in the peritoneal wash. Patients in whom laparoscopically performed wash cytology shows free tumor cells in the peritoneal cavity have a 40% greater increased risk developing PC within one year as compared with patients without tumor cells in the peritoneal wash cytology. Such high-risk patients should in addition to a gastrectomy additionally undergo intraperitoneal chemotherapy (HIPEC) in order to remove as far as possible all free tumor cells and micrometastases and thus reduce the risk of relapse and peritoneal carcinosis. The study is an open-label, monocenter randomized phase II trial. The primary endpoint of this study is the peritoneal carcinosis free 5 year survival. Secondary endpoints are the overall survival, disease-free survival, and incidence of adverse events. The sample size was 20 for each group, determined with a significance level of 0.05, power of 0.80, and a drop out rate of a 10% for a risk reduction of developing peritoneal carcinosis by 50%. The aims of this study are, firstly, to reduce the risk of developing PC by performing a gastrectomy with HIPEC and, secondly, to improve relapse-free survival and overall survival. The study is already approved by the German Federal Institute for Drugs and Medical Devices as well as by the Ethics Committee of the University of Tübingen. The study was also already initiated by monitoring (EudraCT-Nr.: 2011-004405-25 / Studycode: HIPEC_Stomach, ClinicalTrials.gov Identifier: NCT01683864). ID 034 Individualised communication skills training for randomised clinical trials in oncology. Final results of a RCT A. Wünsch1, M. deFigueiredo2, T. Gölz3, G. Ihorst4, H. Bertz5, K. Fritzsche2 Klinikum rechts der Isar, Psychosomatische Medizin und Psychotherapie, Sektion Psychosoziale Onkologie, München, Deutschland 2 Universitätsklinikum Freiburg, Psychosomatische Medizin und Psychotherapie, Freiburg, Deutschland 3 Universitätsklinikum Freiburg, Zentrum für Kinder- und Jugendmedizin, Freiburg, Deutschland 4 Universitätsklinikum Freiburg, Studienzentrum, Freiburg, Deutschland 5 Universitätsklinikum Freiburg, Innere Medizin I, Freiburg, Deutschland 1 Background: One of the hardest communication tasks for physicians is to disclose information about randomized clinical trials (RCT). Physicians have to address complex information, consider ethical and legal aspects, so patients can come to a free and uncoercive decision. Communication Skills Training (CST) was developed to train physicians in this task and was evaluated in a randomized controlled trial. (1) Can CST improve communication skills conveying key information about clinical trials?(2) Can this training improve the feeling of competence of participants? (3) Do improved consultations need more time? Methods: This CST is based upon individual learning goals of participating physicians derived from video assessment. These learning goals were Oncol Res Treat 2014;37(suppl 1):1–133 27 Inhalt Index used in role play with actor-patients in CST to train each physician. For evaluation, 40 physicians were randomly assigned to training or waiting control group. Training success was evaluated by blinded rater using a specific checklist to evaluate video-recorded standardized consultations with actor-patients. Feeling of competence was assessed by a questionnaire. Time of consultations was metered post-hoc. Results: (1) Results show significant improvements in content specific communication skills of trained physicians. (2) Feeling of competence improved significantly. (3) Time did not increase significantly in better rated consultations. Conslusion: The developed CST is the first CST, which can show improvements in communication skills conveying key information about clinical trials evaluated in a randomized controlled design. It integrates ethical standards, patient-orientation and is time efficient. It can prepare physicians in this difficult task effectively. ID 323 Factors associated with clinical trial enrollment among female with gynaecological cancer R. Mavrova, J. Radosa, J. Stroeder, D. Herr, E.-F. Solomayer, I. Juhasz-Böss Uniklinik Homburg/Saar, Gynäkologie, Homburg, Deutschland Purpose: Only few women with gynaecological cancer participate in cancer clinical trials nationwide. Advances in cancer treatment are in part the result of patient involvement in such trials. There is a need to identify the barriers interfering patient accrual. Methods: This study was conducted at the Department for Gynaecology and Obstetrics at the Saarland University Hospital, Germany to investigate factors influencing the participation and enrollment in clinical trials among women with a recently diagnosed gynaecological cancer during 6 months. Patients were educated and offered to participate in the provided study or to receive the standard therapy according to the guidelines for their cancer entity. We analyzed the age of the patient, the stage of the disease, the clinical trial design and subjective reasons for participation or not. Results: 23 patients were offered participation and 14 patients (61%) were enrolled. Our collective consists of women with breast cancer (70%), ovarian cancer (26%) and endometrial cancer (4%). The mean age was 58 years (range 40-72). Analyzed were four different clinical trial designs: neoadjuvant trials (30%), adjuvant trials (22%), no intervention studies (35%) and studies for patients with metastasis (13%). Women were not offered trials because of ineligibility (33%), difficulties getting to the hospital because of long drive distances (56%) and patient refusal (11%). Women participate in trials because of better medical support (7%), the possibility of new drugs (57%), no other therapeutical alternatives (14%) and to help further generations (21%). Conclusions: Studies should be offered in more even small institutions to increase participation and enrollment in cancer clinical trials. ID 369 The Treat CTC trial – a new approach targeting circulating tumor cells (CTC) in early breast cancer (EBC) B. Rack1, C. Messina2, S. Litiere2, C. Dittrich3, D. Mavroudis4, A. Kong5, W. Janni6, J. Koch1, C. Sotiriou7, J.-Y. Pierga8, M. Piccart7, M. Ignatiadis7 Ludwig-Maximilians-Universität, München, Deutschland European Organization for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgien 3 LBI-ACR VIEnna, Kaiser Franz Josef-Spital, Vienna, Oesterreich 4 University General Hospital Heraklion, Crete, Griechenland 5 Oxford University Hospitals NHS Trust – Churchill Hospital, Oxford, Großbritannien 6 Department of Gynaecology and Obstetrics, Universitätsklinikum Ulm, Ulm, Deutschland 7 Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgien 8 Department of Medical Oncology, Institut Curie, Paris, Frankreich 1 2 28 Oncol Res Treat 2014;37(suppl 1):1–133 Background: The presence of CTC is associated with an impaired prognosis in MBC and EBC. Therefore, patients with persisting CTC after (neo)adjuvant chemotherapy might benefit from additional systemic treatment. Recent data have reinforced the hypothesis that trastuzumab can eliminate tumor cells by antibody dependent cell cytotoxicity (ADCC) and that the benefit may be associated with targeting cancer stem cells in a HER2 independent model (Ithimakin 2013). Trastuzumab eliminated CTC, irrespective of the HER2 status of the primary tumor and CTC and this was associated with reduced relapses (Georgoulias 2012). Trial Design: Treat CTC trial is a European randomized phase II trial, sponsored by the EORTC and run under the BIG umbrella. It will assess the efficacy of trastuzumab in eliminating CTC after the completion of (neo)adjuvant chemotherapy and surgery in patients with HER-2-negative EBC. Eligible patients will be randomized to either 6 cycles of trastuzumab or observation.It is estimated that 2175 women will be registered to include 174 patients eligible for randomization. Main Eligibility criteria: - Adequately excised HER2-negative EBC - Evidence of CTC detection using the CellSearch technology after completion of (neo)adjuvant chemotherapy - Completion of adjuvant chemotherapy for node-positive disease or neoadjuvant chemotherapy with residual invasive disease in breast or lymph nodes - Histological Grade > 1 and primary tumor size > 1 cm Perspectives: Given the prognostic relevance of CTC in BC, the Treat CTC trial will be the first multi-center, randomized trial in which CTC are used to guide treatment decisions in EBC. The results of this trial will help to clarify the clinical utility of CTCs in early disease. ID 429 Capecitabine and bevacizumab with radiotherapy as first-line maintenance treatment for patients with oligometastatic colorectal cancer – clinical case report and presentation of an interdisciplinary trial (OLGA trial) A. Stein1, N. Andratschke2, J. Dunst3, J. Quidde1, M. Guckenberger4, R. Hofheinz5, G. Hildebrandt2, C. Roedel6, A. Vogel7, F. Wenz8, C. Petersen9, D. Arnold10 Universitätsklinikum Hamburg-Eppendorf, Universitäres Cancer Center Hamburg II. Medizinische Klinik und Poliklinik, Hamburg, Deutschland 2 Universitätsmedizin Rostock, Klinik und Poliklinik für Strahlentherapie, Rostock, Deutschland 3 Universitätsklinikum Schleswig-Holstein, Klinik für Strahlentherapie, Kiel/ Lübeck, Deutschland 4 Universitätsklinikum Würzburg, Klinik und Poliklinik für Strahlentherapie, Würzburg, Deutschland 5 Universitätsmedizin Mannheim, III. Medizinische Klinik, Mannheim, Deutschland 6 Universitätsklinikum Frankfurt, Klinik für Strahlentherapie und Onkologie, Frankfurt, Deutschland 7 Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Hannover, Deutschland 8 Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie, Mannheim, Deutschland 9 Universitätsklinikum Hamburg-Eppendorf, Klinik für Strahlentherapie und Radioonkologie, Hamburg, Deutschland 10 Klinik fuer Tumorbiologie, Freiburg, Deutschland 1 Background: Metastatic colorectal cancer (MCRC) often present with oligometastatic disease. Currently available highly active standard treatment regimens enable tumour response or disease control in most patients, thus raising the question of further management. Secondary resection and/or ablation, e.g. by surgery or radiofrequency, may contribute to long-term survival and even cure, or at least allow a relevant chemotherapy free interval. These approaches are often limited by anatomical site, invasiveness and morbidity of the respective procedure. Radiotherapy is an already established treatment approach in localized (colo)rectal cancer potentially enabling non-invasive local ablation with low toxicity to nearly every site of the body. Combining chemoradiation with an antian- Abstracts Inhalt Index giogenic agent (e.g. bevacizumab) has a strong biological rationale, and studies consistently show an increase in radiosensitivity. Methods/Design: This multicentre, single arm phase II trial conducted in Germany evaluates the role of chemoradiation with capecitabine and bevacizumab in 72 patients with oligometastatic colorectal carcinoma (up to 5 lesions/3 sites) neither being progressive nor resectable after 3-6 months of induction chemotherapy. The primary objective is to evaluate the efficacy of chemoradiation; primary endpoint is progression free survival rate at 12 months. Secondary objectives include efficacy, safety and tolerability. The trial is approved and registered EudraCT Nr: 2011005296-16. Conclusion: The OLGA trial is designed to evaluate the benefits and limitations of chemoradiation with capecitabine and bevacizumab in the treatment of oligometastatic CRC. ID 450 DETECT IV – a multicenter, single arm, phase II study evaluating the efficacy of Everolimus in combination with endocrine therapy in patients with HER2-negative, hormone-receptor positive metastatic breast cancer and exclusively HER2-negative circulating tumor cells (CTCs) C. Melcher1, F. Schochter2, S. Albrecht2, C. Hagenbeck1, T.W. Friedl2, B. Jäger2, B.K. Rack3, V. Müller4, P.A. Fasching5, W. Janni2, T.N. Fehm3 Heinrich Heine University, Department of Obstetrics and Gynecology, Duesseldorf, Deutschland 2 University of Ulm, Department of Obstetrics and Gynecology, Ulm, Deutschland 3 Ludwig-Maximilians-University, Department of Obstetrics and Gynecology, Munich, Germany, Deutschland 4 University Medical Center Hamburg-Eppendorf, Department of Tumor Biology, Hamburg, Deutschland 5 University Erlangen, Department of Obstetrics and Gynecology, Erlangen, Deutschland 1 Background: Several studies have indicated that determining prevalence and number of circulating tumor cells (CTCs) at various time points during treatment is an effective tool for assessing treatment efficacy in metastatic breast cancer (MBC). However, even if the prognostic value of CTCs in MBC is well understood, the role of both CTC prevalence and CTC phenotype in predicting treatment response needs further investigation. Specific Aims/Trial Design: DETECT IV is a prospective, multicenter, open-label, single arm phase II study aimed at postmenopausal patients with hormone-receptor positive, HER2-negative MBC and exclusively HER2-negative CTCs. The primary objective of the trial is to estimate the clinical efficacy of the mTOR inhibitor everolimus in combination with endocrine therapy as assessed by progression-free survival (PFS). Additional research on CTC dynamics and characteristics will provide a better understanding of the prognostic and predictive value of CTCs and is one step towards a more personalized therapy for MBC. Eligibility Criteria: Postmenopausal female patients with hormone-receptor positive, HER2-negative MBC and exclusively HER2-negative CTCs having an indication for endocrine therapy will be included. Methods/Target Accrual: DETECT IV will start in October 2013 and aims at recruiting 400 patients. It is estimated that 2000 patients with HER2-negative MBC have to be screened for the presence of exclusively HER2-negative CTCs. The primary endpoint PFS will be assessed using the Kaplan-Meier method. Prevalence and number of CTCs at various time points will be determined using the FDA-approved CellSearch System (Veridex, USA). Abstracts ID 451 DETECT III – a multicenter, randomized, phase III trial to assess efficacy of lapatinib in patients with HER2negative metastatic breast cancer and HER2-positive circulating tumor cells (CTCs) S. Albrecht1, F. Schochter1, C. Melcher2, C. Hagenbeck2, T.W. Friedl1, B. Jäger1, B.K. Rack3, V. Müller4, P.A. Fasching5, W. Janni1, T.N. Fehm3 University of Ulm, Department of Obstetrics and Gynecology, Ulm, Deutschland 2 Heinrich Heine University, Department of Obstetrics and Gynecology, Duesseldorf, Deutschland 3 Ludwig-Maximilians-University, Department of Obstetrics and Gynecology, Munich, Germany, Deutschland 4 University Medical Center Hamburg-Eppendorf, Department of Tumor Biology, Hamburg, Deutschland 5 University Erlangen, Department of Obstetrics and Gynecology, Erlangen, Deutschland 1 Background: The recently reported discordance of the HER2 status between primary tumor and circulating tumor cells (CTCs) in metastatic breast cancer (MBC) may be an important factor affecting the response to HER2-targeted treatments. Therefore, it is important to determine if therapy based on the HER2 status of CTCs offers a clinical benefit for patients. Specific Aims / Trial Design: DETECT III is a prospective, multicenter, open-label, two-arm, phase-III study for patients with HER2-negative MBC. Patients with HER2-positve CTCs are randomized to standard therapy with or without additional HER2-targeted treatment with Lapatinib. The primary objective of the DETECT III trial is to estimate the clinical efficacy of the HER2-targeted therapy monitored by the disappearance of CTCs after treatment. This-study is the first phase III clinical trial where treatment is based on phenotypic characteristics of CTCs. It may lead to a new strategy for the treatment of MBC. Eligibility Criteria: In DETECT III patients with HER2-negative MBC, HER2-positive circulating tumor cells (CTC) and indication for anti-cancer treatment will be included. Methods / Target Accrual: The DETECT III – trial started February 2012 and aims at recruiting 120 patients overall. Prevalence and number of CTCs at various time points as well as the HER2 status of CTCs are determined using the FDA-approved CellSearch System (Veridex, USA). So far (August 2013), 585 patients have been screened and 383 (65.3%) were positive for CTCs. At least one HER2-positive CTC was found in 71 (18.6%) patients. Developmental Therapeutics: Immunotherapy ID 080 Two immune faces of pancreatic adenocarcinoma: Possible implication for immunotherapy S. Karakhanova, J. Werner, A. Bazhin Chirurgische Uniklinik Heidelberg, Heidelberg, Deutschland Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human neoplasms, having extremely poor prognosis with a five-year survival rate of <1% and a median survival of 6 months. In contrast to other malignancies, pancreatic cancer is highly resistant to chemotherapy and targeted therapy. Therefore, new treatment options are urgently needed to improve the survival of patients with PDAC. Based on our data showing that patients with higher CD8+ T cell tumour infiltration exhibited prolonged overall and disease-free survival compared to patients with lower or without CD8+ T cell tumour infiltration, we suggested that immunotherapy could be a promising treatment option for PDAC. However, clinical data from theCapRitrial (chemoradioimmunotherapy with interferon-α (IFN)) did not point to an improved efficiency of chemoradiation Oncol Res Treat 2014;37(suppl 1):1–133 29 Inhalt Index combined with IFN as compared to chemoradiotherapy alone, suggesting an important role of the immune suppression induced by PDAC and/or unspecific immune stimulation. In support of this hypothesis, we found that the PDAC patients and experimental mice had an increased number of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC). These results allowed us to conclude that PDAC provokes not only an anti-tumour immune response, but also strong immune suppression. Thus, we supposed that new immunotherapeutical strategies should involve not only stimulation of the immune system of PDAC patients, but also exert control over the tumour immune suppressive milieu. ID 156 Outpatient treatment of malignant pleural effusions due to metastatic breast and ovarian carcinoma by intrapleural catumaxomab instillation C.M. Kurbacher, O. Horn, C. Schweitzer, N. Nymbach, S. Herz, G. Wessling, J. Lepique, J.A. Kurbacher Medizinisches Zentrum Bonn-Friedensplatz, Zentrum für Gynäkologie und Geburtshilfe, Bonn, Deutschland Background: Malignant pleural effusion (PE) is among the late sequelae of metastatic epithelial tumors including metastatic breast cancer (MBC) or recurrent ovarian carcinoma (ROC). Recently, pleurodesis with talc is considered standard of care for the treatment of PE. However, this therapy routinely routinely requires hospitalization and admission to an intensive-care unit. The trifunctional monoclonal antibody catumaxomab (CATU), is approved for the treatment of malignant ascites due to epithelial cell adhesion molecule (EpCAM)-positive tumors. We hereby report on our single-institution experiences of local PE treatment with CATU-instillations in an outpatient setting in pts with MBC and ROC. Methods: A total of 7 patients (pts) with PE (MBC, n = 5; ROC, n = 2) were treated with intrapleural (IPL) CATU instillation. In 6 pts, CATU was given as a single-shot with 50 µg. In one MBC patient, CATU was repeatedly administered via an intrapleural (IPL) catheter according to the intraperitonal (IP) schedule (10, 20, 50, 100 µg) over a 14 d period. Two pts were treated with a second CATU-instillation at 50 µg. All patients received antipyretics and antiemetics according to the recommendations for IP CATU (metamizole or paracetamole). Results: IPL CATU was generally well tolerated. Side-effects, including fever, dyspnea, hypotonia, and fatigue, never exceeded CTCAE G2. In 2 pts, re-puncture and second CATU-instillation had been necessary. Three pts of are still alive never after 500, 93 and 90 d. No patient required local treatment related to PE after CATU. Conclusion: IPL CATU instillation is a reasonable and low-toxic alternative to established treatments for malignant PE due to MBC or ROC. IPL CATU is generally well tolerated and allows for clinical routine PE treatment in outpatients. Larger-scaled prospective trials in this setting are therefore strongly recommended. ID 216 Impact of CTLA-4 antibodies Tremelimumab and Ipilimumab on the human immune system. Results of an ex vivo human melanoma model with the oncolytic parvovirus H-1 or cytotoxic drugs K. Goepfert, L. Wittmann, M. Linnig, B. Heinrich, P. Galle, M. Moehler antigen 4) antibodies (AB) Tremelimumab (Treme) and Ipilimumab (Ipi) may additionally strengthen DC maturation. Human Sk29Mel melanoma cells expressed CTLA-4 on cell surface. In immature DCs (iDC) coculture with H-1PV infected or cytotoxic drugs pretreated Sk29Mel tumor cell lysates (TCL) induced maturation of iDCs shown by increased expression of CD80, CD83 and CD86. Treme and Ipi did not negatively affect this DC maturation. Using ELISA, coculture experiments with H-1PV infected TCLs additionally increased cytokine production (IL-6, IFNγ, IL-12 and TNFα). The addition of Ipi or Treme did not further strengthened DC maturation. Furthermore, we analysed these DC TCL cocultures with regulatory T cells (Tregs) to overcome the negative Tregs effects on DC maturation by anti-CTLA-4 AB. Here, both Treme and Ipi significantly increased IL-6 and decreased TGF-ß. H-1PV or cytotoxic drug induced cell killing strengthened immunogenicity of melanoma tumor cell lysates. Tremelimumab and Ipilimumab additionally blocked Tregs favouring a pro-inflammatory milieu and reinforced T-cell activation. This combination of active enhancement of tumor immunogenicity and concomitant blockade of the CTLA-4 silencing process by tumor cells and Tregs is therapeutically promising ID 335 Clinical analysis supports a significant role in tumor progression of the PD-1/PD-L1 pathway in colorectal cancer T. Grimmig1, R. Mönch1, C.-T. Germer2, A.M. Waaga-Gasser1, M. Gasser2 Universitätsklinikum Würzburg, Chirurgische Klinik I, Molekulare OnkoImmunologie, Würzburg, Deutschland 2 Universitätsklinikum Würzburg, Chirurgische Klinik I, Würzburg, Deutschland 1 Background: The programmed death-1/programmed death ligand (PD1/PD-L) pathway in T cell activation has been shown to play an important role in tumor evasion from host immunity. While recent evidence from first clinical data points to beneficial effects of PD-1/PD-L1/L2-inhibitory intervention strategies in several clinical cancers its relevance in colorectal cancer (CRC) remains unclear. Methods: We investigated expression levels of PD-1, PD-L1, PD-L2, CD4, CD8 and Foxp3 in tumors from patients with CRC (n = 116 with completed 5-year survival) by immunohistochemistry and RT-qPCR. Obtained data were analyzed for their prognostic significance with respect to outcome analysis. Results: T cell infiltration was observed in 90.5% of the tumors, with 58% of the patients demonstrating PD-1-positive T cells in their tumors. Patients who developed PD-1-positive T cell infiltration showed increased PD-L1-expression within their tumors than PD-1-T cell negative individuals. Ligand expression (PD-L1/PD-L2) in the cancer tissues combined with dense PD-1-positive T cell infiltration was associated with poor prognosis in affected patients (p < 0.001). Multivariate analysis demonstrated that PD-L expression in the tumors was an independent prognostic factor in CRC. Conclusion: The presented results from clinical tumors suggest for the first time for CRC that negative signaling of infiltrating PD-1-positive T cells through PD-L1 expression within the tumor is promoting tumor progression through downregulation of anti-tumor immunity. In conclusion, this study demonstrates the importance of strategies inhibiting negative PD-1/PD-L1 signaling in CRC. Universitätsmedizin Mainz, Mainz, Deutschland Tumor-directed and immune-stimulating therapies are of special interest in cancer treatment. We analysed the impact of the oncolytic parvovirus H-1 and cytotoxic drugs like temozolomide, fotemustine, dacarbacine and combination of paclitaxel and carboplatin to trigger melanoma cell death and its immunogenicity to induce human dendritic cell (DC). Maturation.. Adding of anti-CTLA-4 (cytotoxic T-lymphocyte-associated 30 Oncol Res Treat 2014;37(suppl 1):1–133 Abstracts Inhalt Index ID 346 Tumor infiltrating B-cells in primary cutaneous T-cell lymphoma correlate with disease progression and might represent a novel target for immunotherapy S. Theurich1,2, M. Schlaak3, H. Steguweit2, L.C. Heukamp4, K. Wennhold2, P. Kurschat3, A. Shimabukuro-Vornhagen1,2, H. Schlösser2, U. Holtick1,2, M. Hallek1, R. Stadler5, M. von Bergwelt-Baildon1,2 Uniklinik Köln, Klinik I für Innere Medizin, Hämatologie und Onkologie, Köln, Deutschland 2 Uniklinik Köln, Klinik I für Innere Medizin, Labor für Interventionelle Immunologie, Köln, Deutschland 3 Uniklinik Köln, Klinik für Dermatologie, CIO, Hauttumorzentrum, Köln, Deutschland 4 Uniklinik Köln, Institut für Pathologie, Köln, Deutschland 5 Johannes Wessling Klinikum, Klinik für Dermatologie, Minden, Deutschland 1 B cells have been recently described to mediate tumor biology but so far their role as a tumor promoting or tumor repressing lymphocyte population remains controversial. Mycosis fungoides (MF) and other primary cutaneous T-cell lymphomas (CTCL) are characterized by an indolent course in early stages. However, advanced stage MF (≥ EORTC Stage IIB) and the follicular MF subtype (FMF) as well as Sézary syndrome (SS) show a more aggressive pattern with a median survival of less than two years. The pathogenesis of these more aggressive courses is still incompletely understood. With regard to a potential role of tumor associated B cells in CTCL, we systematically analyzed the B-cell infiltrate in tumor samples of 33 CTCL patients and correlated these data with the stage, subtype and clinical course. Non-malignant T-cell mediated skin disease (psoriasis, ekzema) samples (n = 10) served as controls. Advanced stage MF, FMF and SS samples contained significantly increased numbers of infiltrating B cells per lymphoma infiltrate. Moreover, time to progression showed a significant inverse relationship with the density of the B-cell infiltrate. Based on our results, we hypothesized that infiltrating B cells might be a therapeutic target in CTCL. In a 77-year old patient suffering from advanced stage FMF with a significant B-cell infiltration and progression after standard treatments, intralesional B-cell depletion with the anti-CD20 monoclonal antibody rituximab resulted in a sustained complete local tumor regression. In summary, we present first evidence for the potential tumor promoting role of CTCL associated B cells which warrants further study as a potential therapeutic strategy. ID 408 Beyond cytotoxicity: Implications for immune mediated mechanisms of action of brentuximab vedotin treatment in CD30+ lymphomas S. Theurich1,2, P. Müller3, K. Martin3, S. Savic4, G. Terszowski3, D. Lardinois5, M. Schlaak6, R. Stadler7, H.-M. Kvasnicka8, G. Spagnoli5, S. Dirnhofer4, D.E. Speiser9, M. von Bergwelt-Baildon1,2, A. Zippelius3,10 Uniklinik Köln, Klinik I für Innere Medizin, Hämatologie und Onkologie, Köln, Deutschland 2 Uniklinik Köln, Klinik I für Innere Medizin, Labor für Interventionelle Immunologie, Köln, Deutschland 3 University Hospital Basel, Cancer Immunology & Biology, Department of Biomedicine, Basel, Schweiz 4 University Hospital Basel, Institute of Pathology, Basel, Schweiz 5 University Hospital Basel, Department of Surgery, Basel, Schweiz 6 Uniklinik Köln, Klinik für Dermatologie, CIO, Hauttumorzentrum, Köln, Deutschland 7 Johannes Wessling Klinikum, Klinik für Dermatologie, Minden, Deutschland 8 University of Frankfurt, Senckenberg Institute of Pathology, Frankfurt (a.M.), Deutschland 9 University of Lausanne, Ludwig Center for Cancer Research, Lausanne, Schweiz 10 University Hospital Basel, Department of Medical Oncology, Basel, Schweiz 1 Abstracts The expression of CD30 is a characteristic feature of distinct nodal or cutaneous lymphomas. Since the clinical approval of brentuximab vedotin (BV), a monoclonal anti-CD30 antibody-drug-conjugate, targeted therapy of CD30+ lymphomas is possible and has revealed impressive efficacy even in heavily pretreated patients. While the CD30-mediated cytotoxicity of BV has so far been regarded as the main way of action, we hereby provide evidence for BV induced changes of the immune response as a further, powerful therapeutic mechanism. In patients suffering from CD30+ lymphomas (Hodgkin lymphoma, CD30+ cutaneous lymphoma), BV treatment remodeled the local and systemic immune reaction towards an enhanced anti-lymphoma response. This could be demonstrated via the induction of circulating lymphoma specific T cells and also by an increased infiltration of CD8+ cytotoxic T cells in the tumor microenvironment. In parallel, inhibitory immune cells such as regulatory FoxP3+ T-cell numbers were decreased after BV treatment. We were able to show such BV induced immune responses in patients with relapsed disease following allogeneic stem cell transplantation but also in a non-transplant setting. Furthermore, in a murine model, elucidation of the underlying mechanisms of action revealed that the cytotoxic component of BV, monomethyl auristatin E (a derivate of dolastatin), is able to induce antigen-uptake, maturation and increased lymph-node migration of dendritic cells. This in turn enhances sustained anti-tumor immune responses. In summary, we present data of a novel mechanism of action of brentuximab vedotin beyond simple cytotoxicity. This provides a rationale for clinical treatment regimens combining dolastatin-based therapies, such as brentuximab vedotin, with immune-based therapies. (ST, PM, KM and MBB, AZ contributed equally.) Developmental Therapeutics: Molecular Therapeutics ID 112 High throughput parallel amplicon sequencing of common driver mutations from FFPE lung cancer samples in molecular pathological routine diagnostics for a regional health care provider network K. König1,2, M. Peifer2,3, M. Bos2, L. Nogova2, S. Merkelbach-Bruse1, K. Stamm4, T. Henkel4, R. Thomas2,3, J. Wolf2, R. Büttner1,2, L. Heukamp1,2 Universitätsklinikum Köln, Institut für Pathologie, Köln, Deutschland Universitätsklinikum Köln, Lung Cancer Group Cologne, Köln, Deutschland 3 Universität zu Köln, Department of Translational Genomics, Köln, Deutschland 4 targos gmbh, Kassel, Deutschland 1 2 Background: Treatment paradigms for non-small-cell lung cancer (NSCLC) have shifted from one based only on histology to one that incorporates molecular subtypes involving particular genetic alterations such as activating mutations in EGFR or translocations of ALK. The list of therapeutically targetable lesions is rapidly increasing. Analysis of these potential targets is becoming a challenge in terms of work load, tissue availability as well as cost. Within the Network Genomic Medicine Lung Cancer (NGM), a regional molecular screening network of the Center for Integrated Oncology Köln Bonn, we aimed to improve on the sequential analysis of a set of 9 target amplicons by Sanger sequencing using bench top ultra-deep parallel sequencing platforms. Methods: We established a multiplex PCR to amplify up to 640 lung cancer relevant target regions from at least 20 ng of FFPE derived tumor DNA. The amplicon libraries were ligated to adapters encompassing medical identifier sequences that allowed multiplexing of up to 48 patients. The resulting libraries were sequenced on a benchtop Illumina Oncol Res Treat 2014;37(suppl 1):1–133 31 Inhalt Index platform (MiSeq). Mutations identified by parallel sequencing were confirmed by Sanger sequencing. Results: 330 patients were analyzed both by traditional single PCR based Sanger sequencing. We found that the NGS approach worked reliably, was less prone to sequencing analysis errors and that the time needed to complete the mutation screening was significantly reduced to 7 working days from previously 21 days. A total of at least 300ng of DNA was needed to complete the analysis of 9 amplicons by Sanger sequencing compared to 20 to 100ng of DNA needed for up to 640 amplicons analyzed by parallel sequencing. ID 255 EL102 – a new strategy for targeting hypoxia-driven cancer A. Maderer1, K. Göpfert1, D. Sauvigny1, M. Linnig1, J.D. Lewis 2, P.R. Galle1, M. Möhler1 1 2 Universitätsmedizin Mainz, Mainz, Deutschland ELARA Pharmaceuticals, Heidelberg, Deutschland EL102, a novel toluidine sulphonamide, is an orally available small molecule inhibitor of HIF1a induced hypoxic signaling pathways. It is a dual-inhibitor of apoptosis and angiogenesis and positively tested for prostate cancer and multiple myeloma. EL102 inhibits directly the androgen -, progesterone -, adenosine 3A receptor and tubulin. We screened one melanoma, 5 gastric and 6 colorectal cancer cell lines by RT-PCR for these target structures. Multiple viability, cell cycle and apoptosis assays were performed in four selected human colon cancer cell lines (HT-29, HCT-116, Caco-2, SW480) with different expression profiles. We analysed single incubation of EL102 and combination with cytotoxic drugs. Additionally, intracellular signalling pathways especially Hif1a, VEGF and cell cycle associated proteins were analysed by Western blotting. The melanoma cell line expressed all, colorectal only a few and the gastric cancer cell lines at most one target structure of EL102. The substance showed clear anti-proliferative and pro-apoptotic effects in the analysed colorectal cancer cell lines in nM range. The effects depended on the availability of the target structures. EL102 induced a G2 shift and showed additive apoptotic effects when combined with irinotecan. Furthermore, Hif1a and VEGF-A were clear down regulated in 3 of the colorectal cancer cell lines. EL102 is an innovative new treatment strategy in normoxic and also hypoxic tumor cell environments in different indications. The experiments argue for a high potency of this substance to complement standard therapy and to overcome possible tumour resistance mechanisms. ID 414 SORAVE: Sorafenib and everolimus for patients with solid tumors and with KRAS mutated NSCLC – results of a phase I study L. Nogova1, C. Mattonet2, M. Gardizi2, M. Scheffler2, M. Bos2, C. Wömpner2, K. Töpelt2, L. Heukamp2, A. Suleiman2, S. Frechen2, F. Sörgel3, U. Fuhr2, R. Schnell4, I. Katay4, D. Behringer5, T. Geist6, B. Kaminski7, M. Eichstaedt8, D. Tummes9, R. Büttner2, J. Wolf2 Universität Köln, Köln, Deutschland Uniklinik Köln, Köln, Deutschland 3 Institut für Biomedizinische und Pharmazeutische Forschung, Nürnberg, Deutschland 4 Praxis Internistischer Onkologie und Hämatologie, Köln, Deutschland 5 Augusta Kliniken, Bochum, Deutschland 6 Pneumologische Praxis, Düsseldorf, Deutschland 7 Krankenhaus Bethanien, Solingen, Deutschland 8 MVZ, St. Marienhospital, Düren, Deutschland 9 Onkologische Schwerpunktpraxis, Aachen, Deutschland 1 2 Background: Inhibition of signaling pathways interfering with cell proliferation and angiogenesis may increase anti-tumor efficacy. Sorafenib as 32 Oncol Res Treat 2014;37(suppl 1):1–133 well as mTOR inhibitors showed preliminary activity in KRAS mutated NSCLC. Methods: In the dose escalation part, patients with relapsed solid tumors were treated with escalating doses of everolimus from 2.5 to 10.0 mg daily p.o. in a 14 days run-in phase followed by the combination with a fixed dose of sorafenib 400 mg bid p.o. The extension phase is currently recruiting patients with KRAS mutated NSCLC. Pharmacokinetic (PK) analyses are performed during run-in and during the combination. Treatment outcome is validated with CT scans on day 57. Results: In the dose escalation part, 19 patients were recruited. The dose limiting toxicity (DLT) was not reached. At everolimus dose level of 10 mg/day, increased rates of grade 3 thrombocytopenia, leukocytopenia and anaemia occurred after the DLT interval of 29 days. Based on these observations, the dose level of 7.5 mg/day everolimus in combination with 400 mg sorafenib bid was defined as a maximal tolerated dose. The best treatment outcome on day 57 was stable disease in 11 patients. Median PFS and OS were 3.7 and 5.5 months, respectively. The extension phase in KRAS mutated NSCLC is currently ongoing. Nine patients have been recruited so far. The CT response at day 57 compared to the baseline of four evaluable patients is ranging from –22% to +5% in the sum of the longest diameter of all targeted lesions. Conclusion: Treatment of patients with relapsed solid tumors with the combination of 7.5 mg everolimus p.o. daily and 400 mg sorafenib p.o. bid is safe and feasible. Current results of an extension phase in KRAS mutated NSCLC patients show preliminary clinical activity in this patient group with an unfavorable prognosis. Economy ID 090 Estimating Site Costs Prior to Conducting Clinical Trials – a Study Site Budgeting Tool D. Arenz1, B. Hero1,2,3, B.F. Eichhorst3,4, M. Langer1,4, L. Pester1,3,4, J. von Tresckow3,4, M.J.G. Vehreschild4, O.A. Cornely1,3,4,5 Universität zu Köln, Zentrum für Klinische Studien, Köln, Deutschland Universitätsklinikum Köln, Klinik für Kinder- und Jugendmedizin, Köln, Deutschland 3 Centrum für Integrierte Onkologie Köln Bonn, Köln Bonn, Deutschland 4 Universitätsklinikum Köln, Klinik I für Innere Medizin, Köln, Deutschland 5 Universität zu Köln, Exzellenzcluster CECAD, Köln, Deutschland 1 2 Objectives: Conducting clinical trials is costly and time-consuming. Underestimating required resources slows enrollment and lowers data quality. We aimed to develop a tool for calculating trial fees prior to initiating a clinical trial. Methods: To develop this tool, trial staff from sites at the University of Cologne, Germany formed a task group. Tasks within a clinical trial were itemized into single activities and basic time expenditures were assigned. Hourly rates for different occupation groups involved were derived from total labor costs. Results were used to design a cost calculation tool. Using round robin tests, study coordinators calculated time expenditures based on the same study protocol and case report forms to validate the tool. In addition, study coordinators of one site calculated time expenditure of all trials initiated and tracked time prospectively over a period of 12 months to assess the predictive value of the tool. Results: The study site budgeting tool (STUDGET) determines hours of work and calculates the hourly rates of staff, totalizing them to fees required. The tool is web-based and available via studget.clinicalsite.org. By improving accuracy of STUDGET in round robin tests, we achieved a median deviation of € 371.59 (range € 43.58 – € 1,152.08) in calculated case payments (reference € 1,671.97). Comparison of predicted and actual hours showed a correlation of 105% median (range 18–228%). Outliers were due to unforeseeable changes in trial execution. Conclusion: We developed the web-based tool STUDGET allowing trial sites to determine the case fee needed to conduct a clinical trial. Abstracts Inhalt Index ID 150 Is the care for women with a hereditary risk for breast and ovarian cancer fundable at all? – Health-economic analysis of genetic testing intensified early cancer detection and prophylactic surgery from the perspective of the health care system and the health care provider L. Brunel-Geuder1, P.A. Fasching1, M.R. Bani1, C.R. Löhberg1, S.M. Jud1, M.G. Schrauder1, K. Geisler1, S. Wagner2, J. Hoyer3, A. Reis3, E. Wenkel4, R. Schulz-Wendtland4, M.W. Beckmann1, M. P. Lux1 Frauenklinik,Universitätsklinikum Erlangen, Universitäts-Brustzentrum Franken, Erlangen, Deutschland 2 Frauenklinik,Universitätsklinikum Erlangen, Kaufmännische Direktion, Dezernat 6, Erlangen, Deutschland 3 Humangenetisches Institut, Universitätsklinikum Erlangen, Universitäts-Brustzentrum Franken, Erlangen, Deutschland 4 Radiologisches Institut,Universitätsklinikum Erlangen, Universitäts-Brustzentrum Franken, Erlangen, Deutschland 1 Objective: 10–15% of all breast and ovarian cancer cases have a hereditary origin. It is essential to identify high-risk families to offer genetic testing and intensified care. The question is whether these procedures are refundable in the actual health care (HC) system. Methods: This health economic evaluation considered the process from initial consultation, genetic testing up intensified screening and prophylactic surgery. The analysis is based on the interdisciplinary consultations for high-risk patients at the University Breast Center Franconia (370 consultations, 71 patients with BRCA mutation). Results: Long-term HC resources can be saved regarding genetic testing and prophylactic procedures, e.g. savings of 239,539.52 €, if prophylactic mastectomy is performed in all mutation carriers of this collective. However, some parts of the care are underfunded for the HC provider, e.g. intensified screening with a loss of -466.08 €/patient/year or prophylactic mastectomy with primary reconstruction by allografts with a deficit of -3.504.09 €. Considering the gain of additional life years each prophylactic procedure is cost- effective for the HC system. Regarding the perspective of the HC provider, adnexectomy and prophylactic mastectomy costs 83.29 € per gained life year (-949.35 € in combination with primary reconstruction by allografts) – cost-effective for the society but in deficit for the HC provider. Conclusion: The care for high-risk families is cost-effective. In the longterm monetary resources can be saved. This does not apply to the HC provider as several prophylactic options lead to a financial deficit. Therefore specialized care centers need additional charges if they care for numerous high-risk families. ID 462 Performance-based cost allocation in a Comprehensive Cancer Center J.-P. Glossmann1, M. Kron1, A. Bernschein1, B. Funke2, P. Görgen2, I. Schmidt-Wolf2, M. Hallek1, J. Wolf1 Universitätsklinikum Köln, Centrum für Integrierte Onkologie, Köln, Deutschland 2 Universitätsklinikum Bonn, Centrum für Integrierte Onkologie, Bonn, Deutschland 1 limited existing financial resources such as the grants for «Onkologische Spitzenzentren» by the German Cancer Aid. Methods: Diagnosis Related Groups (DRGs) are used to allocate CCC-specific overhead costs to the departments which benefit from the structures. Annual cancer-specific revenues for each department are identified by selecting DRGs with a cancer diagnosis. A margin is calculated by subtracting the revenues of a baseline year for each department. A positive value indicates a growth in cancer-related revenues and results in an additional fee added to a base fee of 5000.00 Euro. Results: In 2012 a total of 444,240.00 Euro (Köln: 344,240.00 Euro, Bonn: 100,000.00 Euro) was invested in the CIO Köln Bonn by 52 departments (Köln: 25 departments, Bonn: 27). The sum per department ranged from 5000.00 Euros to 79,960.37 Euros. Conclusion: To our knowledge this is the first performance-based internal cost-allocating model in a German CCC. Ultimately, overhead costs for CCCs should be reimbursed by statutory health insurances. Epidemiology ID 037 Update on incidence of amino-bisphosphonate associated osteonecrosis of the jaw Y. Begus-Nahrmann1, P. Kästner1, C. Walter2 Konzept Pharma Service GmbH, Freden (Leine), Deutschland Universitätsmedizin der Johannes-Gutenberg-Universität Mainz, Klinik für Mund-Kiefer-Gesichtschirurgie, Mainz, Deutschland 1 2 Background: Osteonecrosis of the jaw (ONJ) is a frequent adverse effect for doses of amino-bisphosphonates (aBP) used in metastatic settings. Comparing incidence rates from recent reports to the last review 2009 provide details, whether preventive measures to minimize the ONJ risk could be transferred to daily practice. M&M: To identify current ONJ incidence rates (2009 to date) a PubMed literature research was performed using the search terms: ‘bisphosphonate’, ‘osteonecrosis’, ‘incidence’, ‘prevalence’ and ‘denosumab’. Articles were screened for incidence rates. Further articles from the references were included. Results: 26 articles reported interpretable incidences of ONJ. The average incidences for breast cancer patients were 6% (0.6–20.8%), for multiple myeloma 6.3% (1.3–15.6%), for prostate cancer 6.7% (1–18.3%). Compared to the incidence reported 2009, a difference of +1.4%, –1.3% and –3.6% is detected. ONJ incidences are significantly influenced by range of aBP administration and dramatically potentiated by combination with chemotherapeutics. Denosumab was also reviewed for the incidence of ONJ. The incidences for breast cancer were 2%, prostate cancer 3.5% (2–5%), and multiple myeloma patients 1.5% (1.1–1.83%). Conclusion: No remarkable changes for the incidence of aBP associated ONJ are observed for breast and multiple myeloma patients. For prostate cancer the incidence is reduced but still relevant. Denosumab shows low but considerable ONJ incidence, yet more long-term studies will be essential. Beside the awareness of ONJ risk due to aBP treatment and prevention measures data from the last years demonstrate that ONJ is still a present issue. Introduction: Statutory health insurances, politicians and patient advocacy groups in Germany call for high-end cancer care provided by Comprehensive Cancer Centers (CCCs). CCCs such as the Center for Integrated Oncology Köln Bonn (CIO Köln Bonn) maintain a cancer-specific infrastructure such as patient navigators, a clinical cancer registry, quality management, psycho-oncological support and a tissue bank. However, little progress has been made in re-financing the additional financial burden related to these structures. Aim: To develop and implement an internal, performance-based cost-allocating system to bridge the financial gap of growing overhead costs and Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 33 Inhalt Index ID 044 Socio-economic deprivation and cancer survival in Germany L. Jansen1, A. Eberle2, K. Emrich3, A. Gondos1, B. Holleczek4, H. Kajüter5, W. Maier6, A. Nennecke7, R. Pritzkuleit8, H. Brenner1,9 Deutsches Krebsforschungszentrum (DKFZ), Abteilung für klinische Epidemiologie und Alternsforschung, Heidelberg, Deutschland 2 Leibniz-Institut für Präventionsforschung und Epidemiologie – BIPS GmbH, Bremen, Deutschland 3 Johannes Gutenberg Universität Mainz, Krebsregister Rheinland-Pfalz, Instituts für Medizinische Biometrie, Epidemiologie und Informatik (IMBEI), Mainz, Deutschland 4 Krebsregister Saarland, Saarbrücken, Deutschland 5 Krebsregister Nordrhein-Westfalen, Münster, Deutschland 6 Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Institut für Gesundheitsökonomie und Management im Gesundheitswesen, Neuherberg, Deutschland 7 Behörde für Gesundheit und Verbraucherschutz, Hamburgisches Krebsregister, Hamburg, Deutschland 8 Universität Lübeck, Institut für Krebsepidemiologie, Lübeck, Deutschland 9 Deutsches Konsortium für Translationale Krebsforschung (DKTK), Heidelberg, Deutschland 1 Background: While socio-economic inequalities in cancer survival have been demonstrated both within and between countries, evidence on the variation of inequalities over time past diagnosis is sparse. Furthermore, no comprehensive analysis of socio-economic differences in cancer survival in Germany has been conducted. Our study aimed to analyze in detail variations in cancer survival for patients diagnosed with one of the 25 most common cancer sites in 1997–2006 in Germany. Methods: Data from 10 population-based cancer registries in Germany (covering 32 million inhabitants) were combined. Patients were assigned a socio-economic status according to the district of residence at diagnosis. Period analysis was used to derive age-standardized relative survival within 5 years from diagnosis for 2002–2006 for each deprivation quintile in Germany. Relative survival of patients living in the most deprived districts was compared to survival of patients living in all other districts by model-based period analysis. Results: For 21 of 25 cancer sites, 5-year relative survival was lower in the most deprived districts than in all other districts combined. The median relative excess risk of death over the 25 cancer sites decreased from 1.24 in the first three months to 1.16 in the following nine months to 1.08 in the following four years. Inequalities persisted after adjustment for stage. Conclusion: The observed major regional socio-economic inequalities indicate a potential for improving cancer care and survival in Germany. As inequalities were largest in the first months and persisted after adjustment for stage, differential quality of medical care should be considered as reason for inequalities. ID 072 FungiscopeTM – Global Emerging Fungal Infection Registry K. Wahlers1, M.J.G. Vehreschild1, A. Hamprecht2, S. de Hoog3, J. Vehreschild1, O.A. Cornely1 Uniklinik Köln, Klinik I für Innere Medizin, Köln, Deutschland Uniklinik Köln, Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Köln, Deutschland 3 CBS Fungal Biodiversity Centre, Utrecht, Niederlande lecular evidence of IFD. Data collected include demographics, underlying conditions, immunosuppressive medication, clinical signs and symptoms, sites of infection, diagnostic tests, pathogen identification, antifungal treatment, surgical procedures, response to treatment, and survival. Results: To date, 340 cases have been captured. Mucorales (n = 146; 43%), Fusarium spp. (n = 55; 16%), yeasts (n = 48; 14%), and Dematiaceae (n = 34; 10%) are the most frequently registered pathogens. Chemotherapy or allogeneic stem cell transplantation were the predominant risk factors (n = 225; 66%), followed by diabetes (n = 67; 20%), intensive care (n = 74; 22%), and chronic renal disease (n = 33; 10%). Sites of infection included lung (n = 160; 47%), followed by blood stream (n = 71; 21%), paranasal sinuses (n = 57; 17%), and deep soft tissue (n = 54; 16%). Favorable outcome was found in 174 (51%) patients. All-cause-mortality and mortality attributable to IFD was 45% and 34%, respectively. Conclusion: We documented a broad biological diversity of IFD across Europe, Asia and the Americas. Patients with malignancies are at particular risk. Mortality is high. Further investigators are cordially invited to contribute to FungiscopeTM. ID 121 Possible Process and Quality Assessment for FullElectronic Cancer Registries S. Friedrich1, S. Hermann1, M. Ketterer2, N. Becker3 Deutsches Krebsforschungszentrum, Epidemiologisches Krebsregister Baden-Württemberg, Heidelberg, Deutschland 2 IT-Choice Software AG, Karlsruhe, Deutschland 3 Deutsches Krebsforschungszentrum, Heidelberg, Deutschland 1 Completely electronic data transfer to population-based cancer registries – as realized in the Federal State Cancer Registry of Baden-Württemberg (KRBW) – may be an efficient alternative to paper-based reporting. It facilitates reporting for physicians and plausibility control immediately at time of data transmission. Data can be made available rapidly for users of the registry. On the other hand, advantages regarding time gain and data quality at time of reporting may be lost by internal data processing if it is too time-consuming and e.g. gaps in data being obvious for hand-working data managers slip through an automatic processing. Thus, indicators for velocity of data processing and outcome quality are needed. In the KRBW reported data enter into the «Vertrauensstelle» (VS), pass to the «Klinische Landesregisterstelle» (KLR) and then on to the Epidemiological Cancer Registry (EKR). A simple indicator for velocity is the mean time span between data entry in the VS and availability for users from the EKR. Data can be manually consistency-checked in the KLR which may increase data quality but also increases processing time. The proportion of detected inconsistencies in the checked data may be another indicator for efficient internal data processing. Completeness of the individual records is a particular issue of clinical cancer registries as the KRBW is. Automatic checks triggering a reminder system for callbacks with the reporting physicians are (a) no reports on treatment more than 3 months after diagnosis, (b) no after-care reports more than 6 months after last information on treatment, (c) no vital status information within the past 12 months. The presentations will provide further indicators and details with exemplary evaluations. 1 2 Background: The relevance of emerging invasive fungal diseases (IFD) is increasing. FungiscopeTM is a global registry for emerging IFD with contributors from >20 countries. The objective is to broaden knowledge on epidemiology, determine clinical patterns, describe and improve diagnostic procedures and therapeutic regimens, and to exchange of clinical isolates among contributors. Methods: Fungiscope™ uses web-based data capture via www.fungiscope.net. Case enrollment requires cultural, histological, antigen or mo- 34 Oncol Res Treat 2014;37(suppl 1):1–133 ID 131 Interim results from the German randomized lung screening trial LUSI A. Eigentopf1, N. Becker1, E. Motsch1, M.-L. Groß1 DKFZ Heidelberg, Epidemiologie von Krebserkrankungen, Heidelberg, Deutschland 1 In 2011, first results of the USA lung screening trial (NLST) were published indicating a 20% reduction of lung cancer with multi-slice-CT (MSCT). However, since important questions cannot be resolved by this Abstracts Inhalt Index trial (e.g. magnitude of overdiagnosis), parallel running European trials which share a different study design have been continued and are o ngoing. The German Lung Cancer Screening Intervention Trial (LUSI) is a component of these European studies. Currently, the first three screening rounds are completed and all participants are undergoing the fourth or fifth round of screening / observation or finished already screening and are under follow-up observation. For basic characteristics of the German trial the most recent data will be presented. A crucial issue is e.g. compliance which is with currently 92% excellent. Contamination in the control group is extremely low. The detection rate in the screening rounds 2–5 is with about 0.5% within the expected range and comparable to the other European studies. Overall, 52 lung cancer cases were identified so far and 81 participants died from any cause. The distribution of overall mortality in the both study arms is an important quality indicator for a balanced randomization and can be presented at time of the congress for about 3 years of mortality observation after randomization. With power calculations based on the observed lung cancer incidence in the European trials, it will be estimated at which time a final evaluation will be reasonable. ID 140 Also, first degree relatives of CRC patients have an increased CRC risk. It is our goal to create population based data on familial CRC risk in a German population. Concept: Incident CRC cases in Upper Bavaria are collected and their family trees constructed. The Patient’s relatives are documented by name, address and date of birth, but without health related information. Cancer history is added to a family by a record linkage procedure combining members of the family trees with cancer histories in the Munich Cancer Registry (MCR). A specific data protection concept guarantees anonymity for families and their cancer histories. Prevalence of familial CRC risk in upper Bavaria and the posterior probability of a family to carry CRC risk can be inferred from the anonymous data. Strength of simple familial CRC risk detection tools can also be assessed. Experience: Per year, 141 clinical departments and 24 oncological practices report about 1300 incident CRC cases (below 70 years) to the MCR. During the first year, we recruited 456 patients in 27 clinical departments and 6 oncological practices and contacted 1600 relatives. Participation of relatives is reluctant in spite different information sources (leaflet, call center, internet) on the study purpose. Record linkage creates an anonymous collection of CRC family histories. 37 families with a CRC patient below the age of 50 are recorded. They are recruited into a psycho-oncological substudy. «Cancer in Germany» 2013 – Current Epidemiological Cancer Statistics Acknowledgement: The study is sponsored by the BMFSFJ and supported by the Felix-Burda Stiftung and the Netzwerk gegen Darmkrebs. B. Barnes, U. Wolf, J. Haberland, J. Bertz, S. Dahm, K. Kraywinkel ID 179 Robert Koch-Institut, Zentrum für Krebsregisterdaten, Berlin, Deutschland We present here the latest statistics from the ninth Edition of the report «Cancer in Germany», published in 2013 by the German Centre for Cancer Registry Data (ZfKD) at the Robert Koch Institute (RKI) and the Association of Population-based Cancer Registries in Germany (GEKID). This report includes nationwide analyses of incident cancer cases through the year 2010. The data for this report were transferred to the ZfKD in anonymised form by all German population-based cancer registries. As in previous years, cancer incidence and mortality are presented by age and sex. Current trends are analysed and put into international context. Additional focus is placed on prevalence, five-year survival and tumour extent (T-stage) at diagnosis. The spectrum of presented localisations was expanded again to include mesothelioma and vulvar cancers, among others. For the year 2010, the RKI estimates that 477,300 cases of invasive cancer were newly diagnosed. The annual number of incident cases increased by approximately 16% among men and 11% among women from 2001 to 2010. As with previous estimates, the most common cancer sites were the prostate among men, with 65,800 cases, and the breast among women, with 70,300 cases. These were followed by colorectal cancers among women and lung cancers among men. The ZfKD may provide, upon application, the verified dataset from the population-based cancer registries to third parties for analyses. Furthermore, the Homepage of the ZfKD has been expanded to include an interactive database. Anmerkung: Die Krebsregisterdaten wurden auf Vollzähligkeit geprüft und endgültig ausgewertet. Die Ergebnisse im zweiten Absatz wurden demensprechend aktualisiert. ID 155 Strengthening and protecting families – how to handle the familial colorectal cancer risk. A prospective observational study – concept, structure, and first experience Internationally agreed lymphoma classification: Different applications lead to strongly different incidence figures K.-H. Adzersen1, S. Friedrich1, N. Becker2 Deutsches Krebsforschungszentrum, Epidemiologisches Krebsregister Baden-Württemberg, Heidelberg, Deutschland 2 Deutsches Krebsforschungszentrum, Heidelberg, Deutschland 1 After decades of competing and incommensurable lymphoma classifications, the WHO classification of 2001 for ‘Tumours of Haematopoietic and Lymphoid Tissues’ was the first internationally agreed classification for this important and complex group of malignancies. It promised internationally comparable incidence figures and e.g. the potential to pool epidemiologic data from different countries for common evaluations. However, looking into details of the practical use of the WHO classification reveals partially substantial differences leading to strongly different incidence figures. We used the data of the Federal State Cancer Registry of Baden-Württemberg from the years 2010 and 2011 and applied three different variants of usage of the classification for computing incidence figures: (a) the original WHO classification, renewed in 2008, (b) the European Network of Cancer Registries (ENCR), Haemacare 2009, and (c) the grouping of RKI (Robert Koch Institute) using the International Classification of Diseases 10th revision 2010 (ICD-10-GM). The WHO classification comprises 56 specific NHL morphologies, the ENCR 51 and the RKI grouping ICD-10 (2010) 28, leading to 3912 NHL cases (WHO), 3509 (ENCR) and 2792 (RKI), respectively. Lymphomas belong to the cancer sites for which long-lasting upwards trends in incidence have been observed. For a reliable description of future trends and the analysis of their determinants, a common disease definition is indispensible. The currently existing strong differences in the application of internationally agreed standards require urgently consensus arrangements at least among the cancer registries to ascertain comparability. U. Mansmann, G. Wölke, J. Engel, J. Stausberg LMU München, IBE, München, Deutschland Background: Lynch defines patients with familial colorectal cancer (CRC) risk as those with two or more first- or second-degree relatives (or both) with CRC. They make up about 20 percent of all CRC patients. Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 35 Inhalt Index ID 225 On the way towards an ‘Evidence Based Cancer Registration Software’ for Clinical Cancer Registries and Organ Centers – an experience report of the Comprehensive Cancer Center Ulm W. Voigt1, P. Kuhn1, E. Kuhn2 Universitätsklinikum Ulm, CCCU Comprehensive Cancer Center Ulm, Ulm, Deutschland 2 Fachochschule Trier, Wirtschaftsinformatik, Trier, Deutschland Conclusion: The number of patients with bisphosphonate-associated osteonecrosis of the jaws has increased in the recent years despite preventive measures that have been implemented and which were not able to reduce the overall number of osteonecroses. Reasons might be an increased alertness regarding the disease so that more necroses are being diagnosed and that more bisphosphonates hav e been prescribed. 1 Issue: In context of the «Nationaler Krebsplan», an initiative of the German government, the cancer registries play an important role in the field of quality assurance, to improve the cancer patient care. The directives of the registries are data reduction and economy. The problem is, to find an adequate software to register the data needed as prescribed. Methods: In developing our registration program within a group of 14 clinics [1], we tried to follow the rules of Evidence based Medicine (EBM). EBM means, the diagnostic or therapeutic measurement has to be proofed by scientific methods. How can you prove the evidence of a program? The evidence can be proved 1.) by the contentedness of the users 2.) by the quality of the software (functional, user friendly, only basic data needed, economical, correctness of data), and 3.) by application (by taking part in national benchmarking, in the certification process of the organ centers and by fulfilling the requirements of the national and state registries. Results: To 1: this is shown by a survey of the user group, to 2: this is shown by the way, the system has been designed and is continually enhanced to 3: this is shown by benchmarking samples on the «Deutscher Krebskongress» and by the number of certifications of the Organ centers Conclusion: Our model: ‘CREDOS user group’ is very close to the requirements of EBM. It supports the requirements of the data registration in the best possible way and enables the registries to generate data, which help to control and ensure the best treatment for our cancer patients. Nevertheless the quality of a cancer register depends on the quality of the documentaries (knowledge, experience and most important of all: motivation) [1]www.ccc-ulm.delast entry: 14.9.2013. ID 236 Bisphosphonate associated osteonecrosis of the jaws, osteoradionecrosis and osteomyelitis C. Walter1, K. Sagheb1, J. Bitzer1, R. Rahimi-Nedjat1, K.J. Taylor2 1 2 Universität Mainz, MKG-Chirurgie, Mainz, Deutschland Universität, IMBEI, Mainz, Deutschland Introduction: Several reasons can lead to osteonecrosis of the jaws. In addition to medication such as bisphosphonates, osteonecrosis can be caused by radiation therapy or local factors. The aim of this study was to analyse the distribution of osteonecrosis of the jaws in patients being treated in an oral and maxillofacial surgical department and to detect changes in the distribution by comparing the latest data with an earlier study. Material and Methods: All patients with either osteonecrosis of osteomyelitis treated from April 2005 until July 2012 were analysed. In case of recurrence of the disease or synchronous presence of several affected areas, the patient was only counted once. The results were compared to a similar study performed with patients treated from January 2000 until April 2005. Results: In 45% bisphosphonates were responsible for the osteonecroses. Odontogenic or surgically-induced osteonecroses were present in 32%. 17% had an osteoradionecrosis; in 4% a trauma was the reason for the necroses, and in another 4% no reason was obvious. From 2000 to 2005 only 10% of all necroses were caused by bisphosphonates. Aside from bisphosphonate-associated osteonecrosis, all other reasons did not change their frequency between the two studies. 36 Oncol Res Treat 2014;37(suppl 1):1–133 ID 252 Krebsregisterdokumentation im Praxisalltag A. Matzdorff1, F. Kowalski1, T. Muche1, A. Fuchs1, C. Stegmaier2 Caritasklinikum Saarbrücken, Klinik f. Hämatologie/Onkologie, Saarbrücken, Deutschland 2 Epidemiologisches Krebsregister Saarland, Saarbrücken, Deutschland 1 Einleitung: Im April ist das Gesetz zur Krebsfrüherkennung und zur Qualitätssicherung durch klinische Krebsregister in Kraft gesetzt worden. Die Arbeitsgemeinschaft Deutscher Tumorzentren (ADT) hat dafür einen einheitlichen onkologischen Basisdatensatz entwickelt. Fragestellung: Wie hoch ist der Zeitaufwand bei der Anwendung des ADT-Basisdatensatzes und welche Probleme ergeben sich in der klinischen Praxis? Methode: Für 20 aufeinanderfolgende Patienten einer hämato-onkologischen Kliniksambulanz eines Tages wurde der Basisdatensatz erhoben. Ergebnisse: Der Zeitaufwand betrug 50 min pro Fall (Durchsicht der Papierakte, der Eintragungen im KIS, ggf. Rückfragen beim Arzt). Probleme ergaben sich bei (Auswahl): –– Unterschiedliche ICD-10 und TNM-Klassifikationen in Berichten verschiedener Institutionen. Fehlen der ICD-O. –– Fehlende Histologie (z.B. multimorbide Patienten, die für eine tumorspezifische Therapie nicht in Frage kommen). –– Patienten, die an verschiedenen, z.T. räumlich oder zeitlich weit auseinanderliegenden Orten behandelt werden. –– Patienten mit mischzelligen Tumoren oder mit mehreren gleichzeitig behandelten Tumoren. –– Erfassung von neuen Wirkstoffen (Tyrosinkinasehemmern). –– Problematische Fragen des ADT Fragebogens: ob von Leitlinien abgewichen wurde, ob ein Tumorkonferenzbeschluss vorgelegen hat. Schlussfolgerung: Der ADT-Basisdokumentationsbogen erfasst Daten, die über die Vorgaben der Onkologie-Vereinbarung und die Empfehlungen der Fachgruppen (z.B. Grundsatzpapier der DGHO „Onkologische Zentren») hinausgehen und in Arztberichten nicht abgebildet werden. Der Zeitaufwand für die Basisdokumentation ist erheblich . ID 258 The Risk of Developing Subsequent Primary Tumour among Adult Patients with Leukaemia and Lymphoma in Germany N. Baras1,2, S. Dahm1, J. Haberland1, K. Kraywinkel1 Robert-Koch Institute, German Centre for Cancer Registry Data, Berlin, Deutschland 2 Charité – Universitätsmedizin, Berlin, Deutschland 1 Background: Survivors of lymphoma and leukaemia have been reportedly shown to be at increased risk for developing other primary malignancies. Methods: We used the national German cancer registry database pooled from 14 population-based cancer registries to calculate the incidence of subsequent tumours among patients with first primary Hodgkin lymphoma (HL, C81), Non-Hodgkin lymphoma (NHL, C82–C85), multiple myeloma (MM, C90) and leukaemia (C91–C95) diagnosed between 1970 and 2010. The ratio of the observed and the expected numbers of subsequent tumours (standardized incidence ratio, SIR) was evaluated using the population-based incidence rates. Results: A total of 209,429 cases were diagnosed with lymphoma and leukaemia, and were followed for 2,982,409 person-years between 1970 and 2010. Among these cases, 11,680 (6%) subsequent tumours, 10,022 Abstracts Inhalt Index of which were solid tumours (C00–C75) were observed in both sexes. The overall risk of subsequent tumours at any site was significantly elevated after HL (SIR = 2.33, CI: 2.17–2.50), NHL (SIR = 1.51, CI: 1.47– 1.55), and leukaemia (SIR = 1.45, CI: 1.40–1.50). There was a very slight increase in the overall risk after MM (SIR = 1.11, CI: 1.06–1.17). The risk of developing a solid tumour was significantly increased between 7% (CI: 2–13%) after MM and 80% (CI: 65–95%) after HL. We found consistently increased risks for the following solid subsequent tumours after HL, NHL and Leukaemia: oropharynx, stomach, colon and rectum, lung, skin melanoma, and kidney. Significant excess risks for subsequent cancers of the thyroid and female breast were only found after HL and NHL. Conclusion: Despite somewhat limited follow-up time for some registries, the pooled German data showed an increased risk of developing subsequent malignancies for leukaemia and lymphoma patients compared to the general population which is consistent with other population-based studies. ID 283 Breast cancer survival in Germany – a population-based high resolution study from Saarland B. Holleczek1,2, L. Jansen2, H. Brenner2 Saarland Cancer Registry, Saarbrücken, Deutschland Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Deutschland implementation of the program and could be seen as a necessary condition for a screening related reduction of breast cancer mortality several years later. Methods: We analyzed data of nine German population based cancer registries which covered 13of 16 federal states and one district for the time period 2002–2010. We calculated age standardized stage specific incidence rates for the age groups 30 to 49, 50 to 69 and 70 years and older. Results: Following a temporary increase, the pooled incidence rate of advanced breast cancer (UICC II–IV) in the target population reached its pre-mammography level in 2010, while the incidence rate of early breast cancer (UICC I) in 2010 was still more than 40% higher compared to the years 2002–2004. In the district of Muenster, where the program was implemented until 2006, the rate of advanced stage tumors was 8% lower in 2010 compared to the initial rate. For older and younger women a slight increase of advanced breast cancer incidence could be observed. The completeness of stage information improved especially for the screening age group. Conclusions: The time trends of stage specific incidence rates so far seem to follow the expected course: far more early stage tumors are being detected than before implementation of screening, while there are first indications that the rates of advanced breast cancer incidence might be reduced about 5 years after implementation of the program. 1 2 Background: Population-based survival studies of breast cancer patients are commonly restricted to age- and stage-specific analyses. This study from Germany aimed at extending available population-based survival data on further prognostic cancer characteristics such as tumor grade, hormone receptor status and human epidermal growth factor receptor type 2 (HER2/neu) expression. Material and Methods: Data from the population-based Saarland Cancer Registry including female patients diagnosed with invasive breast cancer between 2000 and 2009 were included. Period analysis methodology and regression modelling were used to obtain estimates of 5-year relative survival and tumor related excess risks in 2005–2009. Results: Overall age standardized 5-year relative survival was 83%. In addition to age and stage, tumor grade and hormone receptor status were independent predictors of 5-year relative survival. Detailed analyses by age, stage, morphology, tumor grade, hormone receptor status and HER2/ neu expression consistently revealed lower survival of patients with high grade, hormone receptor negative or HER2/neu positive cancers and patients aged 70 years or older. Conclusion: This high resolution study extends available population-based survival data of breast cancer patients. Particular efforts should be made to overcome the persisting large survival deficits, which were observed for elderly patients in all clinical subgroups. Reference Holleczek B, Jansen L, Brenner H (2013) Breast Cancer Survival in Germany: A Population-Based High Resolution Study from Saarland. PLoS ONE 8(7): e70680. ID 317 Time trends of stage specific incidence rates of invasive breast cancer over the first years of the German Mammography Screening Program K. Kraywinkel1, U. Batzler2, A. Katalinic3 1 2 3 Robert Koch-Institut, Zentrum für Krebsregisterdaten, Berlin, Deutschland Krebsregister NRW, Münster, Deutschland Universität Lübeck, Institut für Krebsepidemiologie, Lübeck, Deutschland Background: The German Mammography Screening Program has been introduced between 2005 and 2009 for all women between 50 and 69 years of age. An important parameter for the assessment of its effectiveness is the incidence of advanced malignant breast tumors in the target population. A decrease of this rate would be expected at some point after Abstracts ID 382 Volume of screening colonoscopy increases detection rate of non-advanced adenoma but not of advanced adenoma N. Zwink1, C. Stock2, M. Hoffmeister1, B. Birkner3,4, H. Brenner1 German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Deutschland 2 Institute of Medical Biometry and Informatics (IMBI), Department of Medical Biometry, Heidelberg, Deutschland 3 Gastroenterology Practice, Munich, Deutschland 4 Bavarian Association of Statutory Health Insurance Physicians, Munich, Deutschland 1 Background & Aims: Adenoma detection rates (ADR) have been suggested as an indicator of the quality of screening colonoscopy. The aim of this study was to assess the inter-physician variation in ADR in routine practice in the German healthcare system. Design: Cohort study. Setting: Quality assurance program of the Bavarian Association of Statutory Health Insurance Physicians («Qualitätsmaßnahme Koloskopie»),Germany. Patients: Individuals aged ≥55 years who underwent screening colonoscopy between 2007 and 2009. Main Outcome Measurements: Variation in ADR (95% confidence intervals [CI]) per physician and year. Physicians were grouped according to the number of screening colonoscopies per year (≤50, 50–99, 100–199, ≥200 colonoscopies). Results: In total, 203,363 individuals (mean age 64 years, 55.2% women) underwent screening colonoscopy between 2007 and 2009 in Bavaria, Germany. Screening colonoscopies were performed by 509 physicians. Detection rate of any adenoma (including non-advanced and advanced adenoma) ranged from 21.0% (95% CI 20.0–22.1%) to 26.2% (95% CI 24.9–27.5%), of non-advanced adenoma from 13.0% (95% CI 12.4– 13.7%) to 17.7% (95% CI 16.8–18.6%) and of colorectal cancer from 0.8% (95% CI 0.8–0.8%) to 1.2% (95% CI 1.1–1.3%) in the group of physicians with less than 50 to at least 200 screening colonoscopies per year, respectively. Detection rate of advanced adenoma did not increase with increasing colonoscopy rate per physician and varied between 8.0% (95% CI 7.6–8.4%) and 9.1% (95% CI 8.7–9.6%). Conclusions: The overall ADR as an indicator of the quality of screening colonoscopy must be treated with caution. Stratification showed the volume of screening colonoscopies to be related to the detection rate of non-advanced adenomas only but not of advanced neoplasms. Oncol Res Treat 2014;37(suppl 1):1–133 37 Inhalt Index ID 444 Clinical Practice of Gastric Cancer Diagnosis and Treatment in Upper Franconia: Potential and Pitfalls of Cancer Registration D. Salomo1,2, D. Eckert2, T. Maisel1,2, A. Kiani1,2 1 2 Klinikum Bayreuth GmbH, Medizinische Klinik IV, Bayreuth, Deutschland Tumorzentrum Oberfranken e.V., Bayreuth, Deutschland In several regions of Germany, population-based epidemiological cancer registries have been established, that have the task to register and analyze the incidence, regional distribution and mortality of all tumor entities. In bavaria, for example, six regional cancer registries cover more than 95% of all cancer cases. The quality of the registry data depends on the information provided by the reporting physician, and the accuracy of the data is largely unknown. In addition, epidemiological cancer registries do not contain detailed clinical information about the disease. The aim of the current study was to retrospectively analyze the completeness and accuracy of a given data set of an epidemiological cancer registry, and to supplement this data by specific enquiry with clinical information. All 222 patients diagnosed in 2007 with gastric cancer and registered in the epidemiological cancer registry of upper franconia were analyzed. A questionnaire was developed, in which all clinically relevant modalities of gastric cancer diagnosis and treatment were addressed. The registry data was analyzed before and after the questionnaire was sent to the treating physicians. Before the enquiry, the epidemiological data necessary to assess tumor prognosis was incomplete. For example, information about the UICC stage was lacking in 30%, but could be obtained by enquiry in 95% of the patients. Clinical data was scarce, but could be complemented to a great extent by enquiry. Information about the practice of cancer treatment in upper franconia was obtained. Clinical registries will be important tools to analyze the practice of cancer treatment on a population basis, but the quality of the data must be verified in order to obtain reliable information. ID 446 Elderly cancer patients want information but no participation in onco-surgical treatment decisions. Observational study in two tertiary university hospitals. M. Schmidt, B. Neuner, F. Degel, C. Spies Charité Universitaetsmedizin Berlin, Klinik für Anästhesiologie m. S. operative Intensivmedizin, Berlin, Deutschland Introduction: The relationship between physician and patients has undergone important changes. Emancipation of patients has led to real partnership in medical decision-making.Objectives: To evaluate elderly (>65 years) onco-surgical patients desire for autonomy and information in clinical decision making. Methods: Between February 2010 and September 2012 and after ethical committee approval and written informed consent the study was conducted in 2 tertiary university hospitals in Germany. Included patients were older than 65 years and were scheduled for abdominal onco-surgery. The need for information and involvement were evaluated using the Autonomy Preference Index (API) before surgery. Basic demographic data included age, gender, cancer site, marital status and educational level. Multivariate analysis was done by linear regression analysis. Results: Overall 658 patients (mean age 71.8 years, 68.4% males) were included. Cancer sites were prostate cancers (38.8%), ovarian cancers (13.7%), cancers of the genitourinary tract (16%), upper gastrointestinary tract (21.1%) and colorectal cancers (10.5%). Sixty-seven per cent of the patients were married, 10% were widowed, 9% were divorced and 6% lived alone. One third (32%) of the patients had 12 to 13 years of education. The mean API for participation (DPMS) score was 39 (SD 5.1) whereas the API for information showed a ceiling effect. In multivariate analysis adjusted for age, marital status, educational level and cancer site, only gender (female vs male, p = 0.004, CI 95% -10,22 – -1.92) was 38 Oncol Res Treat 2014;37(suppl 1):1–133 found to be an independent predictor for need of information and participation. Conclusion: The majority of elderly onco-surgical patients want to be informed about their disease and their treatment. The desire for participation in treatment decisions is low. Women want to be more actively involved in treatment decisions than men. Functional Imaging ID 054 Assessment of therapy effects in lymphoma patients at end-of-treatment using volume perfusion computed tomography (VPCT) M. Horger, C.D. Claussen, R. Syha Eberhard-Karls-Universität Tuebingen, Radiologische Diagnostik, Tübingen, Deutschland Purpose: To determine the diagnostic benefit of using volume perfusion computed tomography (VPCT) at end-of-treatment for response assessment in lymphoma patients. Materials and Methods: 75 patients with different lymphoma subtypes were prospectively enrolled. The local ethics board approved this study. 50/75 patients presented residual masses at end-of-treatment. 26/50 patients underwent VPCT both at baseline and at end-of-treatment; 24/50 patients only had end-of-treatment-VPCT studies. We measured each time size of the main lymphoma mass, its blood flow(BF), blood volume(BV) and k-trans, and calculated ratios, their sensitivity/ specificity/negative(NPV) and positive predictive values(PPV). For patients undergoing VPCT only at end-of-treatment, a cut-off threshold between responders and non-responders was calculated. CT-imaging obtained >12 months afterwards was used for validation. Results: For patients undergoing VPCT, both at baseline and end-oftreatment, the paired t-test revealed a significant reduction in size (p < 0.001), BF(p < 0.001), and k-trans (p < 0.001) for responders. For non-responders, only reduction in size (p = 0.0125) proved significant, but misleading. In aggressive lymphomas changes in all parameters proved significant. Identification of non-response in patients undergoing VPCT only at end-of-treatment was reached only for BF (p < 0.001) at a BF value of 18.51 (sensitivity 92.86%, specificity 72,73%, accuracy 84%, positive predictive value 81,25%, negative predictive value 88.89%). Baseline perfusion parameters alone did not predict response. Discussion: VPCT seems adequate for assessment of lymphoma response at end-of-treatment and for prediction of progression free survival. ID 417 High specificity of Positron Emission Mammography (PEM) in diagnosis of breast cancer F.H.H. Müller1, M. Hentschel2, A. Müller1, J. Farahati3 Praxis für Radiologie und Nuklearmedizin, Nuklearmedizin, Ludwigshafen, Deutschland 2 Univerisität, Nuklearmedizin, Bern, Schweiz 3 Elisabeth Krankenhaus, Nuklearmedizin, Dorsten, Deutschland 1 Aim: How is the diagnostic performance of PEM, a HR-PET with intrinsic resolution of 1.6 mm and similar diagnostic sensitivity and higher specificity in detection of breast cancer (B-Ca), compared to other diagnostic features? Methods: PEM was performed in 119 lesions with suspicious breast lesions 90 min after i.v. application of 3.5 MBq F-18-FDG per KG body weight. A ROI marked the target lesion, measured by the maximum PEM uptake value (PUVmax) and was correlated with a corresponding non-target ROI in the contra lateral healthy breast determining the target/non-target ratio. Two independent readers analysed images of all 119 lesions and compared the results to histopathology (11 PEM-Biopsies/8 Breast-Cancers) later. The group analyses for all malignant, benign, corresponding Abstracts Inhalt Index non-target lesions and the mean target/non-target ratio were calculated by paired Student t-Test. Results: 22 out of 119 lesions were malignant. Mean of PUVmax was measured 4.3±2,7 in malignant lesions and 1.1±0.4 for the contra-lateral healthy breast (p = 0.001). The mean target/non-target ratio in patients with B-Ca of 3.7 ± 1.5 was significantly higher compared to benign lesions 1.1 ± 0.4 (p = 0.001). Considering a PUVmax >1.9, PEM was true-positive in all 22 cancers resulting in a sensitivity of 100%, specificity of 97%, PPV of 88% and NPV of 100%. Detecting of B-Ca by PEM was at it´s best observed with a PUVmax cutoff level of ≥1.9 combined with a target/non-target ratio of ≥1.4. Conclusion: PEM can detect breast cancer with high accuracy using PUVmax as well as target/non-target ratio even with high specificity. A higher rate of examinations improves the accuracy of results compared to other diagnostic features. Gastrointestinal (Colorectal) Cancer (including liver metastases) ID 006 Population Pharmacokinetics Analysis of Regorafenib and its active Metabolites from the Phase III CORRECT study of metastatic colorectal cancer M. Karthaus1, Z. Jirakova Trnkova2, A. Grothey3, A. Sobrero4, S. Siena5, A. Falcone6, M. Ychou7, Y. Humblet8, O. Bouché9, L. Mineur10, C. Barone11, A. Adenis12, J. Tabernero13, T. Yoshino14, H.J. Lenz15, F. Cihon16, S. Reif2, D. Laurent2, K. Diefenbach17, E. van Cutsem18 Städtisches Klinikum München, Klinikum Harlaching, München, Deutschland 2 Bayer Healthcare, Berlin, Deutschland 3 Mayo Clinic, Division of Medical Oncology, Rochester, Vereinigte Staaten Von Amerika 4 San Martino Hospital, Genua, Italien 5 Ospedale Niguarda Ca‘ Granda, Mailand, Italien 6 Istituto Toscano Tumori, Pisa, Italien 7 CRLC Val d‘Aurelle, Montpellier, Frankreich 8 St. Luc University Hospital, Brüssel, Belgien 9 Centre Hospitalier Universitaire Robert Debrét, Reims, Frankreich 10 Institut Saint-Catherine, Avignon, Frankreich 11 Universita Cattolica des S.Cuore, Roma, Italien 12 Centre Oscar Lambret, Lille, Frankreich 13 Vall d‘Hebron University Hospital, Barcelona, Spanien 14 National Cancer Center Hospital East, Kashiwa-City, Japan 15 University of Southern California Norris Comprehensive Cancer Center, Los Angeles, Vereinigte Staaten Von Amerika 16 Bayer HealthCare Pharmaceuticals, Montville, Vereinigte Staaten Von Amerika 17 Bayer Pharma AG, Berlin, Deutschland 18 Leuven Cancer Institute, Leuven, Belgien 1 Background: The aim of this study was to develop a population pharmacokinetics (PK) model for Regorafenib (REG) and its two active metabolites M-2 and M-5, and to use this model for evaluation of covariate effects in the phase III CORRECT study. Methods: A population PK model for REG, M-2, and M-5 was developed with NONMEM, based on PK data from a phase I dose-escalation study. Subsequently, this model was applied to the sparsely sampled CORRECT study, by systematically estimating one or more parameters, while fixing the remaining parameters, until the best model was obtained. A model-based covariate analysis was performed to explore the impact of patient demographics and baseline parameters on drug exposure in CORRECT. PK data from 67 densely sampled pts (study 11650) and from 381 sparsely sampled pts (CORRECT)were used. Abstracts Results: PK of REG, M-2, and M-5 were described by a 2-compartmental model. Derived PK parameter estimates were used to calculate the individual exposure (Cavmd) of REG, M-2, and M-5 in CORRECT. Overall, a moderate to high variability in the REG PK was observed in CORRECT, with a coefficient of variance of clearance of 44% and even higher variability in exposure to M-2 and M-5. Covariate analysis of CORRECT showed that higher bilirubin levels at baseline were associated with higher individual exposure of REG and M-2. Higher body weight was associated with lower exposure of M-2 and M-5, and exposure of M-5 was higher in women than in men. The magnitude of observed covariate effects was small compared with the overall high variability in exposure. Conclusion: The combined population PK model adequately described the PK profiles of REG and its two active metabolites M-2 and M-5, in the phase I and in the phase III study. The effects of the covariates tested in population PK analysis of the CORRECT data were not considered clinically relevant in light of the overall high variability in exposure. ID 007 Regorafenib dose modifications in patients with metastatic colorectal cancer in the phase III CORRECT study M. Karthaus1, A. Falcone2, E. van Cutsem3, A. Sobrero4, S. Siena5, M. Ychou6, H.J. Lenz7, T. Yoshino8, F. Cihon9, A. Wagner10, A. Grothey11 Städtisches Klinikum München, Klinikum Harlaching, München, Deutschland 2 Istituto Toscano Tumori, Pisa, Italien 3 Leuven Cancer Institute, Leuven, Belgien 4 San Martino Hospital, Genua, Italien 5 Ospedale Niguarda Ca‘ Granda, Mailand, Italien 6 CRLC Val d‘Aurelle, Montpellier, Frankreich 7 University of Southern California Norris Comprehensive Cancer Center, Los Angeles, Vereinigte Staaten Von Amerika 8 National Cancer Center Hospital East, Kashiwa-City, Japan 9 Bayer HealthCare Pharmaceuticals, Montville, Vereinigte Staaten Von Amerika 10 Bayer Healthcare, Berlin, Deutschland 11 Mayo Clinic, Division of Medical Oncology, Rochester, Vereinigte Staaten Von Amerika 1 Background: CORRECT (NCT01103323) was a randomized, double-blind, placebo-controlled, phase III study that evaluated regorafenib (REG) in patients (pts) with metastatic colorectal cancer (mCRC) that had progressed on standard therapy. REG-treated pts showed a clinically significant improvement in overall and progression-free survival vs placebo (P). Adverse events (AEs), such as hand-foot skin reaction (HFSR), could be managed with dose interruptions or reductions. Methods: The CORRECT study randomized pts to receive REG 160 mg or P once daily for weeks 1–3 of each 4-week cycle. AEs could be managed with interruption or a reduction in treatment dose by 40 mg. In addition, the study protocol provided specific dose modification recommendations for HFSR, hypertension and liver function abnormalities. Results: 753 pts (500 REG, 253 P) received at least one dose of treatment (median 2 cycles in each group, mean 3.3 cycles of regorafenib, 2.3 cycles of placebo). Dose modifications were reported in 76% of REG-treated pts and 38% of P recipients. The most common AEs requiring dose reduction were HFSR (18% of REG-treated pts vs 0.4% of P recipients), diarrhea (4% vs 0%), hypertension (3% vs 0.4%), fatigue (3% vs 2%), and rash/desquamation (3% vs 0%). The most common AEs requiring dose interruption were HFSR (19% vs 0%), fatigue (6% vs 2%), diarrhea (6% vs 1%), rash/desquamation (5% vs 0%), and hypertension (3% vs 0.4%). AEs leading to permanent discontinuation were reported in 18% and 13% of pts in the REG and P groups, respectively. Conclusion: Although significantly more REG-treated pts than P recipients had dose modifications due to AEs, the difference in the incidence of permanent treatment discontinuation was relatively small. This suggests that dose modifications are effective for managing AEs, and allow pts to continue REG treatment. Oncol Res Treat 2014;37(suppl 1):1–133 39 Inhalt Index ID 008 A. Stein1, S. Siena2, A. Grothey3, A. Sobrero4, A. Falcone5, M. Ychou6, H.J. Lenz7, T. Yoshino8, F. Cihon9, V. Pawar9, E. van Cutsem10 Hubertus Wald Tumorzentrum, II.Medizinische Klinik und Poliklinik, UKE, Hamburg, Deutschland 2 Ospedale Niguarda Ca’ Granda, Mailand, Italien 3 Mayo Clinic, Division of Medical Oncology, Rochester, Vereinigte Staaten Von Amerika 4 San Martino Hospital, Genua, Italien 5 Istituto Toscano Tumori, Pisa, Italien 6 CRLC Val d’Aurelle, Montpellier, Frankreich 7 University of Southern California Norris Comprehensive Cancer Center, Los Angeles, Vereinigte Staaten Von Amerika 8 National Cancer Center Hospital East, Kashiwa-City, Japan 9 Bayer HealthCare Pharmaceuticals, Montville, Vereinigte Staaten Von Amerika 10 Leuven Cancer Institute, Leuven, Belgien 1 Background: In the phase III CORRECT trial, regorafenib (REG) showed signif. improvement in OS and PFS vs placebo (P) in patients (pts) with mCRC whose disease had progressed on standard therapies. We examined the impact of REG efficacy and tolerability on quality of life (QoL). Methods: CORRECT was an international multicenter, randomized, placebo-controlled trial sponsored by Bayer HealthCare. Adults with mCRC progressing after all standard therapies were randomized 2:1 to receive REG 160 mg (n = 505) or P (n = 255) once daily for the first 3 weeks of each 4-week cycle. Prespecified QoL analyses were undertaken using the EORTC QLQ-C30 and EQ-5D. QoL outcomes were expressed as time-adjusted area under the curve (AUC) to allow descriptive evaluations of QoL in the REG and P groups across the entire treatment period. Individual domains were compared using descriptive statistics. Results: Overall, changes in QoL were similar in the REG and P groups: difference in least-squares (LS) mean time-adjusted AUC of EORTC QLQ-C30 score: –1.19 (95% confidence interval [CI] –3.13 to 0.75); differences in LS mean time-adjusted AUC for EQ-5D index and visual analog scale (VAS) scores: 0.00 (95% CI –0.03 to 0.03) and –1.21 (–3.04 to 0.61), resp. Changes from baseline did not differ between Reg and P on most of the 6 domains assessed in the EORTC QLQ-C30. Change from baseline on the role functioning scale was similar overall in both groups, although scores appear to differ between REG and P at cycles 3 and 4 for the diarrhea subscale and at cycle 4 for the social functioning subscale. Conclusion: No substantial differences in overall change in QoL were seen between REG-treated pts and P recipients. Role functioning may be impaired by AEs, but remained similar in both groups; management of AEs with dose modifications may improve role functioning and diarrhea in REG-treated pts. ID 009 Time to health status deterioration in regorafenib-treated patients with metastatic colorectal cancer (mCRC): a post-hoc analysis of the phase III CORRECT study A. Stein1, V. Pawar2, A. Grothey3, A. Sobrero4, S. Siena5, A. Falcone6, M. Ychou7, H.J. Lenz8, T. Yoshino9, A. Wagner10, E. van Cutsem11 Hubertus Wald Tumorzentrum, II.Medizinische Klinik und Poliklinik, UKE, Hamburg, Deutschland 2 Bayer HealthCare Pharmaceuticals, Montville, Vereinigte Staaten Von Amerika 3 Mayo Clinic, Rochester, Vereinigte Staaten Von Amerika 4 San Martino Hospital, Genua, Italien 5 Ospedale Niguarda Ca‘ Granda, Mailand, Italien 6 Istituto Toscano Tumori, Pisa, Italien 7 CRLC Val d‘Aurelle, Montpellier, Frankreich 1 40 University of Southern California Norris Comprehensive Cancer Center, Los Angeles, Vereinigte Staaten Von Amerika 9 National Cancer Center Hospital East, Kashiwa-City, Japan 10 Bayer Healthcare, Berlin, Deutschland 11 Leuven Cancer Institute, Leuven, Belgien 8 Effects of regorafenib therapy on health-related quality of life in patients with metastatic colorectal cancer in the phase III CORRECT study Oncol Res Treat 2014;37(suppl 1):1–133 Background: The phase III CORRECT study was a randomized, double-blind, placebo-controlled study. The study showed that regorafenib (REG) improved OS and PFS in pts with mCRC refractory to standard therapy. This post-hoc analysis assessed time to deterioration (TTD) of health status in CORRECT. Methods: Pts with mCRC progressing after all standard therapies were randomized to receive REG 160 mg (n = 505) or placebo (P; n = 255) once daily for weeks 1–3 of each 4-week cycle. TTD was analysed using three definitions of deterioration: a 3-component composite of ≥10 point reduction in EORTC QLQ-C30 global health status (GHS) score, disease progression, or death; a 2-component composite of ≥10 point reduction in GHS score or death; and ≥10 point reduction in GHS score alone. Additional analyses assessed these endpoints using physical functioning (PF) score in place of GHS. Results: REG was associated with significantly longer TTD vs P when assessed with the GHS-based 3-component endpoint (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.65–0.91; pvs P using the 2-component composite and GHS only definitions (HR 0.91; 95% CI 0.75–1.09; p = 0.35 and HR 0.96; 95% CI 0.77–1.20; p = 0.80, respectively). Results for analyses performed with the PF-based endpoints were consistent with those for GHS, with HRs for the 3-component, 2-component, and PF-only endpoints of 0.74; 0.62–0.88. Conclusion:REG is associated with a significantly longer median TTD than P when deterioration is measured using a 3-component composite endpoint, but not when deterioration is measured using a 2-component endpoint or GHS alone. This suggests that deterioration in health status in this patient group is driven by disease progression, not by quality of life. The 1 and 2-component analyses should be interpreted with caution due to high patient censoring. ID 045 Stage-specific associations between beta blocker use and prognosis after colorectal cancer L. Jansen1, M. Hoffmeister1, V. Arndt1, J. Chang-Claude2, H. Brenner1,3 Deutsches Krebsforschungszentrum (DKFZ), Abteilung für klinische Epidemiologie und Alternsforschung, Heidelberg, Deutschland 2 Deutsches Krebsforschungszentrum (DKFZ), Abteilung Krebsepidemiologie, Heidelberg, Deutschland 3 Deutsches Konsortium für Translationale Krebsforschung (DKTK), Heidelberg, Deutschland 1 Background: Recent observational studies have suggested that use of beta blockers might be associated with better prognosis among patients with various cancer sites. As evidence is limited for colorectal cancer, we investigated the association of beta blocker use and prognosis in a large population-based cohort of colorectal cancer patients. Methods: Between 2003 and 2007, information on beta blocker use at diagnosis and potential confounders was collected by personal interviews for 1,975 colorectal cancer patients. Vital status, cause of death, and recurrence status were assessed during a median follow-up time of 5.0 years. The associations of beta blocker use and overall, colorectal cancer specific, and recurrence-free survival were estimated by Cox proportional hazard regression. In addition, beta blocker subgroup, site, and stage-specific analyses were performed. Results: After adjustment for covariates including socio-demographic, cancer-related and lifestyle factors as well as comorbidity and medications, no significant association between beta blocker use at diagnosis and prognosis was observed for all stages combined. However, in stage-specific analyses beta blocker use was associated with longer overall survival (hazard ratio: 0.50, 95% confidence interval: (0.33–0.78), p = 0.0023) and CRC specific survival (0.47 (0.30–0.75), p = 0.0017) in stage IV pa- Abstracts Inhalt Index tients. For these patients, median overall survival was 18 (38 versus 20 months) and colorectal cancer specific survival was 17 months longer (37 versus 20 months) for beta blocker users than for non-users. Conclusion: Our results suggest that beta blocker use might be associated with longer survival in stage IV colorectal cancer patients. ID 056 The prognostic inhomogeneity of ypT3 in mid and low rectal carcinomas after neoadjuvant chemoradiotherapy S. Merkel1, K. Weber1, V. Schellerer1, J. Göhl1, R. Fietkau2, A. Agaimy3, W. Hohenberger1, P. Hermanek1 Universtätsklinikum Erlangen, Chirurgische Klinik, Erlangen, Deutschland Universitätsklinikum Erlangen, Strahlenklinik, Erlangen, Deutschland 3 Universitätsklinikum Erlangen, Pathologisches Institut, Erlangen, Deutschland 1 2 Introduction: In 2001, we demonstrated the prognostic differences between pT3 rectal carcinomas with invasion into the perirectal fat up to 5 mm (pT3a) and those with more than 5 mm (pT3b) in patients with surgery alone. pT3a carcinomas had a significant lower rate of locoregional recurrences and a superior cancer-related survival (similar to pT2) compared to pT3b carcinomas (similar to pT4). Now we analysed the prognostic impact of the subdivision of ypT3 carcinomas after neoadjuvant chemoradiation (nCRT). Methods Data from 300 consecutive patients with nCRT and curative resection of a rectal carcinoma (<12 cm) between 1995 and 2007 were analysed. In the category ypT3 a subdivision was performed based on the maximal tumour invasion beyond the outer border of the muscularis propria: ypT3a ≤5 mm (n = 81), ypT3b >5 mm (n = 43). Results: Significant differences between ypT3a and ypT3b were found in locoregional recurrences (5-year rate 6.5% vs 17.5%; p = 0.049), distant metastases (20.1% vs 41.1%; p = 0.002), disease-free (72.8% vs 46.5%; p = 0.001), observed (79.0% vs 74.4%; p = 0.036) and cancer-related survival (81.3% vs 74.4%, p = 0.007). ypT3a behaved more similarly to ypT2, while ypT3b behaved more similarly to ypT4. Apart from locoregional recurrences this could be confirmed for ypN0 carcinomas. The ypT3 subclassification was identified as an independent prognostic factor for disease-free, observed and cancer-related survival. The ypN category had no prognostic impact in ypT3 carcinomas. Conclusion: In ypT3 rectal carcinoma, the proposed subclassification is superior to ypN classification in predicting prognoses. Further validation is recommended prior to inclusion of the T3 subclassification into the official TNM staging system. ID 088 A lymph node count <12 has no prognostic impact in colorectal cancers when lymph node examination follows current quality standards H. Bläker1, B. Hildebrandt2, H. Riess2, M. von Winterfeld1, B. Ingold-Heppner1, W. Roth3, M. Kloor3, P. Schirmacher3, M. Dietel1, S. Tao4, L. Jansen4, J. Chang-Claude5, A. Ulrich6, H. Brenner4, M. Hoffmeister4 Charite Universitätsmedizin, Institut für Pathologie, Berlin, Deutschland Charite Universitätsmedizin, Abteilung Onkologie, Berlin, Deutschland 3 Universität Heidelberg, Institut für Pathologie, Heidelberg, Deutschland 4 Deutsches Krebsforschungszentrum, Abteilung Klinische Epidemiologie und Alternsforschung, Heidelberg, Deutschland 5 Deutsches Krebsforschungszentrum, Abteilung Krebsepidemiologie, Heidelberg, Deutschland 6 Universitätsklinik Heidelberg, Chirurgische Klinik, Heidelberg, Deutschland 1 2 Purpose: Previous studies on colorectal cancers report an association of a low lymph node yield with adverse outcome. The quality of lymph examination in the studied cohorts, however, was lower than current standards. Improvement of lymph node examination may influence the prognostic impact of a low lymph node count. Thus, we investigated the prognostic Abstracts impact of a lymph node count <12 in cohort of cancers diagnosed according to current quality standards. Patients and Methods: Colorectal cancers from 1899 patients enrolled into a population based study were investigated. Cancers were diagnosed between 2003 and 2007 and included 441 stage I, 588 stage II, 610 stage III, and 260 stage IV cases. The prognostic impact of a lymph node count <12 was analysed. Results: A lymph node count <12 was more common in patients with cancers of low tumor stage, low T-category, and left sided location (p < 0.0001, each). After a median follow-up time of 4.9 years, no impact of a lymph node count <12 on overall, cancer specific, or disease free survival was observed (adjusted hazard ratios 1.04-1.06). Compared to studies reporting an adverse prognostic impact of a low lymph node count, adherence to the 12 lymph node minimum was significantly higher in the present study (79%). Conclusions: This is the first study to investigate the prognostic impact of lymph node count <12 in a cohort of colorectal cancers in which almost 80% of cases were diagnosed compliant with the 12 node minimum. Our study does not reveal an association of <12 investigated lymph nodes with adverse outcome for any tumor stage, questioning integration of a low lymph number as a risk factor in stage II disease. ID 089 The colorectal carcinoma – treatment research and treatment reality in oncology practices F. Strohbach1,2, R. Göttel3, H.-W. Tessen2,4 Onkologische Schwerpunktpraxis Berlin, Berlin, Deutschland Projektgruppe Internistische Onkologie (PIO), Goslar, Deutschland 3 rgb Onkologisches Management GmbH, Sarstedt, Deutschland 4 Onkologische Schwerpunktpraxis Goslar, Goslar, Deutschland 1 2 Approach: Which share does a continuous, systematic case documentation and evaluation contribute to treatment research? Methods: Data from oncology practices from 2003 to 2013 (PIO), analysis of the ONCOReg. index, 7,142 histories of diseases in 118 oncology practices from 15 federal states. Results: Pat. in UICC-state I: 220 (3%), II: 929 (13%), III: 3,214 (45%), IV: 2,685 (38%), n/a: 94 (1%) Gender: m: 4,285 (60%), f: 2,857 (40%) Age: median 66 (18–92) years Primary Surgery.: 6,626 (93%) pat. Adjuvant Ctx: 3,813 (53.4%) pat., 2,580 (68%) of which with Oxaliplatin, 607 (24%) of which > 70 years, 50 (19%) in UICC-state II. Palliative Ctx: 4,655 pat. had spread metastasis. A resection of metastasis was performed on 750 (16%) of the patients. 4,613 (99%) of the patients received a 1st-line ctx, 3,079 (66%) a 2ndline, 1,589 (34%) a 3rd-line, 723 (16%) a 4th-line (max. 9 lines), 3,342 (72%) an antibody. Survival: 2,853 (40%) of the patients have died, loss of contact to 827 (12%) of them. Monitoring period of adjuvant ctx >/= 3 years: 1,189 (31%). After adjuvant ctx: DFS: 37.9 mths. 3-year OS: 80% all therapies; Oxaliplatin-based therapies 81%, </= 70 years 89%; >70 years 79%; UICC II 87%. After palliative ctx: PFS: 1st/2nd-line 9.4/6.2 mths. OS: 1st/2nd-line 24.3/14.9 mths. OS from initial metastasis: 27.4 mths.; with/without antibody 28.7/23.0 mths. With/without resection of metastasis 49.5/24.8 mths. Conclusion: The data collected over a long period of time depict very precisely the reality of treatment in oncology practices in Germany. The evaluation presented contributes an important share to the complex of treatment research and answers a series of patient-related questions. Further evaluations will be presented regularly. Oncol Res Treat 2014;37(suppl 1):1–133 41 Inhalt Index ID 093 Potential role of new MSI-target gene AGO2 in German Lynch syndrome patients B. Majchrzak1, K. Schulmann2, C. Bernhardt2, A. Maghnouj1, W. Schmiegel2, S. A. Hahn1 Ruhr Universität Bochum, Molekulare Gastroenterologische Onkologie, Bochum, Deutschland 2 Universitätsklinikum Knappschaftskrankenhaus Bochum Langendreer, Bochum, Deutschland 1 Lynch syndrome (LS) is the most common form of inherited colorectal cancer (CRC), accounting for approximately 5% of all CRC cases. This autosomal dominant genetic disorder is characterized by germline mutations in one of the mismatch repair genes (MSH2, MLH1, PMS2, MSH6). Especially genes containing microsatellite sequences are particularly susceptible for increased rates of mutations resulting in microsatellite instability (MSI). MSI-H LS tumours are commonly known to display a unique microRNA profile, whose reasons can be manifold and are not yet sufficiently understood. Evidence suggests that enzymes belonging to the RNAi machinery themselves might be targets of genetic disruption due to MSI. Recent studies showed that among the miRNA regulation-related factors harboring microsatellite tracts in their coding sequences, TRBP, AGO2 and XPO5 showed frameshift mutations due to MSI-H CRC-tumours, therefore being new MSI-target genes. However, limited data is available about the frequency of these mutations especially in LS patients. Here we thoroughly analyzed microsatellite repeats of AGO2, TRBP and XPO5 in 25 primary MSI-H LS tumour samples using high resolution PAA gels and single clone capillary sequencing. We were able to confirm AGO2 frameshift mutations in 4% of the tested LS samples. A functional assay revealed a distinct loss of functionality of the mutated form resulting from the frameshift mutation. Overall, our results support AGO2 as a MSI-target gene in this German HNPCC population. Further analysis using TALEN- induced mutation models might reveal a potential role of these mutations in LS patients. ID 095 Growth of intrahepatic colorectal tumors after liver resections in mice V. Nißler1, H. Brandt1, A. Liebl2, A. Perrakis1, V. Schellerer1, W. Hohenberger1, C. Becker3, M. Stürzl2, R. Croner1 Chirurgische Klinik des Universitätsklinikums Erlangen, Erlangen, Deutschland 2 Abteilung für Molekulare und Experimentelle Chirurgie (AMEC)/ Division of Molecular and Experimental Surgery (AMEC), Erlangen, Deutschland 3 Medizinische Klinik I, Kussmaul Campus für Medizinische Forschung Universitätsklinikum Erlangen, Erlangen, Deutschland 1 Introduction: The high incidence of tumor recurrence after resection of liver metastases remains an unsolved problem. In colorectal carcinomas (CRC) 30–50% of the patients develop recurrent tumors after a complete resection of liver metastases. If the tendency to relapse and the intrahepatic tumor growth are influenced by hepatic proliferation mediators after liver resection remains unclear. Material and Methods: In athymic nude-foxn1nu/nu mice MC38 tumor cells were either injected subcutaneously (SC) or intrahepatically (IH). Subsequently, either a single laparotomy (LAP SC, LAP-IH) or a 1/3 liver resection (LR1/3-SC, LR1/3-IH) or a 2/3 liver resection (LR2/3-SC, LR2/3-IH) was performed. In each group, 10 animals were examined for 14 days. Tumor size, tumor proliferation and liver regeneration (liver hypertrophy-index) were quantified. Results: After 14 days, almost complete regeneration of the remaining liver following 1/3 or 2/3 liver resections (liver hypertrophy-index; LR1/3-SC, LR1/3-IH: 1,06; LR2/3-SC, LR2/3-IH: 0,8) was observed. After single laparotomy the average weight of intrahepatic tumors was 330 mg (range: 10–1534 mg). The mean tumor weight of intrahepatic tumors was 660 mg (range: 76–1873 mg) after 1/3 LR. vs 960 mg (range: 42 Oncol Res Treat 2014;37(suppl 1):1–133 189–3030 mg) after 2/3 LR (p < 0.05). After 1/3 LR, tumor size was 166 mm2 (range: 51–399 mm2) vs. 199 mm2 (range: 71–406 mm2) after 2/3 LR (p < 0.05), and 113 mm2 (range: 15–290 mm2 ) after laparotomy alone. The subcutaneous tumors showed no differences in tumor size and volume after LR or SC. Conclusion: Minor and major hepatic resections lead to an activation of tumor growth within the remaining liver. There is no systemic effect on extrahepatic tumors. The influence of hepatic regeneration mechanisms on intrahepatic tumor progress requires further molecular analyzes. ID 113 Phase II study in metastatic colorectal cancer patients treated with pharmacokinetically (PK) dose adjusted weekly or biweekly 5-fluorouracil (5-FU) regimes K. Link1, T. Bertsch2, K. Weigang-Köhler1, L. Müller3, Y.-D. Ko4, O. Stoetzer5, V. Kunzmann6, I. Suttmann7, M. Roessler8, B. Moritz8, S. Salamone9, U. Sonnenschein10, M. Wilhelm1 Klinikum Nürnberg Nord, Med. Klinik 5, Nürnberg, Deutschland Klinikum Nürnberg Nord, Institut für Klinische Chemie, Nürnberg, Deutschland 3 Onkologische Schwerpunktpraxis, Leer, Deutschland 4 Evangelische Kliniken Bonn, Hämatologie/Onkologie, Bonn, Deutschland 5 Hämato-Onkologische Gemeinschaftspraxis, München, Deutschland 6 Universitätsklinikum Würzburg, Med. Klinik II, Würzburg, Deutschland 7 Klinikum Dritter Orden, Klinik für Innere Medizin I, München, Deutschland 8 CESAR, A-Wien, Deutschland 9 Saladax Biomedical, USA, Deutschland 10 Saladax Biomedical, CH-Oberwil, Deutschland 1 2 Patients and Methods: In this currently ongoing study (CESAR C-II009), patients with metastatic colorectal cancer received first- or second line treatment with infusional 5-FU (AIO-regimen, FUFOX, mFOLFOX6) +/- Oxaliplatin, Bevacizumab or Cetuximab. The dose of the first application of 5-FU was calculated according to BSA. Plasma concentrations of 5-FU were measured by the MyCare™ 5-FU immunoassay, 18 hours after start of the infusion, when steady state concentrations had been reached. If the 5-FU plasma concentration was not within the target AUC range of 20–30 mg x h/L and/or toxicity occurred, the subsequent dose was adjusted according to an appointed algorithm. Measurements of the 5-FU plasma concentration were repeated for the following 5 applications of chemotherapy. Conclusions: So far 48 patients from 6 study sites in Germany have been included in this trial. AUC-guided dose adjustment of 5-FU seems to be feasible and is showing promising results in the patients treated so far. Notable is a strong dose increase which could be achieved in some patients, which was well tolerated, resulting in an impressive tumor response. Preliminary results and corresponding PK-data will be presented at the meeting. ID 115 Individual variations in the rate of hyperthermia induced apoptosis and necrosis S. Winkler, P. Hoppe, M. Haderlein, R. Fietkau, L. Distel Strahlenklinik / Universität Erlangen-Nürnberg, Erlangen, Deutschland Objective: Individualization of cancer therapy is referred to as the key technology of the future. Aim of the study was to evaluate whether there are hyperthermia specific individual differences in cancer patients. The induction of apoptosis and necrosis after in vitro hyperthermia was used to analyze interindividual differences. Methods: The study collective consists of 101 head and neck and rectal cancer patients and 20 healthy individuals. Lymphocytes were isolated by density gradient centrifugation and then treated with 42 or 43 degrees C hyperthermia for 1 h. 48h later lymphocytes were stained with Annexin V-FITC and 7AAD and analyzed by flow cytometry. Lymphocyte subgroups were additionally immunostained with anti CD4 and CD8 antibodies. Abstracts Inhalt Index Results: At 42 degrees C and after subtracting the apoptosis rate of the untreated samples the apoptosis rate of the CD8 positive cells of the control group isn’t significantly different from the patient’s group. However, the necrosis rate of the patient’s group is significantly higher (p < 0.001) compared to the healthy individual’s group. At 43 degrees C the latter finding is the same (p < 0.001) while there is a lower apoptosis rate of CD8 positive cells of the cancer patients group compared to the healthy individuals group (p = 0.02). In the cancer patients group there are distinct interindividual differences. Conclusion: There are distinct hyperthermia induced differences between healthy individuals and cancer patients and additionally there are clear interindividual differences. It indicates that there may be interindividual differences in response to hyperthermia on cancer cells and normal tissue. ID 126 Updated Overall Survival (OS) analysis of novel predictive KRAS/NRAS mutations beyond KRAS exon 2 in PEAK: A 1st-line phase 2 study of FOLFOX6 plus panitumumab (pmab) or bevacizumab (bev) in metastatic colorectal cancer (mCRC) M. Karthaus1, L. Schwartzberg2, F. Rivera3, G. Fasola4, J.-L. Canon5, H. Yu6, K. Oliner6, W. Go6 Städtisches Klinikum München GmbH – Klinikum Neuperlach, Munich, Deutschland 2 The West Clinic, Memphis, Vereinigte Staaten Von Amerika 3 Hospital Universitario Marques de Valdecilla, Santander, Spanien 4 University Hospital S. Maria della Misericordia, Udine, Italien 5 Grand Hôpital de Charleroi, Charleroi, Belgien 6 Amgen Inc., Thousand Oaks, Vereinigte Staaten Von Amerika 1 ID 125 Targeted therapies of two different braf mutated cell lines and the establishment of a 3D tumor model on the basis of a decellularized intestinal matrix Aim: A prospective secondary analysis of PEAK showed trends towards improved PFS and OS in wild-type (WT) RAS (exons 2, 3, 4 of KRAS/ NRAS) mCRC treated with FOLFOX6 +pmab vs +bev. We report updated OS and PFS data. Methods: All 285 randomised intent-to-treat pts (ITT) were assessed WT KRAS exon 2. This analysis assessed FOLFOX6 +pmab vs +bev in WT RAS mCRC, which was determined by mutational analyses of KRAS exon 2, 3, 4 and NRAS exon 2, 3, 4. Result: The table shows PFS and OS results according to RAS mutational status: ITT; WT RAS; or KRAS exon 2 WT and ‘other’ RAS mutation (MT). Conclusion: In the ITT population (WT exon 2 KRAS), HR for OS favored FOLFOX6 +pmab vs +bev. In WT RAS pts (WT exons 2, 3, 4 KRAS/NRAS), HR for both PFS and OS favored FOLFOX6 +pmab vs +bev. Additional RAS mutations beyond KRAS exon 2 appear predictive for pmab effect. F. Baur, S. Sieber, G. Dandekar, S. Nietzer, H. Walles Universitätsklinikum Würzburg, Lehrstuhl für Tissue Engineering & Regenerative Medizin, Würzburg, Deutschland The heterogeneity of colorectal carcinomas (CRCs) is an obstacle in the development of drugs and the prediction of clinical outcome. Vemurafenib is a potent inhibitor of BRAF in braf mutant melanomas but shows response rates of just 5% in braf mutant CRCs (Corcoran et al. 2012). It has been reported that the inhibition of BRAF increases the phosphorylation of the epidermal growth factor receptor (EGFR) via a feedback loop in CRC cell lines (Prahallad et al. 2012). Thus we tested combination therapies with vemurafenib and the EGFR inhibitor gefitinib as well as the effect of accessory tipifarnib, a farnesyl transferase inhibitor, to block the Pi3K/Akt/mTOR pathway. We used different combinations of all three inhibitors in two cell lines (HROC24, HROC87) carrying a braf mutation (V600E) but differing in other mutations (Maletzki et al. 2012). Vemurafenib mono-treatment decreased the cell number in HROC24 but not in HROC87 cells, whereas gefitinib alone showed a cell number decreasing effect only in HROC87. The combination of two or three drugs was more efficient than the respective mono-therapy in HROC87 but not in HROC24 cells. This leads to the conclusion that the determination of a single genetic lesion is not always sufficient to choose the most effective therapy. In general, it is reported that 3D tumor models are more resistant to chemotherapies than 2D cell culture models and that they show more reliable results in drug testing (Stratmann et al. 2013). For this reason, we established a 3D model on a decellularized intestinal matrix to compare the effect of the drugs on cell number, proliferation and apoptosis of common 2D cell culture with our 3D cell culture models. ID 129 Colon carcinoma in the elderly: What is different? V. Schellerer1, M. Langheinrich1, K. Weber1, J. Göhl1, R. Croner1, W. Hohenberger1, S. Merkel1 Friedrich-Alexander-Universität, Allgmein- und Visceralchirurgie, Erlangen, Deutschland 1 Introduction: Colorectal carcinoma is one of the leading cancers in western countries and the number of elderly patients is rising. While the incidence of rectum carcinomas decreases the number of colon cancers increases. Target of the following article was to evaluate the preoperative characteristics, the surgical procedure, the post-operative complications and prognosis related to age. Table of ID 126 Population WT KRAS exon 2 (ITT) PFS OS WT RAS (exons 2, 3, 4 KRAS / NRAS) PFS OS WT exon 2 KRAS + MT exons 3/4 KRAS or MT exons 2,3, 4 NRAS PFS OS NR = not reached Abstracts FOLFOX6 +pmab Patients, N Median months (events, n) (95% CI) FOLFOX6 +bev Patients, N Median months (events, n) (95% CI) HR (95% CI) Descr. p-value 142 (100) (52) 10.9 (9.7–12.8) 34.2 (26.6-NR*) 143 (108) (78) 10.1 (9.0–12.0) 24.3 (21.0–29.2) 0.84 (0.64–1.11) 0.62 (0.44–0.89) 0.224 0.009 88 (57) (30) 13.0 (10.9–15.1) 41.3 (28.8–41.3) 82 (66) (40) 10.1 (9.0–12.7) 28.9 (23.9–31.3) 0.66 (0.46–0.95) 0.63 (0.39–1.02) 0.025 0.058 24 (22) (10) 8.4 (6.5–10.7) 27.0 (15.1-NR) 27 (23) (21) 8.8 (7.3–11.2) 16.6 (13.3–21.6) 1.13 (0.63–2.05) 0.41 (0.19–0.87) 0.683 0.020 Oncol Res Treat 2014;37(suppl 1):1–133 43 Inhalt Index Methods: We included all patients receiving a resection for a colon carcinoma between 1995 and 2007 (n = 1268). Patients were divided by age as follows: less than 65 years (n = 526), between 65 and 79 years (n = 587) and older than 80 years (n = 155). Results: In patients >80 years we found significantly more women, a higher ASA classification, more emergency presentations and a higher incidence of preoperative and postoperative complications (p < 0.001). In extended resections, the number of examined regional lymph nodes was significantly lower (p < 0.001), whereas no differences were found comparing the number of positive nodes. Comparison of pathological stages revealed no differences. However, in patients >80 years less stage IV carcinomas were treated curatively (R0; p = 0.088). After R0 resection and exclusion of postoperative deaths, the observed 5-year survival rate of older patients was significantly lower (p < 0.001): < 65 years 84.4%, 65–79 years 74.4%, > 80 years 53.2%. The 5-year cancer-related survival rates were similar (p = 0.484): <65 years 89.3%, 65–79 years 85.1%, >80 years 89.4%. Conclusion: Older patients present with higher complication rates according to their preexisting health status. Only approximately 10% of the patients >80 years with curative resection die within 5-years due to their colon carcinoma. mor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumour development remains elusive. Tumor invasion and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. In this study we aimed to assess the role of CCR1 in colon cancer cell lines. CCR1 expresion was determined in five human (SW480, SW 620, HT29, LS174T and Caco) and one rat (CC531) colon cancer cell lines. We silenced CCR1 expression by RNA interference (RNAi) and then examined the effects of CCR1 gene knockdown on biological properties of the colorectal cancer cell lines by in vitro functional tests. We found that CCR1 was expressed in four of these cell lines (HT29, SW620, CC531 and SW480). After siRNA exposure the concentration of CCR1 was reduced by 78–99% after 24 to 72 hours. With regard to functional tests, CCR1 knockdown had only a minor effect on cell proliferation (10 to 20%), except for CC531 cells in which the proliferation was reduced by 80% after 24 hours. The siRNA treatment reduced also the ability of cells to produce small and large colonies by 10 to 80%. These findings suggest that the expression of CCR1 favours cell proliferation as well as colony formation of colorectal cancer cells in vitro. Future experiments will focus on the influence of CCR1 in colorectal cancer cell lines growing in vivo. ID 143 ID 206 Inhibition and blockage of CCR5: A possible therapeutic option for colorectal cancer A. Pervaiz, M.R. Berger, H. Adwan Molecular mechanisms of receptor tyrosine kinase inhibition in colorectal cancer cells and indications for therapeutical options DKFZ, Heidelberg University, Toxicology and Chemotherapy Unit, Heidelberg, Deutschland R. Oberthür1, S. Kaulfuß1, J. Meyer1, H. Seemann1, R. Dressel2, M. Rave-Fränk3, J.-G. Scharf4, P. Burfeind1 The C-C chemokine receptor type 5 (CCR5 or CD195) is predominantly expressed on T cells, macrophages, dendritic cells and microglia. CCR5 is a major receptor for HIV entry and is found on tumor cells in primary and metastatic colorectal cancer. We aimed at evaluating the role of CCR5 in colorectal cancer. To that purpose we used CCR5 knockdown by RNAi methodology and blockade by maraviroc for alterations in biological properties of SW480 and SW620 colorectal cancer cell lines in vitro. Methods included implantation of rat colorectal CC531 cancer cells in the rat liver and expression profile studies by mRNA micro-array analysis, transient knockdown of CCR5 in SW480 and SW620 cells confirmed by RT and qPCR, and study of functional effects of CCR5 knockdown and blockade on SW480 and SW620 cells by proliferation, migration, colony formation and scratch assays. Implanted colorectal CC531 cancer cells exhibited 20x higher expression in the rat liver for the initial 3 days and came back to normal level after week 4. Exposure to siCCR5 reduced the expression of CCR5 mRNA after 24–72 h by maximally ~70 and ~75% for SW480 and SW620 cells after 48 hr. Significant declines in proliferation and migration of SW480 and SW620 cells were found after knockdown and blockade of CCR5 by siRNA and maraviroc as well as moderate reductions in clonogenicity and the ability to cover scatched area. In conclusion, high expression of CCR5 contributes to enhanced proliferation and migration, while colonization and wound healing abilities of colorectal cancer cell lines are diminished. Controlling the expressional level and development of antagonists for CCR5 could be a future therapeutic option for the treatment of colorectal cancer. 1 ID 145 CCR1 Chemokine effect on colorectal cancer I. Akram, H. Adwan, M.R. Berger DKFZ, Chemotherapy and Texocology, Heidelberg, Deutschland Chemokines are small molecular weight proteins, which mainly function as chemoattractant cytokines for leukocyte migration. Chemokine receptors (CCRs) are important co-stimlatory molecules associated with various diseases. Expression of the CC chemokine receptor 1 (CCR1) by tu- 44 Oncol Res Treat 2014;37(suppl 1):1–133 Universitätsmedizin Göttingen, Institut für Humangenetik, Göttingen, Deutschland 2 Universitätsmedizin Göttingen, Zelluläre und Molekulare Immunologie, Göttingen, Deutschland 3 Universitätsmedizin Göttingen, Strahlentherapie und Radioonkologie, Göttingen, Deutschland 4 HELIOS Klinikum Erfurt, Gastroenterologie & Hepatologie, Erfurt, Deutschland Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Receptor tyrosine kinases (RTKs) are known to be key players in the development of CRC. Recently, we could show that inhibition of the RTKs insulin-like growth factor-I receptor (IGF-IR) and epidermal growth factor receptor (EGFR) in CRC cells results in decreased proliferation and induction of apoptosis. Furthermore, CRC cells display higher sensitisation to 5-FU based radiochemotherapy (RCT) when both RTKs were inhibited simultaneously. To identify the molecular mechanisms underlying this sensitisation we analysed DNA repair mechanisms, apoptosis and cell cycle distribution. Phospho-H2AX staining as a marker for DNA double strand breaks reveals impairment of DNA repair after single inhibitor treatments 24 h after RCT in CRC cells and even more pronounced effects after dual inhibition of IGF-IR and EGFR. Simultaneous inhibition of IGF-IR and EGFR reduces phosphorylation and therefore the anti-apoptotic potential of AKT. In addition, DLD-1 cells showed a cell cycle arrest in G2 phase when treated with erlotinib (anti-EGFR) or erlotinib and NVP-AEW541 (anti-IGF-IR) simultaneously in addition to RCT after 24 h, whereas induction of apoptosis was observed in Caco-2 and SW837 cells 24 h after RCT. In vivo studies using the SW837 xenograft model demonstrated reduced tumour weight and volume after simultaneous RTK inhibition. Furthermore, we could show that IGF-IR and EGFR form heterodimers in a ligand-dependent manner. Taken together, these results indicate that IGF-IR and EGFR play important roles in the resistance of CRC to neoadjuvant RCT and that simultaneous treatment of RCT resistant CRC with a combination of RTK inhibitors can circumvent these problems. Abstracts Inhalt Index ID 254 Characterization of tumor associated b cells in colorectal cancer H.A. Schlößer1, A. Shimabukuro-Vornhagen2, P. Scherwitz3, T. Koslowsky4, S. Eidt5, D.L. Stippel1, M.S. von Bergwelt-Baildon2 University Hospital, Department of General, Visceral and Cancer Surgery, Cologne, Deutschland 2 University Hospital Cologne, Department I of Internal Medicine, Cologne, Deutschland 3 Marien Hospital, Department of Surgery, Brühl, Deutschland 4 St. Elisabeth Hospital, Department of Surgery, Cologne, Deutschland 5 St. Elisabeth Hospital, Insitute of Pathology, Cologne, Deutschland 1 Introduction: A precise understanding of the mechanisms by which human immune cell subsets affect tumor biology will be critical for a successful treatment of cancer with immunotherapeutic approaches. Little is known about the role that B cells play in cancer pathophysiology. Recent evidence suggests that B lymphocytes can both promote and inhibit the development and progression of tumors. Whether B cells support or hinder tumor growth seems to depend on a variety of factors such as tumor entity, timing, and composition of the B cell subsets. Materials and Methods: In this study we characterized B cell subsets in tumor, metastases, mucosa and peripheral blood of 51 patients with a diagnosis of colorectal cancer. Naive-, virgin naive-, virgin activated-, activated-, memory- and regulatory B cells were identified by 10 color flow cytometry. PBMCs of ten age matched healthy donors were analyzed as controls. Results: A significant amount of B cells could be identified in 28 analyzed tumor samples and the percentage of B cells within tumor samples was higher than in peripheral blood of CRC patients (6.8 vs. 4.9%). Tumor associated B cells are highly activated and of a more mature phenotype than in mucosa or peripheral blood. PBMCs of colorectal cancer patients contain a significantly higher percentage of memory B cells than PBMCs of age matched healthy controls (19.7 vs 8.2%). CD24high CD38high B cells as a regulatory B cell subset are increased in the tumor of advanced stage disease (1.7 vs. 0.6%). Conclusion: B cells can be identified in CRC tissue and show a highly activated phenotype suggestive for a specific response. On the other hand we could identify an increase of transitional B cells in advanced stage disease as a possible mechanism of immune ecape ID 268 S100A4-RAGE interaction triggers MAPK/ERK and hypoxia signaling in human colorectal cancer cells M. Dahlmann1, A. Okhrimenko1, P. Marcinkowski1, M. Osterland2, P. Herrmann2, J. Smith1, C.W. Heizmann3, P.M. Schlag2,4, U. Stein2 Max-Delbrück-Centrum Berlin, Translationale Onkologie solider Tumore, Berlin, Deutschland 2 Experimental and Clinical Research Center, Translationale Onkologie solider Tumore, Berlin, Deutschland 3 University Children‘s Hospital, Clinical Chemistry and Biochemistry, Zürich, Schweiz 4 Charité Universitätsklinikum, Charité Comprehensive Cancer Center, Berlin, Deutschland 1 Colorectal cancer is one of the most common cancer diseases worldwide, with high mortality if patients develop distant metastases. S100A4 is an acknowledged as prognostic biomarker and inducer for colorectal cancer metastasis. Besides exerting intracellular functions, S100A4 is also secreted into the tumor microenvironment and can initiate cellular responses, leading to cancer progression. One of its extracellular interaction partners is the receptor for advanced glycation end products (RAGE). The impact of the S100A4-RAGE interaction for cell motility and metastasis formation in colorectal cancer was not elucidated so far. We demonstrate here the direct interaction of S100A4 and RAGE in colorectal cancer cell lines leading to hyperactivation of ERK and hypoxia signaling Abstracts pathways. The increase in cellular motility upon S100A4 treatment was reversed with the use of RAGE antagonists. In patient primary colorectal tumors of stages I, II and III high RAGE expression correlates with reduced overall as well as metastasis-free survival rates. Therefore, the employment of RAGE as a biomarker can improve the prognosis for colorectal cancer. Therapeutic approaches targeting RAGE or intervening in RAGE dependent signaling early in tumor progression might represent alternative strategies restricting the S100A4-induced metastasis in colorectal cancer. ID 293 Survival benefit in colorectal cancer – an analysis of a population-based clinical cancer registry A. Schlesinger-Raab1, R. Eckel1, G. Schubert-Fritschle1, D. Hölzel2, J. Engel1 Institut für Epidemiologie, Biometrie und Medizinische Datenverarbeitung, Tumorregister München, München, Deutschland 2 Tumorregister München, München, Deutschland 1 Objective: The study aim was to evaluate improvement in survival of colorectal cancer over a time period of 20 years. Methods: About 41,000 patients’ diagnoses with colorectal cancer between 1990 and 2010 in the catchment area of the Munich Cancer Registry (population 4.6 million) were evaluated. Distributions of patient and tumour characteristics as well as overall (OS) and relative survival (RS) were analysed in regard to time period of initial diagnosis. Results: Demographic ageing were observed over time with an average increase of age at diagnosis of about three years and an increase in the proportion of patients ≥70 and ≥80 years (e.g. ≥80 years from 18 to 26% in colon and from 11 to 18% in rectal cancer). These older cohorts had a worse prognosis. The 5-year RS for colon cancer remained stable over time (from 65.9 to 66.6%) and only minor differences were observed for rectal cancer (from 62.7 to 64.3%). However, after stratification by age, metastases at diagnosis, and UICC stage, benefits could be seen clearly in patients < 70 with initial diagnosis of M0 (5-year RS increased from 80.9 to 87.4% for colon and from 75.3 to 84.6% for rectal cancer) as well as in patients with UICC stage III in colon cancer (from 58.3 to 72.9%) and UICC stages II and III in rectal cancer (stage II from 78.6 to 83.7%, stage III from 51.3 to 71.4%). Survival improvement for patients with M1 at diagnosis was lower and only observed for patients < 70 years of age. Conclusion: Survival benefits are superposed by the effect of demographic ageing. In colon cancer, especially for patients < 70 years with M0 at diagnosis or UICC stage III, and in rectal cancer particularly in patients < 70 years with M0 at diagnosis and UICC stage II/III survival improvements were observed. ID 296 KRAS mutation heterogeneity in rectal cancer after preoperative chemoradiotherapy P. Jo1, J. Salendo1, J. Kitz2, L.C. Conradi1, A. Azizian1, H.A. Wolff3, M. Grade1, P. Ströbel2, M. Ghadimi1, J. Gaedcke1 UMG, Allgemein-, Viszeral- und Kinderchirurgie, Göttingen, Deutschland UMG, Pathologie, Göttingen, Deutschland 3 UMG, Strahlentherapie und Radioonkologie, Göttingen, Deutschland 1 2 Introduction: Anti-EGFR targeted therapy is of increasing importance and prior KRAS mutation testing is mandatory. In colon cancer a certain degree of KRAS mutation heterogeneity has been reported. For rectal cancer patients treated preoperatively by chemoradiotherapy (CRT) it remains to be analyzed if the pre- and posttherapeutic KRAS status is comparable. Aims: Therefore, tumor tissue from 47 patients was analyzed comprising 114 preoperative biopsies and 85 tissue blocks from resected specimens. Oncol Res Treat 2014;37(suppl 1):1–133 45 Inhalt Index Intratumoral KRAS heterogeneity was assesed in pretherapeutical biopsies of 34 (mean 3.0 biopsies/patient) and resected specimens of 12 patients (mean 4.2 tissue blocks/ patient). Methods: Primer extension method was used to assess the KRAS mutation status for Codons 12, 13, 61, and 146. Results: Comparison of pre- and posttherapeutic KRAS mutation status revealed a discrepancy in 6 of 47 patients (12.8%). Intratumoral KRAS heterogeneity in pretherapeutical biopsies was found in only one patient showing wild type and G12V mutation, respectively. In the residual a KRAS mutation and wildtype was found side-by-side in six patients (50%). Conclusion: Taken together, KRAS mutation heterogeneity in posttherapeutical tumor is not negliable. Depending on the degree of residual tumor the assessment of the mutation status should be performed on more than one tumor tissue block. ID 298 Different bidirectional HIPEC regimens after CRS in patients with peritoneal matastasis from colorectal cancer G. Glockzin1, M. Gerken2, S.A. Lang1, P. Piso3, H.J. Schlitt1 Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg, Deutschland 2 Universität Regensburg, Tumorzentrum, Regensburg, Deutschland 3 Krankenhaus Barmherzige Brüder Regensburg, Allgemein- und Viszeralchirurgie, Regensburg, Deutschland 1 Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) might be an effective additive treatment option within an multidisciplinary therapeutic regimen for patients with peritoneal metastasis arising from colorectal cancer. Nevertheless, multiple HIPEC regimens with different drug combinations and concentrations are used. Patients and Methods: 32 consecutive patients with colorectal peritoneal metastasis that underwent CRS with complete macroscopic cytoreduction (CC-0/1) and bidirectional HIPEC have been analyzed regarding morbidity mortality and 3-year survival. Twenty patients received oxaliplatin-based and twelve patients received irinotecan-based HIPEC. Results: Morbidity rates were not significantly diffrent between the OX group and the IRI group (p = 1.000). The morbidity rate was 0% in both groups. 3-year survival rates were 65.0% in the OX group vs. 41.7% in the IRI group, respectively (p = 0.295). Conclusion: The morbidity and toxicity rates of bidirectional irinotecan-based and oxaliplatin-based HIPEC are comparable. Based on the not significant difference regarding 3-year and median survival oxaliplatin-based HIPEC might be preferred. Prospective randomized trials are needed to determine the optimal HIPEC regimen. ID 299 A pipeline for generating patient-derived 3D cell cultures and their application for individualized, targeted therapeutic regimens. D. Schumacher1, K. Boehnke2, M. Lange3, C. Davies1, U. Keilholz4, J. Haybäck5, J. Velasco2, M.-L. Yaspo6, H. Lehrach6, D. Henderson3, R. Schäfer1,4, C. Regenbrecht1 Charité Universitätsmedizin Berlin – Institut für Pathologie CCM, Molekulare Tumorpathologie, Berlin, Deutschland 2 Eli Lilly, Madrid, Spanien 3 Bayer Pharma AG, Berlin, Deutschland 4 Charité Comprehensive Cancer Center, Berlin, Deutschland 5 Medizinische Universität Graz, Institut für Pathologie, Graz, Oesterreich 6 Max Planck Institute for Molecular Genetics, Berlin, Deutschland 1 Colon cancer is the 3rd most common type of cancer and the 4th leading cause of cancer-related deaths worldwide. Though early diagnosis and molecular characterization (COSMIC, TCGA) have improved signifi- 46 Oncol Res Treat 2014;37(suppl 1):1–133 cantly during the last years, rapid and cost-effective means to address molecular genotyping and therapeutic options are still in high demand. An ever growing inflow of data from whole-genome and exome sequencing studies into the community of colon cancer researchers continues to increase the number of potentially harmful genomic alterations, thereby pinpointing to putative novel targets for anti-cancer drugs, and yet, drug development and approval is naturally not able to keep up with these discoveries. Here, we present an experimental pipeline starting from 3D cell cultures of patient-derived colon cancer cells. 3D cell cultures are increasingly recognized as suitable models for basic and translational research, preserving an in-vivo like architecture, preventing tumor cells from differentiating, allowing the investigation of intra-tumor heterogeneity and cancer stem cell like sub-populations, while at the same time observing effects like hypoxia within the growing in-vitro tumor mass. We then use these cell cultures for cost-efficient benchtop sequencing of selected clinically relevant oncogenes and tumor suppressors, complemented by automated drug screenings aiming to increase therapeutic response when compared to standard therapy. With an overall growth-rate of more than 60%, our strategy allowed for almost 50% of samples to be processed within 3 weeks upon reception. Sequencing, drug screening and IHC based QC took less than 3 weeks, allowing for an evidence-based treatment decision within 6 weeks after surgery. ID 312 Interaction of the CXC-chemokines SDF-1 and I-TAC in the regulation of tumor angiogenesis of colorectal cancer O. Kollmar1, K. Rupertus2, J. Sinistra3, M. Menger3 Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Göttingen, Deutschland 2 Universität Tübingen, Department of Hematology, Oncology and Immunology, Tübingen, Deutschland 3 University of Saarland, Institute for Clinical and Experimental Surgery, Homburg/Saar, Deutschland 1 Background: The chemokine SDF-1 has a decisive role in tumor progression by mediating pro-angiogenic and pro-metastatic effects through its receptor CXCR4. The SDF-1 pathway is connected with another chemokine, I-TAC, through its second receptor CXCR7. I-TAC also binds to the CXCR3 receptor. I-TAC function in tumor angiogenesis is likely receptor dependent because CXCR3 predominantly mediates angiostatic signals whereas CXCR7 mediated signaling is rather angiogenic. We therefore studied the interaction of SDF-1 and I-TAC in an in vivo model of colorectal cancer metastasis. Material and Methods: GFP-transfected CT26.WT colorectal cancer cells were implanted into the dorsal skinfold chamber of syngeneic BALB/c mice. The animals received either peritumoral application of I-TAC or intraperitoneal injections with neutralizing antibodies against I-TAC, SDF-1 or both. Tumor growth characteristics, angiogenesis, cell migration, invasive tumor growth, tumor cell proliferation and apoptosis were studied by intravital fluorescence microscopy and immunohistochemistry during an observation period of 14 days. Results: Local exposure to I-TAC significantly stimulated tumor growth compared to controls and enhanced invasive growth characteristics without affecting tumor angiogenesis and tumor cell migration. Neither I-TAC nor SDF-1-blockade had a significant impact on tumor growth and angiogenesis, whereas the combined neutralization of I-TAC and SDF-1 almost completely abrogated tumor vessel formation. As a consequence, tumor growth and invasive growth characteristics were reduced compared to the other groups. Conclusion: The results of the present study underline the interaction of SDF-1 and I-TAC during tumor angiogenesis. The combined blockade of both signaling pathways may provide a strong anti-angiogenic approach for anti-tumor therapy. Abstracts Inhalt Index ID 326 Efficacy of palliative chemotherapy in elderly patients with metastatic colorectal cancer – a retrospective analysis of a single center experience D. Biesenbaum, M. Kind, J. Rüssel, H.-J. Schmoll Universitätsklinikum Halle (Saale), Klinik für Innere Medizin IV – Onkologie/Hämatologie, Halle, Deutschland Background: Generally well tolerated combination chemotherapies (CTs) are available for patients (pts) with metastatic colorectal cancer (mCRC) that considerably increase survival. However, the reality outside clinical trials is commonly characterized by an unselected population of elderly patients with a lower performance status and a higher comorbidity. Few data are available in elderly pts, although the incidence rate is more than 15 times higher in individuals 50 years and older. Methods: We reviewed the files of 98 pts with mCRC from 2007 to 2012 who received CT in our department. We predefined 3 groups with cut-off ages (COAs) at 65, 70, and 75 to compare younger (Y) with older (O) pts. Progression free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier analysis from the first day of 1st line CT. The p-value was calculated by log-rank test. Results: We detected a significant difference in OS between Y and O at the COA of 75 (p = 0.005). The median age of O75 was 79 years. 25% presented with an ECOG performance status >1. The median OS was 8.4 months with a median PFS of 6.9 months. The population of Y75 presented with an ECOG >1 only in 4% and showed a median OS of 21.2 months with a median PFS of 10.5 months. There was no difference in PFS by comparison (p = 0,824). Conclusion: Just at the COA of 75 there is a significant difference between O75 und Y75 concerning OS but there is no significant difference in PFS although Y75 presented with a better performance status. Even if the study is limited by its retrospective nature, this real life data supports the assumption that pts with mCRC up to 75 years benefit from chemotherapy in a likewise extent. ID 331 Impact of KRAS signaling on MACC1 expression in colorectal cancer cells K. Ilm1, W. Kemmner2, S. Shirasawa3, T. Sasazuki 3, U. Stein2 Max-Delbrück-Center for Molecular Medicine, Berlin, Deutschland Experimental and Clinical Research Center, Berlin, Deutschland 3 Fukuoka University, Department of Cell Biology Faculty of Medicine, Fukuoka, Deutschland 1 2 MACC1 was identified as a prognostic marker for the identification of colorectal cancer (CRC) patients at high risk for metastasis. Tumors, staged I, II, and III, which developed metachronous metastases, showed significantly higher MACC1 expression levels compared to non-metastasizing tumors. Apart from its role in transcriptional activation of c-Met, the regulation of MACC1 itself is poorly understood. Experimental evidence indicates that MAPK signaling regulates MACC1 expression. Our studies aim at the impact of KRAS on regulation of MACC1 expression and MACC1-associated metastasis in CRC. Thus, RNAi strategies were used to analyze the impact of KRAS signaling on MACC1 in several CRC cell lines with different KRAS mutation status. Further, we compared HCT116 cells harboring the activating KRAS G13D mutation with the HCT116-derived cell line Hkh-2 lacking the mutated KRAS allele. Interestingly, transient knock-down of G13D mutated KRAS increases MACC1 expression in HCT116 cells. Similarly, knock-out of the mutated KRAS allele through gene targeting in these cells increases MACC1 promoter activity as well as MACC1 mRNA and protein expression. Modulation of the endogenous MACC1 expression has no impact on KRAS expression. Additionally, tumor samples from CRC patients were analyzed concerning KRAS mutation in codon 12 and 13 and MACC1 expression. Interestingly, patients with KRAS mutation in codon 13 showed a significantly decreased metastasis-free survival compared to patients with Abstracts wild type KRAS. Taken together, MACC1 expression levels and KRAS mutations in codon 13 contribute to the identification of patients at high risk for metastasis formation and for the prediction of metastasis-free survival. ID 344 Inhibition of tumor growth of colorectal liver metastases after trans-arterial chemoembolization using different chemoembolisats in a rat model C. Ziemann1, J. Sperling2, M. Malter3, K. Keller3, J. Roller1, S. Dold1, O. Kollmar2, M. Laschke3, M. Glanemann1, M. Menger3 Universitätsklinikum des Saarlandes, Homburg, Allgemeine Chirurgie, Viszeral-, Gefäß- und Kinderchirurgie, Homburg, Deutschland 2 Universitätsmedizin Göttingen, Allgemein-, Viszeral- und Kinderchirurgie, Göttingen, Deutschland 3 Universität des Saarlandes, Institut für Klinisch-experimentelle Chirurgie, Homburg, Deutschland 1 Introduction: The transarterial chemoembolization (TACE) of the liver is an established method for liver metastases and primary hepatocellular carcinoma. However, there are no comparative studies on the effectiveness of various chemoembolisats. Therefore, in the present study we have examined the influence of 3 different chemoembolisats on the growth of colorectal liver metastases in a rat model. Material und Methods: 32 Wistar albino Glaxo from Rijswijk (WAG / Rij) rats were randomized into 4 groups and received a subcapsular implantation of 5 × 105 colorectal tumor cells (CC531) in the left liver lobe. A TACE were performed in all groups via the gastroduodenal artery on day 8th. The animals received in accordance to the experimental protocol Embocept S® (20–70 μm), Lipiodol Ultra Fluid® or DC Bead® (70–150 μm). Animals of the control group received only saline. The tumor size was measured on day 8th and 11th by using a three-dimensional 40 MHz ultrasound device. On day 11th the tumor and liver tissue were taken for histological and immunohistochemical analyzes. Results: Animals of the control group showed at day 11th a tumor volume of ~ 160% compared to day 8th. The administration of Lipiodol Ultra Fluid® did not significantly influence (140%) the tumor growth. In contrast, tumor growth from day 8th to day 11th was completely inhibited (100%) by Embocept S® and DC Beads®. Immunohistochemical analysis of the tumors showed significantly more necrotic areas after administration of Embocept S® and DC Bead®. The proliferation rate of the tumor cells in the various groups showed no differences between all groups. Conclusion: Our study shows that a TACE of Embocept S® and DC Bead® can inhibite the growth of colorectal liver metastases completely in the given time period. The inhibition of the tumor growth seems to be caused by increased tumor cell necrosis. ID 345 Surgical quality following rectal cancer surgery without neoadjuvant chemoradiation in patients selected by preoperative magnetic resonance imaging – preliminary results of the OCUM Study. M. Kreis, J. Strassburg, R. Ruppert, H. Ptok, C. Maurer, T. Junginger, S. Merkel, P. Hermanek Charité Universitätsmedizin Berlin, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Campus Benjamin Franklin, Berlin, Deutschland Introduction: Neoadjuvant chemoradiation adds functional impairment to patients undergoing total mesorectal excision (TME). Surgical quality is of paramount importance to achieve low local recurrence rates in patients operated without neoadjuvant chemoradiation when a negative circumferential margin was shown by preoperative magnetic resonance imaging (MRI). We aimed to determine surgical quality in a prospective multicenter cohort study (OCUM) in patients selected by MRI for surgery without neoadjuvant chemoradiation. Oncol Res Treat 2014;37(suppl 1):1–133 47 Inhalt Index Methods: Quality of TME was assessed in three categories for 282 patients from 12 hospitals enrolled for surgery without neoadjuvant chemoradiation (Nagtegaal et al. 2005, Quirke and Morris 2007). Tumor perforation, local tumor cell dissemination and number of lymph nodes were assessed. Further, negative predictive value of MRI for histopathological involvement of the circumferential margin was determined. Results: In patients undergoing TME the muscularis propria plane (category III) was reached in 1/282 patients (0,4%). Intraoperative tumor cell dissemination was observed in 3/282 patients (1,1%). Total number of lymph nodes was 25 (median, range 10–79) and 79/282 patients had positive lymph nodes (28%). The number of 12 lymph nodes recommended by UICC was not reached in one patient. Preoperative MRI correctly predicted a negative circumferential margin involvement as determined by histopathological workup in 98,9% of patients. Conclusions: Excellent results in terms of surgical quality are possible justifying surgery without pretreatment in patients with MRI-negative circumferental margin tumors. This concept may help to avoid additional functional impairment and reduced quality of life following neoadjuvant chemoradiation in selected patients. ID 364 Status quo of the endurance performance capacity and physical strength of patients with esophageal and gastric cancer C.T.H. Baltin1, P. Zimmer2, E. Bollschweiler1, A. Hölscher1, W. Bloch2, F. Baumann2 Universitätsklinik Köln, Allgemein-, Viszeral- und Tumorchirurgie, Köln, Deutschland 2 Institut für Kreislaufforschung und Sportmedizin, Deutsche Sporthochschule Köln, Abteilung molekulare und zelluläre Sportmedizin, Köln, Deutschland 1 Introduction: Exercise therapy or sport therapy for cancer patients aims to improve the quality of life. For patients with esophageal and gastric cancer there are hardly any studies that have analyzed the holistic effects of sport therapy. In order to perform a sport-specific therapeutic intervention for these patients, a diagnosis of endurance performance capacity and physical strength is necessary. The present study aims to quantify for the first time the endurance performance capacity and physical strength for these patients using reproducible measurements. Methods: In a prospective cross-sectional study a total of 30 inpatients (median age 55 years, minimum 27 years, maximum 76 years, 80% men) with esophageal or gastric cancer were analyzed preoperatively from May to September 2013 with respect to their physical performance capacity. The endurance performance capacity was evaluated using the maximum oxygen uptake (VO2max). The maximum physical strength of patients was determined using the ‘8-repetition-maximum’ (8RM) test on a leg extension and bench press machine. Results: The mean relative VO2max of esophageal and gastric cancer patients of the sample is 22.4 ml/min/kg (SD 5.21). Compared to the reference values of the American Heart Association, the endurence performace capacity is classified as ‘sufficient’. Mean results of leg extension and bench press machine testing of patients are 36.3 kg (SD 14.6), respectively, 39.4 kg (SD 16.3) and, therefore, significantly lower compared to the reference values for healthy subjects of the general population. Conclusion: Preoperative training programs should be conceived with regard to the revealed performance deficits of patients with esophageal and gastric cancer. In this way, the potential outcome of overall treatment could be increased including the quality of life of these patients. 48 Oncol Res Treat 2014;37(suppl 1):1–133 ID 372 Individualized Stereotactic Body Radiotherapy (SBRT) in Liver Metastases of CRC Patients – only Rank 3rd after Surgery and Interventional Radiology? I. Ernst1, C. Moustakis1, F. Büther2, B. Greve1, S. Scobioala1, U. Haverkamp1, H.T. Eich1 Universitätsklinikum Münster, Radioonkologie – Strahlentherapie, Münster, Deutschland 2 European Institute for Molecular Imaging (EIMI), Münster, Deutschland 1 Purpose/Objective(s): Stereotactic body radiotherapy (SBRT) allows efficient and safe treatment for patients suffered from liver tumors or metastases. Nevertheless other local ablative methods like surgery or interventional radiology techniques tend to be of higher account in interdisciplinary decisions. Aim of this study is to evaluate free breathing liver SBRT by using 4 D list mode PET/CT based PTV for Tomotherapy and Linac with regard to local control, toxicity, and patient acceptance. Materials/Methods: 175 patients (p) suffered by CRC and 1 to 4 liver metastases were enrolled. Planning procedure encompassed contrast enhanced MRI and 4 D list mode PET/CT. All patients underwent SBRT with prescribed radiation dose to the 65% enclosing isodose. Normally, 3 × 12.5 Gy were delivered. Tumors close to stomach or small bowel received 7.0 Gy in 5 fractions. Clinical history, laboratory findings, early and late toxicity scores including quality of life scores, PET/CT, and MRI were gathered before SBRT, at the 6-week follow-up visit and then at 3-month, 6-month, 9-month, 12-month, 18-month, 24-month, 30-months, and 36- months follow-ups. Results: All patients tolerated planning procedure and SBRT very well. No early or late toxicity ≥ °2 (CTCAE v.3.0) was reported. The application time was 2 to 49 min (mean 11.8 min). Local control is 98.3%, mean observation time 25.3 months. Conclusions: 4 D list mode PET/CT allows valid acquisition of tumor movements for free breathing SBRT with high tumor control rate. Low toxicity and short application time using Tomotherapy® or Linac lead to high patient acceptance. Therefore SBRT should be rated high in interdisciplinary decisions for therapy of patients with liver metastases. ID 388 IntraPeritoneale Druck-AerosolChemotherapie (PIPAC) mit oxaliplatin beim kolorektalen Karzinom mit fortgeschrittener Peritonealkarzinose: Erste klinische Ergebnisse M. Reymond1, U. Giger-Pabst1, W. Solaß1, D. Strumberg1,2, J. Zieren1 Ruhr-Universität Bochum, Marienhospital Herne, Klinik für Chirurgie, HERNE, Deutschland 2 Ruhr-Universität Bochum, Klinik für Onko-Hämatologie, Herne, Deutschland 1 Einleitung: Wir berichten über die ersten Ergebnisse der PIPAC bei Patienten mit Peritonealkarzionose (PK) und kolorektalem Karzinom (KRK). Material und Methoden: Seit 8.2012 wurden 34 PIPAC bei 19 Pat. mit PK and KRK durchgeführt (zugelassene Heilversuche). Bis auf 2 hatten alle Pat. eine systemische Chemotherapie erhalten. Kein Patient hatte Organmetastasen. Bei keinem Pat. war eine CRS und HIPEC indiziert. Das mittlere Alter war 59 ± 13 Jahren. Karnofsky war 83 ± 20%. Mittleres PCI war 18 ± 12. Das Follow-up erfolgte bis 4.9.2013 oder bis zum Tod. Das Tumoransprechen wurde makroskopisch (PCI) und histologisch begutachtet. Es wurde oxaliplatin 92 mg/m2 bei 12 mmHg und 37 °C für 30 min appliziert. Ergebnisse: In 2/19 Fällen war kein Zugang möglich. Es kam zu einer intraoperativen Komplikation (Darmläsion beim Zugang). Mittlere Operationszeit (PIPAC allein) betrug 86 Minuten. Die PIPAC konnte bei 10 Patienten wiederholt werden. Zwei Patienten hatten kombinierte CRS und PIPAC, davon entwickelte 1 Patient eine Magenperforation mit Peritonitis. Vier sonstige Nebenwirkungen CTCAE > 2 wurden registriert Abstracts Inhalt Index (1x abdominelle Schmerzen, 3x Erbrechen). Es gab keine Krankenhausmortalität. Von den 10 Patienten mit wiederholter PIPAC, 4 zeigten eine komplette intraperitoneale Remission (CR), 3 hochgradige regressive histologische Veränderungen (PR), 1 eine stabile Krankheit (SD). Vierzehn Patienten leben. Das aktuarielle Überleben nach 271 Tagen ist 69,9%, das mediane Überleben wurde nach 9 Monaten noch nicht erreicht. Schlussfolgerung: Diese ersten, preliminären Ergebnisse sind positiv. Die PIPAC mit oxaliplatin kann eine Tumorregression bei fortgeschrittener PK eines KRK induzieren, die Clinical Benefit Rate (CBR) ist 8/10. PIPAC wird gut vertragen wenn nicht mit CRS kombiniert. ID 411 10 Jahre Chirurgie des Rektumkarzinoms – Daten aus prospektiven klinisch-systematischen Beobachtungsstudien H. Ptok1,2, A. Mundt3,2, F. Meyer4,2, H. Lippert4,2, I. Gastinger2 Carl-Thiem-Klinikum, Chirurgische Klinik, Cottbus, Deutschland Otto-von-Guericke-Universität, AN-Institut für Qualitätssicherung in der operativen Medizin, Magdeburg, Deutschland 3 Carl-Thiem-Klinikum, Klinik für Anästhesiologie und Intensivmedizin, Cottbus, Deutschland 4 Universitätsklinikum Magdeburg A.ö.R., Klinik für Allgemein-, Viszeralund Gefäßchirurgie, Magdeburg, Deutschland 1 2 Die Behandlung des Rektumkarzinoms hat sich in den letzten 2 Dekaden deutlich gewandelt. Durch konsequenten Einsatz neoadjuvanter Therapieverfahren und Anwendung der totalen mesorektalen Exzision beim tief sitzenden Rektumkarzinom konnte die lokale Tumorkontrolle signifikant gebessert werden. Mit der vorliegenden Analyse sollen die Umsetzung der multimodalen Therapie beim Rektumkarzinom unter den Bedingungen der Routineversorgung sowie die erreichten Ergebnisse über einen 10-Jahres-Zeitraum untersucht werden. Methode: Es wurden die Daten der prospektiven multizentrischen Beobachtungsstudie „Qualitätssicherung – Rektumkarzinom» der Jahre 2000 bis 2010 ausgewertet. N = 33 724 Patienten wurden erfasst. Die Resektionsrate betrug 95,2%. Die Rate kurativer Resektionen betrug 84,2%. Ergebnisse: Die postoperative Gesamtmorbidität und Letalität zeigten keine Änderung im Verlauf der Beobachtung. Der Anteil neoadjuvant behandelter Patienten mit kurativer Resektion stieg von 5,6% (2000) auf 40,5% (2010). Die TME-Rate stieg bei tiefsitzenden Karzinomen von 75,2% (2000) auf 95,3% (2010). Für Patienten, die in den Jahren 2000/2001 kurativ reseziert wurden, lag die 5-Jahres-Lokalrezidivrate bei 11,7%, während diese für in den Jahren 2005/2006 resezierte Patienten bei 4,6% lag (p < 0,001). Eine Verbesserung des Gesamtüberlebens zeigte sich nicht. Schlussfolgerung: Bei gleichbleibender Gesamtmorbidität und Letalität hat der zunehmende Einsatz neoadjuvanter Behandlungen und die Etablierung der TME in der flächendeckenden Routineversorgung von Patienten mit Rektumkarzinomen zu einer signifikanten Verbesserung der lokalen Tumorkontrolle geführt, ohne dass ein Einfluss auf das Gesamtüberleben der Patienten nachweisbar ist. ID 427 Pulmonary Metastasectomy for Colorectal Cancer: Lymph Node Metastases and Factors affecting Long-term survival S. Bölükbas1, S. Sponholz1, N. Kudelin1, M. Eberlein2, J. Schirren1 HSK Wiesbaden, Klinik für Thoraxchirurgie, Wiesbaden, Deutschland Carver College of Medicine, University of Iowa, Division of Pulmonary, Critical Care and Occupational Medicine, Iowa, Vereinigte Staaten von Amerika 1 2 Objective: To investigate the role of lymph node metastases and longterm outcome in patients undergoing pulmonary metastasectomy and systematic lymph node dissection of colorectal cancer. Methods: Retrospective review of 165 patients with colorectal cancer undergoing pulmonary metastasectomy and systematic lymph node dissec- Abstracts tion with curative intent from 1999–2009. Chi-square tests, Kaplan-Meier analyses, log-rank test and Cox regression analyses were used to estimate survival and to determine prognosticators of survival and lymph node metastases. Results: Lymph node metastases (prevalence 22.4% in the present cohort) were more often detected in case of rectal cancer, anatomic resections for pulmonary metastasectomy and multiple metastases, respectively. Median survival for all patients was 64 months. Lymph node metastases were associated with inferior but promising survival (44 vs. 78 months, P=0.03). Survival advantage was seen in the univariate analyses in case of disease-free intervall ≥36 months, colon cancer, response to pre-metastasectomy chemotherapy and single pulmonary metastasis.Combined liver and lung resections had no significant impact on survival.Rectal cancer and response or stable disease to pre-metastasectomy chemotherapy were independent significant prognosticators. Conclusions: Lymph node metastases are associated with inferior but promising long-term survival. Systematic lymph node dissection should be recommended due to high prevalence of lymph node metastases in case of rectal cancer, required anatomic resections and multiple metastases. Rectal cancer and response to pre-metastasectomy chemotherapy are independent prognosticators for long-term survival. ID 428 Locoregional application of temsirolimus is effective to inhibit tumor growth of CC531 colorectal liver metastases even after stimulation by hepatectomy or portal branch ligation J. Sperling1, C. Ziemann2, A. Gittler2, A. Benz-Weißer3, M.D. Menger3, O. Kollmar1 Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Göttingen, Deutschland 2 Universitätsklinik des Saarlandes, Homburg/Saar, Deutschland 3 Universitätsklinik des Saarlandes, Institut für Klinisch-Experimentelle Chirurgie, Homburg/Saar, Deutschland 1 Background: Temsirolimus (Te) is an effective antitumor agent for the treatment of various solid tumors when given systemically. However, locoregional application has the potential to increase antitumor effects compared to systemic administration. Herein we studied whether a hepatic-arterial infusion (HAI) of Te is effective to inhibit tumor growth of colorectal rat liver metastases. Methods: WAG/Rij rats (n = 36) were randomized to 6 groups and underwent subcapsular implantation of CC531 cancer cells in the left liver lobe with or without performing a 70% liver resection (Phx) or a portal branch ligation (PBL). Ten days later animals received either a HAI of Te (TEM, Phx-TEM, PBL-TEM) or, when serving as controls, of a comparable amount of saline solution (Sham, Phx-Sham, PBL-Sham). Tumor growth was determined on day 10 and 13 by threedimensional ultrasound. On day 13 tissue was taken for histological and immunohistochemical analysis. Results: From day 10 to day 13 controls showed an increased tumor growth, most pronounced after Phx (Phx-Sham: +63.17±9.91%). In contrast, HAI of Te results in an almost complete inhibition of tumor growth (TEM: +0.47±7.68%). Of interest, after Phx and PBL tumor growth was even significantly reduced by HAI of Te (Phx-TEM: –8.26±13.13%, PBL-TEM: –1.08±4.69%). Immunohistochemistry revealed an increased cleaved caspase-3 activity together with a significant reduction of PECAM-1 positive cells after HAI of Te. Conclusion: HAI of Te is effective to inhibit tumor growth of CC531 colorectal rat liver metastases even if growth stimulating procedures like Phx or PBL were performed previously. Tumor growth Inhibition is provided by increased tumor cell apoptosis and decreased tumor vascularisation. Oncol Res Treat 2014;37(suppl 1):1–133 49 Inhalt Index Gastrointestinal (Noncolorectal) Cancer ID 027 Metastatic Pancreatic Cancer Patients May Benefit from Stop and Go Treatment Strategies (Induction and Reinduction) with FOLFIRINOX: A Case Report F.K. Tauchert, M. Ruppert, E. Jäger Krankenhaus Nordwest, Klinik für Onkologie, Frankfurt am Main, Deutschland Background: Metastatic pancreatic cancer is a lethal disease with limited treatment options. We give an account on a patient, who benefits of multiple reinductions of his therapy according to FOLFIRINOX-regime. Case report: Fifty-five years old patient with metastatic pancreatic cancer (lung- & liver metastases) with a progressive disease after four month firstline-therapy with Gemcitabin started secondline treatment according to the FOLFIRINOX-regime in January 2011. CT-scan after 5 and 8 cycles showed partial response. Due to personal reasons, he ended chemotherapy after 8 cycles in May 2011. Next ct-scan in august 2011 showed progression of liver metastases. Chemotherapy according to FOLFIRINOX-regime was re-induced. CT-scan after another five cycles of chemotherapy in October 2011 revealed shrinkage of the liver-metastases again. Again, the patient stopped treatment due to personal reasons again, resulting in a progressive disease in February 2012. FOLFIRINOX was applied for the third time. In May 2012 after four cycles of chemotherapy ct-scans showed a stable disease. Conclusion: With FOLFIRINOX as a highly active regimen, stop and go strategies may become of clinical interest in metastatic pancreatic cancer. This case provides a rational for a clinical trail. ID 038 Sex Hormone Binding Globulin Is Deregulated in Aggressive Hepatocellular Carcinoma and Predicts Early Tumor Recurrence F. Weber1, N. Wellenberg1, M. Ahrens2, S. Swoboda1, M. Trippler3, B. Sitek2, A. Hoffmann4, H. Meyer2, H. Baba5, M. Eisenacher2, J. Schlaak3, A. Paul1 Medizinische Fakultät, Universität Duisburg-Essen, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie,, Essen, Deutschland 2 Ruhr Universität Bochum, Medizinisches Proteom Center Ruhr, Bochum, Deutschland 3 Medizinische Fakultät, Universität Duisburg-Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Deutschland 4 Medizinische Fakultät, Universität Duisburg-Essen, Klinik für Innere Medizin – Tumorforschung, Essen, Deutschland 5 Medizinische Fakultät, Universität Dusiburg-Essen, Institut für Pathologie, Essen, Deutschland 1 Introduction: Curative surgical intervention for HCC is hindered by the high rate of tumor recurrence. Prognostic markers can help to tailor therapeutic management. Due to organ shortage this is especially important in the setting of liver transplantation. Methods: We utilized high density gene expression platforms in order to elucidate the molecular signature of HCC. Molecular markers were further validated in a third independant set of in total 61 patients with HCC by RT-PCR. SHBG (Sex hormone-binding globulin) expression was normalized and correlated to clinical data. In vitro studies are beeing conducted to elucidate the functional properties utilizting siRNA knockdown and gene transfection experiments. Results: SHBG is signicicantly downregulated in HCC showing a poor prognosis (relative expression 0.14 vs 0.94, p = 0.01). Furthemore, the median overall survival and tumor free survival for patients with low SHBG expression was 49 and 23 months, respectively. This was significantly shorter when compared to those with high SHBG expression (76 and 59 months, p < 0.015). The SHBG deregulation was not associated with other variables. Functional studies correlated SHBG expression with 50 Oncol Res Treat 2014;37(suppl 1):1–133 altered cell migration but did not show any effect on cell cycle or proliferation. Conclusion: We show that the deregulation of SHBG is associated with early tumor recurrence as well as poor overall survival in patients with HCC. This holds true independantly of gender, underlying hepatopathy and type of surgical intervention. Our extensive validation underline the potential clinical implication to identify high risk HCC patients and provides evidence to elucidate SHBG as a traget for adjuvant therapies. ID 049 Outcome of somatostatin-receptor targeted PRRT with 177Lu-octreotate in advanced pancreatic neuroendocrine tumors G1-2 S. Ezziddin1, F. Khalaf1, M. Vanezi1, T. Haslerud1, K. Mayer2, H. Ahmadzadehfar1, W. Willinek3, H.-J. Biersack1, A. Sabet1 Uniklinik Bonn, Nuklearmedizin, Bonn, Deutschland Uniklinik Bonn, Med. Klinik III, Bonn, Deutschland 3 Uniklinik Bonn, Radiologie, Bonn, Deutschland 1 2 Purpose: The clinical benefit of peptide receptor radionuclide therapy (PRRT) has not been fully outlined for pancreatic neuroendocrine tumors (P-NET). This study analyses standardized PRRT with 177Lu-octreotate in a well-characterized patient population of advanced P-NET G1-2. Methods: Retrospective assessment of n = 68 P-NET patients with inoperable metastatic disease consecutively treated with 177Lu-octreotate (4 intended cycles at 3 monthly intervals; mean activity per cycle, 8.0 GBq). 46 patients (67.6%) had documented morphologic tumor progression within treatment; PRRT was the first-line systemic therapy in 35 patients (51.5%). Assessment of response, toxicity and survival according to previous work. Results: Median follow-up was 58 months (95% CI, 47-69). Reversible hematotoxicity (≥ grade 3) occurred in 4 patients (5.9%). No significant nephrotoxicity (≥ grade 3) was observed; the mean relative change per year of the glomerular filtration rate was –2±21%. Treatment response consisted of PR in 41 (60.3%), MR in 8 (11.8%), SD in 9 (13.2%), and PD in 10 (14.7%) patients. Median progression-free survival (PFS) and overall survival (OS) were 34 (95% CI, 26–42) and 53 months (95% CI, 46–60), respectively. G1 grading was associated with increased PFS (p = 0.04) and OS (p = 0.044) on multivariate analysis. Other variables with significant contribution to OS were reduced performance status (Karnofsky score ≤70%; p = 0.007), high hepatic tumor burden (≥25% liver volume; p = 0.017), and elevated plasma NSE (>15 ng/ml; p = 0.035). Conclusion: PRRT seems to be highly effective in advanced P-NET G1-2 yielding very promising response rates and survival outcomes. Independent predictors of survival are the proliferation index, patient’s performance status, tumor burden and the baseline plasma NSE level. ID 074 Correlation of histopathological Response with Prognosis for perioperative Chemotherapy with Epirubicin, Cisplatin and 5-FU (ECF) for resectable gastro-esophageal Adenocarcinoma. C. Treese1, D. Bichev2, M. von Winterfeld3, S. Daum1, P. Thuß-Patience2 Charité Berlin, Campus Benjamin Franklin, Medizinische Klinik I für Gastroenterologie, Infektiologie und Rheumatologie, Berlin, Deutschland 2 Charité, Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Berlin, Deutschland 3 Charité, Campus Mitte, Institut für Pathologie, Berlin, Deutschland 1 Background: Perioperative chemotherapy with ECF-like regimes is the recommended treatment in Europe in patients with adenocarcinoma of the gastro-esophageal junction/stomach (AGE/GaCa) stage UICC II and III. However, only limited data exist on histological response and relevance for prognosis. Here we report our experience administering this regimen concerning clinical and histological outcome. Abstracts Inhalt Index Methods: In this retrospective analysis all patients, treated from 09/2004 to 09/2008 with AGE/GaCa who received preoperative chemotherapy with ECF were included. Cisplatin and 5-FU were substituted with oxaliplatin or capecitabine when indicated. Histologic response was assessed using Becker score. Results: 79 patients were analysed with a median follow up of 41 months. Median age was 64 years, 56 pts were male. Surgery including D2 lymph node dissection was performed on 70 pts. So far 38 pts (54.3%) had tumor recurrence and 40 pts (57.1%) died, 30 (42.9%) of them tumor related. Median overall survival was 25 mths (CI 95% 9.0–40.9) and the median event free survival was 14 mths (CI 95% 2.6–25.3). Cumulative survival at one year was 74.0% and 42,5% at three years follow up. Histological response to chemotherapy: complete:10 pts, near complete: 3 pts, partial: 21 pts, no response 27 pts. 3-year survival of complete responders was 84.6%, of partial- 42% and non-responders 28%. Conclusion: Our results show complete histological remission in 12.7% of the intent to treat group, a similar range as seen with taxane based regimens. These patients had a significantly better 3-year overall survival (84.6%) than patients with lower remission rates. A randomised phase III trial comparing ECF to a taxane based regimen is being conducted. ID 092 Outcome of patients (pts) with advanced pancreaticobiliary cancers treated with sequential chemotherapies at the West German Cancer Center (WTZ) S. Kasper1, A. Abendroth1, M. Abramczyk1, R. Noureddine1, A. Paul2, G. Gerken3, K.W. Schmid4, P. Markus5, J. Meiler1, M. Wiesweg1, G. Kaiser2, A. Dechene3, M. Schuler1 Westdeutsches Tumorzentrum, Universitätsklinik Essen, Innere Klinik (Tumorforschung), Essen, Deutschland 2 Westdeutsches Tumorzentrum, Universitätsklinik Essen, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Essen, Deutschland 3 Westdeutsches Tumorzentrum, Universitätsklinik Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Deutschland 4 Westdeutsches Tumorzentrum, Universitätsklinik Essen, Institut für Pathologie und Neuropathologie, Essen, Deutschland 5 Elisabeth Krankenhaus Essen, Klinik für Allgemein-, Viszeral- und Unfallchirurgie, Essen, Deutschland 1 Introduction: The prognosis of pts with advanced pancreaticobiliary cancers (PBC) is still dismal with median survival rates below 1 year. Recently, aggressive multiagent therapy (FOLFIRINOX) was found superior over gemcitabine in pancreatic cancer. However, sequential therapies may provide disease control with less toxicity. To obtain a benchmark for future trials we have analyzed the outcome of PBS pts treated at the WTZ, one of 12 Oncology Centers of Excellence in Germany. Methods: The outcomes of 450 pts with advanced or metastatic PBC cancers treated at the WTZ were studied. Response rates (ORR), disease-free survival (DFS) and overall survival (OS) was analyzed in relation to pts characteristics and treatments. Results: The majority of pts had metastatic disease (74.8%). Curative or palliative surgery was performed in 33.6% pts, which was followed by adjuvant/additive chemotherapy in most cases. First line therapy consisted of gemcitabine (38.4%), platinum combinations (38.0%) or others. ORR was 23.7%, with significantly higher ORR in pts receiving platinum combintaions (31.2% vs. 15.6%, p = 0.015 χ-square). Median PFS was 5 months (interquartile range 2–9) without significant difference in both groups. Second (65.6%) and 3rd line (38.9%) therapies were given to a large proportion of patients. Median OS of the entire population was 11 months (interquartile range 5–19), and 10 months (4–18) in pts with metastatic disease. Conclusion: The outcome of unselected pts with advanced PBC treated at the WTZ compares favourably with recently reported results from FOLFIRINOX-type chemotherapy protocols. Prospective comparison to sequentially administered two-agent regimens is warranted in the palliative setting. Abstracts ID 141 Identifying of new genetic factors that are involved in the ability of PDAC clones to grow in the rat liver H. Adwan, K. Kadhim, M.R. Berger Deutsches Krebsforschungszentrum, Heidelberg, Deutschland Introduction: 60% of all patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed initially with advanced disease. Furthermore, two thirds of the remaining 40% will develop liver metastasis within the next three years. In order to improve early diagnosis of PDAC patients, we aimed at Identifying new genes and miRNA species that are linked to the origin and metastasis of that disease. Methods: Initially, 50 clones were isolated from the ASML rat PDAC mother cell line by FACS. These clones were tested for their cellular properties (proliferation, migration and colony formation) and thereafter, 20 clones were chosen for additional investigation in vivo. To that purpose, the clones were tested for their ability to grow in rat liver by injecting 4 million cells from each clone into the portal vein of 5 BDX rats, respectively. The most promising 10 clones were further selected to compare growth ability with the respective gene expression by using micro-array analysis. Results: From the 20 clones tested, only 6 were able to grow aggressively and consistently in the rat liver. Another 8 clones were able to grow weakly or moderately and the remaining 6 clones were not able to grow in the rat liver. The chip-array analysis demonstrated that some 500 genes and 100 miRNA species were found to be associated with the ability of the clones to grow in the liver. Conclusions and Perspectives: Genetic factors seem to be involved in the ability of PDAC clones to grow in the rat liver. The characterization of these factors may help identifying new diagnostic tool. ID 160 Impact of objective response and overall survival in patients with inoperable or metastatic gastric and esophagogastric junction (EGJ) cancer: Landmark analysis of 10 year data from first-line clinical trials T.A. Bolt1, C. Pauligk1, D. Werner1, F. Mayer2, R. Hofheinz3, H. Nils4, K. Luley5, H. Schmalenberg6, M. Egger7, S.-E. Al-Batran1 Krankenhaus Norwest, Institut für klinisch-onkologische Forschung, Frankfurt, Deutschland 2 University Medical Center, Tübingen, Deutschland 3 University Medical Center, Department of Hematology and Medical Oncology, Mannheim, Deutschland 4 Klinikum Wolfsburg, Wolfsburg, Deutschland 5 Universitätsklinikum Lübeck, Lübeck, Deutschland 6 Universitätstumorcentrum Jena, Jena, Deutschland 7 Ortenau Klinikum, Lahr-Ettenheim, Deutschland 1 Background: The aim of the study is to determine whether the achievement of an objective response to 1st linechemotherapy is prognostic of patient’s outcome in gastric/EGJ adenocarcinoma. Method: Individual patient (pts) data from prospective 1st line trials conducted by a single study group were used. Response data, pts’ characteristics, type of chemotherapy and overall survival (OS) data were analyzed. Responses were evaluated according to WHO criteria in all trials and landmark analysis conducted. Results: Response rates were complete (CR) in 3.1%, partial (PR) in 37.7%, stable disease (SD) in 33.8% and progressive disease (PD) in 15.4% pts (9.9% were not evaluable). Overall response rate (OR= CR + PR) was 40.8%. Median OS in pts with CR vs. PR vs. SD vs. PD were 28.9 vs. 14.8 vs. 10.8 vs. 5.2 months, respectively; p = 2.6 x 10-42. OR also strongly predicted OS (16.7 vs. 8.6 months in pts with vs. no OR; p = 9.0 × 10-14). Landmark studies were established with landmarks set on 2 and 4 months. Median OS at landmark point 2 months in pts with CR vs. PR vs. SD vs. Oncol Res Treat 2014;37(suppl 1):1–133 51 Inhalt Index PD were 17.3 vs. 14.5 vs. 11.1 vs. 5.4 months, respectively; p = 3,7 × 10-12. Pts with OR vs. no OR had a median OS of 14.7 vs. 10.9 months, p = 0.0001. Median OS at landmark point 4 months in pts with CR vs. PR vs. SD vs. PD were 23.9 vs. 14.8 vs. 11.8 vs. 7.7 months, respectively; p = 1.2 × 10-10. Pts with OR vs. no OR had a median OS of 16.1 vs. 11.1 months, p = 7.0 × 10-6. OR remained the strongest predictor of OS in the multivariate analysis (p = 6.3 × 10-7) followed by the presence of peripheral LN as the only site of metastasis (p = 8.2 × 10-5) and ECOG (p = 0.002). Conclusion: The achievement of an objective response is the strongest predictor of survival in pts with gastric and EGJ cancer and could serve as surrogate marker if validated. ID 174 A novel method combining gene and protein platforms on one slide for the detection of HER2 in gastric cancer: Final results D. Werner1, A. Battmann2, K. Steinmetz1, T. Jones3, T. Lamb4, M. Martinez4, S.-E. Al-Batran1 Institut für Klinisch-Onkologische Forschung, Krankenhaus Nordwest GmbH, Frankfurt/Main, Deutschland 2 Institut für Pathologie am Krankenhaus Nordwest, Frankfurt/Main, Deutschland 3 Roche Pharma, Penzberg, Deutschland 4 Ventana/Roche Tissue Diagnostics, Tucson, Vereinigte Staaten Von Amerika 1 Background: Evaluation of gene amplification and/or protein overexpression of HER2 in gastric cancer (GC) is a prerequisite to establish an adequate treatment strategy. GC are heterogeneous, separate evaluations lead to uncertainties in localizing distinct clones and are time consuming. The aim of the study was to evaluate the feasibility of gene-protein platform (GP) in comparison to single staining methods. Methods: Immunohistochemistry (IHC) plus silver in situ hybridization (SISH) and the new GP method for HER2 were performed in randomly collected 100 cases of GC. Evaluation was performed by two observers (ob), in discrepant cases a third ob was consulted to make a decision by consensus. Results of IHC/SISH were compared with GP staining. Rüschoff criteria were applied. Tumors showing HER2 expression (exp) 3+ or amplification were considered HER2 positive. Results: 96/100 samples were eligible. Amplification was observed in 14.6% by both, SISH and GP. 70.8% by IHC and GP had no exp (0) and 10.4%/11.5% (IHC vs. GP) had weak (1+) exp. Moderate exp (2+) was observed in 9.4% by IHC and 7.3% by GP. Rate of overexpression (3+) was similar in IHC (9.4%) and GP (10.4%). There were complete concordances (100%;κ=1) in assessment of cases with score 0 and amplified tumors. High concordance are shown in score 1+ (98.96%;κ=0.95) and 3+ (96.88%;κ=0.83) cases. Concordance in cases with score 2+ was found in 95.83% (κ=0.73) of observations. After third observation, there were 5 discordant cases with most discrepancies in assessment of IHC 2+/3+. Conclusions: GP has been tested for first time in GC. Results showed that this platform can be a feasible alternative to single methods. Discrepancies in cases with score 2+ expression are a result of ob variability. ID 181 E- and P-selectin are essential for peritoneal carcinomatosis in a xenograft model of human pancreatic adenocarcinoma D. Wicklein1, F. Gebauer2, J. Salamon3, J.R. Izbicki2, U. Schumacher1 E- and P-selectins expressed on the luminal surface of mesodermally derived endothelial cells play a crucial role in the formation of haematogenous metastases in a number of malignancies. As peritoneal mesothelial cells are also derived form the mesoderm, we hypothesized that selectins are also of importance in peritoneal tumor spread. Immunohistochemistry was used to identify selectin expression on normal human peritoneum and isolated mesothelial cells. E- and P-selectin interactions with human pancreatic adenocarcinoma cells were investigated in dynamic flow assays and flow cytometry, the latter was also used to determine the main selectin ligands on pancreatic adenocarcinoma cell lines PaCa 5061, BxPC-3 and PaCa 5072 and selectin expression on human mesothelial cells. All cell lines were xenografted into the peritoneum of E- and P-selectin-deficient pfp/rag2 mice and selectin wild-type controls. Peritoneal carcinomatosis was quantified using MR imaging or a scoring system. E- and P-selectin were constitutively expressed on human mesothelial and endothelial cells in the peritoneum. PaCa 5061 and BxPC-3 cells interacted with E- and P-selectins in dynamic flow assays and flow cytometry with CA19-9 (Sialyl Lewis a) being the main E-selectin ligand. For xenografted PaCa 5061 and BxPC-3 cells, peritoneal metastasis was significantly reduced in E- and P-selectin double knockout mice compared with wild-type pfp/rag2 animals. In contrast, PaCa 5072 cells were almost devoid of selectin binding sites and no intraperitoneal tumor growth was observed. Interactions of tumor cells with peritoneal selectins play an important role in the peritoneal spread of pancreatic adenocarcinoma. ID 186 Adding docetaxel to cisplatin based therapy represents a beneficial option for gastric cancer patients in the perioperative situation C. Ilmberger1, K. von Dehn-Rotfelser1, J. Schirra2, M. Joka3, K.-W. Jauch3, B. Mayer1,3 SpheroTec, Martinsried, Deutschland Klinikum der Universität München, Medizinische Klinik und Poliklinik II, München, Deutschland 3 Klinikum der Universität München, Chirurgische Klinik und Poliklinik, München, Deutschland 1 2 5-FU, cisplatin and docetaxel (FCD) is approved for the palliative treatment of gastric cancer and has been reported to have a shorter remission time compared to other perioperative treatment options. Thus, FCD might represent a treatment option in the perioperative situation. Its therapeutic efficacy was investigated using multicellular tumor spheroids (MCTS) derived from patient tumor material, which have been shown to imitate the original tumor regarding tumor architecture, cellular composition, tumor microenvironment and therapeutic response. Tumor biopsies of 10 gastric cancer patients were processed for the culture of MCTS. After 48 h following the formation, these microtumors were treated with FCD, as well as the drug combinations recommended in the perioperative situation, namely 5-FU plus cisplatin (FC) and 5-FU plus oxaliplatin (FO) with or without epirubicin (FCE and FOE, respectively). Therapeutic response was assessed by metabolic inhibition determined using the ATP assay, 48 h after treatment. The addition of epirubicin significantly increased the therapeutic response compared to the double combinations FC and FO in 83% of the samples (p < 0,001). In comparison, FCD was significantly more effective than FCE in 50% of the cases (p = 0,001) and showed the strongest metabolic inhibition in 29% of the samples (p = 0,002). Considering efficacy and the short remission time after chemotherapy FCD seems superior to FCE and should be considered for the perioperative treatment of gastric cancer. Universitätsklinikum Hamburg-Eppendorf, Anatomie und Experimentelle Morphologie, Hamburg, Deutschland 2 Universitätsklinikum Hamburg-Eppendorf, Allgemein-, Viszeral und Thoraxchirurgie, Hamburg, Deutschland 3 Universitätsklinikum Hamburg-Eppendorf, Radiologie, Hamburg, Deutschland 1 52 Oncol Res Treat 2014;37(suppl 1):1–133 Abstracts Inhalt Index ID 199 Presence of circulating tumor cells with stem cell characteristics predicts response to SIRT in hepatocellular carcinoma I. Nel1, H.A. Baba2, A. Höwner1, F. Weber3, B. Sitek4, M. Eisenacher4, H.E. Meyer4, G. Gerken5, J.F. Schlaak5, A.C. Hoffmann1 Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Essen, Deutschland 2 Universitätsklinikum Essen, Institur für Pathologie und Neuropathologie, Essen, Deutschland 3 Universitätsklinikum Essen, Allgemein-,Viszeral- und Transplantationschirurgie, Essen, Deutschland 4 Ruhr Universität Bochum, Medizinisches Proteomcenter, Bochum, Deutschland 5 Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Deutschland 1 Background and Aims: As we recently reported, different circulating tumor cell (CTC) populations are identifiable in the peripheral blood of patients with HCC (Nel et al., Transl Oncol, 2013). We now investigated circulating epithelial and stem cell-like cells and whether their distribution during treatment courses is associated with clinical characteristics. Methods: Before and after SIRT, mononuclear cells and non-hematopoietic cells were isolated from peripheral venous blood using density gradient centrifugation. Cell suspensions were spun onto glass slides. CTC presence was verified by immunofluorescence staining against panCK (epithelial), N-cadherin (mesenchymal), CD133 (stem-cell-like); counterstaining with CD45 (hematopoietic) and hemalm (nucleus; bright field). CTC and hematopoietic cells were enumerated and individual cell type profiles were analyzed and correlated to therapeutic outcome in 10 patients with either disease control or progressive disease. Results: Mann-Whitney test revealed that CK+ cells (p = 0.01) and CD133+ cells (p = 0.12) before and after SIRT, respectively, differed significantly between patients with disease control and progression. The number of CD133+ cells and the ratio CD133+/CK+ cells (prior SIRT) was each split into low and high counting groups at the 50th percentile, respectively. All patients with low counts were combined into one factor (LowCD133). In a backward linear multivariate regression model LowCD133(p = 0.02) and AFP (p = 0.03) were the only factors in this patient cohort showing a significant independent correlation to progression. Conclusions: These results underline that examining individual CTC composition upfront to and during local-ablative therapy of patients with HCC might be used to predict outcome and therefore individualize treatment decisions. Analysis of stem-cell related markers might enhance the predictive power. 69 (34.5%) patients had 25(OH)D3 levels below 10 ng/ml and were classified as insufficient, 76 patients (38%) had levels between 10 and 20 ng/ ml (deficient) and 55 (27.5%) patients had levels above 20 ng/ml. 25(OH) D3 levels differed significantly between Child Pugh stages and showed a negative correlation with the MELD score. Patients with decompensated liver disease had significantly lowered 25(OH)D3 levels. There were significant differences between stages of HCC according to the BCLC staging system and CLIP score. Patients with severe 25(OH)D3 deficiency had a significantly shorter OS (HR 2.631, (CI) 1.354–5.113, P = 0.004). In a multivariate Cox regression model 25(OH)D3 levels < 10 ng/ml and a CLIP score > 2 were independently associated with shorter OS. Conclusion: 25(OH)D3 serum levels differ between HCC stages and correlate with the severity of liver insufficiency. Furthermore, 25(OH) D3 levels below 10 ng/ml were associated with a higher mortality risk in univariate and multivariate analyses. ID 256 Extended cholecystectomy as the essential prognostic factor in T1b-T3 incidental gallbladder carcinoma – results of the German Registry T. Goetze, V. Paolucci Ketteler-Krankenhaus, Klinik für Chirurgie, Offenbach, Deutschland Background: The immediate radical re-resection (IRR) after simple cholecystectomy in incidental gallbladder carcinoma (IGBC) is debated in the literature. The German S3-Guidelines recommend IRR in T2 and more advanced stages. Current literature recommends more extensive surgery already in T1b-tumors. Methods: For data analysis, the German Registry was used. Results: To date more than 900 cases of IGBC have been analyzed. In 20% of patients with T1a-tumor there was an IRR. In 40% of 109 patients with T1b-tumor there was an IRR. There is a significant survival benefit for re-resected T1b patients. There is also a significant survival benefit for the 215 T2-tumors respectively the 75 T3-patients with IRR compared to the 441 T2-tumors respectively 207 T3-tumors without IRR. Comparison of liver resection techniques shows good results for the wedge- resection technique in T1b- and T2-carcinomas. For T3-carcinomas more radical techniques show better results. Less than 50% of T2-3 tumors in the registry have had re- resection. Conclusions: IRR should be highly recommended in patients with T1b and more advanced IGBC`s. Wedge- resection technique is an attractive procedures for T1b- and T2-IGBC`s due to their lower invasiveness in spite oncological adequacy. ID 319 ID 232 Severe 25-hydroxyvitamin D deficiency identifies HCC patients with a poor prognosis F. Finkelmeier1, V. Köberle1, J. Bojunga1, B. Kronenberger1, S. Zeuzem1, J. Trojan1, A. Piiper1, O. Waidmann1 Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Frankfurt am Main, Deutschland 1 Progression and therapy efficacy of liver cancer is determined by macronutrient composition I. Rudolph1, A. Kettelhake1, G. Mastrobuoni2, S. Kempa2, T. Cramer1 1 2 Charite, Gastroenterologie und Hepatologie, Berlin, Deutschland MDC, BISMB, Berlin, Deutschland Objective: Vitamin D is involved in many biological functions. It has been identified as prognostic factor in malignant and non-malignant diseases. However, the role of vitamin D in HCC as a prognostic factor remains inconclusive. Methods: From February 2009 to July 2013, 200 patients with the diagnosis of HCC were consecutively enrolled into the present prospective cohort study. 25-hydroxyvitamin levels were quantified by radioimmunoassay from serum samples obtained at the day of study inclusion. Patients were followed until death or last contact. The primary end point was overall survival (OS). Results: The mean follow-up was 322 days. 19 patients underwent liver transplantation and 60 (30%) patients died within the observation time. Primary liver cancer (Hepatocellular Carcinoma (HCC)) is characterized by rising incidence and robust therapy resistance. Prognosis of inoperable patients is poor within a range of a few months. Detailed molecular and biochemical analysis of HCC pathogenesis is of pivotal importance to identify and develop new therapy targets. The pronounced dependence of cancer on glucose uptake and metabolism together with the association of HCC with the metabolic syndrome led us to hypothesize a role of diet (specifically, macronutrient composition) in HCC pathogenesis. We fed mice harbouring a liver-specific expression of the SV40 large T oncogene (ASV-B mice) carbohydrate-restricted chow (12% carbohydrates compared to 50% in standard chow) and noted several striking effects on tumor biology. ASV-B mice are characterized by an age-dependent adenoma-carcinoma sequence: Adenomas at 12, multiple HCCs around Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 53 Inhalt Index 16 weeks. When low carbohydrate chow (LCC) was started at 14 weeks, adenoma progression to HCC was significantly inhibited (tumor load was reduced from 68% in controls to 35% under LCC). Interestingly, combined treatment with LCC and the glycolysis inhibitor 2-deoxy-glucose (2-DG) further aggravated this effect to 20% tumor load. Initiation of LCC after HCC development (around 17 weeks) resulted in massive tumor regression with microscopic appearance of necrotic tumor areas. MS-based proteomics and metabolomics is currently being applied to deconstruct the molecular nature of this effect. Taken together, our results support a critical role of macronutrient composition, especially carbohydrate content, for both HCC prevention and therapy. As low carbohydrate diets have been safely used for almost a century, clinical application of these results seems feasible. ID 322 An integrated systems medicine approach to deconstruct the metabolism of Hepatocellular Carcinoma A. Kettelhake1, G. Mastrobuoni2, C. Bielow2, I. Rudolph1, O. Demidova1, M. Pietzke2, S. Kempa2, T. Cramer1 Charite, Gastroenterologie und Hepatologie, Berlin, Deutschland 2 MDC, BISMB, Berlin, Deutschland 1 Hepatocellular carcinoma (HCC) is one of the most common tumor types in the world with constantly rising incidence in industrialized countries. Therapeutic options are limited since HCCs are robustly resistant to conventional treatment. Detailed characterization of the molecular and biochemical pathogenesis of HCC is required to identify novel targets for therapy and prevention. Metabolic alterations represent a hallmark of cancer. In previous work, we and others could show that inhibiting glycolysis or glucose uptake results in significant reduction of HCC malignancy in vitro and in vivo, arguing for a causal role of certain metabolic pathways for HCC pathogenesis. The aim of our study is to characterize «translatable» aspects of HCC pathogenesis via a systems medicine approach integrating proteomic and metabolomic data. We performed an in-depth characterization of a murine HCC model (liver-specific expression of the oncogene SV40 large T) and respective benign liver tissue of the proteome and the metabolome via modern mass spectrometry-based methodology. Shotgun proteomics highlighted differentially expressed enzyme isoforms with high glucose affinity. Metabolome studies showed distinct changes in the abundance of glycolytic and TCA cycle intermediates. Interestingly, we could not find experimental evidence supporting a role of the Warburg effect (high glucose uptake and fermentation to lactate) in this HCC model system. To get new insights in the complex metabolic reprogramming and metabolic dependencies of human HCC, we started to perform similar ‘omics’-analyses of human tissues. We will outline the potential relevance of our findings for improved stratification of HCC patients as well as surveillance of patients at-risk (chronic viral hepatitis, NASH, liver cirrhosis) for developing HCC. ID 342 Single measurement of hemoglobin predicts outcome of HCC patients F. Finkelmeier1, D. Bettinger2, V. Köberle1, M. Schultheiß2, B. Kronenberger1, A. Piiper1, O. Waidmann1 Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Frankfurt am Main, Deutschland 2 Universtitätsklinik Freiburg, Medizinische Klinik 2, Freiburg, Deutschland 1 Objective: Cancer related anemia is a common complication in nearly all types of cancer. However, the prognostic potential of hemoglobin has not yet been investigated in patients with hepatocellular carcinoma (HCC). Therefore we performed prospective cohort study in two independent cohorts investigating the relation of Hemoglobin (Hb) levels and overall survival (OS). Methods: From February 2009 to March 2013, 199 patients with confirmed HCC were consecutively enrolled into the present prospective cohort study. Patient characteristics, treatment, and outcome was entered 54 Oncol Res Treat 2014;37(suppl 1):1–133 into a prospectively conducted database. Blood samples were obtained at the day of study inclusion. Patients were followed until death or last contact. The primary end point was overall survival (OS). Results: The mean follow-up time was 323 + 342 days. 18 patients underwent liver transplantation and 57 (28.6%) patients died within the observation time. The mean Hb level was 12.3 +/–2.1 g/dl. Hb levels significantly differed between Child Pugh stages and showed a negative correlation with the MELD score. There were significant differences between stages of HCC according to the BCLC staging system. Patients with Hb level ≤ 13 g/dl had a significantly shorter OS (hazard ratio (HR) 2.422, (CI) 1.357– 4.322, P = 0.003). In a multivariate Cox regression model low Hb levels (≤ 13 g/dl) and high CRP levels (> 0.5 mg/dl) were independently associated with higher mortality. In a second, independent cohort of 87 patients Hb level ≤ 13 g/dl were also associated with a shorter OS. Conclusion: We were able to show that anemia correlates with the prognosis of HCC patients and could be considered as an easy accessible additional risk factor for mortality. ID 355 In vivo RNAi screen for new tumor suppressor genes in Hepatocellular Carcinoma. F. Heinzmann1, T.-W. Kang1, A. Hohmeyer1, P. Schirmacher2, R. Geffers3, T. Longerich2, L. Zender1 University Hospital Tuebingen, Division of Translational Gastrointestinal Oncology, Tuebingen, Deutschland 2 University Hospital Heidelberg, Institute for Pathology, Heidelberg, Deutschland 3 Helmholtz – Centre for Infection Research, Genom Analytics, Braunschweig, Deutschland 1 The protooncogene c-Myc is a tightly regulated transcription factor in normal cells and deregulated c-Myc plays a significant role in the development of human cancers and is overexpressed in a wide range of human tumors like in human hepatocellular carcinoma (HCC) (50%). Hepatocellular carcinoma constitutes the third most common cause of cancer related death worldwide, a fact that is also largely attributed to the lack of effective treatment options. The multikinase inhibitor Sorafenib represents the first systemic treatment resulting in 2.8 month prolonged survival highlighting the need of a better understanding of the molecular mechanisms of hepatocarcinogenesis that should ultimately lead to the development of new treatment strategies. Short hairpin RNAs capable of stably suppressing gene function by RNA interference (RNAi) can mimic tumor-suppressor-gene loss in mice allowing us to analyze passenger and driver mutations in HCC development. Here we used a novel in vivo RNAi screening platform to directly identify new tumor suppressor genes in a c-Myc driven HCC mouse model. Proof of principle experiments using positive control shRNAs against established tumor suppressor genes such as PTEN showed that our screening setup can identify potent tumor suppressor genes in this model. A focused shRNA library targeting the mouse orthologs of genes deleted in human hepatocellular carcinoma was then co-delivered with c-Myc into p53 heterozygous mouse livers. Genomic DNA was isolated from outgrown tumors and scoring shRNAs were identified via PCR amplification and deep sequencing of the shRNA cassette. Our screen identified several new tumor suppressor candidates that will be presented. Some of these were already functionally validated and mechanistically characterized regarding their role in hepatocarcinogenesis. ID 377 Individualized Stereotactic Body Radiotherapy (SBRT) by Linac or Tomotherapy for Patients suffered from inoperable CCC / Klatskin Tumours I. Ernst1, C. Moustakis2, F. Büther1, B. Greve2, S. Scobioala2, U. Haverkamp2, H.T. Eich2 European Institute for Molecular Imaging (EIMI), Münster, Deutschland Universitätsklinikum Münster, Radioonkologie – Strahlentherapie, Münster, Deutschland 1 2 Abstracts Inhalt Index Purpose/Objective(s): Stereotactic body radiotherapy (SBRT) allows efficient and safe treatment for patients suffered from liver tumors or metastases. Aim of this study is to evaluate free breathing liver SBRT for inoperable patients suffered from histologically proven CCC with regard to local control, toxicity, and patient acceptance. Materials/Methods: 34 patients (p) were enrolled. Planning procedure encompassed contrast enhanced MRI and 4 D list mode PET/CT. Planning target volume contained gross tumor volume, 2 mm set-up margin and safety margins based on 4 D list mode PET detected motion. All patients underwent SBRT with prescribed radiation dose to the 65% enclosing isodose. Normally, 3 × 12.5 Gy were delivered. Tumors close to stomach or small bowel received 7.0 Gy in 5 fractions. All patients received prophylactic antiemetic medication one hour before starting SBRT and got proton pump inhibitors for six months starting with first SBRT. Clinical history, laboratory findings, early and late toxicity scores including quality of life scores, PET/CT, and MRI were gathered before SBRT, at the 6-week follow-up visit and then at 3-month, 6-month, 9-month, 12-month, 18-month, 24-month, 30-months, and 36- months follow-ups. Results: All patients tolerated planning procedure and SBRT very well. No early or late toxicity ≥ °2 (CTCAE v.3.0) was reported. Local control is 100%. Mean overall survival is 22.3 months. Patients died on distant metastases, no patient died on local progress. Conclusions: 4 D list mode PET/CT allows valid acquisition of tumor movements for free breathing SBRT with high tumor control rate. Therefore SBRT should be rated high for patients with inoperable CCC. Further interdisciplinary protocols have to be discussed to reduce distant metastases. ID 391 Synergistic effects of Hyperthermia with Taurolidine (TRD) in malignant tumor cells – in vitro study of pancreatic and colon cancer cell lines M. Buchholz, A. Flier, A. Chromik, W. Uhl St.Josefs Hospital, Allgemein und Viszeralchirurgie, Bochum, Deutschland Interrogation: The originally anti-infective agent Taurolidine (TRD) has been shown to have anti-neoplastic properties in vitro and in vivo. In this study we investigated whether a combination of TRD with hyperthermia would have a synergistic anti-neoplastic effect in malignant human cell lines derived from pancreatic cancer (AsPC-1, BxPC-3, HPAF II and MiaPaca-2). Methods: All cancer cell lines were incubated with Taurolidine in two different concentrations 100 and 500 µmol/l). We incubated the cells at a temperature of 40,5 °C for 24h. In another experiment we incubated the cells for 2h or 4h before or after addition of TRD at 42 °C . The anti-neoplastic activity of Taurolidine in combination with hyperthermia was quantified by MTT-assay (cytotoxicity) and flowcytometric FACS-analysis with propidiumiodide and Annexin V (apoptosis induction). Results: In MTT-assay, Taurolidine in combination with hyperthermia revealed a significant higher cytotoxic effect than Taurolidine alone in BxPC-3 and HPAF II pancreatic cancer cell lines – starting with a concentration of 500 µmol/l. FACS analysis was also characterized by a significant higher necrotic response to TRD in combination with hyperthermia than TRD alone in BxPC-3 and AsPC-1 cells. However, the combination of TRD and hyperthermia did not show a significant synergistic effect in all four pancreatic cancer celllines, especially in MiaPaca-2 cells. Conclusions: It could be demonstrated for the first time, that Taurolidine in combination with hyperthermia provides a higher anti-neoplastic effect in some pancreatic cancer cell lines. Therefore our findings suggest that the combination therapy exerted synergistic anti-neoplastic effects, providing a potential new perspective for clinical tumor therapy. Abstracts ID 392 Erste Klinische Ergebnisse der IntraPeritonealen Druck-Aerosolchemotherapie (PIPAC) bei Patienten mit Magenkarzinom und fortgeschrittener Peritonealkarzinose U. Giger-Pabst1, W. Solaß1, D. Strumberg2, J. Zieren1, M. Reymond1 Ruhr-Universität Bochum, Marienhospital Herne, Klinik für Chirurgie, HERNE, Deutschland 2 Ruhr-Universität Bochum, Klinik für Onko-Hämatologie, Herne, Deutschland 1 Einleitung: Die „Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)» ist ein minimal-invasives Verfahren und verbessert die lokoregionäre Chemotherapeutika-Aufnahme. Es werden die ersten Ergebnisse der PIPAC bei Patienten mit PC und GC vorgestellt. Material und Methoden: Seit 11.2011 wurden 38 PIPAC bei 21 Pat. mit GC and PC durchgeführt (zugelassene Heilversuche). Karnofsky war 77 ± 23%. PCI war 18 ± 11. 5 Pat. hatten weitere Metastasen. 15 Pat. hatten Chemotherapie erhalten und 13 waren voroperiert. Alter lag bei 50 ± 13 J.. FU erfolgte bis 17.6.2013 oder bis zum Tod. Tumoransprechen wurde makroskopisch (PCI) und histologisch begutachtet. Ergebnisse: Operationszeit war 90 ± 19 Minuten. Es kam zu zwei Darmläsionen beim Zugang, bei 1 Pat. war kein Zugang möglich. PIPAC wurde bei 11 Pat. im 6-wöchigen Intervall wiederholt. 2 Patienten (beide ASA IV, Karnofsky 40%, refraktärer Aszites) verstarben im Krankenhaus. Eine Nebenwirkung CTCAE 2 wurde registriert (GPT Erhöhung). Von den 11 Patienten mit wiederholter PIPAC-Applikation, 3 zeigten eine komplette intraperitoneale Remission, 5 hochgradige regressive histologische Veränderungen und 3 eine stabile Krankheit. 14 Patienten leben, 7 sind gestorben (davon 4 mit weiteren Metastasen). Das aktuarielle Überleben nach 1 Jahr war 68,5% bei den Patienten mit isolierter Peritonealkarzinose, das mediane Überleben bei den Metastasenpatienten war 3,5 Monate. Schlussfolgerung: In dieser ersten, kleinen Patientengruppe haben 3/4 Pat von der PIPAC profitiert. Die Überlebensdaten sind ermutigend. PIPAC wird gut vertragen, aber nicht bei dekompensiertem Aszitis. Die Effizienz der PIPAC wird jetzt unter Studienbedingungen evaluiert (NCT01854255). ID 394 Anti-neoplastic effects of a new derivative of Taurultam (NDTRLT) in malignant tumor cells – in vitro study of pancreatic cancer cell lines M. Buchholz1, A. Flier1, S. Hahn2, R.W. Pfirrmann3, A. Chromik1, W. Uhl1 St.Josefs Hospital, Allgemein und Viszeralchirurgie, Bochum, Deutschland Ruhr Universität, Molekulare Gastroenterologische Forschung, Bochum, Deutschland 3 Weggis, Luzern, Schweiz 1 2 Interrogation: Taurolidine is a substance with anti-neoplastic activity against many tumor cells. The anti-proliferative and cell death inducing capacity of Taurolidine as been contributed to several metabolities like Taurultam (TRLT). In this study we analyzed a new derivative of Taurultam (NDTRLT) in malignant human pancreatic cancer cell lines in vitro. Additionally, synergistic anti-neoplastic effects of NDTRLT with hyperthermia were determined. Methods: All cancer cell lines were incubated with NDTRLT, a new derivate of TRLT, in increasing concentrations for 6, 12, 24 and 48 h. The anti-neoplastic activity of NDTRLT was quantified by MTT-assay, BrdU-assay and flowcytometric FACS-analysis with propidiumiodide and Annexin V. The effects of a combination therapy with hyperthermia were analyzed by MTT-assay applying 200 and 1000 µmol/l NDTRLT at different hyperthermic temperatures (40.5 and 42 °). Results: In MTT-, BrdU- and real-time cell analyzer-assays, NDTRLT revealed a significant cytotoxic and anti-proliferative effect on all pancreatic cancer cell lines starting with a concentration of 200 µmol/l and Oncol Res Treat 2014;37(suppl 1):1–133 55 Inhalt Index a maximum effect at 1500 µmol/l. FACS analysis was characterized by a significant and strong apoptotic response upon stimulation by NDTRLT. Furthermore, combination therapy of the new derivative and hyperthermia showed a synergistic effect in pancreatic cancer cell lines. Conclusions: It could be demonstrated for the first time, that NDTRLT, the new derivative of TRLT, provides anti-neoplastic effects in pancreatic cancer cell lines – operating with different mechanisms e.g. inhibition of proliferation, direct cell toxicity and induction of apoptosis. The anti-neoplastic effects of NDTRLT are significantly higher compared to TRLT alone. As a result, the new agent NDTRLT offers a promising potential for anti-tumor therapy. ID 409 Langzeitüberleben von Kardiakarzinomen im Vergleich zu distalen Magenkarzinomen – Multizentrische Ergebnisse der Deutschen Magenkarzinomstudie 2 R. Steinert1,2, I. Gastinger2, K. Ridwelski2,3, H. Ptok2,4, S. Wolff2,5, F. Meyer2,5, R. Otto2, H. Lippert2,5 St.-Josefs-Krankenhaus Salzkotten, Klinik für Allgemein- und Viszeralchirurgie, Salzkotten, Deutschland 2 An-Institut für Qualitätssicherung in der operativen MedizingGmbH an der Otto-von-Guericke-Universität, Magdeburg, Deutschland 3 Klinikum Magdeburg gGmbH, Klinik für Allgemein- und Viszeralchirurgie, Magdeburg, Deutschland 4 Carl-Thiem-Klinikum, Chirurgische Klinik, Cottbus, Deutschland 5 Universitätsklinikum Magdeburg A.ö.R., Klinik für Allgemein-, Viszeralund Gefäßchirurgie, Magdeburg, Deutschland 1 Hintergrund: Multizentrische Daten der Versorgungsforschung sollen die aktuelle Behandlungssituation von Magenkarzinomen zeigen. Adenokarzinome des ösophagogastralen Übergangs scheinen dabei eine eigene Entität darzustellen. Methode: Im Rahmen der prospektiven multizentrischen Beobachtungsstudie QCGC 2 erfolgte die Datenerhebung im Zeitraum vom 01.01.2007 bis 31.12.2009. Die proximalen Magenkarzinome wurden für die vorliegende Untersuchung separiert. Es wurde eine vergleichende Auswertung des erfassten onkologischen Langzeitergebnisses vorgenommen. Ergebnisse: In 141 Kliniken wurden 2.897 Patienten mit der Diagnose Magenkarzinom stationär aufgenommen und 2.788 (96,2%) operativ behandelt. Hinsichtlich der Tumorlokalisation fanden sich 544 Karzinome des ösophagogastralen Überganges, welche in 108 (76,6%) der 141 Kliniken operiert wurden. Die Adenokarzinome des ösophagogastralen Überganges zeigten stadienunabhängig ein signifikant kürzeres medianes Überleben (25 Monate) als die distalen Karzinome des Magens (38 Monate). Auch die 5-JÜR sind mit 33,1% für die AEG-Patienten deutlich schlechter gegenüber 41,4% für Patienten mit einem distalen Magenkarzinom. Im Vergleich der einzelnen Tumorstadien war ein signifikant schlechteres 5-Jahresüberleben (p < 0,001) schon im UICC-Stad. II (46,3% Vs. 50%) und besonders gravierend in den Stadien UICC III (0% versus 22%) und UICC IV (7,4% versus 12%) nachweisbar. Schlussfolgerung: Die flächendeckenden Ergebnisse nach Behandlung der Magenkarzinome können trotz multimodaler Verfahren nicht zufriedenstellen. Kardiakarzinome sind prognostisch signifikant schlechter. Eine Zentralisierung dieser Patienten erscheint sinnvoll. ID 443 Cytoreductive surgery for pancreatic cancer may improve overall outcome of gemcitabine-based chemotherapy. U. Pelzer1, M. Bahra2, F. Klein2, G. Puhl2, T. Denecke3, M. Sinn1, J. Stieler1, B. Dörken1, P. Neuhaus2, H. Riess1 Charité – Universitätsmedizin Berlin, Centrum für Tumormedizin, Berlin, Deutschland 2 Charité – Universitätsmedizin Berlin, Klinik für Allgemein-, Visceral- und Transplantationschirurgie, Berlin, Deutschland 3 Charité – Universitätsmedizin Berlin, Abteilung für Radiologie, Berlin, Deutschland 1 56 Oncol Res Treat 2014;37(suppl 1):1–133 Introduction: Pancreaticoduodenectomy, as well as distal and total pancreatectomy are considered as surgical standard procedures of pancreatic adenocarcinoma. Improvements in expertise lowered the mortality rates under 5%. Most patients present with an advanced stage of disease at the time of diagnosis, sometimes isochronal at time of resection. In high volume centers a more aggressive surgical approach developed to enhance the overall outcome. Methods: We identified patients with palliative surgery from our prospective documented single center data base. Definition for non curative surgery was R2,- or M1-stage. These patients were matched with regards to gender, age and pretherapeutic performance status to patients with primary gemcitabine-based chemotherapy in the same period. Patient data were analysed for postoperative morbidity/mortality, begin of palliative chemotherapy and serum markers. Postoperative morbidity was classified according to Clavien Classification. Results: 45 out of 460 resected patients meet the predefined criteria. 38/45 patients underwent pancreatic head resection, 30 patients pylorus-preserving pancreaticoduodenectomy, 8 patients classic Kausch-Whipple procedure, 7 patients underwent total pancreatectomy. Mean length of hospital stay was 23.2 days. Median survival was 10,2 months with initial cytoreductive pancreatic resection vs. 7,4 months without surgery (p = 0.009). The 1-year survival was 38%, 2-year survival was 11% in the resection cohort vs. 18% and 2% without cytoreductive resection. Conclusion: This analysis demonstrates the impact and potentials of specified surgery options of a high volume center, we may have the option of individual survival prolongation due to cytoreductive surgery cancer treatment. ID 457 Gemcitabine and the monoclonal antibody nimotuzumab versus gemcitabine and placebo for the treatment of chemotherapy-naïve patients (pts) with advanced pancreatic cancer (PC): A multicentre, randomized phase IIb/ IIIa study D. Strumberg1, B. Schultheis1, M.P. Ebert2, J. Siveke2, A. Kerkhoff3, W. Berdel3, R. Hofheinz4, D.M. Behringer5, W.E. Schmidt6, E. Goker7, S. De Dosso8, M. Kneba9, S. Yalcin10, F. Overkamp11, F. Schlegel12, M. Dommach13, R. Rohrberg14, T. Steinmetz15, D. Reuter16, F. Bach16 Marienhospital Herne, Hämatologie/ Onkologie, Herne, Deutschland Klinikum rechts der Isar TU München, München, Deutschland 3 University Hospital Münster, Münster, Deutschland 4 University Medical Centre Mannheim, Department of Hematology and Medical Oncology, Mannheim, Deutschland 5 Augusta-Kranken-Anstalt, Bochum, Deutschland 6 St. Josef Hospital, Med. Klinik I, Bochum, Deutschland 7 Ege University Medical School, Izmir, Deutschland 8 Oncology Institute of Southern Switzerland, Bellinzona, Schweiz 9 University Medical Center Schleswig-Holstein, Department of Medicine, Kiel, Deutschland 10 Hacettepe University Hospital, Ankara, Tuerkei 11 Medical Practice for Oncology and Hematology, Recklinghausen, Deutschland 12 St. Antonius Hospital, Eschweiler, Deutschland 13 Sana-Kliniken, Medizinisches Versorgungszentrum Onkologie, Düsseldorf, Deutschland 14 Gemeinschaftspraxis und Tagesklinik fuer Haematologie, Onkologie und Gastroenterologie, Halle, Deutschland 15 Group Practice Hematology/Oncology Cologne, Cologne, Deutschland 16 Oncoscience AG, Wedel, Deutschland 1 2 Background: For the majority of pts with metastatic PC, gemcitabine (gem) remains the mainstay of palliative treatment, although its modest impact on survival and disease progression. However, FOLFIRINOX significantly increases survival, but its use is limited to selected patients, due its high toxicity. This study was aimed to investigate the effect of adding nimotuzumab (nimo), an anti-EGFR monoclonal antibody, to first-line gem in PC. Abstracts Inhalt Index Patients and Methods: Pts with locally-advanced or metastatic PC were randomly assigned to receive gem: 1000 mg/m2/ 30-min iv once weekly (d1, 8, 15; q28) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or placebo, until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). Results: Between 9/2007- 10/2011 a total of 192 pts were randomised (average age 63.6 ±10 years; 60% male; 69% ECOG PS 0), and 186 were evaluable at the ITT analysis. One-year OS was 19.5% with gem+placebo and 34.4% with gem+nimo (HR=0.69; p = 0.034). Median OS and PFS were 6.0 mo in the gem+placebo group, vs. 8.7 mo in gem+nimo (HR=0.83; p = 0.21), and 3.7 vs. 5.4 mo, respectively (HR=0.73; p = 0.06). One-year PFS was 9.5% for gem+placebo, compared with 21.5% for gem+nimo (HR=0.71; p = 0.05). Significantly, in pts ≥ 62 years (60% of the population), median OS and PFS were 5.2 mo in the gem+placebo group vs. 8.8 mo in gem+nimo (HR=0.66; p = 0.034), and 3.2 in gem+placebo vs. 5.5 mo in gem+nimo group, respectively (HR=0.55; p = 0.0096). Nimo was safe and well tolerated, and no grade 3/4 toxicities were observed. Conclusion: This randomized study clearly showed that nimo in combination with gem is safe and well tolerated. The 1-year survival rate is significantly improved. Especially pts ≥ 62 years seem to benefit. Gastrointestinal Stromal Tumors ID 010 Results from a phase III trial (GRID) evaluating regorafenib (REG) in metastatic gastrointestinal stromal tumour (GIST): Subgroup analysis of outcomes based on pretreatment characteristics P. Reichardt1, H. Joensuu2, P.G. Casali3, Y.-K. Kang4, J.-Y. Blay5, P. Rutkowski6, H. Gelderblom7, P. Hohenberger8, M.G. Leahy9, M. von Mehren10, G. Badalamenti11, M.E. Blackstein12, A. Le Cesne13, P. Schoffski14, R.G. Maki15, J.-M. Xu16, T. Nishida17, C. Kappeler18, I. Kuss18, G.D. Demetri19 Helios-Klinikum Berlin-Buch, Sarkomzentrum Berlin-Brandenburg, Berlin, Deutschland 2 Helsinki University Central Hospital, Helsinki, Finland 3 Fondazione IRCCS Istituto Nazionale dei Tumori, Mailand, Italien 4 Asan Medical Center, Seoul, Korea, Republik 5 Centre Léon Bérard, Lyon, Frankreich 6 Maria Sklodkowska-Curie Memorial Cancer Center, Warschau, Polen 7 Leiden University Medical Center, Leiden, Niederlande 8 Universitätsklinikum Mannheim, Klinik für Chirurgie, Mannheim, Deutschland 9 The Christie Hospital NHS Foundation Trust, Manchester, Großbritannien 10 Fox Chase Cancer Center, Philadelphia, Vereinigte Staaten Von Amerika 11 University of Palermo, Medical Oncology Division, Palermo, Italien 12 Mount Sinai Hospital, Toronto, Kanada 13 Institut Gustave Roussy, Villejuif, Frankreich 14 KU Leuven and Leuven Hospitals, Leuven, Belgien 15 Mount Sinai School of Medicine, New York, Vereinigte Staaten Von Amerika 16 Academy of Military Medical Science, Cancer Center, Beijing, China 17 Osaka Police Hospital, Osaka, Japan 18 Bayer Healthcare, Berlin, Deutschland 19 Dana-Farber Cancer Institute, Boston, Vereinigte Staaten Von Amerika 1 Background: REG, an oral receptor kinase inhibitor with activity against KIT, PDGFR, VEGFR, FGFRs, and other oncologic targets, demonstrated significant improvement in progression-free survival (PFS) over placebo (PL) in a phase III study (GRID) of patients (pts) with advanced GIST following failure of at least imatinib (IM) and sunitinib (SU). To understand the impact of pts’ baseline characteristics on outcome, we performed an exploratory analysis of REG effects across pt subgroups based on sex, age, and mitotic index of primary GIST tissue, as well as duration and number of lines of previous therapies. Abstracts Methods: Adult pts with metastatic GIST (n = 199) progressing after at least IM and SU were randomized 2:1 to receive oral REG 160 mg or PL once daily for the first 3 weeks of each 4-week cycle. Subgroup analysis of centrally assessed PFS was performed, based on sex, age (<65, 65 years), mitotic index of primary GIST (<5, 5 to <10, 10 mits/50 hpf), duration of IM and SU treatment (<6, 6 to <18, 18 months), and number of prior anticancer treatment lines (2 or 3). Mitotic index data on primaries were available for 119 patients. Results: REG demonstrated improvement in PFS vs PL in all analysed subgroups, i.e. according to sex, age (<65/≥65 yrs), duration of prior IM and SU (<6, ≥6 to <18, ≥ 18 mos), resp. with HR well below 0.50 for REG vs PL. Conclusions: REG had substantial efficacy in all patient subgroups included in this analysis. Clinical trial information: NCT01271712. ID 011 Mutational analysis of plasma DNA from patients (pts) in the phase III GRID study of regorafenib (REG) versus placebo (PL) in tyrosine kinase inhibitor (TKI)-refractory GIST: Correlating genotype with clinical outcomes P. Reichardt1, G.D. Demetri2, M. Jeffers3, Y.-K. Kang4, J.-Y. Blay5, P. Rutkowski6, H. Gelderblom7, P. Hohenberger8, M.G. Leahy9, M. von Mehren10, H. Joensuu11, G. Badalamenti12, M.E. Blackstein13, A. Le Cesne14, P. Schoffski15, R.G. Maki16, J.-M. Xu17, T. Nishida18, I. Kuss19, P.G. Casali20 Helios-Klinikum Berlin-Buch, Sarkomzentrum Berlin-Brandenburg, Berlin, Deutschland 2 Dana-Farber Cancer Institute, Boston, Vereinigte Staaten Von Amerika 3 Bayer HealthCare Pharmaceuticals, Montville, Vereinigte Staaten Von Amerika 4 Asan Medical Center, Seoul, Korea, Republik 5 Centre Léon Bérard, Lyon, Frankreich 6 Maria Sklodkowska-Curie Memorial Cancer Center, Warschau, Polen 7 Leiden University Medical Center, Leiden, Niederlande 8 Universitätsklinikum Mannheim, Klinik für Chirurgie, Mannheim, Deutschland 9 The Christie Hospital NHS Foundation Trust, Manchester, Großbritannien 10 Fox Chase Cancer Center, Philadelphia, Vereinigte Staaten Von Amerika 11 Helsinki University Central Hospital, Helsinki, Finland 12 University of Palermo, Medical Oncology Division, Palermo, Italien 13 Mount Sinai Hospital, Toronto, Kanada 14 Institut Gustave Roussy, Villejuif, Frankreich 15 KU Leuven and Leuven Hospitals, Leuven, Belgien 16 Mount Sinai School of Medicine, New York, Vereinigte Staaten Von Amerika 17 Academy of Military Medical Science, Cancer Center, Beijing, China 18 Osaka Police Hospital, Osaka, Japan 19 Bayer Healthcare, Berlin, Deutschland 20 Fondazione IRCCS Istituto Nazionale dei Tumori, Mailand, Italien 1 Background: The phase III GRID study showed that REG provides a significant improvement in PFS compared with PL in pts with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib (IM) and sunitinib (SU; HR 0.27). Methods: DNA was isolated from both archival tumor tissue (n = 102) and plasma at baseline (n = 163) and analyzed for mutations via Sanger sequencing (tissue) or BEAMing (plasma). Results: Mutational frequencies for tumor tissue samples were: KIT, 66%; PDGFRA, 3%; KRAS, 1%; BRAF, 0%. For plasma, frequencies were: KIT, 58%; PDGFRA, 1%; KRAS, 1 out of 2 samples, BRAF, 0%. Detection of primary KIT mutations showed 84% concordance between tissue and plasma. Secondary KIT mutations were more commonly detected in plasma (47%) than in tissue (12%). Subgroup analysis based on mutational status showed an improved PFS in REG-treated pts vs PL in all subgroups by both central and local review of imaging studies. The presence of a secondary KIT mutation in plasma was associated with shorter PFS in pts receiving PL (HR 1.82, p = 0.05). Pts with a KIT-exon 9 mutation received IM for a shorter period of time, and SU for a longer period of time, relative to other GIST genotypes. Pts with a PDGFRA mutation showed variable clinical responses, while 1/1 KRAS-mutant GIST did not respond well to IM, SU, or REG. Oncol Res Treat 2014;37(suppl 1):1–133 57 Inhalt Index Conclusions: KIT mutational status correlated to IM and SU treatment duration. While consistent with prior reports using tissue sampling, this validates the utility of plasma-based circulating DNA analysis of target oncogenes. Secondary KIT mutations appear to have a negative prognostic impact in GIST, while the clinical benefit of REG vs PL was not influenced by KIT mutational status. ID 012 Health-related quality of life (HRQoL) of patients with advanced gastrointestinal stromal tumors (GIST) treated with regorafenib (REG) vs placebo (P) in the phase III GRID trial S. Bauer1, J. Chang2, P.G. Casali3, P. Reichardt4, Y.-K. Kang5, J.-Y. Blay6, Y. Wu2, D. Odom7, I. Kuss8, G.D. Demetri9 Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Essen, Deutschland 2 Bayer HealthCare Pharmaceuticals, Montville, Vereinigte Staaten Von Amerika 3 Fondazione IRCCS Istituto Nazionale dei Tumori, Mailand, Italien 4 Helios-Klinikum Berlin-Buch, Sarkomzentrum Berlin-Brandenburg, Berlin, Deutschland 5 Asan Medical Center, Seoul, Korea, Republik 6 Centre Léon Bérard, Lyon, Frankreich 7 RTI Health Solutions, Research Triangle Park, Vereinigte Staaten Von Amerika 8 Bayer Healthcare, Berlin, Deutschland 9 Dana-Farber Cancer Institute, Boston, Vereinigte Staaten Von Amerika 1 Background: The GRID trial demonstrated significant improvement in PFS for REG vs P in pts with metastatic GIST after progression on at least imatinib and sunitinib. Exploratory analyses were conducted to assess the effect of treatment on HRQoL. Methods: The HRQoL analyses were selected a priori based on clinical relevance; the global health status/QoL (QL) and the physical functioning (PF) scales of the EORTC QLQ-C30 questionnaire were used. A linear mixed-effects model was used to examine the treatment effect on HRQoL and trends over time, assuming that missing data were missing at random. Pattern-mixture models were applied to assess the treatment effect while accounting for potentially informative missing data. Time-to-deterioration (TTD) of HRQoL and responder analyses were conducted to determine the treatment effect based on timing and proportion of patients reaching a minimal important difference (MID) change in QL/PF (≥10 points). Results: The QL and PF changes over time were numerically similar between REG and P based on the linear mixed-effects model. The pattern-mixture models grouped patients based on timing of last HRQoL assessment ( P (QL: 6.5 vs 4.0; PF 8.0 vs 4.0 weeks, respectively). Median TTD was comparable between treatments after removing disease progression from the definition. The responder analyses showed that a similar proportion of patients achieved an improvement in MID in REG vs P (QL: 26.2% vs 25.4%; PF: 18.0% vs 15.3%, respectively). Conclusion: The findings of this exploratory analysis demonstrate that HRQoL is similar for REG and P groups, indicating that REG prolongs PFS vs P while maintaining at least comparable HRQoL. ID 013 Time course of adverse events in the phase III GRID study of regorafenib in patients with metastatic gastrointestinal stromal tumors (GIST) S. Bauer1, J.-Y. Blay2, P.G. Casali3, P. Reichardt4, Y.-K. Kang5, P. Rutkowski6, H. Gelderblom7, P. Hohenberger8, C. Kappeler9, I. Kuss9, G.D. Demetri10 Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Essen, Deutschland 2 Centre Léon Bérard, Lyon, Frankreich 3 Fondazione IRCCS Istituto Nazionale dei Tumori, Mailand, Italien 4 Helios-Klinikum Berlin-Buch, Sarkomzentrum Berlin-Brandenburg, Berlin, Deutschland 1 58 Oncol Res Treat 2014;37(suppl 1):1–133 Asan Medical Center, Seoul, Korea, Republik Maria Sklodkowska-Curie Memorial Cancer Center, Warschau, Polen 7 Leiden University Medical Center, Leiden, Niederlande 8 Universitätsklinikum Mannheim, Klinik für Chirurgie, Mannheim, Deutschland 9 Bayer Healthcare, Berlin, Deutschland 10 Dana-Farber Cancer Institute, Boston, Vereinigte Staaten Von Amerika 5 6 Background: Regorafenib (REG), has demonstrated significant improvement in PFS vs placebo (HR 0.27) Methods: Adults with metastatic GIST after treatment with imatinib and sunitinib were randomized 2:1 to receive oral REG 160 mg or matching P once daily for the first 3 weeks of each 4-week cycle. Treatment-emergent AEs and biochemical abnormalities were assessed at each cycle. Results: The safety population comprised 198 patients (pts): REG n = 132; P n = 66. The median treatment duration was 22.9 weeks (range: 9.3–50.9) in the REG group and 7.0 weeks (5.1–25.9) in the P group. Treatment-emergent AEs of any grade occurred in all of the REG pts and 92% of P pts, at grade 1/2 in 24% and 53%, respectively, at grade 3 in 64% and 29%, respectively, and at grade 4 in 7% and 6%, respectively. AE-related deaths occurred in seven REG and four P pts. The most frequent AEs occurring in REG pts were hypertension (59%), hand-foot skin reaction (HFSR) (57%), fatigue (50%), diarrhea (47%), and oral mucositis (41%). The incidence of all of these AEs peaked in cycle 1 and tapered to relatively stable lower incidence rates over later cycles. AEs led to dose modification in 72% of REG pts and in 26% of P recipients. The proportion of planned REG dose actually administered decreased between cycles 1 and 4 (89% of planned dose received in cycle 1 and 77% of planned dose received in cycle 4), and dose intensity was relatively stable in subsequent cycles (planned dose received remained above 72%). Conclusion: In the GRID trial, the incidence of the most common AEs in the REG group peaked early during treatment, and was manageable with dose modification so that lower levels of AEs occurred in later treatment cycles, with no evidence of cumulative toxicity. Few pts (6% REG, 8% P) required discontinuation from study due to AEs. Genitourinary Cancer including Prostate Cancer ID 036 Pain analyses from the phase 3 randomized ALSYMPCA study with radium-223 dichloride (Ra-223) in castrationresistant prostate cancer (CRPC) patients with bone metastases A.J. Schrader1, S. Nilsson2, O. Sartor3, O. Bruland4, F. Fang5, A.-K. Aksnes6, C. Parker7 Universitätsklinikum Ulm, Klinik für Urologie, Ulm, Deutschland Karolinska University Hospital, Stockholm, Schweden 3 Tulane Cancer Center, New Orleans, Vereinigte Staaten Von Amerika 4 University of Oslo, The Norwegian Radium, Hospital, Oslo, Norwegen 5 Bayer HealthCare, Montville, Vereinigte Staaten Von Amerika 6 Algeta ASA, Oslo, Norwegen 7 The Royal Marsden NHS Foundation Trust, Sutton, Großbritannien 1 2 Background: Bone metastases (mets), present in > 90% of patients (pts) with CRPC, may cause severe pain. In a phase 2 dose-response study with a single injection of Ra-223, pain response was seen in up to 71% of CRPC pts with painful bone mets (Nilsson 2012). In the phase 3 ALSYMPCA study, which included 921 CRPC pts with bone mets randomized 2:1 to receive 6 injections of Ra-223 (50 kBq/kg IV) q4wk or matching placebo (Pbo) (Ra-223, n = 614; placebo, n = 307), Ra-223 significantly improved overall survival vs Pbo (median 14.9 vs 11.3 mo; HR = 0.695) and was well tolerated. Post hoc analyses of pain parameters in ALSYMPCA are presented. Methods: A Cox model was used to analyze time to initial opioid use and time to EBRT. Pts with no opioids at baseline were included in the pain analyses and all pts in the analysis for time to EBRT. Concomitant Abstracts Inhalt Index opioids were recorded from first study drug injection to 12 weeks after last injection. Results: Baseline pain was similar between the treatment groups based on WHO pain ladder. Time to EBRT was significantly longer with Ra-223 vs Pbo (HR = 0.670; 95% CI, 0.525–0.854). Despite a longer observation time, fewer Ra-223 pts (50%) than Pbo (62%) reported bone pain as an AE. At baseline, 269 Ra-223 pts and 139 Pbo did not use opioids. Median time to initial opioid use was significantly longer in the Ra-223 group, with a risk reduction of 38%, compared to Pbo (HR = 0.621; 95% CI, 0.456–0.846). Fewer Ra-223 pts (36%) than Pbo (50%) required opioids. The QOL pain score indicated reduced pain for Ra-223 pts relative to Pbo at week 16 (P = 0.001). Ra-223 pts had significant pain reduction vs. baseline at weeks 16 (P P = 0.001). Conclusions: These results provide consistent evidence that Ra-223 reduces pain and opioid use in CRPC pts with bone mets. ID 039 Efficacy and safety of radium-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients with bone metastases who had prior or no-prior docetaxel in the phase 3 ALSYMPCA trial F. König1, N.J. Vogelzang2, S.I. Helle3, D.C. Johannessen4, J.M. O’Sullivan5, J. Garcia-Vargas6, C.G. O’Bryan Tear7, M. Shan6, C. Parker8 Outpatient clinic of Urology, Berlin, Deutschland Comprehensive Cancer Center of Nevada, Las Vegas, Vereinigte Staaten Von Amerika 3 Haukeland University Hospital, Bergen, Norwegen 4 Ulleval University Hospital, Oslo, Norwegen 5 Queens University, Centre for Cancer Research and Cell Biology, Belfast, Irland 6 Bayer HealthCare, Montville, Vereinigte Staaten Von Amerika 7 Algeta ASA, Oslo, Deutschland 8 The Royal Marsden NHS Foundation Trust and Institute of Cancer, Sutton, Großbritannien 1 2 Background: Ra-223, a first-in-class α-emitter, significantly improved median overall survival (OS) at the interim analysis and confirmed at the updated analysis by 3.6 mo vs placebo (Pbo) in CRPC patients (pts) with bone metastases (mets) receiving best standard of care (BSoC) in the ALSYMPCA study (HR = 0.695; 95% CI, 0.581–0.832; P = 0.00007), and had a highly favorable safety profile in the updated ALSYMPCA analysis (Parker et al. ASCO 2012). This predefined subgroup analysis assessed efficacy and safety of Ra-223 in pts who had prior (pD) or no-prior (npD) Docetaxel (D). Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets; had no known visceral mets; were receiving BSoC; and had received pD, or were unfit for or declined D (npD). Pts were randomized 2:1 to 6 injections of Ra-223 (50 kBq/kg IV) q4wk or matching Pbo and stratified by prior D use, baseline alkaline phosphatase level, and current bisphosphonate use. Survival data were compared using a log-rank test. Results: 395/921 (43%) randomized pts had npD (Ra-223, n = 262; Pbo, n = 133); 526/921 (57%) received pD (Ra-223, n = 352; Pbo, n = 174). Median ages were 74 y (npD) and 69 y (pD). In pts with npD, median OS was 16.1 mo in the Ra-223 group vs 11.5 mo in the Pbo group (HR = 0.745; 95% CI, 0.562–0.987; P = 0.039). In pts with pD, median OS was 14.4 mo vs 11.3 mo in the Ra-223 and Pbo groups, respectively (HR = 0.710; 95% CI, 0.565–0.891; P = 0.003). Overall, there was a low incidence of myelosuppression. Incidences of neutropenia and thrombocytopenia were higher in pts with pD vs pts with npD. Conclusions: Ra-223 significantly prolonged OS and had a highly favorable safety profile in CRPC pts with bone mets, regardless of whether they had pD or npD. pD pts had a slightly increased rate of grade 3 and 4 bone marrow suppression with Ra-223. Abstracts ID 047 Hematologic safety of Ra-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients with bone metastases from the phase 3 ALSYMPCA trial A. Strauss1, C. Parker2, J. Garcia-Vargas3, C.G. O‘Bryan-Tear4, F. Fang3, N.J. Vogelzang5 University Hospital Göttingen, Göttingen, Deutschland The Royal Marden NHS Foundation Trust, Sutton, Großbritannien 3 Bayer HealthCare, Montville, Vereinigte Staaten Von Amerika 4 Algeta ASA, Oslo, Norwegen 5 Comprehensive Cancer Center of Nevada, Las Vegas, Vereinigte Staaten Von Amerika 1 2 Background: Updated ALSYMPCA analysis: Ra-223 signif. improved OS by 3.6 mo vs placebo (Pbo) in 921 CRPC pts with BM (HR=0.695; 95% CI, 0.581-0.832; P=0.00007) and had a highly favorable safety profile. The hematologic safety profile and results from a post hoc analysis assessing prognostic factors for changes in hematologic parameters are presented. Methods: Pts were randomized 2:1 to 6 injections of Ra-223 (50 kBq/ kg IV) q4wk or matching Pbo and stratified by prior docetaxel (D) use, total alkaline phosphatase (tALP), and current bisphosphonate use. Multivariate regression analysis was performed to explore the relationshipof 6 baseline factors with maximum % change of hematologic parameters from baseline up to 24 wk on treatment (tx). Results: The updated analysis included 901 pts (safety population; Ra223, n = 600; Pbo, n = 301). Overall grade 3/4 AEs were similar between Ra-223 and Pbo groups (neutropenia: 2% vs 1%; thrombocytopenia: 6% vs 2%; anemia: 13% vs 13%). Tx with Ra-223 + prior D use extent of disease >6 BM, tALP ≥220 U/L, but not current bisphosphonate use, were associated with decreases from baseline in hemoglobin (Hb), neutrophils, or platelets; prior EBRT to bone for pain was associated with an increase. Conclusions: Overall, there was a low risk for hematologic AEs with Ra-223 tx in CRPC pts with BM. The strongest prognostic factors for decreases in neutrophils and platelets were Ra-223 tx + prior D use. Baseline tALP was a strong predictor of decrease in Hb. ID 057 Updated survivl, Qulity of life (QOL), and safety Dta of Radium-223 Chloride (Ra-223) in patients with Castrationresistant Prostate Cancer (CRPC) with Bone Metastases from the phase 3 double-blind, randomized, multinational study (ALSYMPCA) T. Steuber1, C. Parker2, R.E. Coleman3, S. Nilsson4, N. Volgelzang5, A.J. Lloyd6, K. Staudacher7, R. van Gool8, A.O. Sartor9 Martini-Klinik am UKE GmbH, Hamburg, Deutschland The Royal Marden NHS Foundation Trust, Academic Urology, Sutton, Großbritannien 3 Weston Park Hospital, Academic Unit of Clinical Oncology, Sheffield, Großbritannien 4 Karolinska University Hospital, Radiumhemmet, Stockholm, Schweden 5 Comprehensive Cancer Center of Nevada, Las Vegas, Vereinigte Staaten Von Amerika 6 Oxford Outcomes, Patient Reported Outcomes, Oxford, Großbritannien 7 Algeta ASA, Oslo, Norwegen 8 Bayer HealthCare, Montville, Deutschland 9 Tulane Cancer Center, Department of Medicine and Urology, New Orleans, Vereinigte Staaten Von Amerika 1 2 Introduction: Ra-223 is a first-in-class alpha-emitter pharmaceutical that targets bone metastases with high-energy, very short range (<100 μm) alpha-particles. In the interim analysis (IA) of ALSYMPCA, which compared Ra-223 and placebo (Pbo) in CRPC patients (pts) with bone metastases receiving best standard of care, Ra-223 improved overall survival (OS), with a 30.5% reduction in risk of death (HR.695). Updated survival, QOL, and safety data are reported. Oncol Res Treat 2014;37(suppl 1):1–133 59 Inhalt Index Methods: Eligible pts previously received or refused docetaxel, or were docetaxel ineligible, and were randomized 2:1 to receive Ra-223 (50 kBq/ kg IV) or Pbo every 4 weeks x 6. After the IA, an updated analysis of all enrolled pts prior to crossover assessed effects of Ra-223 on the primary (OS, using a stratified log-rank test) and secondary (eg, skeletal-related events [SREs], QOL, and safety) endpoints. QOL was assessed with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EuroQoL (EQ-5D) instruments. Results: The updated analysis data for 921 pts (Ra-223, n = 614; Pbo, n = 307) will be presented. Median OS benefit for Ra-223 was 3.6 mos (HR 0.695). Time to first SRE was 6 mos longer with Ra-223. At week 16, Ra-223 pts reported significantly greater well-being (physical, emotional, functional, prostate cancer score, and total score) (FACT-P) and significantly better QOL (EQ-5D) compared to Pbo pts. The incidence of myelosuppression with Ra-223 was low: 2.2% grade 3/4 neutropenia; 6.3% grade 3/4 thrombocytopenia. Conclusions: The ALSYMPCA updated analysis substantiates that Ra223 is an effective therapy that significantly improves OS and time to first SRE, with a highly favorable safety profile, in CRPC pts with bone mets. Ra-223 showed significantly better preservation of QOL, with improved functioning and well-being, compared to Pbo. ID 064 Safety of cytotoxic chemotherapy following Radium-223 Chloride (Ra-223) therapy in the phase 3 alsympca study in patients with Castration-resistant Prostate Cancer (CRPC) with Bone Metastases P. Strölin1, O. Sartor2, R.E. Coleman3, S. Nilsson4, N. Vogelzang5, A. Cross6, C.G. O’Bryan Tear7, K. Staudacher8, J.E. Garcia Vargas8, J. Zou8, C. Parker9 Martini-Klinik am UKE GmbH, Hamburg, Deutschland Tulane Cancer Center, Department of Medicine: Section of Hematology & Medical Oncology and Department of Urology, New Orleans, Vereinigte Staaten Von Amerika 3 Weston Park Hospital, Academic Unit of Clinical Oncology, Sheffield, Großbritannien 4 Karolinska University Hospital, Radiumhemmet, Stockholm, Schweden 5 Comprehensive Cancer Center Nevada, Developmental Therapeutics, Las Vegas, Vereinigte Staaten Von Amerika 6 PharmaNet, Biostatistics, Hemel Hempstead, Vereinigte Staaten Von Amerika 7 Algeta ASA, Oslo, Norwegen 8 Bayer HealthCare Pharmaceuticals, Montville, Kanada 9 The Royal Marsden NHS Foundation Trust, Academic Urology, Sutton, Großbritannien 1 2 Introduction: Ra-223 is a first-in-class alpha-emitter pharmaceutical that targets bone metastases with high-energy, extremely short range (<100 μm) alpha-particles. ALSYMPCA compared efficacy and safety of Ra223 vs placebo (Pbo) in CRPC patients ( pts) with bone metastases receiving best standard of care. In the updated analysis of all 921 randomized pts (Ra-223, 614; Pbo, 307) prior to Pbo crossover, the median overall survival (OS) benefit for Ra-223 was 3.6 months (hazard ratio 0.695) and the incidence of myelosuppression was low. The use of cytotoxic chemotherapy (Chemo) after completion of study treatment was evaluated. Methods: The cohort for this analysis consisted of all pts who received Chemo after completion of Ra-223 or Pbo. Chemo agents were identified, and length of time from last injection of study drug to start of Chemo and its duration calculated. Available hematology data were reviewed, and post hoc analysis of survival conducted. Results: The proportion of pts receiving subsequent Chemo was 90/614 (15%) in the Ra-223 group and 54/307 (18%) in the Pbo group. Docetaxel (n = 102), mitoxantrone (n = 23), and cyclophosphamide (n = 19) were the most commonly used. Duration of Chemo and available docetaxel dosage data were similar in both groups. Median time to Chemo was 2 weeks longer following Ra-223. Median OS from start of Chemo was 15.6 mos and 14.6 mos in the Ra-223 and Pbo groups, respectively 60 Oncol Res Treat 2014;37(suppl 1):1–133 (P = .6930). Number of deaths and causality during and 30 days post Chemo andlimited available hematologic data were similar in both groups. Conclusions: Patients were able to receive Chemo following Ra-223 and have a similar safety profile and outcome as for Chemo following Pbo. No toxic deaths occurred. Prospective studies to evaluate Chemo following Ra-223 are warranted. ID 065 Erectile dysfunction one year after a (first) hospitalization for prostate cancer – results of a survey of health insurance beneficiaries E.M. Bitzer, S. Neusser, C. Lorenz, T. Grobe Pädagogische Hochschule Freiburg, Public Health & Health Education, Freiburg, Deutschland Background: Due to demographic changes hospitalizations associated with prostate cancer increased from 1994 to 2010 by 40%. The therapeutic options may cause harm. Little is known on the frequency of erectile dysfunction (ED) and factors associated with the occurrence in routine health care . Methods: We conducted a survey on 1.165 beneficiaries (up to 75 years of age) hospitalized for prostate cancer (ICD C61) in 2010 without prior hospitalizations for ICD C61 in the years 2005 to 2009. ED was assessed with the German version of the EORTC Prostate Specific Module (PSM). Patient reports were obtained one year after discharge and linked with insurance hospital claims data . The ED-scale ranges from 0 to 100 with larger values representing higher impairment. We estimated the probability of reporting maximal ED impairment via multiple logistic regression. Result: Questionnaires of 825 men (mean age 67.6 yrs., 80% treated with radical prostatectomy) were available for analyses (response 70.8%). The mean score of the EORTC-PSM-Subscale ED was 89.9. Compared to men aged 71–75 yrs the odds for ED are reduced in men 40–60 years (OR 0.35, 95%-CI 0.2–0.64) and 61 to 65 years of age (OR 0.53 95%CI 0.40–10.89). Further ED-protective factors are nerve-sparing surgical technique (OR 0.30 95%-CI 0.20–0.47), no-operation (OR 0.26 95%-CI 0.14–0.48), and Brachytherapy (OR 0.25 95%-CI 0.11–0.57). Co-morbidity, self reported post-operative complications, radiation, and hormonal treatment increased the likelihood of ED. The C-value of the model was 0,75. Conclusion: ED is a common sequelae of surgical and non-surgical treatment approaches in routine health care. ID 106 Comparing epidemiological data from the United States and Germany reveals different treatment habits for lowrisk prostate cancer J. Huber1, B. Hager1, B. Keck2, M. Fröhner1, M. Wirth1, K. Kraywinkel3 Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Urologie, Dresden, Deutschland 2 Universitätsklinikum Erlangen, Klinik für Urologie, Erlangen, Deutschland 3 Robert Koch-Institut, Zentrum für Krebsregisterdaten, Berlin, Deutschland 1 Introduction: For low-risk prostate cancer recent guideline updates considerably strengthened defensive treatment strategies. Aim of the study was to analyze changes in primary treatment over time and across different healthcare systems. Methods: We compared ‘Surveillance Epidemiology and End Results’ data (USA) with reports from four German federal epidemiological cancer registries (Eastern Germany, Bavaria, Rhineland-Palatinate, Schleswig-Holstein), both from 2004 to 2010. We excluded metastatic disease and patients older than 79 years. Thereof, we identified 88,829 (USA) and 27,003 (Germany) patients with low-risk according to the 2013 EAU guidelines. Results: Referred to all age groups the use of defensive treatment strategies including hormonal therapy has increased from 23.7% to 37.9% Abstracts Inhalt Index in the USA and from 26.5% to 30.2% in Germany from 2004 to 2010. In Germany this proportion was fairly stable until 2009 and increased in 2010. In contrast, there was a continuous increase in the USA. Treatment habits for active therapy are rather stable over time in each country, but they differ largely across healthcare systems. Exemplary, in 2010 radical prostatectomy was applied more frequently in Germany (46.4% vs. 17.9%) and radiotherapy was dominant in the USA (43.4% vs. 20.4%). Conclusion: For low-risk disease defensive treatment strategies are becoming more frequently applied. This trend is more continuous in the USA. Partly habits for active treatment appear system dependent, because the observed differences are not sufficiently explicable by diverging adoption of scientific evidence or varying patient preferences. ID 122 Is a fatal family history of prostate cancer a prognostic factor for survival? K. Herkommer1, E. Donel1, J. Gschwend1, M. Kron2 Klinikum rechts der Isar der TU München, Urologische Klinik und Poliklinik, München, Deutschland 2 Universität Ulm, Institut für Biometrie und Medizinische Statistik, Ulm, Deutschland 1 zu rü ck ge zo ge n Purpose: InGermany 20% of all prostate cancer patients have a positive family history. These patients often worry about having a worse outcome or having a higher risk of dying of prostate cancer. The aim of this study was to determine the impact of a fatal family history (FH) on survival of prostate cancer patients after radical prostatectomy inGermany. Material and Methods: 2883 patients after radical prostatectomy with at least one first-degree relative with pc of the nationwide database familial pc inGermany were stratified according to family history (fatal vs. nonfatal). Fatal FH was defined as patients who had at least one first-degree relative and/or one second-degree relative who died of pc. Biochemical progression free survival (BPFS), overall survival (OS) and cancer specific survival (CSS) for each epidemiological feature were analyzed according to the method of Kaplan and Meier and subgroups were compared in a proportional hazard regression calculating hazard ratio (HR) and p-value. Results: In the subgroup with fatal pc we observed less organ confined tumors (60.6% vs. 67.1%), higher rates of male to male transmission (66.9% vs. 54.4%), more hereditary patients (53.2% vs. 18.6%), more patients with more than 2 affected relatives (67.3% vs. 25.9%) and an earlier age of onset (median age of diagnosis 62.5 yr vs. 63.6 yr). Survival was comparable in the fatal subgroup and the nonfatal subgroup: BPFS HR=0.96 (p = 0.695), OS HR=1.13 (p = 0.506), CSS HR=0.92 (p = 0.788). Conclusion: Survival was not remarkably different in familial patients with fatal family history compared to those with non-fatal FH. Now we can calm down our patients after radical prostatectomy because our findings suggest that a fatal family history is not associated with worse clinical outcome or poorer survival. ID 134 Changes in prognostic and therapeutic parameters in prostate cancer from an epidemiological view over 20 years M. Dörr, A. Schlesinger-Raab, G. Schubert-Fritschle, J. Engel Tumorregister München (TRM), München, Deutschland Objective: The aim of this analysis was to examine changes in prognosis and treatment of prostate cancer patients over the last 20 years, and to evaluate their impact on survival. Patients and Methods: 36,008 prostate cancer patients diagnosed between 1990 and 2010 and living in the catchment area of the Munich Cancer Registry (Upper Bavaria and in part Lower Bavaria, population 4.6 million) were analysed. Results: Pretherapeutic PSA testing increased dramatically in the early 1990’s. A shift from capsule exceeding tumours to capsule limited tu- Abstracts mours also took place especially in the 1990s. In the early 1990s nearly 10% of the diagnosed tumours were stage T4, approximately 35% T3, 23% T2, and circa 13% T1. By 2010 only about 3% of the diagnosed tumours were stage T4, 15% T3, 40% T2 and 23% T1. Concurrently, initial therapeutic strategies changed noticeably over the last 20 years. Radical prostatectomy increased continuously, from 20% to almost 50% of all initial treatments. Hormone therapy developed oppositely, with initial hormone therapy as the most selected treatment until 1994 and then continuously decreased from 55% in 1990 to 18% in 2010. Radiation therapy and transurethral resection of the prostate slightly increased from about 5 to 10%. Over the observed time period, 5- and 10-year relative survival improved from 92 to 97% and from 86 to 92%, respectively. Conclusion: We interpret the small rise in prostate cancer survival rates over the last 20 years, along with the dramatic reversal in tumour staging toward more prognostically favourable T-categories, and noticeable changes in initial therapy strategies as a consequence of overdiagnosis due to the introduction of PSA tests as well as a result of more initial radical prostatectomies. ID 142 Management of low risk Prostate Cancer, Preliminary Results of HAROW L. Weißbach1, D. Schnell1, B. Häussler2 1 2 Stiftung Männergesundheit, Berlin, Deutschland IGES, Berlin, Deutschland Five treatment options were offered to men with low risk carcinoma of the prostate (T ≤2, PSA ≤10 ng/ml, Gleason 6, positive cores ≤2, PSA-density <0,2 ng/ml 2): Hormonal treatment, Active Surveillance (AS), Radiotherapy (RT), Operation (RP), and Watchful Waiting (WW). The AS arm is of special interest. The study aims at evaluation of therapeutic strategies regarding tumor biology and feasibility of AS. Methods: From 07-2008 to 07-2013, 3.185 men were entered in a 5-arm prospective non-randomized trial. AS was carried out by 249 urologists in private practice. Surveillance included quarterly PSA, digital rectal examination (DRE) and yearly rebiopsy. If increasing growth at DRE, fast rising PSA, increasing tumor volume and aggressiveness indicated progression, AS was abandoned and conventional therapy initiated. QL and patients’ assessment of medical performance were investigated by questionnaire. Results: 53% of men chose RP, 12% RT, 7% hormonal treatment, 4% WW, 13% other. 467/3185 (15%) men favored AS. 72/467 AS patients required therapeutic intervention: 42 had progression, 30 other various reasons. Preliminary results: to date, none of the AS patients (median follow up 2 years) died of PCA, 3 men died of other causes; none has systemic progression. So far 98.7% survive. QL and assessment of doctors’ performance was good. Conclusions: Patients’ AS acceptance was higher than expected (15% vs. 8-10% in international comparison). Attendant urologists adapted quickly to, and showed increasing acceptance of AS. Feasibility of AS was rated high by doctors and patients. Sponsored by GAZPROM Germania. ID 159 Efficacy of a specialized rehabilitation program on physical strength and mental power after radical prostatectomy D.-H. Zermann, M. Heydenreich Vogtland-Klinik Bad Elster, Urologie/ Onkologie/ Nephrologie, Bad Elster, Deutschland Introduction: Specialized rehabilitation programs allow an early social and occupational reintegration of patients after prostate cancer surgery. Aim of this prospective study was an evaluation of the efficacy of a complex training program on functional, physical and mental parameters. Oncol Res Treat 2014;37(suppl 1):1–133 61 Inhalt Index Methods: 60 patients after prostate surgery were evaluated. All patients completed a 3-week-rehabilitation program including an 1-hour-pad-test, a 6-minutes-walk-test and evaluation of quality of life (FACT-G, FACT-P, FACIT-Fatigue). Results: The following results (pre-post-comparison) were obtained: –– significant reduction of urinary incontinence (38.2 g to 23 g/1-hour pad test) –– significant increase of 6-minute walk distance – Ø 57.15 m –– significant improvement of quality of life (FACT-G: 83.2 to 87.5; –– FACT-P: 31.05 to 33.25; FACIT-Fatigue von 41.7 to 43.9 points). Conclusion: A specialized rehabilitation program after prostate cancer surgery allows a significant improvement of functional deficits, physical and mental health. Therefore a rehabilitation program should be offered to all prostate cancer patients. ID 200 Leupaxin acts on cell adhesion and cytoskeletal remodeling and influences integrin expression in prostate cancer cells S. Dierks, S. von Hardenberg, L. Hartmund, P. Burfeind, S. Kaulfuß Institut für Humangenetik, Tumorgenetik, Göttingen, Deutschland Prostate cancer still is the most common cancer type and third leading cause of cancer-related deaths in Germany. Recently, we could identify the focal adhesion protein leupaxin (LPXN) to be overexpressed in approximately 20% of prostate carcinomas (PCa) and that this overexpression leads to the progression of PCa. Knockdown of LPXN in PC-3 and DU-145 cells resulted in reduced adhesion, migration and invasion. To identify candidate proteins that could mediate the LPXN-induced cytoskeletal changes necessary for adhesion and migration, we performed a Yeast-two-Hybrid screen and identified the actin stabilizing protein Caldesmon (CaD) as a putative interaction partner of LPXN. Using proximity ligation assays (PLA) we could show that during migration of PCa cells LPXN interacts with CaD and more interestingly with its phosphorylated form which detaches from actin leading to highly dynamic cytoskeletal structures. Further investigations involving PLA and inhibitor experiments revealed the extracellular signal-regulated kinase (ERK) to be responsible for CaD phosphorylation. Here we report a possible mechanism for cytoskeletal rearrangement during migration and invasion of PCa cells involving LPXN as an adapter molecule that regulates CaD-phosphorylation through ERK. In addition to cytoskeletal rearrangements, we observed changes in integrin expression and increased radio-sensitivity of PCa cells after LPXN knockdown. These findings could be linked to the alterations in adhesion and the response to radiotherapy of PCa cells. ID 264 Functional outcomes and their impact on long-term quality of life after open retropubic radical prostectomy B. Löppenberg, C. von Bodman, M. Brock, F. Roghmann, J. Palisaar, J. Noldus Results: Between 2003 and 2008, 2373 patients had RP with nerve-sparing (NS) in 56.5% (n = 1341). Return-rate of the questionnaires was 58.3% (n = 1383), representing the study cohort. Median follow-up (FU) was 61 months. Mean age at surgery and FU was 63.6±6.4 and 69.2±6.3 years, respectively. Biochemical recurrence (BCR) occurred in 16.7% (n = 231) of the patients and 2.2% (n = 51) died. The mean GHS was 71.3±20.7. In the ICIQ 28% (n = 386) scored 0 indicating continence and 10.2% (n = 141) scored ≥11 indicating severe incontinence, the GHS was 78±19.3 and 54.9±21.4, respectively. No pads were used by 69.1% (n = 955) patients and 17.9% (n = 247) used ≥2 pads, the GHS was 74.7±19.9 and 58.5±20.4. Of patients with NS 23.3% (n = 189) and 39.8% (n = 322) had no erectile dysfunction according to IIEF-5 and EHS, GHS was 81.6±17.1 and 78.8±16.9, respectively. Patients with BCR had a GHS of 66.8±21.8 as compared to 72.3±20.4 without. Conclusions: The long-term HQL after RP for PCA is diminished severely by incontinence and to a lesser effect by erectile dysfunction and BCR. ID 281 Presence of high-risk human papillomavirus DNA is associated with nuclear expression of p16INK4a, noninvasive growth pattern and favourable cancerspecific survival in penile squamous cell carcinoma J. Steinestel1, A. Al Ghazal1, M. Schrader1, A. J. Schrader1, P. Möller2, K. Steinestel2,3 Universität Ulm, Abt. Urologie, Ulm, Deutschland Universität Ulm, Institut für Pathologie, Ulm, Deutschland 3 Institut für Radiobiologie, München, Deutschland 1 2 Up to 50% of penile squamous cell carcinomas (pSCC) develop against the background of high-risk human papillomavirus (HR-HPV) infection. Whether HPV-triggered carcinogenesis in pSCC has an impact on tumour aggressiveness or cancer-specific survival, however, is still subject to research. In 60 tissue specimens from 58 patients with surgically treated pSCC, we performed p16INK4a immunohistochemistry and DNA extraction followed by HPV subtyping using a PCR-based approach. We found that 88% of tumours showed a keratinizing growth pattern; HR-HPV DNA was detected in 29%, while p16INK4a staining was observed in 59% of samples. Overall sensitivity and specificity of p16INK4a to predict presence of HR-HPV DNA was 100% and 59%, respectively; taking into account only intense nuclear p16INK4a staining improved specificity to 80%. Both approaches correlated significantly with presence of HR-HPV DNA in the samples (p < 0.001). Expression of p16INK4a or presence of HR-HPV DNA was inversely associated with pSCC tumour invasion (p = 0.004 and p = 0.016), but did not correlate with nodal involvement or distant metastasis. Presence of HR-HPV but not histologic grade or p16INK4a positivity predicted slightly better cancer-specific survival (p = 0.118 vs. p = 0.283 and 0.493, respectively). Our results confirm intense nuclear staining for p16INK4a, rather than a certain growth pattern, to be a good predictor for presence of high-risk HPV DNA in pSCC. Furthermore, we show for the first time that HPV-triggered pSCCs seem to be associated with less aggressive local behavior, and that presence of HR-HPV DNA is a better predictor of cancer-specific survival compared to histologic differentiation and p16INK4a positivity. Ruhr Universität, Urologische Klinik, Bochum, Deutschland Background: Patients who underwent radical prostatectomy (RP) for prostate-cancer (PCA) have excellent long-term survival. Functional results are important, as adverse outcomes may have a detrimental effect on health-related quality of life (HQL). We report long-term functional outcomes and their influence on HQL after RP. Methods: Men treated with RP for PCA at an academic center received a set of questionnaires (International consultation on incontinence questionnaire (ICIQ), International index of erectile function (IIEF-5), Erection hardness score (EHS)), to assess functional outcomes five years after RP. The results were correlated with the global-health score (GHS) of the EORTC QLQ-C30 to assess the impact on HQL. 62 Oncol Res Treat 2014;37(suppl 1):1–133 ID 284 Oncological outcome and complications after radical nephrectomy in patients with renal cell carcinoma and tumor thrombus of the inferior vena cava C. Piper, D. Pfister, A. Thissen, D. Porres, A. Heidenreich, C. Piper RWTH Uniklinik Aachen, Klinik für Urologie, Aachen, Deutschland Introduction: Radical nephrectomy represents the only curative treatment approach in patients with RCC and TT-IVC. It was the aim of our retrospective analysis to analyse (1) the oncological results, (2) periop- Abstracts Inhalt Index erative morbidity and (3) role of adjuvant therapy following RN in these patients. Patients and Methods: 205 patients with RCC and TT-IVC were identified in a data bank. The mean age was 65 (42–76) years. 58 (28.3%) patients had a level I thrombus, 79 (38.5%), 47 (22.9%), and 21 (10.2%) patients exhbited a level II, III & IV thrombi. 170 (82.9%) patients were without evidence of metastases at time of RN (group 1), 21 (10.2%) had retroperitoneal (group 2), and 14 (6.8%) visceral metastases (group 3) and were treated with MTKI postoperatively. ECOG Performance Status was 0-1 in all patients. Progression-free (PFS), overall (OS) and cancer specific (CSS) survival was analysed. Postoperative complications were classified according to the Clavien classification. Results: Perioperative complications developed in 21%: 13.2% Clavien Grad I-III and 7.3% Grad IV complications, perioperative mortality was 0%. Relapses developed in 62 (30.2%) patients independend on the thrombus level. The mean PFS was 45.8, 12.4, and 0.4 months in groups 1, 2, and 3 (p = 0.0004), resp. The mean CSS was 74.1, 35.5, and 21.7 months in groups 1, 2 and 3 (p = 0.0014), resp.. Postoperative MTKI were without evidence on PFS and CSS. 5-year CSS was 56%, 25% and 15% in groups 1, 2, and 3. (p = 0.003), resp. Summary: RN with thrombectomy results in good long-term survival if patients do not exhibit systemic metastases. Complete resection of locoregional lymph node metastases and/or visceral metastases results in a long-term survival of only 20%. Adjuvant MTKI do not seem to have a positive effect on long-term outcome. ID 286 Management of growing teratoma syndrome (GTS): Aachen university experience A. Thissen, D. Pfister, C. Piper, D. Porres, A. Heidenreich RWTH Uniklinik Aachen, Klinik für Urologie, Aachen, Deutschland Background: GTS is rare constituting only about 2% of all testis cancer patients. GTS is defined as an enlarging metastatic mass during systemic chemotherapy for advanced nonseminomatous germ cell tumours (NSGCT) despite decreasing serum tumor markers. Complete surgical resection is mandatory to achieve a favourable outcome. We report on our single center experience in the management of GTS. Methods: Postchemotherapeutic retroperitoneal lymph node dissection (PCRPLND) was performed in 162 pts. with advanced NSGCT. 14 pts. (4.9%) fulfilled the criteria of a GTS: enlarging metastatic mass in the retroperitoneum or visceral organs during systemic chemotherapy with normalized or regredient tumour markers. In all cases complete radical bilateral PCRPLND including the resection of adjacent visceral and vascular structures was performed. Results: Median patient age was 24.5 (18–52) years. All patients exhibited NSGCT with a good or intermediate prognosis according to IGCCCG; 10 and 4 patients presented with clinical stage IIC and III, resp. Median tumour diameter at time of surgery was 6.5 (3.0–35) cm. Tumour markers were normalized in 12/14 patients and plateauted in 2/14 patients. Tumour masses were localized in the retroperitoneum in 12 pts.; 2 patients had additional pulmonary metastases. Median time from chemotherapy to surgery was 4.8 (1.5–26.5) months 4 pts. required resection of the inferior vena cava or abdominal aorta; adjunctive nephrectomy was performed in 3 pts. After a median follow-up of 4.2 years 2 pts. developed recurrent disease; the remainder are alive without evidence of disease. Conclusions: GTS is a rare phenomenom among pts. with advanced NSGCT and necessitates complete surgical resection of all masses with curative intention. Due to the complex surgery, treatment should be performed at specialized centres. Abstracts ID 311 National Second-Opinion Project of the German Testicular Cancer Group (GCTSG): Improving Quality of Care for Testicular Cancer Patients F. Zengerling1, M. Hartmann2, A. Heidenreich3, S. Krege4, P. Albers5, A. Karl6, J. Bedke7, W. Wagner8, M. Retz9, L. Weißbach10, S. Kliesch11, K.-P. Dieckmann12, H.U. Schmelz13, M. Kuczyk14, E. Winter15, T. Pottek16, A.J. Schrader1, M. Schrader1 Universitätsklinikum Ulm, Klinik für Urologie, Ulm, Deutschland Universitätsklinikum Hamburg-Eppendorf, Klinik für Urologie, Hamburg, Deutschland 3 RWTH Aachen, Klinik für Urologie, Aachen, Deutschland 4 Alexianer Krefeld, Klinik für Urologie, Krefeld, Deutschland 5 Universitätsklinikum Düsseldorf, Klinik für Urologie, Düsseldorf, Deutschland 6 Universität München, Klinik für Urologie, München, Deutschland 7 Universitätsklinikum Tübingen, Klinik für Urologie, Tübingen, Deutschland 8 Bundeswehrkrankenhaus Hamburg, Klinik für Urologie, Hamburg, Deutschland 9 Klinikum Rechts der Isar, Technische Universität München, Klinik für Urologie, München, Deutschland 10 Stiftung Männergesundheit, Berlin, Deutschland 11 Universität Münster, Zentrum für Reproduktionsmedizin und Andrologie – Klinische Andrologie, Münster, Deutschland 12 Albertinenkrankenhaus, Klinik für Urologie, Hamburg, Deutschland 13 Bundeswehrkrankenhaus Koblenz, Klinik für Urologie, Koblenz, Deutschland 14 Medizinische Hochschule Hannover, Klinik für Urologie, Hannover, Deutschland 15 HELIOS Klinik Schwerin, Klinik für Urologie, Schwerin, Deutschland 16 Asklepios Westklinikum, Klinik für Urologie, Hamburg, Deutschland 1 2 Background: The treatment of testicular germ cell tumors is subject to constant change. In order to meet this challenge, numerous national and international guidelines have been published since the 1990s. Since 2006, the National Second-Opinion Project of the German Testicular Cancer Group (GCTSG) aims to improve the implementation of guidelines as well as the quality of care for testicular cancer patients. Methods: Before determining their therapy, participating urologists could communicate with the second-opinion center (SOC), which is formed by more than 30 urologists from the German-speaking area. Via an internet based platform therapy-relevant data were sent to the SOC by the participating urologists, allowing the SOC to give an individual treatment recommendation. Primary end points of the study were congruence between first and second opinion, treatment changes based on the second opinion, and relapse-free 2-year survival. Results: A previous analysis in 2011, which included 927 cases, showed a high rate of discrepant first and second opinions of about 40%, which significantly increased in advanced tumor stages (clinical stage ≥IIa: 52.3% vs. Conclusion: Guidelines for the treatment of germ cell tumors are inadequately implemented, particularly in advanced tumor stages. Every fifth second opinion implied a relevant change in the scope of therapy. SOCs are a viable tool for the improvement of cancer care in Germany. ID 313 Surgical Management of Testicular Cancer Patients with Complex Postchemotherapy Residual Masses: Aachen University Experience A. Heidenreich, A. Thissen, C. Piper, D. Porres, D. Pfister RWTH Uniklinik Aachen, Klinik für Urologie, Aachen, Deutschland Background: Postchemotherapy retroperitoneal lymphadenectomy (PCRPLND) represents the treatment of choice in patients with residual masses following systemic chemotherapy for advanced testicular nonseminomas (NS). Involvement of major retroperitoneal vessels or thoracic/lumbar spine is rare and challenging but needs complete resection for curative intent. We report on our single centre experience in the management of such complex cases. Oncol Res Treat 2014;37(suppl 1):1–133 63 Inhalt Index Patients and Methods: PCRPLND was performed in 162 pts. with advanced NS and normalized/plateauing tumour markers. A total of 13 patients required adjunctive skeletal and vascular surgery to the lumbar spine and the aorta/inferior vena cava in conjunction with a full bilateral radical PC-RPLND Results: Median patient age was 24.5 (18–52) years. All patients were of intermediate or poor prognosis according to IGCCCG. Median tumour diameter at time of surgery was 18.6 (9.0–35) cm. In 5 patients 1-2 metastatic lumbar vertebral bodies were completely resected, stabilized and replaced. In 6 patients the infrahilar aorta/inferior vena cava was replaced by a graft. In 2 patients complete resection of the common iliac arteries and veins with graft replacement was performed. In addition, retrocrural lymph nodes had to be resected in 5 patients and 3 patients required adjunctive nephrectomy. After a median follow-up of 2.5 years 1 patient developed recurrent disease. Conclusions: Few patients with advanced NS need complex surgery in an interdisciplinary setting with good functional and oncological outcome. Even the presence of vertebral metastases should not restrain the surgeon to perform PC-RPLND. Due to the complexity, treatment should be performed at specialized centres. ID 354 Oncological efficacy and toxicity of Docetaxel and Prednison in the management of patients with castration resistant prostate cancer: Single centre experience A.K. Thissen, D. Pfister, D. Porres, C. Piper, A. Heidenreich Uniklinikum Aachen, Urlogie, Aachen, Deutschland Docetaxel is the recommended first line therapy for metastatic CRPC. Data on therapeutic effectiveness and side effects are basically not available from the real-world population of patients. We report on our experience with DOC/Pred of non-selected CRPC patients treated in a tertial referral centre. The charts of 109 patients with metastatic, progressive CRPC were retrospectively reviewed and the following parameter were recorded besides patient characteristics: duration and type of androgen deprivation prior to DOC, PSA↓>30%, PSA↓>50%, PFS and OS, treatment associated side effects, mean number of cycles, dose reduction, dose delay, frequency and duration of hospitalisation due to side effects. The mean age was 63.9 (47–83) years, mean PSA was 338.8 (1.0–7728) ng/ml. Mean duration of ADT was 231.3 (12–924) weeks and 59.7% of pts received LHRH monotherapy. PSA responses with PSA↓>30% and PSA↓>50% were observed in 56% and 45%, resp. Mean PFS was 184 (97–1367) days, mean OS was 605 (72–2018) days. Grad 3/4 toxicities developed in 67% with neutropenia (41.6%) and anemia (19.4%) as the most common side effects. 5.9% experienced neutropenic fever. 77.5% had to be hospitalised for the management of infections (34.7%), surgical or interventional procedures due to local progression (29.1%), or cardiovascular complications (15.2%). Mean duration of hospital stay was 17.3 (2–190) days and a mean of 2.04 (1–10) hospital admissions were necessary. Treatment with DOC/Pred results in oncologically equivalent results when compared to the TAX327 trial. Due to the unselected cohort of patients, treatment associated side effects and cancer associated complications occur significantly more often as in the TAX327 study. These data have to anticipated by treating uro-oncologists, patients have to be informed and followed accordingly. 64 Oncol Res Treat 2014;37(suppl 1):1–133 ID 367 Reduction of planning target volume margins for prostate cancer radiotherapy on helical tomotherapy using implanted fiducial markers and daily image-guidance S. Drozdz, M. Schwedas, T.G. Wendt Universitätsklinikum Jena, Klinik für Strahlentherapie und Radioonkologie, Jena, Deutschland Purpose: Internal organ motion (prostate, rectum, bladder) and the daily set up error can lead to a geographic miss of the target volume. These uncertainties are generally handled by a safty margin. The aim of this study is to evaluate the appropriate margin for prostate cancer radiotherapy on helical tomotherapy using fiducial markers and daily image-guidance. Methods & Materials: The study included 20 patients diagnosed with locally advanced prostate cancer radically treated with a 6 MV helical tomotherapy up to a dose of 74 Gy. Three implanted fiducial markers were used to determine interfractional prostate movement and the daily set up error. For each patient a mega-voltage computed tomography scans (MVCT) were acquired prior to the daily treatment. The difference between fiducial marker matching and bony anatomy matching were quantified. From its deviation the margin was calculated based on the van Herk formula. Results: The safty margin can be reduced with image-guidance and fiducial markers. The calculated difference between the set up error of the online matching of markers and of the offline matching of the bony anatomy is 2, 3 and 2 mm in LR, SI, AP direction. It means, based on the van Herk formula, a margin reduction of 5, 7 and 5 mm (LR, SI, AP) when using marker matching. The greater margin reduction in the SI-direction is caused by poor resolution in the SI-direction in the MVCT scans. But there should be an intrafractional prostate motion considered which is a limiting factor on margin reduction, as shown in our former study. Conclusions: Using fiducial-based image-guidance is the best way of correctly identifying the position of the target. It improves dose coverage of the target volume, significant determination of planning margins and reduces doses in the organs at risk. ID 371 C-acetate PET/CT imaging for detection of recurrent disease following radical prostatectomy in patients with prostate cancer 11 V. Müller-Mattheis1, H. Hautzel1,2, M. Fahlbusch1, P. Albers1 1 2 Heinrich-Heine-Universität, Urologische Klinik, Düsseldorf, Deutschland Institut für Medizin, Forschungszentrum, Jülich, Deutschland Background: Patients showing rising PSA levels after definitive local therapy of prostate carcinoma often present a diagnostic dilemma, because a local recurrence or metastatic lymph node lesions would be amenable to additional local therapy. The effectiveness of 11C-acetate PET (AC-PET) matched with corresponding CT scans was evaluated. Methods: 103 patients with adenocarcinoma of the prostate were enrolled in this study because of rising PSA values following radical prostatectomy [RP] (n = 97) or radiotherapy [RT] ( n = 6). 11C-acetate whole-body PET images were obtained. Additionally, a CT scan from the neck to the pelvic floor was performed. An image overlay of corresponding CT and PET scans was done. By using attenuation corrected PET data, standardized uptake value (SUV) was calculated, cut-off 2. Results: Out of 103 patients n = 42 were AC-PET positive. PSA level in 16 of this subset was between 0.5 and 1.45 ng/mL (mean value 1.14 ng/mL), in 16 patients between 2.7 and 9.01 ng/mL, and 7 patients had a PSA distribution between 13.4 and 30.5 ng/mL, respectively. In 16/42 AC-PET positive patients hypermetabolic lymph node lesions were found, histopathologically confirmed in 10/16 cases. In the remaining 6, unspecific inflammatory tissue alterations were identified. In 9 patients with corresponding AC-PET and CT scans RT of detected lymphnode lesions was performed followed by decreasing PSA level. 23/42 patients were treated with either hormone manipulation (21/23) or chemotherapy (2/23). Combining the patients hav- Abstracts Inhalt Index ing undergone surgery and RT (n = 25), there were 19/25 true positive in terms of AC-PET, in 13/25 PSA level was <2.0 ng/mL. Conclusions: Although AC-PET seems to be a promising tool in the detection of recurrent prostate cancer even with PSA levels <2 ng/mL, false positive patients with a different metabolism marked by 11C-acetate decrease the specifity of the approach. ID 405 Urothelial cell and lung cancer: An epidemiologic and clinical analysis of their coincidence B. Keck1, B. Wullich1, J. Giedl2, B. Walter3, K. Kraywinkel4, S. Dahm4, S. Pahernik5, M. Hohenfellner5, S. Petsch6, S.J. Klug7, V. Novotny8, M. Wirth8, J. Huber8 University Hospital, Department of Urology, Erlangen, Deutschland University Hospital, Department of Pathology, Erlangen, Deutschland 3 Hospital Altötting, Department of Urology, Altötting, Deutschland 4 Robert Koch Institute, Centre for Cancer Registry Data, Berlin, Deutschland 5 University of Heidelberg, Department of Urology, Heidelberg, Deutschland 6 Tumor Centre at the University Erlangen-Nueremberg, Erlangen, Deutschland 7 University Cancer Centre University Hospital «Carl Gustav Carus», Tumor Epidemiology and Outcome Research, Dresden, Deutschland 8 University Hospital «Carl Gustav Carus», Department of Urology, Dresden, Deutschland 1 2 Objective: As tobacco smoking is a common risk factor of urothelial carcinoma (UC) and lung cancer (LC) we set up a clinical and epidemiological analysis to study the clinical significance of LC in UC patients. Material and Methods: We analyzed 6029 UC patients of a multicentre cohort (university hospitals Erlangen, Dresden, and Heidelberg) as for their coincidence of UC and LC. We identified 145 patient and analyzed epidemiological and clinical data using Student’s t-test. Results: There were 145/6029 patients with a coincidence of UC and LC. That represents 2.4% of all patients and is in line with the population-based incidence of 2.5% (3509/142210) derived from the German national registry. Of these 145 patients 89% were male and 11% female. The median age at diagnosis was 66.5±9.3 years. 53.1% of the patients suffered from UC first, 27.6% presented with LC first, and 17.2% suffered from synchronously diagnosed diseases. Moreover, there was no difference of synchronous and metachronous disease regarding the median age at diagnosis of the first malignancy. The median interval until the diagnosis of the secondary cancer was 3.6±2.5 years for primary LC and 5.0±4.4 years for primary UC (p = 0.03). 61.4% (89/145) of the patients died during follow-up. Of these 12.4% died from UC and 71.9% from LC. 15.7% died from another cause. Patients who suffered from synchronous disease survived much shorter (1.3 vs. 6.1 years, p < 0.001). Conclusion: The incidence of LC in UC patients is higher than it is expected in a healthy population and affects mainly male patients. Thereby LC defines the patients’ prognosis. Patients who develop synchronous malignancies may harbor distinct molecular aberrations causing their poor prognosis. ID 423 Methods: 18 pts with biopsy proven, completely resectable PCA, minimal bone metastases (≤ 3 hot spots on bone scan), absence of visceral or extensive lymph node metastases were included in the pilot study. All pts underwent neoadjuvant ADT with LHRH analogues for 6 months. If the PSA decreased to < 0.4 ng/ml and bone lesions disappeared on control scan, pts were considered suitable for extended RP followed by 2 years adjuvant ADT. Results: Mean age was 61 (42–69) years, mean PSA was 96.3 (72–139) ng/ml and 0.29 (0–0.39) ng/ml at recruitment and at 6 months. Mean number of bone lesions was 1.9 (1–3). All lesions disappeared after 6 months of ADT. Pathohistology revealed pT2c in 4 (22.2%), pT3a and pT3b in 3 (16.7%) and 11 (61.11%) pts. 7 (38.9%) pts and 3 (16.7%) pts had lymph node metastases or positive surgical margins (PSM). PSM were treated with adjuvant radiation therapy ad 66.6Gy. No Clavien grade 3–5 complications occurred. The mean follow-up is 29 (3–52) months, 3 (16.7%) pts relapsed. The remainder is without evidence of disease. Conclusions: CRP is feasible in well selected men with low volume bone metastases who respond well to neoadjuvant ADT. These men have a life expectancy of 7 years. CRP reduces the risk of local complications. CRP might be a new treatment option in the multimodality management of PCA and minimal metastatic disease. Gynecologic Cancer ID 082 Entscheidungsfindung im Kontext einer familiärer Disposition für Brust- und Eierstockkrebs Positionen des BRCA-Netzwerk – Hilfe bei fam. Brustund Eierstockkrebs und Erfahrungen aus der Beratung betroffener Familien durch selbst Betroffene A. Hahne BRCA-Netzwerk – Hilfe bei fam. Brust- und Eierstockkrebs e.V., Königswinter, Deutschland Einleitung: das BRCA-Netwzerk – Hilfe bei fam. Brust- und Eierstockkrebs hat sich 2008 gegründet. Es bietet Austausch und Informationen für Familien mit einer bekannten oder vermuteteten genetischen Veranlagung für Brust- und Eierstockkrebs. Seit Gründung wurden bundesweit 20 Gesprächskreise gegründet, die lokale Anlaufstelle sind. darüber hinaus berät das BRCA-Netzwerk online und via Telefon. Verständlich Informationen sowie Ansprechpartner sind über die Website www.brca-netzwerk. de niedrigschwellig abzurufen. Fragestellung: Der Stellenwert von Selbsthilfe und Patienteninitiative im Entscheidungsfindungsprozess für oder gegen eine Gensequenzierung, für oder gegen prophyl. Maßnahmen (Mastektomie / Ovariektomie). Methode: Einzelfallbeschreibung aus der Selbsthilfearbeit. Ergebnisse: Selbsthilfe als Part der Entscheidungsfindung ist eine notwendige Ergänzung der medizinischen und psychosozialen Versorgungsstrukturen. Schlussfolgerung: Weiterentwicklung und Finanzierung von Selbsthilfestrukturen. Cytoreductive Radical Prostatectomy (CRP) in Patients with Prostate Cancer (PCA) and Low Volume osseous Metastases ID 103 C. Piper, D. Pfister, D. Porres, T. van Erps, A. Heidenreich C. Gründker, E. Schmidt, M. Haase, G. Emons Uniklinik Aachen, Urologie, Aachen, Deutschland Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Deutschland Background: Androgen deprivation (ADT) represents the standard treatment in men with PCA and bone metastases. RP is usually ignored due to the common view that the biology of the disease is attributed to preexisting metastases. Recently, it has been shown that potentially lethal cancers persist even after neoadjuvant ADT and chemotherapy. We explored the outcome of patients with PCA and low volume skeletal metastases who were subjected to ADT and CRP. Abstracts Role of SDF-1 in endometrial cancer metastasis The crosstalk between metastatic cancer cells and target sites is critical to the development and progression of metastases. Disruption of this interaction will allow us to design mechanism-based effective and specific therapeutic interventions for metastases. We have established a coculture system of cells derived from different tumor entities and MG63 human osteoblast-like cells to analyze tumor cell invasion. We have shown that Oncol Res Treat 2014;37(suppl 1):1–133 65 Inhalt Index ovarian, endometrial and breast cancer cell invasion was dramatically increased when cocultured with MG63 cells. Using this model we examine tumor cell invasion on cellular as well as molecular level. In the present study we have analyzed whether stromal derived factor-1 (SDF-1) is responsible for human endometrial cancer cell invasion and whether Kisspeptin-10 (KP-10) treatment affects SDF-1-induced invasion of endometrial cancer cells. Endometrial cancer cell invasion was significantly increased when cocultured with MG63 cells. Treatment with KP-10 significantly reduced the invasiveness of endometrial cancer cells. During coculture SDF-1 protein expression of MG63 cells was significantly increased. The MG63 coculture-induced increase of endometrial cancer cell invasion could be blocked by anti-SDF-1 antibodies. Treatment of endometrial cancer cells in monoculture (without MG63) with SDF-1α, SDF-1β or the combination of both isoforms resulted in a significant increase of endometrial cancer cell invasion. The SDF-1-induced increase of endometrial cancer cell invasion was significantly reduced after treatment with KP-10. Our findings suggest that SDF-1 plays a major role in endometrial cancer invasion. SDF-1-induced invasion can be inhibited by KP-10 treatment. ID 104 Inhibition of GPR30 by estriol successfully prevents growth stimulation of triple-negative breast cancer cells by 17β-estradiol However, there are limitations in the adherence and application of guideline changes. Objectives: To evaluate the awareness of modern antiemetic guidelines (GL) and their practical use in pts receiving anthracycline plus cyclophosphamide (AC)-containing chemotherapy. ASCO recommends prophylaxis with 5-HT3-receptorantagonist (RA), Neurokinin1-RA and dexamethasone. Methods: 49 practices used the ODM Quasi® GYN system for the documentation of data on institutions, patients, knowledge and application of antiemetic GL. Antiemetic treatment was documented in 250 breast cancer pts who received cycle 1 and 3 of AC chemotherapy (80% adjuvant, 20% neoadjuvant). Results: Awareness of antiemetic GL: AGO* 76%, ASCO 82%, NCCN 31%, MASCC 22%; application of GL: AGO 57%, ASCO 53%, MASCC 12%, NCCN 8%, none (2%). 94% were aware of the change of the emetic group of AC in the ASCO GL. Active use of triple drug antiemesis: 84%, planned use: 12%, no use: 4%. Antiemetic treatment documentation in 246 pts: Cycle 1: 82 (33%) received the triple drug schedule according to GL, 113 (46%) a combination of 5HT3-RA and DEX. Cycle 3: triple: 35%, 5HT3-RA +Dex: 44%. 4 pts were lost to follow up. Conclusions: Only 33% of pts received the triple combination according to GL in the first cycle of AC, 35% in the third cycle. * AGO- German Working Group of Gynecologic Oncology. R. Girgert, C. Gründker, G. Emons Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Deutschland Clinical success of therapy in triple-negative breast cancer (TNBC) is still poor and urgently awaits improvement. The majority of TNBC express the membrane bound estrogen receptor GPR30. As proof of principle we recently showed that a knock-down of GPR30 expression prevents growth stimulation of TNBC cell lines by 17β-estradiol and 4-hydroxytamoxifen. Cells of TNBC cell lines were treated with 10-4 M estriol, an antagonist to GPR30 and activation of c-Src and EGF-receptor was assessed using Western blots. Expression of c-fos, cyclin D1 and aromatase was quantified by RT-PCR. Gα-specific signaling of GPR30 was analyzed by CREB-phosphorylation on Western-blots and electrophoretic mobility shift assay. Activity of Src kinase was increased by 10-8 M estradiol and 10-4M estriol treatment clearly lowered p-src induction. Transactivation of the EGF-receptor was increased by 17β-estradiol and estriol completely prevented EGF-receptor transactivation. Subsequently, 17β-estradiol increased c-fos-, cyclin D1- and aromatase- expression. Estriol prevented this mRNA induction in all three tested cell lines. Inhibition of GPR30 with 10-4 M estriol completely abolished activation of all these signaling pathways responsible for the enhancement of cell proliferation by 17β-estradiol. 10-8 M 17β-estradiol enhanced proliferation of all three TNBC cell lines whereas cotreatment with 10-4 M estriol kept cell number up to 20% under control level. Though TNBC does not express ERα it is sensitive to estrogen stimulation and the blockade of the estrogen receptor GPR30, a pharmacological inhibition of GPR30 by specific small molecular inhibitors might become a promising targeted therapy of TNBC in the future. ID 146 How Office Based Gyneco-Oncologists in Germany Apply Antiemetic Guidelines in Patients Receiving ACContaining (Neo) Adjuvant Chemotherapy J. Schilling, H.-J. Hindenburg BNGO e.V., Neuenhagen b. Berlin, Deutschland ID 157 Bevacizumab-based therapy in patients with intensively pretreated epithelial and other Mullerian tract carcuinomas: A single institution experience C.M. Kurbacher1, W. Nagel2, S. Herz1, G. Wessling1, J. Lepique1, J.A. Kurbacher1 Medizinisches Zentrum Bonn-Friedensplatz, Zentrum für Gynäkologie und Geburtshilfe, Bonn, Deutschland 2 Medizinisches Zentrum Bonn-Friedensplatz, Praxis für Urologie, Bonn, Deutschland 1 Background: We hereby report on our single-institution experience with bevacizumab (Bev)-based therapy (Tx) in patients (pts) with heavily pretreated recurrent Mullerian tract carcinomas (MTC) including ovarian (C), fallopian tube (FTC), peritoneal papillary-serous (PPSC), and type II endometrial carcinoma (EC-II). Methods: 78 pts (OC, n = 69; FTC, n = 2; EC-II, n = 4; PPSC, n = 3) were included in this retrospective study with 45 pts (57.7%) being platinum-resistant. Pts had received a median of 4 (range 1-10) prior chemotherapies (CTx). Tx was was given as Bev monotherapy (group A, n = 19), Bev+metronomic CTx (group B, n = 38), and Bev+conventionally dosed CTx (Group C, n = 21). Bev was administered at either 10 mg/ kg q2w or 15 mg/kg q3w. Adverse effects were classified according to CTCAE 4.0. TTP was calculated from the start of Bev until progression, OS was calculated from the start of Bev until death or loss to follow up. Results: Most common adverse effects were hypertension, proteinuria, headache, infection, epistaxis, and subileus. Hypertension was limiting in only case, as were renal toxicity, subileus, and infection. Median TTP was 29.9 wks and median OS was 55.1 wks with no significant difference between platinum-resistant and -sensitive pts. In regard to both TTP and OS, there was a non-significant trend favoring group A (36.0/66.4 wks) and B (29.9/61.6 wks) vs group C (20.3/36.0 wks). Conclusion: Bev based Tx was active and generally well tolerated in this hard-to-treat population of pts with recurrent MTC. Both TTP and OS were equal or even superior to any conventional Ctx used in this setting. Clinical Platinum-resistance did not predict a worse clinical outcome. We conclude that, Bev should be preferably given either as single agent or alongside with metronomic CTx in pts with intensively pretreated MTCs. Introduction: Supportive care guidelines are an important instrument to maintain quality of treatment and quality of life in cancer patients (pts). 66 Oncol Res Treat 2014;37(suppl 1):1–133 Abstracts Inhalt Index ID 164 Changes in the Progesterone-, Estrogen-, HER2/neureceptor status and the proliferation marker Ki-67 in metastasized breast cancer: Discordance rates and time to progression in brain metastasis M. Timmer, C. Cramer, G. Röhn, R. Goldbrunner Uniklinik Köln, Allgemeine Neurochirurgie, Köln, Deutschland Estrogen receptor (ER), progesterone receptor (PgR), human EGF receptor 2 (Her2), and Ki-67 are important predictive and prognostic markers for making effective treatment decisions. Out of 90 patients with breast cancer brain metastasis in our tumor tissue bank from 2001 to 2012, there were 23 consecutive patients from whom both, the primary lesion and the brain metastasis were operated in our hospital. The lesions were resected and ER, PgR, Her2 and Ki-67 were evaluated by immunostaining and molecular technique. The median age of the patient cohort was 56±9 years at first diagnosis. At that time 85% of the patients who developed a brain metastasis later on already had lymph node involvement. The Ki-67 proliferation index increased significantly from a mean of 21% at primary tumor site to 60% at relapse (p < 0.001). Most patients developed one single brain metastasis at diagnosis (74%), but 26% had multiple brain metastasis. The localisation of the filiae was mainly either the cerebellum (39%) or fronto-temporal (43.5%). The hormone receptor positive rate from the primary tumor to recurrence decreased from 43% to 17% and from 43% to 26% for ER and PgR, respectively. On the other hand, the rates of Her2+ tumors increased from 45% to 86%. 22% of all cases were triple negative. ER and PgR decreased while Her2 and Ki-67 increased due to relapse. Interestingly, there was a doubling of Her2+ cases in the relapse situation. These findings could get important for making effective treatment in the era of targeted therapies. ID 167 E- and P-selectin determine peritoneal spread of ovarian cancer in a xenograft model C. Schröder1, D. Wicklein1, T. Streichert2, C. Bartmann3, J. Dietl3, K. Milde-Langosch4, U. Schumacher1 Universitätsklinikum Hamburg-Eppendorf, IAEM, Hamburg, Deutschland Universitätsklinikum Hamburg Eppendorf, Institut für Klinische Chemie, Hamburg, Deutschland 3 Universitätsklinikum Würzburg, Gynäkologie, Würzburg, Deutschland 4 Universitätsklinikum Hamburg Eppendorf, Gynäkologie, Hamburg, Deutschland 1 2 Background: Ovarian cancer is the seventh most common cause of cancer death in women world-wide. The high mortality is caused both by the late detection and the early intra-peritoneal spread, a process that is in general scarcely appreciated. However, recent progress in the understanding of the peritoneal spread of pancreatic cancer indicated that Eand P-selectin carbohydrate ligand interactions play a decisive role in the intra-abdominal spread of this neoplasm. Methods: Two human ovarian carcinoma cell lines (SKOV3 and OVCAR3) were xenografted into the peritoneal cavity of E- and P-selectin-deficient scid mice and wild-type controls. Kaplan-Meier curves were prepared for the survival analysis and engrafted tumours were used for RNA isolation and for transcriptome analysis. The results of selected genes were validated by FACS and immunohistochemistry. Results: Both xenografted SKOV3 and OVCAR3 cells engrafted significantly less in E- and P-selectin-deficient scid mice compared to wild type scid mice (days versus days). Kaplan-Meier analysis showed that a significantly (p = 0.0001) higher overall survival was linked to the loss of Eand P-selectin. Affymetrix cDNA microarray data of the engrafted tumours indicate an up-regulation of adhesion molecules of the leukocyte cascade. Conclusion: The engraftment of tumour cells in the peritoneal cavity significantly depends on their adhesion to the mesothelium mediated by selectins and other cell adhesion molecules of the leukocyte adhesion cascade. Abstracts ID 180 Vulvar cancer on the rise. A German population based cancer registry study using pooled data at the Centre for Cancer Registry Data at Robert Koch-Institute (ZFKD) N. Buttmann, K. Kraywinkel RKI, ZfKD, Berlin, Deutschland Objectives: A substantial increase of invasive vulvar cancer in younger women over the past three decades has been described in a retrospective analysis of medical records in Western-Central Germany. Cancer of the vulva in younger women has etiologically been linked to HPV, preceded by histologically corresponding intraepithelial lesions. We aimed to provide recent trends on the vulvar cancer burden in Germany, using population based cancer registry data. Methods: We accessed the data of twelve German cancer registries which provided data for the period from 1999 to 2010. ICD-10 and morphology codes in ICD-O-3 were used to select site and histologic types. The annual percentage change has been calculated on age adjusted rates with a joinpoint regression model. Results: The annual incidence of invasive carcinoma of the vulva nearly doubled in the past decade. Age standardized incidence rates annually increased by 6.3% from 2.7 per 100,000 women in 1999 to 5.0 per 100,000 women in 2010. The largest rise was observed among younger women (30–49 years). Mortality rates also slightly increased by 3.4% per year. A tendency towards higher relative proportions of squamous cell carcinoma (SCC) and an increase of clitoral tumors was seen. The fraction of cases detected at small tumor size (restricted to vulva/perineum) slightly increased, from 67.6% to 74.4% while larger tumors proportionally remained stable. Conclusion: Compared to internationally available data, Germany witnessed substantially higher rates of invasive vulvar cancer over the past decade, accompanied by an increase in mortality. Several risk factors as HPV infection, smoking and immunosuppression might have contributed to this development. ID 185 Differentielle Expression von Transkripten und mikroRNAs während der Progression des Mammakarzinoms S. Schultz1, H. Neubauer1, H. Bartsch2, K. Sotlar2, K. Petat-Dutter2, M. Bonin3, S. Poths3, M. Walter3, O. Riess3, D. Wallwiener4, T. Fehm1 Universitäts-Frauenklinik Düsseldorf, Forschungslabor Life Science Center, Düsseldorf, Deutschland 2 Institut für Pathologie, München, Deutschland 3 Institut für medizinische Genetik, Microarray Facility, Tübingen, Deutschland 4 Universitäts-Frauenklinik Tübingen, Tübingen, Deutschland 1 Die Analyse molekularer Mechanismen beim Übergang vom duktalen in situ Karzinom (DCIS) der Brust zum invasiven duktalen Karzinom (IDC) trägt zum Verstehen der Vorgänge der Tumorprogression bei. Die Ziele dieses Projektes sind die Identifizierung und Validierung von Transkripten und miRNAs, die (1) zwischen DCIS und IDC differentiell exprimiert sind und die (2) aggressive DCIS mit hohem Potential für invasives Wachstum detektieren. Es wurden 15 FFPE-Mammakarzinomproben mit reinem DCIS ohne invasive Komponente selektiert, sowie 15 FFPE-Proben mit DCIS/IDC-Komponenten. Die Gewebeschnitte wurden durch einen Pathologen charakterisiert und die Tumorzellen mittels Lasermikrodissektion isoliert, die Gesamt-RNA extrahiert, und auf Microarray-Plattformen hybridisiert und bioinformatisch analysiert. Die Expression ausgewählter Transkripte/miRNAs wurde mittels qRT-PCR in unabhängigen Gewebeproben validiert. Zwischen reinen DCIS und DCIS aus invasiven Mammakarzinomen sind 2117 Transkripte und 24 miRNAs differentiell exprimiert (P<0.05); zwischen DCIS und IDC sind es 1748 Transkripte und 33 miRNAs (P<0.05). Oncol Res Treat 2014;37(suppl 1):1–133 67 Inhalt Index In der qRT-PCR bestätigt sich ein kontinuierlicher Expressionsanstieg von MMP11 und COL10A1 von reinen DCIS über DCIS der invasiven Mammakarzinome zum IDC. Hsa-miR-214 und hsa-miR-199a-5p sind im Vergleich zum DCIS im IDC hochreguliert. Auch hier konnte ein kontinuierlicher Expressionsanstieg beobachtet werden. Mit MMP11, COL10A1 und hsa-miR-199a-5p konnten mögliche prognostische Marker identifiziert und validiert werden, die zum Verstehen der biologischen Mechanismen der Tumorprogression beitragen, und die darüber hinaus DCIS mit einem hohen Potential für invasives Wachstum charakterisieren können. ID 187 Hsa-miR-199a-5p is functionally relevant in progression from ductal carcinoma in situ to invasive breast tumours S. Schultz1, H. Neubauer1, H. Bartsch2, K. Sotlar2, K. Petat-Dutter2, M. Bonin3, S. Poths3, M. Walter3, O. Riess3, D. Wallwiener4, T. Fehm4 Universitäts-Frauenklinik Düsseldorf, Forschungslabor Life Science Center, Düsseldorf, Deutschland 2 Institut für Pathologie, München, Deutschland 3 Institut für medizinische Genetik, Microarray Facility, Tübingen, Deutschland 4 Universitäts-Frauenklinik Tübingen, Tübingen, Deutschland 1 A fundamental and clinically important step during the breast tumourigenesis is the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). At this point, cancer cells gain the potential to spread and metastasize. Since the molecular characteristics of this step still remain poorly understood an improved knowledge of the transition from pre-invasive to invasive breast cancer will pave the way for novel preventative and therapeutic strategies. We analyzed miRNA expression profiles in 15 matched pairs of DCIS and IDC areas isolated by laser capture microdissection (LCM) from formalin fixed and paraffin embedded (FFPE) breast cancer tissues using Illumina miRNA BeadChip microarray platform. Differential expression of two candidate miRNAs – hsa-miR-199a-5p and hsa-miR-214 – was further investigated by quantitative RT-PCR in additional independent samples from 25 breast cancer patients. Invasion assays were performed in combination with knock down of hsa-miR-199a-5p. In total, matched pair microarray analysis revealed 33 significantly differentially expressed miRNAs (P<0.05). Expression of hsa-miR-199a-5p is upregulated in IDC according to our microarray data – a result which we were able to validate by qRT-PCR in independent samples. Knock down of hsa-miR-199a-5p in invasive MDA-MB-231 and TMX2-28 breast cancer cells using a specific inhibitor significantly reduced invasiveness by approx. 73% and 71%, respectively (both P<0.05). We identified candidate progression miRNAs which are differentially expressed between DCIS and IDC using LCM and microarray analysis on FFPE breast cancer tissues. Hsa-miR-199a-5p could be validated in an independent sample cohort, is influencing in vitro cell invasiveness and may therefore be a potential drugable regulator of tumour progression and invasion in breast cancer. ID 197 Increased detection of glandular lesions of the cervix uteri by using Pap smears U. Hahlbohm, C. Noble-Pyott, G. Richter Institut Dr. Richter, Zytologie, Hameln, Deutschland Aims: The aim is to assess glandular lesions with more certainty using conventional Pap smears. They are dedicated with PAP group III in the Münchener NomenklaturII in German- speaking areas and in Englishspeaking areas according to Bethesda AGUS. In already existing publications about this theme the finding rate of glandular lesions is described as <10%. On the basis of the criteria here applied the finding rate of glandular lesions in cytological smears should be increased. 68 Oncol Res Treat 2014;37(suppl 1):1–133 Methods: During microscopic inspection a particular polarization deficiency of cells exists, which let the cell picture appear strong bizarre disorderly, coupled with the known malignant criteria and a ball-like three dimensional cell group formation this can be classified. A single cell capture however is not sufficient for appraisal of glandular atypia. The relevance of the naked cell nucleus should be observed. A familiar tumor diatheses cannot be found here. Results: In 2009 and 2010 in a total number of 145,986 Pap smears the PAP group III was given 108 times (=0.07%). This equals a patient number of 108 women. The histological clarification could be asserted in 27 cases with the following distribution: Adenocarcinoma of the Cervix uteri : 6 = 22.2%, Adenocarcinoma of the Endometrium: 1 = 3.7%, AIS: 4 = 14.8%, ECIN II: 1 = 3.7%, ECIN I: 2 = 7.4%, Squamous cell carcinoma: 1 = 3.7%, CIS: 2 = 7.4%, CIN III: 1 = 3.7%, CIN II: 3 = 11.1%, CIN I: 4 = 14.8%, negative: 2 = 7.4% Conclusions: The established results show a finding rate of 23% for lesions. Thereby an increase of 131% compared with the already existing finding rate of <10% is obtained. This can express the heightened sensitivity of glandular lesions in cytological smears using the above mentioned malignancy criteria. ID 222 Progression-free survival in patients in with advanced ovarian cancer defined by GCIG criteria vs. RECIST criteria: Analysis of the secondary endpoint of the AGOOvar16 trial S. Mahner1, C. Jackisch2, J. Sehouli3, J. Rau4, B. Schmalfeldt5, A. Belau6, B. Richter7, G. Emons8, T.-W. Park-Simon9, H.-J. Lueck10, A. Burges11, T. Fehm12, G. Feisel-Schwickardi13, M. Clemens14, A. du Bois15 University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland Klinikum Offenbach, Offenbach, Deutschland Charite Campus Virchow, Berlin, Deutschland 4 KKS, Marburg, Deutschland 5 Technische Universität, München, Deutschland 6 Unversität Greifswald, Greifswald, Deutschland 7 Frauenklinik, Radebeul, Deutschland 8 Universitätsfrauenklinik Götingen, Göttingen, Deutschland 9 MHH, Hannover, Deutschland 10 Frauenarztpraxis, Hannover, Deutschland 11 Klinikum Grosshadern, München, Deutschland 12 Universitätsfrauenklinik Tübingen, Tübingen, Deutschland 13 Klinikum Kassel, Kassel, Deutschland 14 Klinikum Trier, Trier, Deutschland 15 Kliniken Essen Mitte, Klinik für Gynäkologie und Gynäkologische Onkologie, Essen, Deutschland 1 2 3 Background: AGO-OVAR16 is a randomized, double-blind trial of pazopanib as maintenance therapy in patients with advanced epithelial ovarian cancer (AEOC). Methods: Patients with AEOC (N=940) were randomly assigned 1:1 to receive pazopanib 800 mg once daily or placebo for up to 24 months. Primary endpoint was investigator-assessed progression-free survival (PFS) by RECIST v1.0. A secondary endpoint was PFS by Gynecologic Cancer InterGroup ‘GCIG’ criteria, based on radiology and tumor-marker CA-125. Results: By RECIST criteria there were 273 progression and 195 censoring events in the placebo arm, 237 progression and 235 censoring events in the pazopanib arm (investigator review). By GCIG criteria, there were 290 progression events in the placebo arm (213 per RECIST and 77 per CA-125) and 255 progression events in the pazopanib arm (184 per RECIST and 71 per CA-125). Using RECIST criteria, pazopanib increased PFS compared to placebo by investigator review (HR=0.77; 95% CI: 0.640.91; P=0.0021; median 17.9 vs 12.3 months). Analyses by GCIG were consistent (HR=0.79; 95% CI: 0.67–0.93; P=0.0047; median 16.8 vs 11.9 months). The proportion of patients with CA-125 progression as the first progression event was nearly identical between both arms (16% and 15%). For subjects with both CA-125 and RECIST PD (~10%), the time interval Abstracts Inhalt Index from CA-125 progression to RECIST progression was also well balanced between the placebo and pazopanib arms (mean 2.6 vs 2.8 months). Conclusions: Maintenance therapy with pazopanib provided a significant PFS benefit in patients with advanced epithelial ovarian cancer, irrespective of the applied diagnostic criteria. Recurrent disease was diagnosed by GCIG criteria approximately 2.5 months earlier than RECIST. ID 230 Effect of Estrogen Receptor β Agonists on proliferation and gene expression of ovarian cancer cells S. Schüler, C. Lattrich, J. Häring, O. Treeck, O. Ortmann Universitätsfrauenklinik Regensburg am Caritas-Krankenhaus St. Josef, Lehrstuhl für Gynäkologie und Geburtshilfe, Regensburg, Deutschland Introduction: Estrogen receptor (ER) b has been reported to affect ovarian carcinogenesis. We examined the effects of four ERβ agonists on proliferation and gene expression of OVCAR3 and OAW-42 cells. Methods: OVAR3 and OAW-42 ovarian cancer cells were treated with the ERβ agonists ERB-041, WAY200070, Liquiritigenin and 3β-Adiol (10 mM each) and cell growth was measured by means of the Cell Titer Blue Assay (Promega). Proliferation was also examined after knockdown of ERβ using specific siRNA. Additionally, transcriptome analyses were performed with these cell lines after treatment with ERB-041, WAY200070 and Liquiritigenin by means of Affymetrix GeneChip arrays. Results: After treatment of OVCAR3 and OAW-42 cells with the ERβ agonists, all of these drugs were observed to significantly decrease proliferation in both cell lines even at a low concentration of 10 nM. Maximum effects were induced by Liquiritigenin, which inhibited growth of OVCAR3 cells down to 68.8% after 5 days of treatment, and ERB-041 suppressing proliferation of the same cell line by about 30%. In OAW-42 cells, the agonist WAY200070 induced maximum effects and inhibited cell growth down to 73.2%, whereas ERB-041 decreased proliferation down to 75.6% after 5 days of treatment. On the other hand, knockdown of ERβ with specific siRNA increased cell growth of OVCAR3 cells by 45%. Transcriptome analyses revealed a set of genes regulated after addition of ERb agonists. EPCAM gene, known to be upregulated in ovarian cancer, was 2.2-fold downregulated after treatment in OAW42 cells. Conclusion: In conclusion, the observed growth-inhibitory effects of all ERβ agonists on ovarian cancer cell lines in vitro encourage further studies to test its possible use in the clinical setting. ID 231 Influence of the postoperative residual tumor on the outcome of therapy with pazopanib in ovarian cancer (OC): A subgroup analysis of an international intergroup trial (AGO-OVAR16) M. Gropp-Meier1, B. Schmalfeld2, A. Belau3, J. Rau4, B. Richter5, G. Emons6, P. Hillemanns7, H.-J. Lück8, A. Burges9, T. Fehm10, P. Harter11, P. Wimberger12, K. Baumann13, C. Kurzeder14, U. Canzler15, W. Meier16, L.C. Hanker17, S. Mahner18, J. Kosse19, J. Sehouli20, M. Sütterlin21, A. Zorr22, A. du Bois23 Krankenhaus St. Elisabeth, Frauenklinik, Ravensburg, Deutschland 2 Klinikum rechts der Isar der Technischen Universität, Frauen- und Poliklinik, München, Deutschland 3 Universitätsklinikum Greifswald der Ernst-Moritz-Arndt Universität, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Greifswald, Deutschland 4 KKS Marburg, Marburg, Deutschland 5 Elblandkliniken Meißen-Radebeul GmbH & Co KG, Frauenklinik, Radebeul, Deutschland 6 Georg-August Universität Göttingen, Gynäkologie und Geburtshilfe, Göttingen, Deutschland 7 Medizinische Hochschule Hannover, Frauenklinik, Hannover, Deutschland 8 Gynäkologisch-onkologische Praxis, Hannover, Deutschland 9 Klinikum der Universität, Campus Großhadern, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, München, Deutschland 10 Universitätsklinikum Tübingen, Universitätsfrauenklink, Tübingen, Deutschland 1 Abstracts HSK Dr. Horst-Schmidt-Klinik, Klinik für Gynäkologie und Gynäkologische Onkologie, Wiesbaden, Deutschland 12 Universitätsklinikum Essen, Klinik für Frauenheilkunde und Geburtshilfe, Essen, Deutschland 13 Universitätsklinikum Gießen und Marburg GmbH Standort Marburg, Klinik für Gynäkologie, gynäkologische Endokrinologie und Onkologie, Marburg, Deutschland 14 Universitätsklinikum Ulm, Universitätsfrauenklink, Ulm, Deutschland 15 Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Dresden, Deutschland 16 Evangelisches Krankenhaus, Frauenklinik, Düsseldorf, Deutschland 17 Klinikum der J.W. Goethe Universität, Zentrum für Frauenheilkunde und Geburtshilfe, Frankfurt, Deutschland 18 Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Gynäkologie, Hamburg, Deutschland 19 Klinikum Offenbach GmbH, Klinik für Gynäkologie und Geburtshilfe, Offenbach, Deutschland 20 Charité, Campus Virchow Klinikum, Frauenklinik, Berlin, Deutschland 21 Universitätsklinikum Mannheim, Frauenklink, Mannheim, Deutschland 22 Klinikum Lippe-Detmold, Frauenklinik Lippe, Lippe, Deutschland 23 Klinikum Essen-Mitte, Klinik für Gynäkologische Onkologie, Essen, Deutschland 11 Despite of aggressive primary therapy prognosis of OC is still pure. VEGF/ PDGF seem to play a major role in the pathogenesis of the disease. Improvement of progression free survival (PFS) has already been reached by the incorporation of an VEGF antibody. Pazopanib is an orally administered tyrosine kinase inhibitor targeting ATP binding sites of VEGFR, PDGFR and c-kit receptors. We examined the influence of the postoperative residual tumor (PRT) on the response to maintenance therapy with Pazopanib. From 06/2009 until 08/2010 a total of 940 patients with OC FIGO II – IV have been randomized in the AGO-OVAR16 trial. Patients without progressive disease and a measurable tumor < 2cm after primary therapy were randomized and received either Pazopanib 800 mg daily (n = 472) or placebo (n = 468) for up to 24 months. Patient characteristics (PS, FIGO stage, histology, PRT, chemotherapy, best response to initial therapy, time to randomization) were well balanced between the two arms. In the pazopanib group 265 (56%) patients had no PRT and 282 (60%) in the placebo group respectively. The median PFS of the primary ITT analysis was 17,9 months in the pazopanib group and 12,3 months in the placebo group (HR=0.77; 95% CI: 0.64; 0.91). This effect was shown consistently between the arms in the subgroup analyses of FIGO II or III & tumor size ≤ 1 cm with a HR=0.82 (95% CI: 0.65; 1.03) as well as in the subgroup of FIGO III & tumor size > 1 cm with HR=0.78 (95% CI: 0.56; 1.09). In the subgroup with PRT > 0 cm the effect of Pazopanib was lightly more pronounced with HR=0.69 (95% CI: 0.54; 0.9). Additional subgroup analyses regarding differential effects with respect to tumor size will be presented. Pazopanib maintenance therapy shows a clinical benefit over different subpopulations. ID 234 Role of IGF1 in primary ovarian cancer – a study of the OVCAD European Consortium I. Rohr1, E.I. Braicu1, R. Zeilinger2, N. Concin3, R. Richter1, M. Heinrich4, S. Mahner5, T. Van Gorp6, F. Trillsch5, D. Cacsire Castillo-Tong 2, R. Chekerov1, J. Sehouli1 Charite Berlin, Gynäkologie, Berlin, Deutschland Medizinische Universität, Wien, Oesterreich Medizinische Universität, Innsbruck, Oesterreich 4 Alice Salomon Hochschule, Berlin, Deutschland 5 Universitätsklinikum Hamburg Eppendorf, Hamburg, Deutschland 6 Division of Gynaecological Oncology, Maastricht, Niederlande 1 2 3 Objective: IGF 1 is a hormone that has a direct affect on cellular proliferation and also in a number of cancers. Aim of our study was to analyze the impact of IGF1 circulatory levels on patients with primary ovarian cancer. Methods: In the FP6 European Multicentric Project ‘OVCAD’, 275 consecutive patients with primary EOC were enrolled. Patients were eligible Oncol Res Treat 2014;37(suppl 1):1–133 69 Inhalt Index if radical cytoreductive surgery was performed and platinum-based chemotherapy was applied. Samples of plasma and ascites were collected before or during surgery. Results: Increased plasma IGF 1 levels were more frequently found in low-grade serous and non-serous carcinoma (p = 0,0047) than in highgrade ovarian cancers. No significant correlations with other clinicopathological factors such as FIGO stage, residual tumor mass, age at initial diagnosis, histology or CA 125, have been found. No association between IGF1 expression and BMI was observed. Conclusions: IGF1 seems to be overexpressed in patients with low grade serous ovarian cancer patients. A significant impact on overall survival in this patient subgroup couldn’t be found due to low number of patents. Further studies are needed to elucidate the role of IGF1 in the pathogenesis of low grade ovarian cancer and to possibly further evaluate the impact of IGF1 targeted therapy. The presented data suggests that increased IGF 1 expression occurs rather in well-differentiated serous and non-serous ovarian cancer. ID 243 Uterine Cancer: Intraoperative cytology during endoscopic surgery A. Gittler, S. Takacz, R. Mavrova, S. Baum, E.F. Solomayer, I. Juhasz-Böss Universität des Saarlandes, Gynäkologie, Homburg, Deutschland Introduction: The laparoscopic treatment of uterine cancer is an oncologically safe treatment option in early stage carcinoma. However, there still is no information whether surgery can lead to an intraperitoneal tumor cell dissemination. The aim of our study was to investigate the peritoneal cytology at the beginning and at the end of laparoskopic operations. Method of Application: A prospective study of intraperitoneal cytology at the beginning and at the end of laparoscopic surgery of patients suffering from cervical and endometrial cancer with stage I and II grade cancer. Results: A first evaluation of the data of 31 patients ( 20 endometrial cancer and 11 cervical cancer) is available. At the beginning of the operation only one patient showed a positive cytology. None of the patients had a tumor cell dissemination during surgery. All patients were free of recurrence at the time of data analysis. Conclusion: During laparoscopic surgery of earlier stages of cervical Cancer and endometrial cancer no conversion of cytology can be detected, which proves that laparoscopic surgery is a safe option of oncologic therapie. ID 244 AGO Vulva CaRE-1 multicenter study – adjuvant radio(chemo)therapy in vulvar cancer P. Hillemanns1, L. Wölber2, J. Jückstock3, P. Neuser4, F. Hilpert5, P. Harter6, N. De Gregorio7, A. Hasenburg8, J. Sehouli9, A. Habermann10, S.T. Fürst3, H.-G. Strauß11, K. Baumann12, F. Thiel13, A. Mustea14, W. Meier15, A. Du Bois6, P. Wimberger16, L. Hanker17, B. Schmalfeldt18, U. Canzler19, T. Fehm20, A. Luyten21, M. Hellriegel22, J. Kosse23, C. Heiss24, P. Hantschmann25, P. Mallmann26, B. Tanner27, J. Pfisterer28, B. Richter29, C. Petersen30, S. Mahner2 Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe, Hannover, Deutschland 2 Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland 3 LMU München, München, Deutschland 4 KKS Marburg, Marburg, Deutschland 5 Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland 6 Kliniken Essen-Mitte, Essen, Deutschland 7 Universitätsklinikum Ulm, Ulm, Deutschland 8 Universitätsklinikum Freiburg, Freiburg, Deutschland 9 Charité, Campus Virchow Klinikum, Berlin, Deutschland 10 Universitätsklinikum Magdeburg, Magdeburg, Deutschland 11 Universitätsklinikum Halle/S., Halle, Deutschland 12 Universitätsklinikum Gießen u. Marburg, Marburg, Deutschland 1 70 Oncol Res Treat 2014;37(suppl 1):1–133 Universität Erlangen, Erlangen, Deutschland Universitätsklinikum Greifswald, Greifswald, Deutschland 15 Evangelisches Krankenhaus, Düsseldorf, Deutschland 16 Universitätsklinikum Essen, Essen, Deutschland 17 Klinikum der J.W. Goethe-Universität, Frankfurt, Deutschland 18 Klinikum rechts der Isar, München, Deutschland 19 Universitätsklinikum, Dresden, Deutschland 20 Universitätsklinikum, Tübingen, Deutschland 21 Klinikum, Wolfsburg, Deutschland 22 Georg-August-Universität, Göttingen, Deutschland 23 Klinikum, Offenbach, Deutschland 24 Klinik am Eichert, Göppingen, Deutschland 25 Kreisklinik, Altötting, Deutschland 26 Klinikum der Universität, Köln, Deutschland 27 Oberhavel Klinikum, Oranienburg, Deutschland 28 Städtisches Klinikum, Solingen, Deutschland 29 Elblandkliniken, Meißen-Radebeul, Deutschland 30 UKE, Hamburg, Deutschland 13 14 Aim: This study evaluates the impact of postoperative radio(chemo)therapy (RT/CTX) in patients with lymph-node positive vulvar carcinoma compared to surgery alone. Methods: Patients with primary squamous-cell vulvar cancer treated at 29 gynecologic cancer centers in Germany between 1998 and 2008 were included in a centralized database and analyzed retrospectively. Results: 1618 patients were documented with a median follow-up of 38.8 months (T1b 35.9%, T2 50.6%, T3 9.9% and T4 1.9%). 30.6% had lymph node metastases (N+) with a median progression-free survival (PFS) of 15.9 months and overall survival (OS) of 46.9 months, compared to 99.1 and 208.8 months for N- patients, resp. 34.8% had 1 N+, 20.6% 2 N+, 12.5% 3 N+ and 17.6% >3 N+. 254 (51.3%) of N+ patients underwent adjuvant RT/CTX with a longer median PFS and OS compared to N+ pats. without adjuvant treatment [PFS: 18.5 vs. 12.0 months, p = 0.0003, HR 0.63 (95% CI: 0.50–0.81); OS: 111.6 vs. 37.1 months, p = 0.029, HR 0.71 (95% CI: 0.52–0.97)]. This effect remained consistent in multivariate analysis adjusted for age, ECOG, UICC-stage, grade, invasion depth, number of N+ (PFS: HR 0.57, 95% CI: 0.43–0.74, p < 0.0001; OS: HR=0.61, 95% CI: 0.43–0.86, p = 0.005). However, in subgroup analyses statistical significance favoring adjuvant therapy was only reached in patients with 2 or more LN metastases. Conclusions: This large multicenter study in vulvar cancer shows that prognosis of node-positive patients was improved with adjuvant radiotherapy but still remains poor compared to the outcome of node-negative patients. A substantial benefit of adjuvant therapy can be seen in patients with 2 or more positive lymph nodes. The AGO CaRE-1 study may provide the basis for a prospective trial investigating the role of adjuvant radio(chemo)therapy in vulvar cancer. ID 250 Prognostic impact of the time interval between primary and re-staging surgery in patients with borderline ovarian tumours (BOT): An analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group F. Trillsch1, S. Mahner1, J.D. Rützel1, E. Vettorazzi2, A. Reuß3, P. Hillemanns4, L. Hanker5, A. Hasenburg6, H.-G. Strauß7, M. Hellriegel8, P. Wimberger9, B. Klaus10, M.-D. Keyver-Paik11, U. Canzler12, K. Wollschlaeger13, D. Forner14, J. Pfisterer15, W. Schröder16, K. Münstedt17, B. Richter18, C. Fotopoulou19, B. Schmalfeldt20, A. Burges21, T. Fehm22, W. Meier23, N. Ewald-Riegler24, N. De Gregorio25, F. Hilpert26, A. Du Bois27 Universitätsklinikum Hamburg-Eppendorf, Klinik für Gynäkologie und Gynäkologische Onkologie, Hamburg, Deutschland 2 Universitätsklinikum Hamburg-Eppendorf, Institut für Medizinische Biometrie und Epidemiologie, Hamburg, Deutschland 3 Philipps-Universität Marburg, Koordinierungszentrum für Klinische Studien, Marburg, Deutschland 4 Medizinische Hochschule Hannover, Frauenklinik, Hannover, Deutschland 5 Klinikum der J.W. Goethe-Universität, Zentrum für Frauenheilkunde u. Geburtshilfe, Frankfurt/M., Deutschland 1 Abstracts Inhalt Index Universitätsklinikum Freiburg, Frauenklinik, Freiburg, Deutschland Universitätsklinikum Halle/S., Universitätsklinik und Poliklinik für Gynäkologie, Halle/S., Deutschland 8 Georg-August-Universität Göttingen, Gynäkologie und Geburtshilfe, Göttingen, Deutschland 9 Universitätsklinikum Essen, Klinik für Frauenheilkunde und Geburtshilfe, Essen, Deutschland 10 Universitätsklinikum Gießen u. Marburg GmbH, Klinik für Gynäkologie, Gyn. Endokrinologie und Onkologie, Marburg, Deutschland 11 Rheinische Friedrich-Wilhelms-Universität, Universitäts-Frauenklinik, Bonn, Deutschland 12 Universitätsklinikum Carl Gustav Carus, Klinik u. Poliklinik für Frauenheilkunde u. Geburtshilfe, Dresden, Deutschland 13 Universitätsklinikum Magdeburg, Universitäts-Frauenklinik, Magdeburg, Deutschland 14 Sana-Klinikum Remscheid, Klinik für Frauenheilkunde und Geburtsmedizin, Remscheid, Deutschland 15 Städtisches Klinikum Solingen gGmbH, Klinik für Gynäkologie und Geburtshilfe, Solingen, Deutschland 16 GYNAEKOLOGICUM Bremen, Bremen, Deutschland 17 Universitätsklinikum Gießen, Zentrum für Frauenheilkunde u. Geburtshilfe, Gießen, Deutschland 18 Elblandkliniken Meißen-Radebeul GmbH & Co. KG, Frauenklinik, Radebeul, Deutschland 19 Charité, Campus Virchow Klinikum, Frauenklinik, Berlin, Deutschland 20 Klinikum rechts der Isar der Technischen Universität, Frauen- und Poliklinik, München, Deutschland 21 Klinikum der Universität München, Campus Großhadern, Klinik u. Poliklinik für Frauenheilkunde u. Geburtshilfe, München, Deutschland 22 Universitätsklinikum Tübingen, Universtitätsfrauenklinik, Tübingen, Deutschland 23 Evangelisches Krankenhaus, Frauenklinik, Düsseldorf, Deutschland 24 HSK, Dr. Horst Schmidt Klinik GmbH, Klinik für Gynäkologie u. gynäkologische Onkologie, Wiesbaden, Deutschland 25 Universitätsklinikum Ulm, Frauenklinik, Ulm, Deutschland 26 Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Gynäkologie und Geburtshilfe, Kiel, Deutschland 27 Kliniken Essen-Mitte, Klinik für Gynäkologische Onkologie, Essen, Deutschland 6 7 Background: Primary surgery for BOT often results in incomplete surgical staging. Hence, re-staging procedures are indicated but little is known about the impact of the time interval between primary and re-staging surgery on prognosis. Methods: Clinical parameters of 950 BOT patients treated between 1998 and 2008 in 24 German centers were investigated with prospective reference pathology and follow-up. Prognostic significance of the time interval was assessed by cox regression models. Time interval was then categorized in ≤30days vs. >30days and compared regarding patient characteristics. Results: Of 560 patients incompletely staged in primary surgery 308 patients with distinct information on surgical timing underwent re-staging procedures (55.0%). A significant increase of recurrence risk could be confirmed for patients undergoing restaging after >30days opposed to ≤30days (HR 2.43; p = 0.04) in univariate analysis. Rates for fertility-sparing surgery in primary treatment (28.6% vs. 16.1%, p = 0.009) and for uni- or bilateral cystectomy (15.0% vs. 5.0%, p = 0.003) were significantly higher in patients with time interval >30days. In multivariate analysis prognostic significance regarding PFS could be confirmed for the time interval and FIGO stage but not for fertility-preservation. Conclusions: A longer time interval between primary and re-staging surgery in BOT patients was associated with increased risk for recurrence. Since fertility-preservative procedures requiring more time for informed consent were more frequently observed in patients with longer time interval this supports current efforts to establish a short-termed centralized diagnosis of BOT in reference pathology. Abstracts ID 273 GPER-1 acts as a tumor suppressor in ovarian cancer L. Seiz1, T. Ignatov2, S. Modl2,3, C. Weißenborn2,3, A. Zenclussen3, S. Dan Costa2, O. Ortmann1, A. Ignatov1,2 Department of Obstetrics and Gynecology, University Medical Center Regensburg, Regensburg, Germany., Deutschland 2 Department of Obstetrics and Gynecology, University Clinic, Magdeburg, Germany., Deutschland 3 Department of Experimental Obstetrics and Gynecology, University Clinic, Magdeburg, Germany., Deutschland 1 Background: It is known that the new membrane-bound estrogen receptor GPER-1 acts suppressive in breast cancer cells and its expression decreases during disease progression. This study was conducted to evaluate the GPER-1 expression in ovarian cancer and its correlation with progression. Its function was tested in vitro in ovarian cancer cells. Patients and Methods: GPER-1 expression was analyzed by immunohistochemistry in 35 benign ovarian tumors, 35 tumors of low-malignant potential and in 124 ovarian cancers. GPER-1 expression was correlated to the prospectively evaluated disease-free survival of ovarian cancer patients. We also tested GPER-1 expression in ovarian cancer cells and the effect of GPER-1 stimulation on cell growth. Results: GPER-1 expression was significantly lower in ovarian cancer tissue than in benign and low-malignant ovarian tumors. GPER-1 expression was observed in 83.1% of malignant tumors and was higher in early stage cancers and tumors with high histological differentiation. GPER-1 expression was associated with favourable clinical outcome. The difference in 2-year disease-free survival by GPER-1 expression was significant, 28.6% for GPER-1 negative and 59.2% for GPER-1 positive cases (p = 0.002). GPER-1 expression was observed in SKOV-3 and OVCAR-3 ovarian cancer cell lines. G-1, a selective GPER-1 agonist, suppressed proliferation of the two cell types via inhibition of cell cycle progression in G2/M phase and stimulation of caspase-dependent apoptosis. The blockade in G2/M phase was associated with increased expression of cyclin B1 and Cdc2 and phosphorylation of histone 3. Conclusion: GPER-1 emerges as a new tumor suppressor with unsuspected therapeutic potential for ovarian cancer. ID 303 Sexual activity and function in patients with gynecological malignancies after completed treatment D. Grimm1, A. Hasenburg2, L. Steinsiek1, F. Trillsch1, S. Mayer2, S. Eltrop2, S. Mahner1, L. Woelber1 University Medical Center Hamburg-Eppendorf, Department of Gynecology and Gynecologic Oncology, Hamburg, Deutschland 2 University Hospital Freiburg, Department of Gynecology, Freiburg, Deutschland 1 Background: Sexual activity (SA) and function (SF) after completion of treatment are central for quality of life (QoL) in women affected by gynecological cancers. Aim of this study was to analyse the SA, SF and QoL of women with primary cervical-, endometrial- or vulvar cancer compared to patients with breast cancer. Methods: In a multicenter cross-sectional study, women, aged 18–70 years, were surveyed at least 12 months after completion of primary therapy for cervical-, endometrial- or vulvar cancer. A cohort of breast cancer patients served as control. Data was collected through validated questionnaires. Results: Patients in the gynecological cancer group (GCG) (n = 77) and the breast cancer group (BCG) (n = 186) were of similar age (median 55 vs. 56.5 years) and menopausal status (90.5% vs. 88.6%). 41.3% of the patients in the GCG were sexually active and 45.8% in the BCG. The most common reason for sexual inactivity in the GCG was «the-presence-of-a physical-problem» (40.9% vs. 37.8%) whereas in the BCG «low-interestin-sex» was most common (44.9% vs. 34.1%). Overall, there was a better SF in the GCG with a trend towards higher sexual satisfaction (p = 0.09), significantly more pleasure (p = 0.02) and less discomfort during inter- Oncol Res Treat 2014;37(suppl 1):1–133 71 Inhalt Index course (p = 0.03). QoL and overall health were not significantly different between the two groups (EORTC-QLQ-C30 score 68.25 vs. 67.50) and comparable to populations without cancer. Conclusion: The high number of sexually inactive women indicates that women suffer from persistent functional problems after therapy of gynecological malignancies. However, women who regain sexual activity after completed treatment have a very good overall SF. ID 328 Berlin Tumor Center implemented Online Registry for Patients with Borderline Tumors of the Ovary – a Prospective Evaluation L. Kretzschmar , R. Chekerov , A. Jagota , M. Abou-Dakn , S. Braun4, A. Ebert5, E. Keil6, C. Kronenberg7, B. Müller8, C. Olbrich9, J. Potenberg10, S. Rothe11, J.-P. Scharf12, U. Torsten13, U. Ulrich14, J. Sehouli1 1 1 2 3 Charité -Universitätmedizin Berlin, Berlin, Deutschland Tumor Centrum Berlin, Berlin, Deutschland 3 Sankt Joseph Krankenhaus, Berlin, Deutschland 4 Sankt Gertrauden Krankenhaus, Berlin, Deutschland 5 Vivantes Humboldt-Klinikum, Berlin, Deutschland 6 Park-Klinikum Weißensee, Berlin, Deutschland 7 Vivantes Auguste-Viktoria Klinikum, Berlin, Deutschland 8 Vivantes Klinikum Hellersdorf, Berlin, Deutschland 9 DRK Kliniken Westend, Berlin, Deutschland 10 Evangelisches Waldkrankenhaus Spandau, Berlin, Deutschland 11 Helios Klinikum Berlin Buch, Berlin, Deutschland 12 Sana Klinikum Lichtenberg, Berlin, Deutschland 13 Vivantes Klinikum Neukölln, Berlin, Deutschland 14 Martin Luther Krankenhaus, Berlin, Deutschland 1 2 BOT are a rare, usually coincidental diagnose, commonly found after surgery for suspect ovarian tumors. Due to the limited amount of data the Coordinating Tumor Center of Berlin established an online-based platform allowing the participating clinics in Berlin to register patients with BOT and their clinical information. Results of the first four years after implementation shall be presented. Beginning 2010 all thirteen participating gynaecological departments of Berlin have been entering their anonymised patient data concerning age, fertility, date of diagnoses, surgical procedures, histopathology, adjuvant therapy and follow-up data. To date 232 patients have been registered in BOT. The median age was 47 years. Histology showed most patients having serous type tumors (52%) followed by mucinous intestinal (16%), serous-papillary (15%) and mucinous endocervical (13%), with 25% presenting peritoneal implants of which 15% were of invasive nature (absolute 4%). The majority of patients presented FIGO I (79%).Every patient was treated surgically, with an average of 2 surgeries/person, 60% laparoscopically; the most common surgical procedures besides USO being omentectomy, cytology, peritoneal biopsy, BSO, hysterectomy and appendectomy. The online BOT Registry is the first prospective collection of clinical data for patients with BOT in Germany. The current data shows that the average patient treated for BOT is young, with serous histopathology and early stage disease. BOT Registry proves to be a feasible and well-accepted tool for common data collection within the departments of gynecology of Berlin clinics and can be considered representative and a valuable tool for further clinical and epidemiological study projects. ID 329 Outcome parameters in node-negative vulvar cancer – a subset analysis of the AGO CaRE-1 study L. Wölber1, J. Jueckstock2, F. Hilpert3, P. Neuser4, P. Harter5, N. De Gregorio6, S. Iborra7, J. Sehouli8, A. Habermann9, P. Hillemanns10, S. Fürst11, H.-G. Strauss12, K.H. Baumann13, F. Thiel14, A. Mustea15, W. Meier16, A. Du Bois5, P. Wimberger17, L.C. Hanker18, B. Schmalfeldt19, U. Canzler20, T. Fehm21, A. Luyten22, M. Hellriegel23, J. Kosse24, C. Heiss25, P. Hantschmann26, P. Mallmann27, B. Tanner28, J. Pfisterer29, B. Richter30, L.-F. Griebel1, S. Mahner1 Universitätsklinikum Hamburg-Eppendorf, Klinik für Gynäkologie und gynäkologische Onkologie, Hamburg, Deutschland 2 Klinikum Universität München Campus Innenstadt, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, München, Deutschland 3 Universitätsklinikum Schleswig-Holstein, Klinik für Gynäkologie und Geburtshilfe, Kiel, Deutschland 4 Philipps-Universität, Koordinierungszentrum für Klinische Studien, Marburg, Deutschland 5 Kliniken Essen Mitte, Klinik für Gynäkologie und gynäkologische Onkologie, Essen, Deutschland 6 Universitätsklinikum Ulm, Klinik für Frauenheilkunde und Geburtshilfe, Ulm, Deutschland 7 Universitätsklinikum Freiburg, Klinik für Gynäkologie, Freiburg, Deutschland 8 Charite Universitätsmedizin Berlin Campus Virchow, Klinik Für Gynäkologie, Berlin, Deutschland 9 Universitätsklinikum Magdeburg, Universitätsfrauenklinik, Magdeburg, Deutschland 10 Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe, Hannover, Deutschland 11 Universitätsfrauenklinik München – Großhadern, München, Deutschland 12 Universitätsklinikum Halle, Klinik und Poliklinik für Gynäkologie, Halle, Deutschland 13 Philipps Universität Marburg, Klinik für Gynäkologie, gyn. Endokrino- und Onkologie, Marburg, Deutschland 14 Universitätsklinikum Erlangen, Frauenklinik, Erlangen, Deutschland 15 Universitätsfrauenklinik Greifswald, Greifswald, Deutschland 16 Evangelisches Krankenhaus, Klinik für Gynäkologie, Düsseldorf, Deutschland 17 Universitätsklinikum Essen, Klinik für Frauenheilkunde und Geburtshilfe, Essen, Deutschland 18 Universitätsklinikum Frankfurt, Klinik für Gynäkologie, Frankfurt, Deutschland 19 Technische Universität München, Frauenklinik und Poliklinik, München, Deutschland 20 Uniklinikum Dresden, Klinik für Frauenheilkunde und Geburtshilfe, Dresden, Deutschland 21 Universitätsklinikum Tübingen, Universitäts-Frauenklinik, Tübingen, Deutschland 22 Klinikum Wolfsburg, Frauenklinik, Wolfsburg, Deutschland 23 Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Deutschland 24 Sana Klinikum Offenbach, Klinik für Gynäkologie und Geburtshilfe, Offenbach, Deutschland 25 Klinik am Eichert, Frauenklinik, Göppingen, Deutschland 26 Kreiskliniken Altöttingen-Burghausen, Abteilung für Gynäkologie und Geburtshilfe, Altötting, Deutschland 27 Uniklinik Köln, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Kölln, Deutschland 28 Oberhavel Kliniken – Klinik Oranienburg, Frauenklinik, Oranienburg, Deutschland 29 Städtisches Klinikum Solingen, Klinik für Frauenheilkunde und Geburtshilfe, Solingen, Deutschland 30 Elblandkliniken, Klinik für Frauenheilkunde und Geburtshilfe, Radebeul, Deutschland 1 Aim: To identify possible prognostic factors in node-negative vulvar cancer. Methods: The AGO CaRE-1 study was designed as retrospective survey of treatment patterns and prognostic factors in vulvar cancer. Pts with primary vulvar cancer stage ≥1b treated at 29 German gynecologic cancer centers 1998-2008 were included in a centralized database. Results: Of the 1618 pts documented, 702 were node negative (pN0) after surgical staging and received no additional treatment despite sur- 72 Oncol Res Treat 2014;37(suppl 1):1–133 Abstracts Inhalt Index gery. Median age of these pts was 66 yrs (21–94). 380 (54.1%) had pT1b, 300 (42.7%) pT2, 22 (3.1%) pT3 tumors. Median tumor size was 20 mm (1-345) and depth of invasion 4 mm (0.75–60). 634 (90.3%) pts had an R0 resection with a minimal margin of 5 mm (1–33); there were 23 R1 (3.3%) and 45 (6.4%) Rx resections. 622 pts (88.6%) received a full groin dissection and 80 pts (11.4%) a sentinel node procedure only. Median follow-up was 42.5 months. 145 pts (20.7%) developed disease recurrence (thereof 95 (65.5%) at the vulva only) after a median of 17.5 months. 82 pts (11.7%) died. To assess potential prognostic factors, multivariate analyses were performed including age, stage, tumor size, invasion depth, tumor grade, resection margin, and mode of groin dissection [sentinel vs. full]) showing age as the only consistent prognostic factor for recurrence-free and overall survival. Conclusions: Even in the large patient cohort of the AGO-CaRE database with more than 700 node-negative pts it was not possible to identify reliable clinicopathologic prognostic factors for node-negative disease. Identification of new markers will be necessary to select high risk pts for adjuvant treatment. analyses of symptomatic pts included only those with a baseline score ≥ 15 (sufficient to show ≥15-point improvement). Mixed-model repeated measures (MMRM) analysis was used to compare Qs from all time points until PD/death. Results: Qs were available at baseline from 89% of 361 randomized pts and at wk 8/9 from 81% and 68% of pts in the BEV-CT or CT arm, respectively. More BEV-CT than CT pts had a ≥15% improvement in the OV28 abdo/GI symptom subscale at wk 8/9 (21.9% vs 9.3%, 12.7% difference [95% CI 4.4–20.9]; p = 0.002). The sensitivity analysis showed a 13.3% difference [95% CI 4.5–22.1] and the subgroup analysis of 233 symptomatic pts a 16.9% difference (95% CI 6.1–27.6) favoring BEVCT (29.6% vs 12.7%). MMRM analysis also favored BEV-CT (6.4-point difference [95% CI 1.28–11.6]). More BEV-CT than CT pts had a ≥15% improvement in FOSI score at wk 8/9 (12.2% vs 3.1%, 9.0% difference [95% CI 2.9–15.2]). Conclusions: Adding BEV to CT improved patient-reported abdo/GI symptoms in platinum-resistant OC. ID 347 ID 337 Health-related quality of life (HRQoL) results from the AURELIA trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum-resistant recurrent ovarian cancer (OC) F. Hilpert1, P. Wimberger2, J. Sehouli3, A. Reuss4, P. Harter5, R. Hils6, N. De Gregorio7, H.-J. Lück8, B. Gerber9, T. Fehm10, L. Hanker11, C. Uleer12, A. Burges13, J. Kosse14, M. Thill15, M. Beckmann16, J.-P. Scharf17, W. Meier18, G. Gebauer19, E. Pujade-Lauraine20 UKSH Campus Kiel, Klinik für Gynäkologie und Geburtshilfe, Kiel, Deutschland 2 Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Dresden, Deutschland 3 Charité, Klinik für Gynäkologie, Berlin, Deutschland 4 Philipps-Universität, KKS, Marburg, Deutschland 5 Kliniken Essen-Mitte, Gynäkologie und Gynäkologische Onkologie, Essen, Deutschland 6 HSK, Gynäkologie und Gynäkologische Onkologie, Wiesbaden, Deutschland 7 Universitätsklinikum, Frauenheilkunde und Geburtshilfe, Ulm, Deutschland 8 Gynäkologisch-Onkologische Schwerpunktpraxis, Hannover, Deutschland 9 Klinikum Südstadt, Universitätsfrauenklinik, Rostock, Deutschland 10 Universitätsklinikum, Frauenklinik, Düsseldorf, Deutschland 11 UKSH Campus, Klinik für Frauenheilkunde und Geburtshilfe, Lübeck, Deutschland 12 Frauenärzte am Bahnhofsplatz, Hildesheim, Deutschland 13 LMU Campus Grosshadern, Frauenklinik, München, Deutschland 14 Sana Klinikum, Gynäkologie und Geburtshilfe, Offenbach, Deutschland 15 Agaplesion Markus Krankenhaus, Klinik für Gynäkologie und Geburtshilfe, Frankfurt am Main, Deutschland 16 Universitätsklinikum, Frauenklinik, Erlangen, Deutschland 17 Sana Klinikum, Frauenklinik, Berlin-Lichtenberg, Deutschland 18 Evangelisches Krankenhaus, Frauenklinik, Düsseldorf, Deutschland 19 Marienkrankenhaus, Frauenklinik, Hamburg, Deutschland 20 Hôpital Hôtel-Dieu, Paris, Frankreich 1 Background: Adding BEV to CT significantly improved PFS in platinum-resistant OC in the phase III AURELIA trial. HRQoL was a key secondary aim of AURELIA. Methods: Patients (pts) with OC were assigned to receive monochemotherapy (peg-lip doxorubicin, topotecan, or weekly paclitaxel) and than randomized to CT ± BEV. HRQoL was assessed at baseline and every 2 or 3 cycles until PD using the EORTC OC Module (OV28) and FOSI. The primary HRQoL endpoint was an absolute improvement of ≥15% on the 100-point OV28 subscale for abdominal (abdo)/GI symptoms at wk 8/9. Pts with missing questionnaires (Qs) were included and considered not to have improved. A sensitivity analysis excluded pts with Qs missing for reasons other than PD/death or switch from CT to BEV. Subgroup Abstracts Folate Receptor Alpha (FRA) expression in endometrial cancer (EC) P. Kosian1, E. Somers2, D.J. O’Shannessy2, M. Nassir1, C. Fotopoulou1, R. Chekerov1, J. Sehouli1, E.I. Braicu1 Charité – Universitätsmedizin Berlin, Department of Gynecology, Berlin, Deutschland 2 Morphotec, Exton, Vereinigte Staaten Von Amerika 1 Background: Folate receptor alpha (FOLR1/FRA) is expressed in a high percentage of serous ovarian, endometrial, lung and breast cancers but expression in normal tissues is restricted to the apical surfaces of a limited subset of polarized epithelial cells. Therefore, FRA is an interesting candidate for new targeted therapies. The aim of the present study was to evaluate the expression of FRA in endometrial cancer and evaluate its relationship to clinical and histopathological parameters. Methods: Immunohistochemistry with MAb 26B3 was performed on paraffin -embedded tissues from 113 primary endometrial cancer patients. A positive result was defined as membrane staining of ≥5% of tumor cells. Further, staining was calculated using the M-score, a semi-quantitative algorithm which incorporates both intensity and percentage tumor staining. Results: An endometrioid subtype was present in 75.9% of the cohort and FRA IHC was positive in 91.7% of the cohort. Significantly higher FRA expression was observed in G3 compared to G1 (p = 0.042) and in serous papillary compared to endometroid endometrial cancer (p = 0.005). Oestrogen receptor negativity correlated with a high folate receptor expression (p = 0,033). M-score cut-off value of 35% was a significant prognostic factor for overall survival (p = 0.014). Conclusion: This study that FRA overexpressed in high risk EC tumors, correlating with poor overall survival. Therefore there might be a benefit from FRA targeted diagnostics and therapeutics. Further multi-centre studies are warranted. ID 352 Endometriosis as a risk factor for Ovarian or Endometrial Cancer – results of a hospital based case control study S. Burghaus1, L. Häberle1, M.G. Schrauder1, K. Heusinger1, K. Beckmann1, F. Thiel1, A. Hein1, D. Wachter1,2, A. Hartmann2, M.W. Beckmann1, P.A. Fasching1, S.P. Renner1 1 2 Universitätsklinikum Erlangen, Frauenklinik, Erlangen, Deutschland Universitätsklinikum Erlangen, Pathologie, Erlangen, Deutschland Background: There is no screening program for ovarian or endometrial cancer. One reason for that could be the relatively low incidence with subsequently low positive predictive values for tests with low specifity. One way to address the problem could be the utilization of risk factors to define sub-populations with a higher incidence. Recently, there were hints that endometriosis could be a risk factor for ovarian cancer. Oncol Res Treat 2014;37(suppl 1):1–133 73 Inhalt Index Methods: We conducted a hospital based case control analysis. Cases were patients with endometrial or ovarian cancer who participated in studies aiming at risk assessment for these diseases. Controls were women who were invited by newspaper advertisement. A total of 289 cases and 1016 controls were included. Two logistic regression models were used, one with the predictors age, number of pregnancies and previous oral contraceptive (OC) use and another one including additionally whether the patient was diagnosed with endometriosis. Both models were compared with the likelihood ratio test. Results: Endometriosis was present in 21 controls (2.1%) and 14 cases (4.8%). Relevant predictors for case control status were previous OC use (OR=0.41; 95%CI: 0.30–0.55) and endometriosis (OR=2.53; 95%CI: 1.23–5.21). The prediction model that included endometriosis was slightly better (p = 0.01, likelihood ratio test) than the model without endometriosis (AUC=0.67 vs. AUC=0.66). Conclusion: In our case control study endometriosis could be described as a risk factor for endometrial or ovarian cancer. Studies addressing this question are rare and the implementation into a clinical prediction model would demand a predise characterization of the risk factor endometriosis. For this purpose we initiated a multicentric cohort study (www.myendometriosis.org). Material und Methoden: In einer prospektiven Fallstudie wurden Cisplatin 7,5 mg/m2 und Doxorubicin 2,5 mg/m2 bei 12 mmHg und 37 °C für 30 min intraabdominell mittels PIPAC appliziert. Das Tumoransprechen wurde mittels histologischer Tumorregression in der Biopsie und Peritonealkarzinose-Index (PCI) in der Video-Laparoskopie beurteilt. Ergebnisse: Bei 18 Patientinnen wurden insgesamt 34 PIPAC-Prozeduren durchgeführt, in 8 Fällen in Kombination mit zytoreduktiver Chirurgie (CRS). Es gab keine perioperative Mortalität. Es traten 5 Nebenwirkungen ≥ 2 Grad WHO auf, davon 3 im Zusammenhang mit CRS. Das mediane Follow-Up betrug 192 Tage (min. 13, max. 639). Das kumulative Überleben nach 400 Tagen war 62% und das mittlere Überleben 442 Tage. Bei 8 Patientinnen wurde die PIPAC im Intervall von 28-42 Tagen wiederholt appliziert und in 6 dieser Fälle konnte ein objektives Tumoransprechen beurteilt werden (komplette Remission: 1; partielle Remission: 2; stabile Krankheit: 3). In einer multivariaten Analyse mit PIPAC, Alter, Serum CA-125 und Vorkommen von Aszites konnte die PIPAC die objektive Tumorantwort auf die Therapie unabhängig vorhersagen. Schlussfolgerung: Die Wirksamkeit der PIPAC bei Patientinnen mit rezidivierendem, Platin-resistentem Ovarialkarzinom konnte in dieser ersten, kleinen Fallserie nachgewiesen werden und wird zurzeit in einer klinischen Studien untersucht (NCT01809379) ID 368 ID 416 A rare case of isolated subcutaneous implantation of a borderline ovarian tumor M. Banys, B. Yeganeh, R. Langenberg, G. Gebauer Marienkrankenhaus Hamburg, Frauenklinik, Hamburg, Deutschland Laparoscopy-related subcutaneous tumor implantations of gynecological malignancies are considered rare. We report the case of a 46-year-old woman who presented with an isolated metastasis of a borderline ovarian tumor in the abdominal wall. The patient presented with an asymptomatic cyst with papillary excrescences in her right ovary, measuring 28 × 25 mm. CA125 was 38.7 U/ml. Patient’s concomitant diseases at time of presentation were obesity, hypothyreosis and arterial hypertension. The patient had a history of previous two laparoscopies (ectopic pregnancy 1990, sterilization 1996) and one vaginal birth. We conducted laparoscopic right adnexectomy; histopathological workup of the right ovary revealed mucinous papillary borderline tumor. Consequently, nine days later the patient underwent explorative median laparotomy with hysterectomy, left adnexectomy, omentectomy and appendectomy. No intraperitoneal implants were found. Further exploration revealed a cystic-solid structure (5 × 5 cm) in the subcutaneous fat tissue above the fascia with no contact to intraperitoneal cavity. The structure was resected; histopathological examination confirmed the diagnosis of a non-invasive implant of a papillary borderline tumor. Possibly, tumor cells were displaced during previous laparoscopies (the last one fourteen years prior to presentation). ID 384 Wirksamkeit der intraperitonealen DruckAerosolchemotherapie (PIPAC) mit Cisplatin und Doxorubicin bei rezidivierendem, Platin-resistentem Ovarialkarzinom: Preliminäre klinische Ergebnisse. W. Solaß1, I. Celik2, B. Bürkle2, U. Pabst1, D. Strumberg3, J. Zieren1, M. Reymond1, C. Tempfer2 Ruhr-Universität Bochum, Marienhospital Herne, Klinik für Chirurgie, HERNE, Deutschland 2 Ruhr-Universität Bochum, Frauenklinik, Herne, Deutschland 3 Ruhr-Universität Bochum, Klinik für Onko-Hämatologie, Herne, Deutschland 1 Einleitung: Prüfung der Wirksamkeit und der Verträglichkeit der intraperitonealen Druckaerosolchemotherapie (PIPAC) bei Patientinnen mit rezidivierendem, Platin-resistentem Ovarialkarzinom und Peritonealkarzinose. 74 Oncol Res Treat 2014;37(suppl 1):1–133 AGO-OVAR 12: A Randomized Placebo-controlled GCIG/ ENGOT-Intergroup Phase III trial of standard frontline chemotherapy +/- Nintedanib for advanced ovarian cancer P. Harter1, R. Kimmig2, N. de Gregorio3, A. Reuss4, J. Pfisterer5, D. Cibula6, F. Hilpert7, W. Meier8, L.C. Hanker9, U. Canzler10, J. Sehouli11, K. Baumann12, A. Burges13, M. Gropp-Meier14, A. Hasenburg15, A. Belau16, T. Fehm17, J. Kosse18, S. Mahner19, B. Schmalfeldt20, F. Marme21, B. Richter22, U. Herwig23, C. Liebrich24, B. Gerber25, J. Potenberg26, P. Krabisch27, M. Thill28, M. Merger29, A. du Bois1 Kliniken Essen-Mitte, Essen, Deutschland Universitätsklinikum, Essen, Deutschland 3 Universitätsklinikum, Ulm, Deutschland 4 KKS, Marburg, Deutschland 5 Zentrum f. Gyn. Onkologie, Kiel, Deutschland 6 Universitätsklinikum, Prag, Tschechische Republik 7 Universitätsklinikum, Kiel, Deutschland 8 Ev. Krankenhaus, Düsseldorf, Deutschland 9 Universitätsklinikum, Frankfurt, Deutschland 10 Universitätsklinikum, Dresden, Deutschland 11 Charite, Campus Virchow, Berlin, Deutschland 12 Universitätsklinikum, Marburg, Deutschland 13 Klinikum der Universität München-Großhadern, München, Deutschland 14 Onkologie, Ravensburg, Deutschland 15 Universitätsklinikum, Freiburg, Deutschland 16 Universitätsklinikum, Greifswald, Deutschland 17 Universitätsklinikum, Tübingen, Deutschland 18 Sana Klinikum, Offenbach, Deutschland 19 Universitätsklinikum, Hamburg, Deutschland 20 Klinikum rechts der Isar, München, Deutschland 21 NCT, Heidelberg, Deutschland 22 Elblandkliniken Meißen-Radebeul, Radebeul, Deutschland 23 Albertinen Krankenhaus, Hamburg, Deutschland 24 Klinikum, Wolfsburg, Deutschland 25 Universitätsklinikum, Rostock, Deutschland 26 Ev. Waldkrankenhaus Spandau, Berlin, Deutschland 27 Klinikum, Chemnitz, Deutschland 28 Universitätsklinikum, Lübeck, Deutschland 29 Böhringer Ingelheim Pharma, Biberach, Deutschland 1 2 Background: Angiogenesis plays an established role as target in the treatment of ovarian cancer(OC). Nintedanib(N), an oral inhibitor of VEGFR, PDGFR, and FGFR, has shown activity in OC in phase II trials. Methods: Pts with FIGO IIB-IV OC and upfront debulking surgery were randomized 2:1 to N 200 mg bid + Carboplatin (C AUC5 or 6) and Paclitaxel (T 175 mg/m2), or placebo (Pl) + TCq21. Primary endpoint Abstracts Inhalt Index was investigator assessed PFS, analysis of stratification factors were preplanned. Results: 1,366 patients were recruited 12/2009–7/2011 by 9 study groups; 911 TC+N and 455 received TC+Pl. Overall, 39% had a very high risk with FIGO III and residuals >1cm or FIGO IV while 61% had FIGO III and residuals ≤1cm or FIGO II (283 in TC-Pl, 556 in TC+N). After 752 observed events, PFS was significantly longer with N+TC than Pl+TC (median 17.3 vs 16.6 months; HR 0.84; 95% CI: 0.72–0.98; p = 0.0239). Post-hoc analysis of pre-defined subgroups showed a higher benefit in patients of the low risk subgroup: median PFS 20.8 vs 27.1 months; HR 0.74 (0.61–0.91). OS data are still immature. Increased adverse events (at least +10% difference G3-5 in TC+N) included thrombocytopenia (+11.3%), ALT/AST increase (+13.3%), Diarrhea (+19.6%). Conclusion: Nintedanib in combination with TC significantly prolongs PFS in first-line OC; its impact was highest in pts with low post-OP tumor burden. Nintedanib appears to be a valuable treatment option in advanced OC, however, further studies should focus on patient selection and optimization of tolerability. ID 419 Epigenetic silencing of KBTBD12, a member of the kelch protein family, is involved in invasiveness of breast cancer cells E. Honisch1, C. Melcher1, L. Brandi1, C. Wiek2, H. Hanenberg2, T. Fehm1, D. Niederacher1 Universitäts-Frauenklinik Düsseldorf, Molekulargenetisches Labor, Düsseldorf, Deutschland 2 Universitätsklinikum Düsseldorf, Hals-Nasen-Ohren-Klinik, Düsseldorf, Deutschland 1 A growing number of breast cancer risk associated SNPs are identified by genome wide association studies. However, causative genes and mechanisms behind the associations remain largely unknown. During validation of known risk loci from the CGEMS project in BRCA negative familial or genetically enriched cases from Germany, a variant in KBTBD12, a member of the kelch repeat family of proteins could be identified. The aim of this study was to initially characterize this so far undefined gene. RNA expression was analyzed by quantitative real-time PCR. Methylation of a promoter associated CpG island was measured by direct bisulfite sequencing and methylation specific PCR. Mutation analyses were conducted by dHPLC and Sanger sequencing. Breast carcinoma cell lines were stably transfected by retroviral transfection. Migration and invasion capabilities were determined by monolayer wound healing assay and matrigel invasion assay respectively. KBTBD12 mRNA expression was significantly downregulated in breast carcinoma cell lines and tissues compared to normal tissues (tumor flanking and reduction mammoplasties). Reduced expression was associated with promoter methylation and restored by cell line exposure to a demethylating agent. Germ line mutation analyses of 71 BRCA negative high risk breast cancer patients showed no clearly pathogenic sequence alterations. Metastatic breast cancer cell line MDA-MB-231 transfected to express KBTBD12 showed significantly reduced migratory and invasive potential in vitro. Subcellular fractionation as well as microscopic analyses suggests an association of KBTBD12 protein with the endoplasmic reticulum. Our findings raise the possibility of KBTBD12 as a breast tumor suppressor gene. Abstracts ID 432 Results of an international Intregroup randomized phase III trial of pazopanib versus placebo (AGO-OVAR16). Subgroup Analysis of toxicity and clinical outcome in the Asian and Non-Asian population J. Sehouli1, P. Harter2, P. Wimberger3, J. Rau4, K. Baumann5, C. Kurzeder6, U. Canzler7, W. Meier8, L.C. Hanker9, S. Mahner10, P. Krabisch11, W.W. Reiter12, B. Aminossadati4, A. du Bois13 Charité Universitätsmedizin, Campus Virchow Klinikum, Frauenklinik, Berlin, Deutschland 2 Dr. Horst-Schmidt-Klinik,, Klinik für Gynäkologie und Gynäkologische Onkologie,, Wiesbaden, Deutschland 3 Universitätsklinikum Essen,, Klinik für Frauenheilkunde und Geburtshilfe,, Essen, Deutschland 4 KKS, Marburg, Deutschland 5 Universitätsklinikum Gießen und Marburg, Gyn. Endokrinologie und Onkologie,, Marburg, Deutschland 6 Universitätsklinikum Ulm,, Universitätsfraeunklinik, Ulm, Deutschland 7 Universitätsklinikum Carl Gustav Carus ,, Klinik u. Poliklinik für Frauenheilkunde u. Geburtshilfe, Dresden, Deutschland 8 Evangelisches Krankenhaus, Fraeunklinik, Düsseldorf, Deutschland 9 Klinikum der J.W. Goethe-Universität,, Zentrum für Frauenheilkunde u. Geburtshilfe, Frankfurt. M., Deutschland 10 Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Gynäkologie, Hamburg, Deutschland 11 Klinikum Chemnitz, Frauenklinik, Chemnitz, Deutschland 12 Schwerpunkt-Praxis;, Viersen, Deutschland 13 Kliniken Essen Mitte, Klinik für Gynäkologische Onkologie, Essen, Deutschland 1 Pazopanib is an oral, multikinase inhibitor of VEGFR-1-3, PDGFR-α/β, and c-Kit. This international study evaluated the efficacy, safety, and tolerability of pazopanib maintenance therapy in patients (pts) who have not progressed after 1-line chemotherapy for AEOC. Methods: Pts with histologically confirmed AEOC, FIGO IIb-IV, and no evidence of progression after 1st-line therapy were randomized 1:1 to receive 800 mg pazopanib once daily or placebo for up to 24 months (mo). Primary endpoint was PFS by RECIST. Within this study 373 Non-Asia and 104 Asia pts were included and is the basis for this subgroup analysis. Results: The global results of the study (n = 940) were presented at ASCO 2013. Pts in the pazopanib arm had a prolonged PFS vs placebo (HR = 0.766; 95% CI: 0.64–0.91; p = 0.0021; medians 17.9 vs 12.3 mo, respectively). In the present subgroup analysis there were significant differences between Asian and Non-Asian population.For Asian and Non-Asia pts, dose reduction occurred in 75% vs. 53%, respectively. Non-Asian pts in the Pazopanib arm had a prolonged PFS vs. placebo (HR = 0.694; 95% CI: 0.57–0.84; p =0.0001; medians 17.8 vs 11.9 mo, respectively). Within Asian population no significant improvement of the PFS in the pazopanib arm vs, placebo arm was found (HR= 1.164; 95% CI: 0.782–1.734, p = 0.4528; medians 18.0 vs 23.9 mo, respectively). In non-Asian pts the incidence of neutropenia (6% vs. 24%), thrombocytopenia (1% vs. 8%), palmar plantar-erythrodysaesthesia (1% vs. 5%), hypertension (30% vs. 35%) was lower compared to Asian pts. Diarrhoe (9% vs 4%), liver related toxicity (10% vs. 6%) and asthenia (3% vs. 1%) were more often encounterd in Asian vs. non-Asian pts, respectively. Conclusions: This study describes significant differences of the tolerability and toxicity and the clinical outcome between Asian and Non-Asian AEOC pts. Further clinical trials should address this relevant topic. Oncol Res Treat 2014;37(suppl 1):1–133 75 Inhalt Index Head and Neck Cancer ID 051 Primary surgery versus primary surgery followed by adjuvant radiotherapy in patients with pT1/T2 pN1 oral squamous cell carcinoma – results of an international multicenter study M. Kreppel1, M. Amit2, J. Zöller1, M. Scheer1,3, S. Patel4, Z. Gil2 University of Cologne, Department for Oral and Maxillofacial Plastic Surgery, Cologne, Deutschland 2 Rambam Medical Center, Rappaport School of Medicine, the Technion, Israel Institute of technology, Haifa, Department of Otolaryngology, Haifa, Israel 3 Mühlenkreiskliniken Minden, Department for Oral and Maxillofacial Plastic Surgery, Minden, Deutschland 4 Memorial Sloan Kettering Cancer Center, NY, NY, Head and Neck Surgery, New York, Vereinigte Staaten Von Amerika 1 Background: In patients with advanced stage oral squamous cell carcinoma (OSCC), adjuvant radiotherapy (RT) leads to improved survival and locoregional control rates. For small tumors (pT1 & pT2) with a small solitary ipsilateral cervical lymph node metastasis however, there is no definite recommendation whether an adjuvant RT should be carried out in comparison to a solely surgical treatment. Methods: 216 patients with OSCC of histologically proven pT1/T2 pN1 status were included in this international multicenter study. Further inclusion criteria were clear resection margins, the absence of lymphangiosis carcinomatosa and extracapsular spread. Overall survival (OS) and locoregional control (LRC) were determined by using the Kaplan-Meier method. Prognostic factors were analyzed by the log rank test and the Cox regression. Results: Mean and median follow up were 54.5 and 55 months respectively. 61 patients received a surgical treatment while adjuvant RT was administered in 155 patients after surgery. Patients receiving adjuvant RT showed a significantly higher 5-year OS rate than patients treated with surgery only. (70% vs. 42%, p = 0.001). In multivariate analysis, only adjuvant RT (p = 0.001) and age (p = 0.015) had a significant impact on OS. LRC-rate after 5 years was also significantly better for patients, who were treated with adjuvant RT (80% vs. 46%, p < 0.001) Conclusion: Adjuvant RT in patients with small OSCC and pN1-status seems to be beneficial for survival and locoregional control in comparison to a solely surgical treatment. ID 097 Impact of human papilloma virus infection on the response of head and neck cancers (HNSCC) to antiepidermal growth factor receptor (EGFR) antibody therapy* T.C. Gauler1, M. Pogorzelski1, S. Ting2, F. Breitenbuecher1, I. Vossebein1, S. Hoffarth1, S. Lang3, C. Bergmann3, J. Abu Jawad4, J. Markowetz1, K.W. Schmid2, M. Schuler1, S. Kasper1 Westdeutsches Tumorzentrum, Universitätsklinik Essen, Innere Klinik (Tumorforschung), Essen, Deutschland 2 Westdeutsches Tumorzentrum, Universitätsklinik Essen, Institut für Pathologie und Neuropathologie, Essen, Deutschland 3 Westdeutsches Tumorzentrum, Universitätsklinik Essen, Klinik für Hals-, Nasen-, Ohrenheilkunde, Essen, Deutschland 4 Westdeutsches Tumorzentrum, Universitätsklinik Essen, Klinik für Strahlentherapie, Essen, Deutschland 1 Introduction: The monoclonal antibody cetuximab targeting the EGFR has clinical activity in patients with advanced or metastatic HNSCC. Up to 40% of HNSCC are associated with HPV infection. The functional association of HPV status with the cetuximab response in HNSCC remains to be defined. Methods: Formalin-fixed, paraffin-embedded tumor samples from 69 cetuximab-treated patients with recurrent or metastatic HNSCC were 76 Oncol Res Treat 2014;37(suppl 1):1–133 probed for p16INK4a expression, an established biomarker of HPV infection. Response rates, progression-free survival (PFS) and overall survival (OS) were analyzed in relation to p16INK4a status. The impact of cetuximab on apoptosis and proliferation in vitro and tumor growth in mice was studied in HNSCC cell lines with defined HPV status, and in cetuximab-sensitive cancer cell lines stably expressing HPV oncogenes E6 and E7. Results: p16INK4a expression was detected in tumor samples from 18.8% of HNSCC patients with preponderance of oropharyngeal cancers (33%). Response rates (45.5% vs. 45.5%) and median PFS (97 vs. 92 days) following cetuximab-based therapy were similar in patients with p16INK4a -positive and -negative tumors. As expected, OS was numerically longer in the p16INK4a-positive group. Heterologous expression of HPV E6 or E7 or HPV status was shown to have no significant impact on response to cetuximab in vitro. Cetuximab effectively inhibited growth of E6- and E7-expressing tumors grafted in NOD/SCID mice. Conclusions: HPV infection does not impact on the efficacy of cetuximab in HNSCC. Anti-EGFR antibody treatment should be applied independently of HPV status. *Supported by grants from the DKH (110099 to M.P.) and an Oncology Center of Excellence grant of the DKH to the West German Cancer Center. ID 109 Mental disorders and psychosocial support during the first year after total laryngectomy J. Keszte1, H. Danker2, A. Dietz3, E.F. Meister4, F. Pabst5, H.-J. Vogel6, S. Singer7 Universität Leipzig, Medizinische Psychologie und Medizinische Soziologie, Leipzig, Deutschland 2 Universitätsklinikum Leipzig, Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie, Leipzig, Deutschland 3 Universitätsklinikum Leipzig, Klinik und Poliklinik für Hals-, Nasen-, Ohrenheilkunde, Leipzig, Deutschland 4 Städtisches Klinikum St. Georg, Klinik für Hals-, Nasen-, Ohrenheilkunde mit Belegabteilung für Mund-, Kiefer- und Gesichtschirurgie, Leipzig, Deutschland 5 Städtisches Klinikum, Klinik für Hals-Nasen-Ohrenheilkunde, Kopf- und Hals-Chirurgie, Plastische Operationen, Dresden Friedrichstadt, Deutschland 6 Elblandkliniken, Klinik für HNO-Heilkunde, Kopf- und Halschirurgie, Riesa, Deutschland 7 Universität Mainz, Institut für Medizinische Biometrie, Epidemiologie und Informatik, Mainz, Deutschland 1 Objectives: To assess the frequency of mental disorders and the use of psychosocial services in laryngectomized patients during the first year after surgery. Methods: Multi-center prospective study including six structured interviews. Data regarding psychiatric comorbidity,three months (t3) and one year after total laryngectomy (TLE) (t4) is reported in this paper. Results: Mental disorders were diagnosed in 25% of the patients at t3 and in 22% of the patients at t4. 6% of the patients developed a mental disorder between t3 and t4. In general male and female patients suffered from mental disorders with equal frequency (t3: 23% vs. 37%; p = 0.26; t2: 22% vs. 21%; p = 1.00). Women suffered more often than men from posttraumatic stress disorder at t3 (p = 0.01) and generalized anxiety disorder at t4 (p = 0.01). Of the patients who had acquired no voice until t4 80% suffered from alcohol dependence (p = 0.01). There were no differences between men and women in receiving any kind of counselling (p = 0.79) or psychotherapy/psychiatric treatment (p = 0.47). Of those patients diagnosed with any mental disorder at t3, 7% had received psychotherapy by t4. None of the patients diagnosed with alcohol dependence received psychotherapy or psychiatric treatment. Conclusions: Mental disorders occur in laryngectomees as frequently in men as they do in women. TLE patients who were mentally ill did not receive enough psychotherapeutic or psychiatric support. Since mental health seems to be related to successful voice restoration, future research should develop and evaluate special psychosocial supportive programs for laryngeal cancer patients, especially regarding alcohol dependence treatment. Abstracts Inhalt Index ID 111 Reirradiation and Cetuximab in Patients with Locally Recurrent and Unresectable Head and Neck Cancer – Is there any Impact on Survival? – Final Results from Single Institution and Literature Review D. Milanovic, A.L. Grosu, M. Henke Universitätsklinikum Freiburg, Klinik für Strahlenheilkunde, Freiburg, Deutschland Background: Chemotherapy with epidermal growth factor receptor (EGFR) inhibition is established as palliative management in patients with recurrent, unresectable and previously irradiated head and neck cancer (HNC). In this retrospective, monocentric study we analysed feasibility, toxicity, and outcome of Re-RT (reirradiation) and with EGFR blockade with cetuximab. Methods: Between June 2008 and June 2011, we reirradiated (50.4–66.6 Gy) 24 patients with histologically proven HNC, who had been previously treated with external beam radiotherapy (RT). In 23 cases, histology was squamous cell carcinoma (SCC), while 1 patient was diagnosed with high grade mucoepidermoid carcinoma (MEC). Cetuximab was given initially at 400 mg/m2 two days before Re-RT and weekly (250 mg/m2) thereafter. 21 patients completed Re-RT (50.4–66.6 Gy) and received cetuximab as prescribed. Grade 3 acute side effects were documented for dermatitis (35%), dysphagia (30%), acneiform rash (30%) and mucositis (15%). Two patients are still alive – one with MEC 61 months after finishing treatment without signs of clinical or radiological progress and one with SCC 43 months after finishing treatment. A multivariable analysis using the Cox regression model showed significant positive impact of acneiform rash while a period from first radiation to Re-RT longer than 120 months negatively influenced patients survival. Conclusion: Re-RT with concurrent cetuximab was feasible at acceptable toxicity. Similar results were reported from other groups using same regime. Given comparable survival rates, for patients reirradiated only or for patients administered cisplatin based regimes with cetuximab we suggest to sequentially apply these modalities. ID 119 Simultaneous cytoplasmic and nuclear protein expression of MAGE-A family and NY-ESO-1 cancer-testis antigens represents an independent marker for poor survival in head & neck cancer S. Laban1,2, D. Atanackovic2, T. Lütkens2, C.-J. Busch2, M. Freytag2, T.K. Hoffmann1, A. Knuth3, G. Sauter2, R. Knecht2, A. Münscher2, T.S. Clauditz2 Universitätsklinik Ulm, HNO, Ulm, Deutschland Universitätsklinikum Hamburg Eppendorf, Hamburg, Deutschland 3 Hamad Medical Corporation Qatar, National Center for Cancer Care & Research, Doha, Qatar 1 2 Background: Despite enormous efforts, the prognosis of head and neck squamous cell carcinoma (HNSCC) patients is still poor. The identification of immunotherapeutic targets, especially for patients at high risk of death, is needed. The expression of cancer-testis antigens (CTA) has been linked to poor prognosis in other cancer types, however, their prognostic value in HNSCC is unclear, because only small cohorts have been examined regarding CTA protein expression. Methods: A tissue micro array built of tumor samples from 453 HNSCC patients was evaluated for the expression of CTA proteins using immunohistochemistry. Frequency of expression and the subcellular expression pattern (nuclear, cytoplasmic, or both) was recorded. Results: Protein expression of at least one CTA was detected in 47.5% of patients. Positivity for MAGE-A family CTA, MAGE-C family CTA, and NY-ESO-1 was found in approximately 30%, 7%, and 4% of tumors, respectively. CTA protein expression, but most remarkably the expression pattern had a strong impact on the prognosis. Median overall survival (OS) of patients with (1) simultaneous cytoplasmic and nuclear expres- Abstracts sion compared to (2) either cytoplasmic or nuclear expression and (3) negative patients was 23.0 vs. 109.0 vs. 102.5 months, for pan-MAGE (≤0.0001), 46.6 vs. 50.0 vs. 109.0 for MAGE-A3/A4 (p = 0.0074), and 13.3 vs. 50.0 vs. 100.2 months for NY-ESO-1 (p = 0.0019). By multivariate analysis these factors were confirmed as independent markers for poor survival. Conclusions: The expression of MAGE-A family members or NY-ESO-1 identifies a patient subgroup with a high risk of death. Immunotherapeutic strategies targeting these CTA may improve the outcome of HNSCC patients. ID 133 Trends in incidence rates of oral and pharyngeal cancer in Germany K. Hertrampf1, J. Wiltfang1, R. Pritzkuleit2, A. Katalinic3, H.-J. Wenz4, A. Waldmann3 Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland 2 Institut für Krebsepidemiologie, Universität, Lübeck, Deutschland 3 Institut für Sozialmedizin und Epidemiologie, Universität, Lübeck, Deutschland 4 Klinik für Prothetik, Propädeutik und Werkstoffkunde, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland 1 Background: Oral and pharyngeal cancer is still a serious health problem in Germany. Since 2000, the incidence rates have increased from 10,000 to 13, 000 newly diagnosed cases per year. The aim of this evaluation is to describe epidemiologic trends of this tumour in Germany, focusing on incidence rates according to age and gender. Methods: Incidence rates for oral and pharyngeal cancers (ICD-10 C00– C14) for the period 2003–2010 by age, gender, and sub-sites (C00–C06, C07–C08, C09–C14) was retrieved from the Association of Epidemiological Cancer Registries in Germany. Results: In 2010, a total of 13,244 oral and pharyngeal tumours were newly diagnosed. From 2003-2010, the incidence rates of oral and pharyngeal tumours in women increased slightly from 5.3 to 5.8/100 000 (ASR [E]), while incidence rates in men decreased from 19.9 to 19.1/100 000 (ASR [E]). An incidence peak was observed in the age group 60-64 years in men, whereas the incidence rates in women showed not such a marked peak. A detailed analysis by gender and sub-sites reveals interesting differences. The German data did not show an increasing trend of developing oral and pharyngeal cancer in younger people compared to data from other European countries. With regards to the different subsites, incidences of the oral cavity (C00–C06) rank highest in women and showed a slight incidence increase over the observation period. In men, incidence rates of pharyngeal cancer showed a slight decrease and the other sub-sites remained quite constant. Conclusions: The population-based data forGermany showed interesting differences in the trends for incidence rates for both genders and revealed noticeable differences to European neighbours. ID 212 Detection of circulating tumor cell sub-populations in patients with head and neck squamous cell carcinoma (HNSCC) P. Hassenkamp1, I. Nel2, P. Weller1, P. Dountsop3, G. Lehnerdt1, A.-C. Hoffmann2 Universitätsklinikum Essen, Universitäts-Hals-Nasen-Ohrenklinik, Essen, Deutschland 2 Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Essen, Deutschland 3 HNO-Klinik, Evangelisches Krankenhaus, Düsseldorf, Deutschland 1 Background: Circulating tumor cells (CTC) could serve as a ‘liquid biopsy’ for individualizing and monitoring treatment in patients with solid tumors. Standardized approaches with currently available techniques are Oncol Res Treat 2014;37(suppl 1):1–133 77 Inhalt Index challenged by the cellular heterogeneity of CTC as reported recently by our group (Nel et al., Transl Oncol 2013). We assessed which non-hematopoietic cell types are identifiable in the peripheral blood of patients with HNSCC and their distribution before and after resection. Methods:Blood was drawn from HNSCC patients (n = 7) before, during and after resection.Mononuclear cells (PBMNC) and CTC were isolated using density gradient centrifugation and spun onto glass slides. CTC presence was verified by multi-immunofluorescence staining against pan-cytokeratin (CK; epithelial), N-cadherin (mesenchymal); CD133 (stem-cell), CD45 (hematopoietic) and DAPI (nucleus). CTC and hematopoietic cells were enumerated and individual cell type profiles were analyzed. Results: We detected cells with epithelial properties like CK+/CD45-, mesenchymal features such as CK-/CD45-/NCad+ and CK+/CD45-/ NCad+. We also observed cells with stem cell-like features: CK-/CD45-/ CD133+ and CK+/CD45-/CD133+. The total amount of CTC significantly decreased after surgery (p = 0.05). Prior to surgery the number of CK+, CD133+ and NCad+ cells ranged from 2 to 37 (median 6), 1–14 (median 3) and 0–20 (median 3) CTC/1000 PBMNC. After resection the total amount of CK+, CD133+ and NCad+ cells ranged from 0–5 (median 2.5), 0–6 (median 1) CTC and 0-2 (median 0.5), respectively. Conclusions: Our data suggest that different CTC populations are identifiable in peripheral blood of HNSCC patients.Prospective evaluation of recurrence rates in correlation with these distinct cell profiles seems to be warranted. ID 279 Human papillomavirus associated oral squamous cell carcinoma: Is overall survival influenced by the expression of cancer stem cell markers? C. Götz1, E. Drecoll2, M. Straub2, P. Holm3, M. Kesting1, K.D. Wolff1, A. Kolk1 TU München, Klinikum rechts der Isar, Mund-, Kiefer- und Gesichtschirurgie, München, Deutschland 2 TU München, Klinikum rechts der Isar, Pathologie, München, Deutschland 3 TU München, Klinikum rechts der Isar, Experimentelle Onkologie und Therapieforschung, München, Deutschland 1 Introduction: 5-year-overall survival is quoted to be significant better in human papillomavirus (hpv) associated oral squamous cell carcinomas (oscc) than in oscc related to alcohol and tobacco consumption. An explanation for these results could be that adjuvant chemotherapy and radiation are resulting in higher response rates to oscc with hpv positive carcinogenesis. On the other hand the hallmarks of cancer, including the cancer stem cell (csc) theory could be different in hpv associated oscc. In the past only few investigations were done in this field of molecular oncology and were set into correlation to the clinical outcome of the patients. To the detection of hpv infection it is mentioned that staining of p16 shows higher signals than other hpv correlated proteins are doing. Methods: We analyzed the expression of the csc markers ALDH 1, CD 44 and Nanog with methods of IHC on a TMA. We did Western Blot on tissues, which were extracted of hpv positive and negative oscc cell lines. Furthermore we compared the results to hpv negative oscc cell lines. We set the laboratory results into correlation with the overall survival of the 550 patients, on which the TMA is based. Furthermore we detected hpv in IHC with two different molecular patterns, E7 and p16. Results: The results showed significant difference between the expression oft the latter mentioned csc markers in hpv positive and negative oscc. A reduced expression of these markers was found through IHC and WB in hpv positive oscc. We used Spearman rank correlation and set the p-value on <0.05. Conclusion: According to the significant different results between hpv positive and negative oscc we are showing that there is a need to do further research on this subject and to discuss the treatment of hpv postitive oscc. 78 Oncol Res Treat 2014;37(suppl 1):1–133 ID 295 Flexible endoscopy for hyperspectral imaging W. Laffers1, S. Westermann1, R. Martin2, B. Thies2, F. Bootz1, A. Gerstner3 Universitätsklinikum Bonn, HNO, 53105, Deutschland Universität Marburg, Institut für Geographie, Marburg, Deutschland 3 Städtisches Klinikum, HNO, Braunschweig, Deutschland 1 2 Background: Cancer of mucosal surfaces capable for detection by flexible endoscopy (head neck, gastrointestinal, genital, urologic) is the fast majority of malignancies. Early diagnosis is essential for a better outcome for patients but is still challenging. Hyperspectral imaging has been used in remote earth sensing for decades e.g. for analysing and classifying the surface of the earth. We modified hyperspectral imaging to be used for in vivo flexible endoscopy in patients. Method: We choose the larynx as an ideal representative test area. Patients underwent conventional microlaryngoscopies for diagnostic reasons. By using a tuneable monochromatic light source (PolyChrome V, TillPhotonics, Gräfeling) with 10nm single-bands from 390 nm to 680 nm the mucosa of the larynx was illuminated stepwise. The total relexion was detected with a monochromatic CCD-camera (AxioCam, Zeiss, Jena) synchronously. Image cubes were generated and analysed with idrisi® software. Results: Hyperspectral imaging of the larynx was done in patients in accordance with the local ethics committee. Acquisition time was 30sec per image cube. Areas of altered mucose, e.g. cancer, could be detected, in particular without any additional information needed. In comparison to microscopy or rigid endoscopy it was more difficult to find the accurate focus depth for correct analysis. Conclusion: Flexible endoscopy can be applied for hyperspectral imaging in patients in vivo. Its adoption to flexible endoscopes opens the entire area of endoscopy of mucosal surfaces for this technology. Spectral profiles seem to differ according to different histological findings. Further studies have to be performed to determine if hyperspectral imaging by flexible endoscopy can be used for early detection of cancer. ID 301 Radiosensitization of HPV Positive Head and Neck Squamous Cell Carcinomas (HNSCC) by Chk1 Inhibition C.-J. Busch1, M. Kriegs2, S. Laban1, S. Tribius3, R. Knecht1, C. Petersen3, E. Dikomey2, T. Rieckmann2 Universitätsklinikum Hamburg-Eppendorf, HNO Abteilung, Hamburg, Deutschland 2 Univesitätsklinikum Hamburg-Eppendorf, Labor für experimentelle Strahlenbiologie, Hamburg, Deutschland 3 Universitätsklinikum Hamburg-Eppendorf, Klinik für Strahlentherapie, Hamburg, Deutschland 1 Purpose of the Study: Patients with HPV positive HNSCC show remarkably better survival rates than patients with HPV negative HNSCC when treated with radiotherapy (RT) or radiochemotherapy (RCT). To reduce high-grade toxicities of standard cisplatin based RCT we are looking for radiosensitizing substances in order to replace cisplatin. After ionizing radiation (IR) HPV-positive HNSCC cell lines demonstrate a pronounced and sustained G2-arrest which is likely a result of the higher amounts of unrepaired DNA double strand breaks. We speculate that this arrest might partly counteract the repair deficiency by providing the cells more time for repair before entering mitosis. Methods: To abrogate the G2 checkpoint we used PF-00477736 (PF), a selective CHK1 kinase inhibitor. 5 HPV/p16INK4a-positive HNSCC cell lines were treated by IR with and without PF. Chk1-activity and G2-arrest were analyzed by western blotting and propidium iodide staining. The impact of Chk1-inhibition on cell survival after irradiation was assessed by colony formation assay. Results: In all HPV/p16INK4a-positive HNSCC cell lines a pronounced G2-arrest after 6 Gy IR could be observed. The G2-arrest was abrogated sufficiently in all cell lines by PF in a dose dependent manner. An effec- Abstracts Inhalt Index tive dose was reached at 150 nm PF in 4 of 5 cell lines. On average, 150 nm PF in combination with IR showed significant radiosensitization in colony formation assay. Conclusion: The specific inhibition of checkpoint kinase 1 by PF results in a significant radiosensitization of HPV/p16INK4a-positive HNSCC cell lines in vitro. Our findings suggest that G2 checkpoint abrogation by PF might be an alternative to cisplatin based RCT in HNSCC patients. A validation of our data in xenograft models is planned. ID 362 Extent of Fear of Recurrence (FoR) and its Associations with Medical, Treatment-Related, Psychosocial and Demographic Parameters in Cancer Patients after a Partial Laryngectomy A. Meyer1, M. Asen1, A. Dietz2, S. Singer3, J. Keszte1, D. Wollbrück1 Universität Leipzig, Medizinische Psychologie und Medizinsche Soziologie, Leipzig, Deutschland 2 Universitätsklinikum Leipzig, Klinik für HNO-Heilkunde, Leipzig, Deutschland 3 Universitätmedizin Mainz, Epidemiologie und Informatik, Mainz, Deutschland 1 Objectives: Fear of Recurrence (FoR) is a common problem in patients suffering from cancer. However, it is quite unknown in which extent patients who underwent a partial laryngectomy have FoR. The study examines the extent of FoR in this patient group and analysed the associations between FoR and medical, treatment-related, psycho-social as well as demographic parameters. Methods: In a multicentre cross-sectional study, data was taken from 154 patients after partial laryngectomy. The data collection took place in personal interviews and with standardized questionnaires (PA-F, HADS, EORTC QLQ-H&N 35). Results: The study participants had a low level of FoR (MW=6.67; SD=2.43). FoR was higher in young patients (r = –0.265; p = 0.002) and in users of medical rehabilitation programs (U=1480; p = 0.025). The results of a multiple linear regression showed that patients who thought smoking (r = 0.197; p = 0.029) or/and inner conflicts (r = 0.177; p = 0.050) was/were the reason(s) for their cancer and who reported more swallowing problems, had a significantly higher level of FoR (r = 0.496; p < 0.001). Additionally, there was a negative correlation between the extent of FoR and the time which passed by since the last laryngeal surgery (r = –0.322; p < 0.001). Conclusions: Frequently occurring swallowing problems as well as internal causal attributions for the development of cancer as smoking and inner conflicts increase the level of FoR in patients after a partial-laryngectomy. Since internal causal attribution may cause feelings of guilt a psycho-oncological treatment can be indicated for patients with higher levels of FoR. Since fear of recurrence is mainly found in younger individuals, this patient group is requiring more attention by physicians and therapists. ID 389 Neoadjuvant Docetaxel/Cisplatin/5-FU based radiochemotherapy (RT-CT) increases pathologic complete remissions and survival of patients with locally advanced oral cavity carcinomas in comparison to RT-CT with cisplatin alone followed by resection – a long term observational study M. Stuschke1, J. Abu Jawad1, W. Eberhardt2, S. Grehl1, C. Pöttgen1, G. Arnold3, R. Pförtner4, T. Gauler2, C. Schmeling4, C. Mohr4 Universitätsklinikum Essen, Strahlenklinik, Essen, Deutschland Universitätsklinikum Essen, Innere Klinik / Tumorforschung, Essen, Deutschland 3 Zentrum für Pathologie Essen Mitte, Essen, Deutschland 4 Kliniken Essen-Mitte, Mund-, Kiefer-, Gesichtschirurgie, Essen, Deutschland 1 2 Abstracts Background: Neodjuvant RT-CT at moderate RT doses followed by resection of oral cavity carcinomas (OCC) allows the conduct of secondary mandible reconstruction. Long term outcome is analysed in dependence on the intensity of the neoadjuvant protocol. Methods: Data from consecutive patients (pts) with locally advanced OCC treated between 01/2003 and 06/2010 were analysed. Pts received weekly Docetaxel/Cisplatin/5-FU over 5 weeks followed by RT (40 Gy, 5×2 Gy / week) and simultaneous Cisplatin at 15 mg/m2 and Docetaxel at 10–20 mg/m2, twice weekly during weeks 1–3 of RT (TPF-RT). This schedule was offered as a phase I/II trial. No high risk HPV16 genotype was found in tumors form the pts of this trial. Pts with locally advanced tumors not recruited into the TPF-RT trial, were offered P-RT (36 Gy, 5×2 Gy/w, simultaneous Cisplatin at 12.5 mg/m2, d1-5) before resection. Multivariate analyses (MV) as well as propensity score weighting (PS) were used to adjust for imbalances in prognostic factors between both treatment groups. Findings: 102 pts were treated and median follow-up was 80 (39-130) m. TPF-RT pts had larger primary tumors than P-RT pts (p = 0.004). Overall survival at 5 years was 80.4+7% and 64.3+6% in the TPF-RT and P-RT groups, respectively (p = 0.027). MV (p = 0.02) and PS (p < 0.0001) revealed a marked reduction of hazard of death by a hazard ratio of 0.33 (0.13-0.84) or 0.25 (0.13-0.48) in the TPF-RT group. Crude rates of pathologic complete responses (pCR) in TPF-RT and P-RT groups were 19/31 and 12 / 71 (PS odds ratio 9.2 (4.6-18.3, p < 0.0001). pCR was associated with prognosis (p < 0.0001) and it captured the full treatment effect on survival in MV and PS analyses. Interpretation: This study demonstrates a markedly increased effect of TPF-RT on pCR and survival of OCC patients. Health Services Research ID 014 Chemotherapy treatment patterns and outcomes in platinum resistant ovarian cancer (PROC) patients – a German database study J. Schilling1, R. Shinde2, C. Thielecke3, H. Stiegler3, U. Plötner3, T. Burke2, P. Kaskel4 Berufsverband der Niedergelassenen Gynaekologischen Onkologen in Deutschland e.V., Berlin, Deutschland 2 MERCK & CO., INC., Global Health Outcomes, Whitehouse Station, NJ, USA, Vereinigte Staaten Von Amerika 3 OnkoDataMed GmbH, Schöneiche b. Berlin, Deutschland 4 MSD SHARP & DOHME GMBH, Outcomes Research / HTA, Haar (Kreis München), Deutschland 1 Background and Aims: Approx. 25% of advanced ovarian cancer (AOC) patients (pts) suffer from relapse within 6 months (m) after end of initial platinum based chemotherapy (PBC; platinum-resistant ovarian cancer, PROC). PROC pts have an overall survival (OS) of ca. 12 m. The aim of this study was to explore the real world practice pattern and survival in pts with PROC in the outpatient setting in Germany. Methods: AOC pts treated with PBC aged-18+, diagnosed 1990-2012, were included from a German database fed by community based gyneco-oncologists. Baseline data at the onset of platinum resistance and outcomes from subsequent therapy were recorded. Results: 508 pts with AOC were identified. Of these, 480 initially received PBC, with response being refractory (progression while on therapy, N=11), resistant (N=20), partially sensitive (progression 6-12 m after end of PBC, N=22), and complete sensitive (progression >12 m after end of PBC, N=427). 190/480 pts received further chemotherapy (40%). Mean age in PROC was 63.1 years with 13 pts diagnosed at stage IV. All PROC pts received surgery cytoreduction. 15 / 20 PROC pts received up to 4 lines of follow-up chemotherapy (total 26 lines; mean = 1.86 lines; average 6.6 cycles each). The most common chemotherapies were topo- Oncol Res Treat 2014;37(suppl 1):1–133 79 Inhalt Index tecan (N=4), treosulfan (N=4) and PLD (N=2). The median OS for PROC was 30 weeks. Conclusion: As database is community based, many AOC pts were lost over time as they may have transitioned to dedicated and specialized centers after disease advancement, rather than being treated in the outpatient setting. Out of those treated, few were platinum resistant, and a significant number of PROC pts received recommended chemotherapies; but still a poor OS indicated high unmet medical needs in PROC. ID 032 Patient Transition from Acute Care to Rehabilitation – First results of a Survey of German Rehabilitation Clinics (OPTIREHA) H. Schmdit1, J. Abraham1, M. Landenberger1, P. Jahn1,2 Martin-Luther-University Halle-Wittenberg, Medical Faculty, Institute for Health and Nursing Science, Halle Saale, Deutschland 2 Martin-Luther-University Halle-Wittenberg, University Hospital, Halle Saale, Deutschland 1 Background: Rehabilitation for cancer patients aims to achieve better reintegration, improvement of participation and quality of life. To reach these objectives the management of patients’ transition from primary care to rehabilitation should be tailored to meet patients’ individual needs and abilities. Objective: The aim of this study was to gain information about possible problems and potential for optimization of patient transition from primary care hospitals to rehabilitation clinics. Method: This cross sectional observational study used a semi-structured questionnaire to survey 138 German rehabilitation clinics for cancer patients. Results: N=47 (34%) clinics answered the questionnaire. First results suggest considerable potential for optimization of patient transition. Three main problem areas were identified that might impair or complicate the rehabilitation process: 1. Inadequate flow of information regarding the clinical, psychosocial and cognitive condition of the patients can delay the onset of important treatments thus impairing the rehabilitation process. 2. Weak physical or cognitive condition of the patients, multimorbidity or special needs for medical care due to early dismissal can lead to increased efforts or time demands. The achievement of set goals for the rehabilitation might be impeded by these conditions. 3. Patients’ lack of information about aims and means of a rehabilitative treatment and false expectations might reduce motivation and complicate adherence to therapeutic measures. Outlook: A pilot study to develop and test a modular assessment tool to optimize information flow and patient transition will be performed. The tool will be based on nurse routine documentation and ICF criteria. ID 059 Off-Label Use – an unsolved problem in German oncology T. Langenbuch Onkologie Volksdorf, Hamburg, Deutschland Medical Doctors in Germany who use off-label drugs in their treatments need to receive the public health insurances’ agreement to the bearing of costs prior to treatment, to protect themselves from regress payments to health insurances. The numbers shown are taken from an oncologist’s practice between the years 2005 and 2013. They reveal how time-consuming it is to apply for and receive those agreements from the insurance companies, and also illustrate the retardation that occurs in the treatment of a cancer patient due to the current situation with the insurances’ policies. The difficulties that arise, both from the perspective of the patient and his/her relatives as well as the doctor’s, will be highlighted, and alternative options to the present procedure will be discussed. 80 Oncol Res Treat 2014;37(suppl 1):1–133 ID 061 Mortality after (first) hospitalization for colorectal carcinoma E.M. Bitzer, S. Neusser, T. Grobe Pädagogische Hochschule Freiburg, Public Health & Health Education, Freiburg, Deutschland Background: The incidence of colorectal cancer (CRC) in Germany is fairly stable. However population based mortality rates are declining (CRC-mortality 2000–2010: –25%) and relative 5-year survival has increased from the 1980ies to 2000–2004 (45 vs. 60%). Do these developments translate into lower inpatient services utilization and what can be said about mortality for CRC treated in hospital? Methods: We used inpatient claims data and beneficiaries master data of 8.5 million German health insurance beneficiaries to calculate population based rates of inpatient treatment for CRC (ICD C18–C20) for the years 2005 to 2012 (standardized for age and sex to the German population). Using the life-tables method we analyzedthe 5-year mortality of those beneficiaries who underwent inpatient treatment in a German hospital for CRC in the year 2007 without preceding treatment in 2006. Results: Between 2005 and 2012 we observed a decline in both the rate of CRC associated hospitalizations (24.14/10,000 to 17.63/10,000, –21%) and that of individuals affected by a CRC associated hospitalization (11.71/10,000 to 9.28/10,000, –27%). Compared to the (age and sex matched) general population individuals with a CRC associated hospitalization in 2011 had a mortality almost 10times higher (26.3 vs. 2.8%). Individuals with a CRC- hospitalization in 2011 (and no CRC-treatment 2006 to 2010) had 30-day mortality of 7.1% and a one-year mortality of 19.1%. Individuals with a CRC-hospitalization in 2007 without CRC-treatmentin the preceding year had a 30-day mortality of 7.7%, oneyear mortality 20.5% and a five year mortality of 45.1%. Conclusion: Declining CRC-Mortality is accompanied by declining CRC-associated hospitalizations. CRC treated in hospital is still a highly lethal disease. ID 083 Workload and the physician-patient interaction – results of the WIN ON-study H. Pfaff1, N. Ernstmann1, S.E. Groß1, L. Ansmann1, T.D. Gloede1, A. Nitzsche1, J. Jung1, M. Wirtz2, W. Baumann3, S. Osburg3, M. Neumann4 IMVR, Köln, Deutschland Pädagogische Hochschule Freiburg, Abteilung für Forschungsmethoden, Freiburg, Deutschland 3 Winho, Köln, Deutschland 4 Universität Witten/Herdecke, Fakultät für Gesundheit, Department für Humanmedizin, Witten/Herdecke, Deutschland 1 2 Background: The aim of the present study is to examine the association between private practice hematologists’ and oncologists’ (PPOs) job stressors and its influence on the physician-patient interaction and patient reported outcomes. Methods: This study is part of the WIN ON (Working Conditions in Oncology) project. All members of the Professional Organization of Office-Based Hematologists and Oncologists (BNHO) and additional PPOs (n = 578) were invited to a mail survey. Out of 556 eligible oncologists, N=157 sent back the completed questionnaire (response rate 28%). Patients with colorectal cancer being treated by these physicians are also surveyed as part of a four-wave prospective study (N=169). Results: The average workload is high with a median working time of 57 hours per week and a median number of patient consultations of 35 patients per day. About 50% of the PPOs report moderate symptoms of emotional exhaustion (indication for burnout) and 18% report explicit symptoms. In 85% interruptions during patient consultations occurred. Disturbances during clinical encounters are correlated to patients’ fear of cancer progression after the first consultation (r = 0.203; p ≤ 0.019). Abstracts Inhalt Index However, burnout-symptoms and patients’ fear of cancer progression are not significantly correlated. Discussion: In general, PPOs are exposed to high workload and often show burnout-symptoms. Their workload, especially interruptions seem to affect the physician-patient interaction. However the PPOs’ well-being doesn’t seem to affect the physician-patient interaction. We aim to gain deeper insights into this topic by combining physician and patient data from the WIN ON-study and analyzing the data in multivariate regression models. Evaluation of process quality criteria for systemic therapy in a clinical cancer registry of cox regression models. Method of corrected group analysis derived 5-year survival curves. Results: For analysis, 743 out of 877 (84.7%) patients were used. In total, 103 quality indicators were developed. Adherence index increased systematically from 15.1% (1996–97) to 35.2% (2003–04). 5-year survival increased, but differences between time intervals were not significant. More than three decisions divergent from guidelines are suspicious to increase hazard ratios. Conclusion: Service quality increased from a relative low level by factor three despite of more and complex treatment options. Process improvements were not associated with systematic increases in outcomes. However, process related S3-guidelines remain relevant due to the suspicion that a maximum of two consensual decisions against guidelines (e.g. tumorboards) may have the potential to develop protective effects. A. Kimminger, W. Tretter, M. Wiedemann, G. Schubert-Fritschle, J. Engel, D. Hölzel ID 123 ID 084 Tumorregister München, München, Deutschland Background: Systemic cancer therapy nowadays is characterized by individualization and increasing complexity. Little information, however, exists about benefits and harms of guideline-oriented individualised therapies in routine health care. The aim of this project was to describe the compliance and safety of individualised systemic therapy in the region of the Munich Cancer Registry (MCR). Methods: An efficient online documentation system was integrated within a network for physicians and clinics facilitating documentation of indication, dosage and treatment schedules of various prescribed pharmaceuticals, best response, and other quality criteria. Results: The MCR registered treatment schedules for 1914 patients from 2008 to 2012 with 2753 disease courses. Adjuvant dosage was applied as planned in 82.0% and as scheduled in 87.7% of all cases. For the following cancer entities, the percentages for fulfilled dosage and time schedule were as follows: 92.9 and 87.1 (breast), 92.6 and 90.2 (lung), 66.7 and 84.0 (colon), 82.9 and 92.5 (rectum). The main reason for abandonment of protocol was side effects (5.6%). The abandonment of adjuvant therapy due to patient’s request was seldom (2.5%); cancer specific values were 1.4% (breast), 0.8% (lung), 2.5% (colon), and 3.4% (rectum). n palliative care, percentages for applied dosage were almost comparable, the fulfilled time scheduled, however, were clearly lower. Conclusions: These first results about process quality criteria (dosage and time schedule) show better realization than expected. Such analyses demonstrate that the integration of specifications about systemic therapy in cancer registries delivers relevant information about individualised therapy in routine care. ID 105 Comparison of quality indicators, S3-guideline adherence and 5-year survival between 1996–97 and 2003–04 of the breast cancer network Regio in Hesse C.O. Jacke1, M. Kalder2, U. Wagner2, U.-S. Albert2 Decision strategies of the multidisciplinary team for cancer treatment C. Wetzel, S. Seitz, O. Ortmann Universität Regensburg, Klinik für Frauenheilkunde und Geburtshilfe, Regensburg, Deutschland Aim: This study investigates decision strategies of the ‘tumor board’, i.e. the multidisciplinary team (MDT) in cancer care. Uncomplex and complex cases, i.e. cases with comorbidities, metastasis and recurrent disease, were compared in the applied decision approaches. Methods: Decision strategies used in the MDT case discussions for treatment recommendation of our gynecological cancer centre were assessed. A standardised real time observation tool was used. Differences in the frequency of strategies between uncomplex and complex cases were analysed using the Mann-Whitney-U-test. Results: N=105 case discussions were assessed, N=65 uncomplex cases and N=40 complex cases. Rule based decision making considering guidelines and clinical trials was applied as a decision strategy in 84.6% of the uncomplex cases, which was significantly more frequently than in complex cases (52.2%; p < .01). In complex cases, the elimination-by-aspects strategy and ‘if-then-rules’ were used significantly more often (in 15.0% and 37.5%, respectively) than in uncomplex cases (in 1.5% and 7.7%, p < .05 and p < .01, respectively). Conclusions: The application of rule based decision strategies in the MDT became evident, representing high quality decision approaches. Guidelines are primarily available for uncomplex cases, whereas in complex cases a great diversity of individual aspects needs to be considered. Hence, in complex cases clinicians apply alternative strategies, processing relevant information in a rational way. However, increasing the rate of rule based decision strategies, explicit risk communication for transparency of strategy in all case discussions and establishing standards of sophisticated MDT decision approaches would be desirable. ID 147 Zentralinstitut für Seelische Gesundheit, AG Versorgungsforschung, Mannheim, Deutschland 2 University Hospital Marburg Giessen, Location Marburg, Breast Center Network Regio, Marburg, Deutschland The variability of future cancer burden by tumour site Background: In the last decade, breast cancer networks, tumorboards, quality management programmes or S3-guidelines were developed to improve the effectiveness of breast cancer detection and treatment across health care sectors. Aim of study was to assess these efforts from a temporal perspective (1996–97, 2003–04) for inpatient treatment only. Methods: Breast cancer network Regio (Marburg-Biedenkopf) encompassed three hospitals in selected time intervals 1996–97 and 2003–04. In total, 389 and 488 female patients with primary therapy of breast cancer were recruited. Analysis referred to invasive carcinomas without metastasis, distinguishing between residential and non-residential patients. Time interval specific quality indicators were extracted from clinical records and aggregated to one adherence index which defined the group indicator Background: Since the probability of a cancer diagnosis increases with age, demographic changes will have a major influence on trends of cancer incidence and prevalence. The resulting cancer burden on society can be quantified by estimating future cancer cases. Methods: Data from the Munich Cancer Registry (MCR) was used to show the age distribution for the most frequently occurring tumour sites. Incidence rates were calculated and combined with data predicted by the Federal Statistical Office to show the burden of cancer projected 40 years from now. Results: In most tumour sites, the median age at diagnosis is older than 60, with a median age of 68.9 in men and 68.2 in women. Tumour sites with the highest median age are bladder (men/women: 73.3 / 78.1) and Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 1 M. Rottmann, R. Eckel, D. Hölzel, G. Schubert-Fritschle, J. Engel Tumorregister München (TRM), München, Deutschland 81 Inhalt Index stomach (71.4 / 77.5) for both men and women, and with a high median age colorectal cancer (70.3 / 74.5). The total incidence rate for cancer is 535.0 per 100,000 in men and 499.2 per 100,000 in women, with rates highest for prostate and breast cancer. In older age groups (≥ 70), incidence rates are considerably higher with 2321.8 per 100,000 in men and 1502.9 per 100,000 in women. By 2050, the largest increase of incident cancer cases will be in tumour sites with a high median age at diagnosis such as bladder (men/women: +71% / +50%), stomach (+53% / +46%), or colorectal cancer (+43% / +37%), while tumour sites with a relatively low median age such as in breast for women (+8%) or testis (-23%) for men, will have a lower increase or even a decrease. Conclusions: Due to demographic ageing, there will be notably different changes in cancer incidence according to tumour type. Thus, as a result of divergent effects, the resulting burden of cancer will be strongly dependent on cancer site. ID 151 Medical Image Knowledge Extension Using Semantic Networks, Ontologies and the Bayesian Theorem M. Graf1, O. Nix2, W. Schlegel3, R. Floca1 DKFZ Heidelberg, Software Entwicklung für integrierte Diagnostik und Therapie, Heidelberg, Deutschland 2 DKFZ Heidelberg, Qualitätsmanagement klinischer Forschung, Heidelberg, Deutschland 3 DKFZ Heidelberg, Medizinische Physik, Heidelberg, Deutschland 1 Medical images contain more information than their mere digital representations. «Radiological images contain a wealth of information, such as anatomy and pathology, which is often not explicit and computationally accessible» [1]. Data processing induces knowledge which is lost when not linked to the same context, conversely meaning yet unprocessed data which holds this semantic information can help to extract more knowledge later on. Through machine learning, software aided diagnosis and therapy planning will become more tangible in near future. Some effort was made to fight the lack of standardized image annotation and markup, however, most of that work is currently at an early stage [2]. Previous studies target the annotation and information storage based on ontologies. One, (AIM) aims at storing and querying the data in a schema sufficient for data retrieval and automatic processing of annotations and image markups [3]. In research cumulative image processing chains including cutting-edge algorithms that are creating a vast number of information which is not necessarily annotation or markup like. Therefore, we show a system that comprises a generic and extensible information model to store arbitrary semantic connections, adaptive by using Bayesian inference machine. The proposed and in software implemented system presents in combination with medical image processing platforms and applied in three research oriented software systems (e.g. differentiation of progressive disease and pseudo progression of brain tumors), a contemporary, robust environment for data storage, suspending current processes, and enhancing knowledge by triple tagging [4,5], Bayesian networks [6], and thus probabilistic inference. ID 226 Patient participation in multidisciplinary tumor conferences in breast cancer care L. Ansmann1, N. Ernstmann1, C. Kowalski1, R. Würstlein2, M. Wirtz3, H. Pfaff1 Institut für Medizinsoziologie, Versorgungsforschung und Rehabilitationswissenschaft (IMVR) der Universität zu Köln, Köln, Deutschland 2 Klinikum der Universität München, Brustzentrum LMU, München, Deutschland 3 Pädagogische Hochschule Freiburg, Institut für Psychologie, Freiburg, Deutschland 1 82 Oncol Res Treat 2014;37(suppl 1):1–133 Background: According to the Medical Association of Westphalia-Lippe, in breast cancer centers 95% of the patients should be discussed in postoperative multidisciplinary tumor conferences (MTCs). By request patients can take part in the MTC. There is evidence that MTCs improve patient management and survival (Croke et al. 2012). So far, very few studies investigate patient participation in MTCs (Choy et al. 2007). Our study identifies which breast cancer patients are offered to take part in MTCs and make use of the offer. Methods: Survey data from 3856 patients in 86 breast cancer center hospitals in North Rhine-Westphalia from 2010 are analyzed. In regression and multilevel models we analyze whether the offer to participate and the actual participation in the MTC differs by patient characteristics. Results: 14% of the patients were offered to participate. 58% of those took part in the MTC. Patients with advanced staging and older age were less frequently invited to take part. Patients treated with neoadjuvant chemotherapy and with higher grading participated in the MTC more frequently. Patients with mastectomy participated less frequently. Moreover, being offered to participate in the MTC is to 28% dependent on the hospital. In addition, patients in MTCs reported higher involvement in decision making. Conclusion: The offer to participate in MTCs differs by the patient’s disease stage and age. Actual participation is more likely for patients with complex disease status, since the presence and preferences of the patients may help to make difficult decisions. Moreover, the results suggest that patients in MTCs feel more involved in decision making. Further research should focus on the benefits and feasibility of patient participation in MTCs. ID 259 Single Center Register (SCR) ‘Indolent hematological malignancies’: Structure – results – perspectives D. Kämpfe1, F. Killing2, W. Padur3 Praxis für Hämatologie und Onkologie, Lüdenscheid, Deutschland Ärztenetz MK Süd, Lüdenscheid, Deutschland 3 Bürgeramt, Lüdenscheid, Deutschland 1 2 Issue: Public Health Researches are an expanding contemporary movement, which require innovative tools and methods. Our SCR gives a proposal. Methods: Since July 2003 all patients with ensured indolent hematological malignancies ( lymphomas incl. CLL, cMPN incl. CML, MDS, monoclonal gammopathies (mG) have been listed concerning all relevant personal, clinical, paraclinical and therapeutical informations. Diagnoses are enhedged by cooperation of hematologist, hematopathologist and other specialists corresponding to standard definitions (WHO, ELN). Data are ascertained immediately and repeatedly at time of consultation assisted by IT. In cases of loss outcome data are completed by asking general practitioners and Citizens Registration Office. Observation period is preplaned until 2023. Results: Until July 2013 SCR includes (number of patients): CLL (233), other indolent lymphomas (134), cMPN / CML (222), MDS (89) and mG (397). Age and gender ratios, symptoms at time of referral, attendant diseases or seldom constellations are demonstrated exemplarily in CLL here . Furthermore we can calculate prevalences of CLL and cMPN because incidence of CLL corresponds with that of Northern Germany and is similar to that of cMPN. Conclusions: SCR’s bridge the gap between epidemiological registers (widely unselected but data-restricted) and multicenter studies / registers (medical datas more detailed but prospective selected patients). If unselected and carefully documented SCR’s may reflecte real life in diagnoses and situations, which are seldom represented in universities and clinical studies and help to estimate incidences and prevalences. Abstracts Inhalt Index ID 267 The eHealth service CANKADO to overcome nonadherence during oral self-medication T. Schinköthe1, N. Harbeck1,2, R. Würstlein1,2 1 2 Klinikum der Universität München, Brustzentrum, München, Deutschland Klinikum der Universität München, CCC of LMU, München, Deutschland 25% of the cancer drugs, which are currently under development, are intended for oral self-medication. This refers to the wishes of cancer patients, 54–89% of which prefer oral medication. However, the change from intravenous administration to oral self-medication leads to a loss of control of the physician in charge while the patient’s individual responsibility increases dramatically. A lack of therapy adherence is the main problem. Depending on the tumor disease and therapy, up to 84% of all patients are not adequately adherent. CANKADO has been designed to support cancer patients during oral self-medication. It’s intended to increase communication between stakeholders with a multi-channel-communication concept and based on findings of cognitive behavioral therapy. Adherence is supported via a gamification strategy. CANKADO’s approach focuses on those reasons that are related to the patient or therapy itself. The system expands the range of care services of the physician and provides the opportunity to interact apart from personal meetings. In addition CANKADO offers the patients, physicians and their assistants various support measures with separate accesses. CANKADO‘s gamification concept is based on the principles of cognitive behavioral therapy. CANKADO is meant to lead the patient from a lack of adherence to adherence by using both the conventional elements of cognitive behavioral therapy and playful elements. CANKADO provides patient care by means of a combined system of computer application and therapists where the physician in charge takes on the role of the therapist. Taken together, CANKADO provides a complete new approach to overcome non-adherence, based on eHealth. CANKADO is a non-profit service. ID 318 Evalution of vaccination status and knowledge of vaccination prevention and infectious risk after splenectomy C. Lotze, B. Erdmann-Reusch Klinik Bavaria, Kreischa, Deutschland Introduction: Vaccination and education are recommended in published guidelines for the prevention of infectious complications after splenectomy. These patients have a lifelong risk of post-splenectomy sepsis with mortality ratesfrom 50–70%. Methods: We examined the status of vaccinationand the knowledge on vaccination prevention, infectious risks and health precautions of consecutive 116 splenectomy-patients in the rehabilitation clinic with a questionnaire since 2010. This is an actually update our study. Results: Indications for splenectomy of the 116 patients in this analysis included cancer surgery (76), haematological (11), post-trauma (15) and other (14). The interview was performed for 62 patients within 3 months, for 31 within 4 to 24 months and for 23 more than 24 months after the splenectomy. To time of interview 45 patients (38.8%) were without vaccinations. 64 patients (55.1%) received pneumococcal vaccine, 20 patients (17.2%) the haemophilus vaccine and 21 patients (18.1%) the meningococcal vaccine. One of the patients received an antibiotic prophylaxis after splenectomy. 54 patients (46.5%) had knowledge of necessity of vaccination. 47 patients (40.5%) didn’t know about necessity of vaccination. 61.2% of 116 patients didn’t know about infectious risk. 18.1% of 116 patients reported about minimal information about infectious risk and 16.4% were identified as having adequate knowledge about infectious risk. Conclusions: The patient awareness of infectious risk after splenectomy and the vaccination prevention have to be substantially improved. Repetitively educational information through different healt professionals is necessary. Abstracts ID 438 Reimbursement of special medical oncology outpatient care. Cost accounting of transsectorally clinical pathways as a model for a new fee system I. Fackler-Schwalbe, E. Spaeth-Schwalbe Medizinberatung Fackler-Schwalbe, Passau, Deutschland Introduction: Special medical outpatient care was introduced in January 2012 in § 116 b SGB V, an amendment to the care structure law. Its focus is on severe progressive forms of oncological diseases. Reimbursement is made provisionally by EBM. In the mid- to long-term, a new medical fee schedule is to be developed. Methods: Following from the example of palliative colorectal cancer treatment, transsectorally integrated clinical pathways will be developed. Then, with the help of path cost accounting, together with marginal costing, they will be evaluated based on the cost of the care provided. Results will be compared with the billing methods of the health insurance companies in accordance with EBM. Alternatively, profits may be calculated based on the payment agreement for outpatient care laid down in § 116 b. Results: Clinical pathways for outpatient therapy in oncology define process-oriented, standardized procedures; they demonstrate how time-consuming and staff-intensive care for cancer patients is, and they form the basis for performance-based pay for special medical oncology outpatient care using path cost accounting. Conclusions: Cost accounting of transsectoral clinical pathways could be a model for a new fee system of reimbursement in special medical oncology outpatient care and thus serve as a basis for diagosis-related groups (DRGs). ID 459 Standard Operating Procedures help to implement national guidelines by incorporating center specific assets B. Starbatty1, J.-P. Glossmann1, B. Funke2, M. Hallek1, J. Wolf1 Universitätsklinikum Köln, Centrum für Integrierte Onkologie, Köln, Deutschland 2 Universitätsklinikum Bonn, Centrum für Integrierte Onkologie, Bonn, Deutschland 1 Background: S3 guidelines are regarded as the standard in oncology treatment. However, a 100% guideline adherence is not achieved and might never be achieved due to various reasons. One reason might be the lack of center specific infrastructure and clinical trial. Methods: At our center – the Center for Integrated Oncology Köln Bonn (CIO) – we use Standard Operating Procedures published in a web based portal. These electronic documents are based on current national guidelines – including S3-guidelines when applicable – and are blended with center-specific information. The SOPs are one main product of the work of a group of specialists, the Interdisciplinary Oncological Project groups (IOP). Results: In the past years we have published a total of 23 SOPs while 6 additional SOPs are in preparation. The SOP-software’s strength is the visualization and publication of processes. The CIO-specific information includes: – Links to our active clinical trials with inclusion and exclusion criteria – Directions when to involve early intervention palliative care differentiated by tumor entity and stage – An algorithm for identifying patients with need for psycho-oncological services – Directions when to present a patient at one of the numerous tumorboards. Conclusion: We have successfully combined national guidelines with local strengths. Furthermore, SOPs are available for some cancers where national guidelines are still not available. Oncol Res Treat 2014;37(suppl 1):1–133 83 Inhalt Index Leukemia, Myelodysplasia, and Transplantation ID 029 Multiple chloromas in a patient with acute myeloid leukaemia: An interdisciplinary approach U. Vehling-Kaiser1, T. Sternfeld2, L. Rieger3, P. Rexrodt4 Onkologisches und Palliativmedizinisches Netzwerk Landshut, Landshut, Deutschland 2 Praxis für Innere Medizin, Landshut, Deutschland 3 Krankenhaus Landshut-Achdorf, Frauenklinik, Landshut, Deutschland 4 Radiologie Mühleninsel, Strahlentherapie, Landshut, Deutschland 1 We report the case of a 75 year old female patient who was diagnosed 10/2011 with MDS-related acute myeloid leukaemia. The patients showed a good remission under the initial treatment with 5-azacytidine. In 08/2012 the patient complaint about lower back pains when she was walking. The MRT-scan showed multiple chloromas near the lumbar spine and a menigeosis leukaemica was diagnosed. The local radiotherapy for the chloromas was effective and 5-azacytidine was continued. In 03/2013 patient’s sight was severely affected due to the development of retrobulbar chloromas. Radiotherapy was successful again and 5-azacytidine continued to show a good remission in peripheral blood. In 05/2013 symptomatic chloromas developed in the bladder, vagina and both labia. Chemotherapy was changed to 6-mercaptopurine and radiotherapy was started again. Due the progressive disease the patient passed away on the palliative ward 06/2013. The patient survived for about 20 months after the diagnosis of acute leukaemia. Due to the interdisciplinary treatment of the symptomatic chloromas the quality of life was relatively good allowing the patient to stay at home for most of the time. ID 188 Follow-up of the non-interventional TARGET study – efficacy and safety of nilotinib in routine clinical management of CML patients (pts) failing prior therapy F. Stegelmann1, J. Dengler2, P. Le Coutre3, M.C. Müller4, A. Sauer5, U. Schwinger6, C. Losem7, W. Schneider-Kappus8, S. Stern9, U. Vehling-Kaiser10, M. Meincke11, O. Frank12, O.G. Ottmann13 Universitätklinikum, Klinik für Innere Medizin III, Ulm, Deutschland Onkologische Schwerpunktpraxis, Heilbronn, Deutschland 3 Charité, Campus Virchow Klinikum, Berlin, Deutschland 4 Universitätsklinikum, III. Medizinische Klinik, Mannheim, Deutschland 5 MVZ für Blut- und Krebserkrankungen, Potsdam, Deutschland 6 Gemeinschaftspraxis, Stuttgart, Deutschland 7 Facharztzentrum, Neuss, Deutschland 8 Praxis für Hämatologie und Onkologie, Ulm, Deutschland 9 Praxisklinik für integrative Onkologie, Altötting, Deutschland 10 Tagesklinik, Landshut, Deutschland 11 Novartis Pharma GmbH, Onkologie, Altenholz, Deutschland 12 Novartis Pharma GmbH, Onkologie, Nürnberg, Deutschland 13 Universitätsklinikum, Medizinische Klinik II, Frankfurt, Deutschland 1 2 Introduction: Nilotinib is approved for the treatment of Ph+ CML patients in CP and AP with failure of prior therapy including imatinib (IM) as well as for de novo Ph+ CML in CP. Methods: Follow-up analysis of an observational study of nilotinib in 323 pts with Ph+ CML resistant to or intolerant of prior treatment within routine clinical management in 106 centres in Germany (01/2008-03/2013). Results: 61.3% of the pts were older than 60 yrs and predominantly in CP (99.1%). 96.3% of all pts were pretreated with IM (any dose). Further medical pretreatment were chemotherapy (28.8%), IFN (21.4%), dasatinib (18.6%) and other unspecified drugs (13%). Treatment with nilotinib was mostly due to resistance/intolerance against IM (47.4%/44.3%). Initial nilotinib dose was 800 mg/d in 64.1%. Nearly half of the pts were treated in 2nd line. At study entry remission status was 61.6% in CHR, 22.9% in CCyR (missing data in 22.6%), 27.9%/8.4% in MMR/CMR. These responses improved significantly under nilotinib reaching cumula- 84 Oncol Res Treat 2014;37(suppl 1):1–133 tive incidences of CHR, MMR and CMR of 90.1%, 54.2% and 32.2%, respectively. Dose reduction/therapy interruption occurred in 26.6%/15.2%. 72.1% experienced at least one AE which was considered serious in 18.6%. Hematologic toxicity was observed in 15.2%, non-hematologic toxicities occurred in 39.9% of pts. The most frequently reported AEs were pruritus (12.1%), alopecia (7.4%) and rash (10.5%), fatigue (9.6%), arthralgia (5.6%), dyspnoea (5.6%), nausea (6.5%) and upper abdominal pain (5.3%) as well as headache (11.5%). Conclusions: These data support the use of nilotinib as an efficacious and safe drug for treatment of a broad population of CML pts with poor response or intolerance to a prior therapy including IM. ID 191 Interim analysis of the non-interventional MOMENT II study – efficacy and safety of Nilotinib in routine clinical management of newly diagnosed Ph+ CML patients in chronic phase A. Sauer1, B. Lathan2, K. Blumenstengel3, T. Gabrysiak4, S. Tebbe5, M. Meincke6, O. Frank7, H. Tesch8 MVZ für Blut- und Krebserkrankungen, Potsdam, Deutschland Gemeinschaftspraxis für Hämatologie & Onkologie, Dortmund, Deutschland 3 Gemeinschaftspraxis für Hämatologie & Onkologie, Eisenach, Deutschland 4 Onkologische Schwerpunktpraxis, Wolfsburg, Deutschland 5 Onkologische Praxis, Kassel, Deutschland 6 Novartis Pharma GmbH, Onkologie, Altenholz, Deutschland 7 Novartis Pharma GmbH, Onkologie, Nürnberg, Deutschland 8 Hämatologisch-Onkologische Gemeinschaftspraxis, Frankfurt am Main, Deutschland 1 2 Introduction: As a potent and highly selective BCR-ABL inhibitor Nilotinib (NI) is approved for treatment of newly diagnosed Ph+ CML pts in CP as well as for pts with Ph+ CML in CP and AP with failure to prior therapy including imatinib. Methods: Exploratory interim analysis of a non-interventional study of NI in 85 pts with de novo Ph+ CML in CP within routine clinical management in 53 centres in Germany (08/2011–03/2013). Results: All patients were newly diagnosed with a median age of 55 years (range 20–89) and 58% were male. The median observation period was 175 days (range 7–537) with a median daily dose of 600 mg NI (range 300–800 mg). There were 9.4% of pts with one, 2.4% with more than one interruption of therapy with a median of 13 days for the duration of each interruption (range 2–34). At last visit 79.5% (of 73 pts with a hematologic examination) had a CHR, 86.7% (of 15 pts with a cytogenetic examination) had a CCyR, 48.4% (of 51 pts with a molecular examination) had an MMR. In the subgroup of patients with molecular response (n = 33) the median time to MMR or better was 168 days (range 60–393). A premature study discontinuation took place in 11.8% of pts mostly due to AEs/non-hematologic toxicity, in one case due to disease progression. Altogether, 68.2% of pts experienced AEs. Hematologic toxicity was observed in 8.2% of pts, non-hematologic toxicities in 31.8% of pts. The most frequently reported AEs were skin reactions, gastrointestinal symptoms (nausea 4.7%), dyspnoea (4.7%) as well as headache (4.7%). The most frequent biochemical abnormalities were increases in blood bilirubin (8.2%), GGT (7.1%) and lipase (4.7%). Conclusions: These data from routine clinical management support the use of NI as an effective and safe drug for treatment of newly diagnosed Ph+ CML pts in CP. Abstracts Inhalt Index ID 219 Screening supported by a central review allows a precise selection of the population for maintenance therapy within the CLLM1 trial of the German CLL Study Group A. Westermann1, A. Fink1, A. Zey1, J.S. Wesselmann1, R. Busch2, K. Fischer1, C. Wendtner3, K.-A. Kreuzer4, S. Stilgenbauer5, S. Böttcher6, B. Eichhorst4, M. Hallek4 Deutsche CLL Studiengruppe, Uniklinik Köln. Innere Med. I, Köln, Deutschland 2 Technische Universität München, Institut für Medizinische Statistik und Epidemiologie, München, Deutschland 3 Krankenhaus München-Schwabing, Abt. Hämatologie/Onkologie, München, Deutschland 4 Uniklinik Köln, Med. I, Köln, Deutschland 5 Uniklinik Ulm, Innere Med. III, Ulm, Deutschland 6 Universitätsklinikum Schleswig-Holstein Campus Kiel, Med. II, Kiel, Deutschland 1 Introduction: CLLM1 is a phase 3, randomized, placebo-controlled study of the efficacy and safety of lenalidomide as maintenance therapy for patients (pts) with chronic lymphocytic leukemia (CLL) following firstline therapy. Physically fit pts with a high risk for early relapse as defined by the presence of minimal residual disease (MRD) levels of ≥10-2 or a combination of MRD levels of ≥10-4 to <10-2 with either an unmutated IGHV-status or TP53 aberrations are eligible. These high risk pts are known to have not only a median progression free survival of less than 2 years but also a considerably shorter overall survival. Methods: Screening procedures are implemented prior to randomization. The central review covers the assessment of risk factors and a check of at least 15 relevant inclusion/ exclusion criteria; in particular pts’ comorbidities, ECOG performance status, stage of disease and response to firstline therapy. In addition blood samples are to be sent to the central laboratories for confirmation of CLL and to assess cytogenetic aberrations. After firstline therapy MRD is analyzed centrally. A total of 200 Pts will be randomized. Results: Between July 2012 and September 2013 287 pts were registered. 63 (22%) failed to proceed to screening due to other B-cell lymphoma (10/3.5%), pts’ decision (21/7.3%) and other reasons (32/11.1%). Non response or death before randomization was observed with both 2/0.7%. 84 pts were screened after responding to therapy with FCR (49/ 58%), BR (34/ 40%) or FC (1/1.1%). As expected 60 (71%) of them achieved MRD negativity. 17 pts were randomized to receive study drug. Conclusion: The Screening process supports the identification of eligible high risk pts and prevents the inclusion of not eligible subjects. ID 220 Establishment of a human 3D blood vessel model for testing therapeutic agents such as tipifarnib in AML H. Bersi, S. Nietzer, G. Dandekar, H. Walles University Hospital Würzburg, Chair of Tissue Engineering and Regenerative Medicine, Würzburg, Deutschland Amongst all types of leukemia, acute myeloid leukemia (AML) has the worst prognosis. Even today, only 34% of under 60-year-old and 15% of over 60-year-old patients show a long-lasting remission 4–5 years after treatment (dgho aml guidelines 2013). Since there is a lack of sufficient preclinical drug test systems correlating with clinical studies (Kola et al. 2004), our aim was to establish a more efficient preclinical three-dimensional (3D) blood vessel model to test anti-leukemic drugs. The 3D model consists of human leukemia cells (non-adherent THP-1 cells, AML M5) and human primary endothelial cells that grow as a monolayer on a decellularized intestinal scaffold. By using this model system, it is possible to analyze the interaction of malignant cells and endothelial cells in a more natural environment than in conventional cell culture. Moreover, the influence of tested drugs on the endothelium can be investigated and damaging effects can be monitored in our 3D model. Abstracts In our setting, we tested the efficacy of tipifarnib, a competitive farnesyltransferase inhibitor. Farnesyltransferase catalyzes prenylation of many proteins involved in cell proliferation and survival (Weinberg 2013). Tipifarnib shows anti-leukemic, dose-dependent effects on THP-1 in our 3D model. Increased induction of apoptosis in malignant THP-1 was observed by FACS analysis and potential damaging effects on endothelial cells were assessed by immunhistological stainings. Based on our results, it can be shown that our 3D model is a promising tool to investigate the interactions of the therapeutic agent and malignant cells as well as its influence on vasculature. ID 500 Long Term Remissions After FCR Chemoimmunotherapy In Patients With CLL K. Fischer1, J. Bahlo1, A.-M. Fink1, R. Busch2, S. Boettcher6, C. Maurer1, J. Mayer7, P. Dreger5, M. Kneba6, H. Döhner4, C.-M. Wendtner3, S. Stilgenbauer4, M. Hallek1, B. Eichhorst1, K.-A. Kreuzer1 Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Cologne, Germany 2 Technical University, Institute for Medical Statistic and Epidemiology, Munich, Germany 3 Department of Hematology, Oncology, Immunology, Palliative Care, Infectious diseases and Tropical Medicine, Klinikum Schwabing, Munich, Germany 4 Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany 5 Department V of Internal Medicine, University Hospital Heidelberg, Heidelberg, Germany 6 Department II of Internal Medicine, University Hospital Schleswig- Holstein, Kiel, Germany 7 Department of Hematology-Oncology, University Hospital Brno, Brno, Czech Republic 1 Background: Chemoimmunotherapy with Fludarabine, cyclophosphamide (FC) and rituximab (R) is the standard therapy for physically fit patients with previously untreated CLL (M Hallek, Lancet 2010). In this report, we present data on long term safety and long term remissions after FCR with particular emphasis on IGHVmutated patients. Methods: In this prospective, randomized, open-label phase-III trial, 817 treatment-naïve patients with good physical fitness and CD20-positive CLL received six courses of either FCR or FC. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response to treatment, overall survival (OS), safety and survival times in biological subgroups. Results: At median follow-up of 5.9 years, median PFS was 57 and 33 months for the FCR and FC group (hazard ratio (HR), 0.6 (95% confidence interval (CI), 0.5–0.7), p < 0.001). Median OS was not reached for the FCR group and 86 months for the FC group (HR, 0.7 (95% CI, 0.5–0.9), p = 0.001). In IGHVmutated patients, FCR increased PFS and OS compared to FC (PFS HR, 0.5 (95% CI, 0.3–0.7), p < 0.001; OS HR 0.6 (95% CI, 0.3–1.1), p = 0.1, respectively, figure 1A, 1B) for all cytogenetic subgroups except for deletion 17p. FCR induced an increase in prolonged neutropenia during the first year after the end of treatment (16.6% versus 8.8% (p = 0.007)). Secondary malignancies including Richter`s transformation occurred in 13% in the FCR group and in 17% in the FC group (p = 0.1). Conclusions: FCR induced long term remissions in physically fit IGHV mutated patients. This observation is clinically relevant with respect to novel, targeted agents for CLL therapy that are currently being investigated and which not only have to show better tolerability and overall response rates, but also similar long term efficacy. Oncol Res Treat 2014;37(suppl 1):1–133 85 Inhalt Index 28%). Of note, overall 64% of the patients (carbo/vrb: 71%, cis/vrb: 44%) completed combination therapy with the planned number of cycles. Conclusions: The results of this retrospective study are in line with clinical trials of cis in combination with intravenous vrb and show that adjuvant chemotherapy of a platinum-based combination therapy with oral vrb is effective. Carbo was better tolerated than cis resulting in superior treatment compliance and comparable effectiveness. Lung Cancer – Local-Regional Therapy ID 203 Gut differenzierte Neuroendokrine Karzinome der Lunge Figure 1A. Progression-free survival (PFS) in IGHV mutated/unmutated patients (N = 622) Figure 1B. Overall survival (OS) in IGHV mutated/unmutated patients (N = 622 Lung Cancer – Adjuvant Therapy ID 116 Adjuvant treatment of completely resected stage IB-IIIA non-small-cell lung cancer. A retrospective study with cisplatin or carboplatin and oral vinorelbin M. Serke Lungenklinik Hemer, Pneumologie, Hemer, Deutschland Es werden Patienten mit gut differenzierten intrathorakalen neuroendokrinen Tumoren (pulmonale Karzinoide) gezeigt. Beobachtet wurden die Patienten in einer großen Lungenklinik., Beobachtungszeitraum vom 01.09.2008 bis 31.07.2013. Material und Methode: In der Lungenklinik Hemer wurden gemäß Tumordokumentation 3485 Patienten mit gesichertem Lungenkarzinom behandelt. Hierunter fanden sich 90 Karzinoide. Alle Diagnosen wurden in der Lungenklinik gestellt und alle Patienten waren unbehandelt. Zur Diagnostik der neuroendokrinen Differenzierung wurden morphologische und histologische Kriterien angewandt. Die Betreuung erfolgte durch das Zentrum. Ergebnisse: Karzinoide: 73 (81%) typische Karzinoide und 17 atypische Karzinoide (19%), 64% der Pat. waren weiblich. Typisches Karzinoid (TK): Wir beobachteten 73 Patienten mit typischem Karzinoid, mittl. Alter 64 Jahre, atypisches Karzinoid: mittleres Alter: 60 Jahre, Die Patienten mit atypischem Karzinoid (N =17) waren überwiegen weiblich (13 von 17) . Therapie: Die meisten Patienten wurden operiert, bei 3 Pat. erfolgte bei eingeschränkten funktionellen Reserven lediglich eine bronchoskopische Tumorabtragung. Das Überleben war günstig: med. ÜL beim TC 1890 Tage, beim AC 1670 Tage. Diskussion: Intrathorakale gut differenzierte Neuroendokrine Karzinome, Karzinoide gehören zu der Minderheit der prognostisch günstigen intrapulmonalen Neubildungen. Das klinische Bild, Therapieverfahren und Ergebnisse an 90 Patienten werden beschrieben. ID 257 W. Engel-Riedel, F. Magnet, N. Alten, C. Ludwig, A. Bachinger, E. Stoelben CyberKnife Radiosurgery for lung tumors: Report of clinical response and toxicity Kliniken der Stadt Köln, Lungenklinik, Köln, Deutschland S. Temming1, E. Stoelben2, R. Semrau1, M. Kocher1 Background: Adjuvant chemotherapy is implied for early stage NSCLC after R0-resection. Most evidence-based data exist for combination of cisplatin (cis) and vinorelbine (vrb). To analyze effectiveness and tolerability of platinum-based combination therapy with predominantly oral vrb (Navelbine© Oral) we performed a retrospective study in our hospital. Material and Methods: Data from 152 patients with R0-resected NSCLC (stage IB-IIIA) receiving adjuvant chemotherapy with cis or carbo in combination with vrb between 03/2005 and 11/2011 were retrospectively analyzed. The primary endpoint was overall survival (OS), secondary endpoints progression-free survival (PFS) and toxicity. Results: Patients were diagnosed with stage IB (35%), IIA (5%), IIB (38%) or IIIA (22%) NSCLC. Vrb was predominantly administered orally (89%) and most patients received carbo (74%).The estimated 5-year survival was 64% (cis/vrb: 65%, carbo/vrb: 64%) and PFS after five years was 60% (cis/ vrb: 63%, carbo/vrb: 59%). Toxicities mainly concerned the hematologic system with 70% leukopenia (carbo/vrb: 74%), 32% thrombocytopenia (carbo/vrb: 40%) 40% anemia, 28% neutropenia. The treatment caused nausea and vomiting in 47% and 23% of the patients (cis/vrb: 59% and 1 86 Oncol Res Treat 2014;37(suppl 1):1–133 2 Uniklinik Köln, Strahlentherapie, Köln, Deutschland Köln Merheim Lungenklinik, Thoraxchirurgie, Köln, Deutschland Objective: To report clinical efficacy and toxicity of fractionated CyberKnife radiosurgery for the treatment of inoperable lung tumors. Methods: Between April 2012 and September 2013, 51 patients with inoperable NSCLC Stadium I underwent CyberKnife radiosurgery. All were highrisk patients and inoperable because of medical illness through previous surgeries with lungfunction disorder, COPD, cardiovascular disease and age. The age range 55 to 87 years, with a median of 75 years. For Tumor tracking during radiation we placed gold fiducials in 10 patients or used the digital radiographic images of the tumor itself (X-sight Lung Tracking System). The dose was delivered in 60 Gy (65–80% Isodose) in 3–8 fraction relative to size and the position of the tumor. 15 patients were treated with 3× 20 Gy, 5 patients 3× 17 Gy (Monte-Carlo Algorithm), 18 patients 5× 12 Gy and 5 patients 8× 7.5 Gy. 5 patients were treated with 1× 25 Gy. Clinical, pulmonary and radiological evaluation was made after six weeks, 3, 6, and 9 Month post CyberKnife radiosurgery. Results: The overall survival after CyberKnife radiosurgery was 100%. No patient relapsed locally. All tumors decreased in size or disappeared Abstracts Inhalt Index after treatment. However regional recurrence or distant metastases occurred in 8 patients, from them 5 in lymphnodes, 2 in adrenal glands and one in the contralateral lung. Acute toxicity like dyspnea, chestpain were observed in 5 patients. Late toxicity like pneumonitis, esophageal or bronchus fistula were not observed. Conclusion: CyberKnife radiosurgery for Stage I NSCLC patients who are medically inoperable because of COPD, cardiovascular disease and age results in a favorable local control rate, quality of live with a low incidence of toxicity. Lung Cancer – Metastatic Lung Cancer ID 022 Molecular screening in 915 lung cancer patients. Monocentric results within the German Netzwerk Genomische Medizin (NGM) M. Serke, J. Wolf, R. Buettner, M. Bos, L. Heukamp, M. Gardizi Lungenklinik Hemer, Pneumologie, Hemer, Deutschland Material and Methods: Within the German Lung Cancer Genome screening project «Netzwerk Genomische Medizin (NGM)» Köln we analyzed the test results of 915 lung cancer patients of our chest hospital in NRW/ Hemer. Tumor material of all available lung cancer patients was analyzed. Results: 915 patients (pat.) of all tumour stages were analysed. Histology: 493 pat. (54%) with adenocarcinoma (AD), 250 pat. (27%) with squamous-cell carcinoma (SQ), 54 pat. (6% ) NOS (non other specified), 73 pat. (8%) with small-cell lung cancer (SCLC), 27 pat. (3 %) with largecell carcinoma (LC), 18 pat. (2%) with other histologies. Genomic Alterations: within all patients with non-small call lung cancer (842 pat.) we identified 275 pat. (32.7%) with molecular alterations. In the group of patients with non-SQ lung cancer we found molecular alterations in 233 pat. (49 = 8.3% EGFR-mutations, 10 =1.7% EML4/ALK translocations, 13 (=1.7%) B-RAF mutations, 111 (=18.8%) K-RAS-mutations and others. Within the 249 pat. with SQ carcinoma 16% were FGFR1-positiv, within the SCLC patients 8% were FGFR1-positiv. Discussion: A genome-based diagnosis of lung cancer within our large screening project is feasable. In 10% of our patients with non-squamous NSCLC treatable genomic changes may be recognized. We also identified genetic changes in SQ-cell and SCLC lung cancer. The broad introduction of such diagnostics will allow specific genomic driven therapeutic interventions with an improved survival of these patients. (27%) with an UICC III, 172 (9%) UICC II and 141 (7%) UICC I. In 95 (5%) patients the stage was not determinable. Results: A statistically significant change of relative 5-year survival rate (5ysr) within the observation period cannot be determined. The 5ysr of all registered patients is 18.5% (SE = 1.5). The average survival of all patients is influenced by the high portion of late-diagnosed diseases with already existing distant metastases. Primary metastatic patients show a 5ysr of 7.1% (SE = 1.5). The survival rate of patients with an UICC I-III is 29.9% (SE = 2.5). In case of a local finding, the survival rate increases to 48.3% (SE=5.3). If regional lymph nodes are involved, the 5ysr decreases to 25.8% (SE=3.1). Metastatic patients with an adenocarcinoma show a 5ysr of 7.8% (SE=1.8). Whereas patients with a squamous-cell carcinoma show a survival rate of 3.7% (SE=2.7). Conclusion: The analyzed registry data shows correlating survival times of patients the ambulatory oncological care compared to literature data. ID 102 A multi-center phase II study investigating the combination of RAD001 (everolimus) with paclitaxel and carboplatin in first line treatment of patients with advanced Large Cell Lung Cancer with Neuroendocrine Differentiation (LCNEC) – a case report C. Schumann1, W. Engel-Riedel2, J. Kollmeier3, C. Grohé4, J. von Pawel5, W. Eberhardt6, S. Gütz7, I. Nimmrich8, C. Weiß9, M. Potzner9, M. Serke10, M. Thomas11 Universitätsklinikum Ulm, Klinik Innere Medizin II / Sektion Pneumologie, Ulm, Deutschland 2 Kliniken der Stadt Köln, Lungenklinik Merheim, Köln, Deutschland 3 Helios Klinikum Emil von Behring, Klinik für Pneumologie, Berlin, Deutschland 4 Evangelische Lungenklinik, Berlin, Deutschland 5 Asklepios Fachkliniken München Gauting, Gauting, Deutschland 6 Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Essen, Deutschland 7 Evangelisches Diakonissenkrankenhaus, Leipzig, Deutschland 8 Clinical Research i.A. Novartis Pharma GmbH, Berlin, Deutschland 9 Novartis Pharma GmbH, Nürnberg, Deutschland 10 Lungenklinik Hemer, Hemer, Deutschland 11 Universitätsklinik Heidelberg, Thoraxklinik, Heidelberg, Deutschland 1 Introduction: The non-small cell lung cancer (NSCLC) has its highest mortality among men and is the third-most frequent cause of death among women. Considering a medium relative 5-year survival rate of 15–18% after the initial diagnosis, the prognosis is highly unfavorable. We will demonstrate the reality of treatment in relation to the relative survival rate in the period from 2003 to 2013. Methods: The relative survival has been calculated applying periodical analysis according to the method Ederer II. At time of evaluation the registry contains 2,382 patients. Within the observation period a total of 1,985 patients with initial diagnosis has been analyzed. 1,463 patients are male, 522 female. The registry contains 1,032 (52%) patients with primary metastatic NSCLC (UICC IV), 545 Introduction: Large cell neuroendocrine carcinoma of the lung (LCNEC) are rare. With current treatment options like platin derivates and/or etoposide, patients have poor prognosis. Targeted therapies are discussed as an approach to improve outcome of LCNEC. RAD001 (everolimus) is an inhibitor of mTOR, a component of the PI3/AKT/mTOR pathway known to be dysregulated in cancer, especially in neuroendocrine tumors (NETs). RAD001 is approved for treatment of renal cell cancer, breast cancer, and pancreatic NETs. Methods: In the presented trial for advanced (stage IV) LCNEC patients, daily RAD001 is combined with carboplatin and paclitaxel. Patients receive 4 cycles of combined treatment followed by RAD001 maintenance therapy. The primary endpoint is the proportion of patients that are progression-free after 3 months. Main inclusion criteria are histologically confirmed stage IV LCNEC, adequate bone marrow, renal, and liver function. Main exclusion criteria are symptomatic CNS metastases, prior treatment for advanced LCNEC, and any other severe medical condition. Results: A case report of a 78-year old patient enrolled in this trial is presented. The tumor revealed histologically NSCLC morphology of the large-cell type and a clear CD56 staining as well as a proliferation rate of more than 60% in Ki67 staining. The patient received 4 cycles of chemotherapy combined with RAD001 and subsequently RAD001 monotherapy for further 6 months. The tumor response was stable disease (SD) for the first 3 months and partial response (PR) for the following 6 months. Conclusions: These data show that a combined therapy of carboplatin and paclitaxel with the mTOR inhibitor RAD001 might be a promising approach for more efficient treatment of LCNEC patients. Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 ID 035 NSCLC-relative survival in the ambulatory oncological care H. Eschenburg1,2, S. Bartels3, H.-W. Tessen2,4 Onkologische Schwerpunktpraxis Güstrow, Güstrow, Deutschland PIO (Projektgruppe Internistische Onkologie, Goslar, Deutschland rgb Onkologisches Management GmbH, Sarstedt, Deutschland 4 Onkologische Schwerpunktpraxis Goslar, Goslar, Deutschland 1 2 3 87 Inhalt Index ID 108 ID 152 E. Celik, R. Semrau, S. Kunze, M. Kocher D. Fecher, H. Walles, S. Nietzer, G. Dandekar Uniklinik Köln, Strahlentherapie, Köln, Deutschland Lehrstuhl für Tissue Engineering und Regenerative Medizin, Würzburg, Deutschland Cyberknife radiosurgery treatment for adrenal metastases from lung cancer: A single-institution experience Purpose: To present our initial institutional experience with robotic Cyberknife-based stereotactic radiotherapy in the treatment of adrenal gland metastases in 5 consecutive lung cancer patients. Methods and Materials: Between November 2012 and August 2013, 5 patients with solitary adrenal metastatic lesion received stereotactic body radiation therapy (SBRT). SBRT treatments were delivered with Cyberknife. The median age of the patient population was 60.2 years (range, 47–82 years). In all of the patients, the prescription dose was 42 Gy in 7 fractions (65% isodose, 6 Gy per fraction at the isocenter). All patients were clinically and radiologically evaluated with post-therapy clinical exams and computed tomography. Response Evaluation Criteria in Solid Tumors (RECIST)-based tumor response was assessed to determine treatment outcome. Results: At a median follow-up time of 6 months (range, 4–9 months) all five patients were alive. Four of 5 lesions (80%) showed partial response and one of 5 lesions (20%) progressed in the treated area. Overall, the TMC rate at the first post-therapy exam after 4 months was 80%. Distant control was 60%, and OS was 100%. No patient experienced grade 3 toxicity. The most common grade 1–2 acute toxicities were fatigue (60%) and nausea (40%). Conclusion: Hypofractionated robotic Cyberknife-based stereotactic radiotherapy in adrenal gland metastasis is a useful non-invasive treatment option and feasible without significant acute toxicities, providing good local control. Considering our experiences, these first results indicate that radiotherapy in addition to systemic therapy may contribute to survival of patients with adrenal metastases from lung cancer. Establishment of a 3D Lung Tumor Model and Adjustment to Lung Specific Conditions Purpose: High mortality of lung cancer is often associated with tumor recurrences and distant metastases. One fundamental mechanism involved in tumor cell invasion is the epithelial-to-mesenchymal transition (EMT). To analyse this process, we generated a 3D lung tumor model. Methods: A549 and HCC-827 cells were cultivated on decellularized porcine small intestinal submucosa (SIS) segments and stimulated with TGF-β1 at concentrations of 0.05, 0.5 and 5 ng/ml for 14 days. Immunohistology and real-time PCR were applied in order to find phenotypic changes. The invasive potential was quantified by assessing the number of single cells inside the SIS. Results: Both cell types formed a cell layer on its apical side. While HCC827 exhibited a polarized expression of Mucin-1, E-cadherin and ß-catenin, A549 expressed these proteins diffusely. Stimulated with TGF-β1, both cell types showed a concentration-dependent change in morphology, gene expression and invasive behavior. While only 5–10% of single cells were found inside the SIS under control conditions, treatment with 5 ng/ ml TGF-β1 led to an invasion of 35–50% of the cells. Additionally, the expression of epithelial markers was lost, whereas the expression of mesenchymal markers was upregulated after TGF-β1 stimulation. Conclusion: As a conclusion, our in vitro tumor model provides a polarised epithelial layer that exhibits upregulation of tumor relevant genes and produces induction of EMT as well as invasion. It may help studying these processes in greater detail and could be a tool for testing drug candidates targeting EMT and cell invasion. ID 149 ID 204 Rationale for a generic targeted therapy multi‑drug regimen for NSCLC stage IIIB/IV patients without treatment options Circulating tumor cell subgroups and outcome in patients with non-small-cell-lung-cancer receiving platinum based treatment S. Langhammer U. Jehn, I. Nel, M. Schuler, T. Gauler, A.-C. Hoffmann life science consulting, Meerbusch, Deutschland Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Essen, Deutschland Despite more than 70 years of research concerning medication for cancer treatment, the disease still remains one of the leading causes of mortality worldwide. Many cancer types lead to death within a period of months to years. The original class of chemotherapeutics is not selective for tumor cells and often has limited efficacy, while treated patients suffer from adverse side‑effects. To date, the concept of tumor‑specific targeted therapy drugs has not fulfilled its expectation to provide a key for a cure. Most oncology trials are designed using a combination of chemotherapeutics with targeted therapy drugs. However, these approaches have limited outcomes in most cancer indications. Here a rationale to combine targeted therapy drugs for cancer treatment based on observations of evolutionary principles of tumor development and an HIV infection is presented. In both diseases, the mechanisms of immune evasion and drug resistance can be compared to some extent. However, only for HIV is a breakthrough treatment available, which is the highly active antiretroviral therapy (HAART). The principles of HAART and recent findings from cancer research were employed to construct a hypothetical model for cancer treatment with a multi‑drug regimen of targeted therapy drugs. As an example of this hypothesis, it is proposed to combine already marketed targeted therapy drugs against VEGFRs, EGFR, CXCR4 and COX2 in an oncology trial for NSCLC stage IIIB/IV patients without further treatment options. 88 Oncol Res Treat 2014;37(suppl 1):1–133 Backround: Circulating tumor cells (CTC) could serve as a ‘liquid biopsy’ for individualizing and monitoring treatment in patients with lung cancer as recently shown by our group (Nel et al., Br J Cancer 2013). We assessed which non-hematopoietic cell types are identifiable in the peripheral blood of NSCLC patients and correlated those to clinical characteristics. Methods: Mononuclear cells and CTC were isolated from peripheral venous blood of n = 45 patients with NSCLC receiving platinum-based therapy using density gradient centrifugation. Cell suspensions were spun onto glass slides and further characterized by multi-immunofluorescence staining against cytokeratin (CK and EpCAM; epithelial), N-cadherin (mesenchymal); CD133 (stem-cell), CD45 (hematopoietic) and DAPI (nucleus). Results: We detected cells with mesenchymal features such as N-cadherin+/CK-/CD45- and cells with epithelial properties like CK+/N-cadherin-/CD45-; CK+/EpCAM+/CD45- and cells with both characteristics like CK+/N-cadherin+/CD45-. We also detected cells showing stem cell-like features such as CD133+/CK-/CD45- and CD133+/CK+/CD45- cells. Mann Whitney test revealed a significantly increased number of CD133+ cells in the presence of N-cadherin+ cells (p = 0.0004); Kaplan Meier test indicated that the presence of N-cadherin+ cells was significantly associated to shortened PFS (5 vs. 9 months; p = 0.03; [HR]=2.63). Conclusions: Our data suggest that different CTC populations are identifiable in peripheral blood and that these individual cell type profiles might be used to predictoutcome to systemic therapies in lung cancer patients. Abstracts Inhalt Index ID 209 Final Results from REASON, a Registry for the Epidemiologic and Scientific evaluation of EGFR mutation status in newly diagnosed NSCLC patients stage IIIB/IV in Germany W. Schuette1, W. Eberhardt2, J.-M. Graf von der Schulenburg3, M. Dietel4, P. Schirmacher5, S. Zaun6, U. Zirrgiebel7, M. Thomas8 Hospital Martha-Maria Halle-Dölau, Halle, Deutschland University Hospital Essen, University Duisburg-Essen, Department of Medical Oncology, Essen, Deutschland 3 Research Center Health-Economy, Leibnitz-University Hannover, Hannover, Deutschland 4 Pathological Institute Humboldt University Berlin, Berlin, Deutschland 5 Pathological Institute University Heidelberg, Heidelberg, Deutschland 6 AstraZeneca, Wedel, Deutschland 7 iOMEDICO AG, Freiburg, Deutschland 8 Internistische Onkologie der Thoraxtumoren, Thoraxklinik im Universitätsklinikum Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Deutschland 1 2 Background: Somatic EGFR mutations (Mut) predict for sensitivity to EGFR TKI in patients (pts) with advanced NSCLC. As most published data originate from Asia, we aimed at generating data on EGFR Mut rates, treatment and outcomes in Caucasians. Methods: REASON is a non interventional study (NCT00997230) designed to collect data on EGFR Mut status, investigate association with clinico-pathological features, treatment decisions and clinical outcome for EGFR Mut+ pts with advanced NSCLC. Pts with planned EGFR Mut testing were enrolled at 149 sites (85% hospitals). Primary objectives were epidemiological data on EGFR Mut status and their correlation with clinico-pathological features. As secondary aims, clinical outcome of pts with EGFR Mut+ (PFS, OS), clinical management and pharmacoeconomic data will be evaluated for EGFR Mut+ pts. Results: Of 4243 pts enrolled; 4200 are eligible. EGFR Muts were detected in 432 pts (Mut+ 10.3%); in 3593 pts (85.5%) no EGFR Mut was found (Mut-); Mut status was not evaluable in 175 pts (4.2%). In multivariate analyses, the odds of Mut+ was higher in females vs males (OR, SE: 1.85, 0.11), never smokers vs smokers (3.64, 0.11) and pts with adenocarcinoma (ADC) vs other histologies (2.94, 0.16). EGFR TKIs were the most common 1st line treatment for EGFR Mut+ (57% vs 2% in Mut). Platin doublets (79%) were the most common regimens in Mut- NSCLC. Median PFS in Mut+ pts was 9.1 months (9.7 with TKI 1st line), OS 17.2 months. PFS was longer in women vs men, never smokers vs ever smokers, and ADC vs other histologies. Conclusion: REASON provides the largest database on EGFR Mut in Caucasians with newly diagnosed stage IIIB/IV NSCLC. Gender, smoking status and ADC histology were predictive factors for better PFS in EGFR Mut+. ID 233 Clinical activity of the ALK inhibitor LDK378 in advanced, ALK-positive NSCLC M. Thomas1, J. Wolf2, M. Schuler3, M. Goldwasser4, A. Boral4, A.T. Shaw5 Thoracic Oncology Clinic for Thoracic Diseases, Department of Internal Medicine, Heidelberg, Deutschland 2 Lung Cancer Group Cologne, Center for Integrated Oncology, University Hospital Cologne, Cologne, Deutschland 3 West German Cancer Center, University Hospital Essen, Essen, Deutschland 4 Novartis Institutes for BioMedical Research, Inc, Cambridge, Vereinigte Staaten Von Amerika 5 Massachusetts General Hospital Cancer Center, Boston, Vereinigte Staaten Von Amerika 1 Methods: In this phase I study (NCT01283516), 130 pts with advanced malignancies and a genetic alteration in ALK, including 122 with ALK-rearranged (ALK+) NSCLC (by FISH), were enrolled. LDK378 50-750 mg was administered orally once daily (OD). All pts were assessed for PK, response to therapy, and adverse events (AEs). In 19 CRZ-pretreated pts, tumor biopsy was performed before LDK378 treatment to identify potential CRZ resistance mutations. Results: As of October 19, 2012, 130 pts had been enrolled: 59 in dose escalation phase (where MTD of 750 mg OD was established); 71 pts in an expanded cohort at the MTD. Among 114 NSCLC pts receiving LDK378 ≥400 mg, the overall response rate (ORR) was 58% (95% CI, 48–67%). In the subset of 79 CRZ-pretreated pts, the ORR was 57% (95% CI, 45–68%). Responses were observed in CRZ-pretreated pts with different CRZ resistance mutations as well as in pts without detectable mutation in the ALK gene other than the original rearrangement. Responses were also seen in pts with untreated CNS metastases. Among NSCLC pts with partial or complete response, median duration of response (DOR) was 8.2 months (95% CI, 6.9-NE), and 60.6% (95% CI, 34.9–78.8%) receiving 750 mg/day had a DOR of ≥6 months. In all 114 NSCLC pts, median PFS was 8.6 months (95% CI, 5.7–9.9). The 3 most common AEs were nausea (73%), diarrhea (72%), vomiting (58%). The most common Grade 3/4 AEs were ALT elevation (19%), AST elevation (10%), and diarrhea (8%). Conclusions: These results suggest that potent ALK inhibition by LDK378 represents a highly efficacious treatment strategy for ALK+ pts, including those previously treated with CRZ. ID 235 Validation of a three-dimensional human lung tumor test system applied for the analysis of targeted treatment effects on signaling pathway activation C. Göttlich, D. Fecher, S. Nietzer, G. Dandekar, H. Walles Universitätsklinikum Würzburg, Lehrstuhl für Tissue Engineering und regenerative Medizin, Würzburg, Deutschland Non small cell lung cancers (NSCLCs) are quite insensitive to chemotherapy. For this reason, it is very challenging to develop new therapies different from common chemotherapy. In the present study, we introduced a three-dimensional (3D) human tumor model which was developed on the basis of a decellularised porcine jejunum using cell crowns to fix the scaffold in 12-well plates. We used either a human cell line with an activating epidermal growth factor receptor (EGFR) mutation (HCC827) or EGFR wild-type cell lines (H441, A549) in order to simulate the approach of personalized medicine in the clinic where the mutation status of the EGFR is tested prior to targeted therapy. To prove the robustness of our models, we first tested the variance of five different cell crowns of one trial and of three different trials. The variance of the tumor test systems was low concerning cell number and overall morphology. Receptor tyrosine kinases (RTK) like EGFR play an important role in cancer signaling pathways. To block EGFR activation, we treated the models with the EGFR inhibitor gefitinib. RTK phosphorylation status was then determined by using phosphor-RTK arrays (R&D) and results from 2D and 3D cultures were compared. In 3D culture of HCC827 cells, not only the EGFR but also hepatocyte growth factor receptor (HGFR) and ErbB2 were dephosphorylated after gefitinib treatment while in H441 and A549 cells, gefitinib treatment had no strong effect. This fits in with the clinic as EGFR inhibitors have an effect only in patients with an EGFR mutation. Thus our model is a promising tool to investigate the signaling pathways involved here. Background: LDK378 is a novel, more potent ALK TKI than crizotinib (CRZ), with significant antitumor activity in preclinical models. Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 89 Inhalt Index ID 242 Safety profile of afatinib in first-line therapy of patients with metastatic EGFR mutation-positive (M+) non-small cell lung cancer (NSCLC): Comparative analysis of Asian and non-Asian patients from two randomized trials M. Schuler1, L.V. Sequist2, J.C. Yang 3, N. Yamamoto4, K.J. O’Byrne5, T. Mok6, S.L. Geater 7, D. Massey8, S. Wind9, D. O’Brien10, R. Lorence10, Y.-L. Wu11 University Hospital Essen, West German Cancer Center, Essen, Deutschland 2 Massachusetts General Hospital, Cancer Centre, Boston, Vereinigte Staaten Von Amerika 3 National Taiwan University Hospital, Taipei, Taiwan 4 Shizuoka Cancer Center, Cancer Centre, Shizuoka, Japan 5 Princess Alexandra Hospital, Brisbane, Australien 6 The Chinese University of Hong Kong, Hong Kong, China 7 Prince of Songkla University, Songkla, Thailand 8 Boehringer Ingelheim Limited, Bracknell, Großbritannien 9 Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Deutschland 10 Boehringer Ingelheim Pharmaceuticals, Ridgefield, Vereinigte Staaten Von Amerika 11 Guangdong General Hospital, Guangzhou, China 1 Question: Afatinib – an oral, irreversible ErbB Family Blocker – has superior efficacy to standard first-line chemotherapy in Asian (LUX-Lung 6) and non-Asian patients (LUX-Lung 3) with metastatic EGFR M+ NSCLC. In both trials, median progression-free survival (independent review) on afatinib was 11 months and median treatment duration 11–12 months. This analysis was conducted to compare typical EGFR-mediated adverse events (AEs) between Asian and non-Asian patients. Methods: 239 (LUX-Lung 6) and 229 (LUX-Lung 3) patients received afatinib 40 mg daily until progression or intolerable AEs. Dose could be escalated to 50 mg, or reduced to 30 mg or 20 mg based on predefined study criteria. Patients were grouped as Asian vs. non-Asian across both trials. On-treatment AEs were monitored for up to 21 days post-treatment. Results: 404 Asian and 64 non-Asian patients received afatinib. There was no difference in afatinib trough concentrations in Asian vs. nonAsian patients; median treatment exposure was 359 vs. 261 days. All patients reported ≥1 AE. Most common drug-related AEs were EGFR-mediated: Diarrhoea (91.3% [9.7% Grade (G)3] vs. 93.8% [10.9% G3]) and rash/acne (84.9% [15.6% ≥G3 including 1 G4] vs. 84.4% [14.1% G3]). AEs leading to dose reduction were comparable between groups (44.6 vs. 43.8%). Drug-related AEs leading to discontinuation were slightly higher in Asian vs. non-Asian patients (7.2 vs. 4.7%), but at a lower rate than with chemotherapy (25.9%). Related interstitial lung disease-like events occurred in 4 Asian patients (3 ≥G3) and no non-Asian patients. Conclusions: Afatinib has a manageable safety profile in both Asian and non-Asian patients and is suitable for long-term treatment of EGFR M+ NSCLC. ID 340 Multimodal treatment of non-small lung cancer with cerebral metastases N. Kudelin, S. Bölükbas, J. Schirren Dr. Horst Schmidt-Klinik Wiesbaden, Thoraxchirurgie, Wiesbaden, Deutschland Objective: The role of surgical treatment of lung cancer with cerebral metastases remains controversial. The aim of this study was to determine the long-term outcome and to identify potential prognostic factors in patients with cerebral metastatic non-small lung cancer (NSCLC). Methods: The data of patients who underwent a resection of NSCLC with brain metastases from January 1999 to December 2011 were investigated retrospectively at a single institution. Multimodal treatment included resection or radiation surgery of the brain metastases at first followed 90 Oncol Res Treat 2014;37(suppl 1):1–133 by systematic chemotherapy and the surgical treatment of the lung cancer at last. Survival, potential prognostic factors as well as morbidity and mortality was investigated. Results: 26 patients with brain metastases (18 males, 8 females) underwent a surgical resection of primary NSCLC. The mean age was 57.54 years. Morbidity and mortality rates were 15% and 0%, respectively. Lobectomies were performed in 15 patients, pneumonectomy in 5 and sleeve lobectomy in 6 patients, respectively. The brain metastases were treated by resection, stereotactic radiotherapy or whole brain radiotherapy in several combinations. The 5-year survival rate was 24% (median survival 25.7 months). There was no significant difference in patient’s age, gender, histology of the primary tumor, number or treatment of the brain metastases or the type of chemotherapy. The pneumonectomy for resection of the primary NSCLC was associated with inferior survival (15.0 vs. 26.6 months; p = 0.048). Conclusions: Long-term survival is achievable in highly selected patients with NSCLC and cerebral metastasis by multimodal treatment including resection of the primary lung cancer. Pneumonectomy should be avoided. ID 376 The Network Genomic Medicine: A prospective comprehensive molecular screening network for implementation of personalized lung cancer therapy M. Bos1, M. Gardizi2, L.C. Heukamp3, S. Merkelbach-Bruse3, H.-U. Schildhaus3, M. Scheffler2, L. Nogová2, C. Mattonet2, M. Serke4, W.J. Randerath5, U. Gerigk6, T.H. Brümmendorf7, S. Krüger8, J. Panse7, B. Kaminski5, M. Reiser9, R. Büttner3, J. Wolf2 Universität Köln, Translationale Genomik, Köln, Deutschland Uniklinik Köln, Medizinische Klinik I, Köln, Deutschland 3 Uniklinik Köln, Pathologisches Institut, Köln, Deutschland 4 Lungenklinik Hemer, Hemer, Deutschland 5 Bethanienkrankenhaus, Klinik für Pneumologie und Allerologie, Solingen, Deutschland 6 Malteser Krankenhaus, Klinik für Thoraxchirurgie, Bonn, Deutschland 7 Uniklinikum Aachen, Medizinische Klinik IV, Aachen, Deutschland 8 Florence Nightingale Krankenhaus, Klinik für Pneumologie und Allerologie, Düsseldorf, Deutschland 9 Pioh Köln, Onkologische Schwerpunktpraxis, Köln, Deutschland 1 2 Background: The potential of personalized medicine for improvement of lung cancer patient outcome has been shown in advanced EGFR mutation- and ALK translocation positive NSCLC patients (pts) and numerous targeted drugs for molecular defined subgroups are in clinical development. One of the major challenges now is the implementation of comprehensive molecular diagnostics and personalized therapy for all NSCLC pts. regardless of where they are treated. Methods: To increase the availability of molecular testing and subsequently personalized treatment options for NSCLC pts. in the catchement area of the Center for Integrated Oncology Köln-Bonn, we established the Network Genomic Medicine (NGM). NGM encompasses >40 health care providers representing the full spectrum of lung cancer care. The NGM headquarter is based at the University Hospital of Cologne. Within NGM genetic and clinical data are analysed and pts. without approved targeted treatment options are screened for recruitment into NGM-linked personalized trials. Results: We screened 5,145 lung cancer pts. from 01/2010 till 04/2013. Genomic testing was feasible in 75% of samples. In AD we detected: EGFR 13.8%;ALK 3.3%; KRAS 33.8%; BRAF 3.5%;PIK3CA 3.1%; HER2 ampl. 3.6%; RET 4.7% and ROS1 5.1%. The frequencies of RET and ROS1 are overestimated because of preselection of pan negative patients.In SCC we found a frequency of 21% for FGFR1 ampl. and 2.1% for DDR2 mutations. Overall 40% of NSCLC pts. harboured a potentially targetable molecular alteration and more than 40 pts. could be treated in early personalized clinical trials. Conclusion: We established one of the world´s largest platforms for comprehensive lung cancer genotyping. Our experiences underline that cen- Abstracts Inhalt Index tral comprehensive molecular diagnostics is feasible in a large health care provider network and allows implementation of personalized medicine in routine clinical care of lung cancer pts. ID 381 A retrospective analysis of overall survival of ALK translocation – and of EGFR mutation positive NSCLC patients treated with and without personalized therapy M. Bos1,2, M. Gardizi3, L.C. Heukamp4, H.-U. Schildhaus4, S. Merkelbach-Bruse4, L. Nogová3, M. Scheffler3, M. Serke5, H. Schulz6, S. Krüger7, T.H. Brümmendorf8, J. Panse8, S. Schmitz9, U. Gerigk10, W.J. Randerath11, Y.D. Ko12, K. Kambartel13, A.-N. Hünerlitürkoglu14, R. Büttner4,14, J. Wolf3,14 Universität Köln, Translationale Genomik, Köln, Deutschland Pioh Köln, Onkologische Schwerpunktpraxis, Köln, Deutschland 3 Uniklinik Köln, Medizinische Klinik I, Köln, Deutschland 4 Uniklinik Köln, Pathologisches Institut, Köln, Deutschland 5 Lungenklinik Hemer, Hemer, Deutschland 6 Pioh Frechen, Onkologische Schwerpunktpraxis, Frechen, Deutschland 7 Florence Nightingale Krankenhaus, Klinik für Pneumologie und Allerologie, Düsseldorf, Deutschland 8 Uniklinikum Aachen, Medizinische Klinik IV, Aachen, Deutschland 9 Praxis am Sachsenring, Onkologische Schwerpunktpraxis, Köln, Deutschland 10 Malteser Krankenhaus, Klinik für Thoraxchirurgie, Bonn, Deutschland 11 Bethanienkrankenhaus, Klinik für Pneumologie und Allerologie, Solingen, Deutschland 12 Evangelische Kliniken Bonn, Internistische Onkologie, Bonn, Deutschland 13 Bethanienkrankenhaus Moers, Lungenklinik Moers, Moers, Deutschland 14 Lukaskrankenhaus, Innere Medizin II, Neuss, Deutschland 1 2 Background: Erlotinib, gefitinib and crizotinib (C) have been approved by the EMA for the treatment of advanced EGFR mutation positive (EGFR M+) and ALK translocation positive (ALK +) NSCLC patients (pts.), respectively. In randomized clinical trials for ALK + and EGFR M+ pts. comparing chemotherapy (CTx) to TKI treatment so far no significant improvement in overall survival (OS) could be shown, based on the high crossover rate of pts. initially treated in the CTx arm into the TKI arm upon progression. Since prevention of crossover is obsolete due to ethical reasons, registry data may gain in importance for investigating the impact of new targeted drugs on OS. Methods: Since 01/2010 EGFR sequencing and ALK FISH analysis for lung AD was performed within the Network Genomic Medicine, a large molecular screening network in the catchment area of the Center for Integrated Oncology Köln-Bonn as part of a broad genetic screening effort. Clinical and follow-up data were extracted from medical records, directly collected from physicians and pts. Results: 44 ALK+ and 143 EGFR M+ pts. were analysed. The median OS (mOS) of pts. with stage IIIb/IV was 14 months for ALK+ and 29 months for EGFR M+ pts. Both groups showed a significant difference in mOS when separated by targeted treatment status. ALK+ pts. who received C had a mOS of 23 months and pts. who did not receive C had a mOS of 8 months (p = 0.01). EGFR M+ pts. who received an EGFR TKI had a mOS of 31 months and pts. who did not receive an EGFR TKI had a mOS of 9 months (p < 0.001). There were no significant differences with regard to treatment platinum-containing chemotherapy, age or sex between groups. Conclusion: Comparing EGFR+ and ALK+ pts. that only received CTx to those treated with a specific tyrosine kinase inhibitor (TKI) showed a significant improvement in OS. This confirms the predictive value of ALK translocations and EGFR mutations for treatment with the respective TKIs. Abstracts ID 404 TRY: A phase II study to evaluate safety and efficacy of combined trastuzumab and AUY922 in advanced non-small-cell lung cancer (NSCLC) with HER2 overexpression or amplification or mutation. L. Nogova1, M. Gardizi1, M. Bos1, M. Scheffler1, I. Papachristou2, C. Wömpner1, L. Heukamp1, H.-U. Schildhaus3, U. Fuhr1, M. Sos1, W. Eberhardt4, M. Wiesweg4, K.W. Schmid4, M. Schuler4, R. Thomas2, R. Büttner1, J. Wolf1 Uniklinik Köln, Köln, Deutschland Universität Köln, Köln, Deutschland Uniklinik Göttingen, Göttingen, Deutschland 4 Uniklinik Essen, Essen, Deutschland 1 2 3 Background: HER2 amplifications and/or mutations are rare genetic alterations in NSCLC accounting for approximately 4%. Preliminary clinical data suggested efficacy of trastuzumab in patients with HER2 IHC3+ status or FISH positivity. The heat shock protein HSP90 is a molecular chaperone that modulates stability and/or transport of intracellular client proteins including HER2. In breast cancer HSP90 inhibition has shown anticancer activity in HER2-positive patients after trastuzumab failure. Here we are investigating the efficacy of the combination of trastuzumab and the HSP90 inhibitor AUY922 in lung cancer patients with aberrant HER2. Methods: This phase II study recruits metastatic NSCLC patients with HER2overexpression (immunohistochemistry, DAKO-score 3+) or amplification (fluorescence in situ hybridization) or activating mutation after at least one previous standard treatment. In the first part of the study, patients are treated with trastuzumab only. CT scan is scheduled every 6 weeks during treatment. In case of disease progression, patients receive the combination of trastuzumab and AUY922. Results: The study was initiated this year and NSCLC patients are screened within the Network of Genomic Medicine Lung Cancer on HER2 overexpression, amplifications and mutations. Until now, we tested 720 tumor samples by FISH and 63 by genomic sequencing. We identified 55 patients with HER2 amplification, 34 with HER2 overexpression (Dako score 3+) and 7 patients showed a mutation in the HER2 gene (1 exon 19; 6 exon 20). Conclusion: HER2 overexpression, amplification or mutation is a rare genetic alteration in NSCLC patients. Data on treatment with HER2 antibody trastuzumab and HSP90 inhibitor AUY922 will be presented. ID 431 Clinical and Molecular Characteristics of Non-Small Cell Lung Cancer Patients Harboring PIK3CA Mutations M. Scheffler1, M. Gardizi2, M. Bos2, L. Heukamp3, K. König3, M. Serke4, L. Nogova2, K. Töpelt2, E. Stoelben5, W. Engel-Riedel5, W. Randerath6, B. Kaminsky6, J. Panse7, T. Zander1, R. Büttner3, J. Wolf2 Uniklinik Köln, Köln, Deutschland Uniklinik Köln, CIO Köln Bonn, Lung Cancer Group Cologne, Klinik I für Innere Medizin, Köln, Deutschland 3 Uniklinik Köln, CIO Köln Bonn, Institut für Pathologie, Köln, Deutschland 4 Lungenklinik Hemer, Pneumologie, Thorakale Onkologie, Hemer, Deutschland 5 Kliniken der Stadt Köln, Lungenklinik Merheim, Köln, Deutschland 6 Krankenhaus Bethanien, Klinik für Pneumologie und Allergologie, Zentrum für Schlaf- und Beatmungsmedizin, Solingen, Deutschland 7 Uniklinik Aachen, Euregionales comprehensive Cancer Center Aachen (ECCA), Aachen, Deutschland 1 2 Purpose: Mutations of the PIK3CA gene have been frequently described in non-small cell lung cancer (NSCLC), but limited data is available about their biological relevance. This study was performed to characterize PIK3CA-mutated NSCLC clinically and genomically. Patients and methods: Of 2047 patients presenting with NSCLC within a timeframe of two years, 1144 (75.1% adenocarcinoma, 15.6% sqamous cell carcinoma, 9.3% other histological subtypes) were screened for PIK- Oncol Res Treat 2014;37(suppl 1):1–133 91 Inhalt Index 3CA mutations. We identified 42 patients with PIK3CA mutations in exon 9 and exon 20 using dideoxy-sequencing and next-generation sequencing (NGS). Clinical, pathological, and genetic characteristics of these patients are described and compared with a control group of 211 patients with comparable histological and clinical features features without PIK3CA mutation. Results: PIK3CA mutations occured in both genders (male/female ratio 3/2) in squamous-cell carcinoma (16/179, 8.9%) and in adenocarcinomas (25/859, 2.9%) and were significantly associated with smoking. The most common PIK3CA mutation was the exon 9 E545K mutation. Beside the PIK3CA mutations, the majority of patients (59.5%) had additional oncogenic driver aberrations. Further, PIK3CA-mutated patients had significantly more often a history of cancer other than NSCLC in their history. Conclusion: Within this dataset, which represents the largest cohort of PIK3CA mutated NSCLC yet described, the need for comprehensive genetic analyses in order to define further pathway aberrations is obvious. Nevertheless, PIK3CA mutations occur in a relatively high percentage of squamous cell NSCLC and are at great number associated with a history of cancer othe than NSCLC. ID 439 MIMEB: A phase II trial to evaluate FDG-PET/FLT-PET and DCE-MRI for early prediction of efficacy in patients with advanced non-small cell lung cancer treated with erlotinib and bevacizumab M. Scheffler1, M. Bos1, M. Sos1, L. Nogova1, M. Gardizi1, C. Mattonet1, I. Papachristou2, D. Kahraman3, C. Kobe3, A. Lammertsma4, R. Boellaard4, T. Persigehl5, L. Heukamp6, R. Büttner6, T. Elter5, K. Töpelt1, W. Engel-Riedel7, E. Stoelben7, B. Neumaier8, M. Dietlein3, T. Zander5, J. Wolf1 Uniklinik Köln, CIO Köln Bonn, Lung Cancer Group Cologne, Klinik I für Innere Medizin, Köln, Deutschland 2 Universität, Zentrum für Klinische Studien, Köln, Deutschland 3 Uniklinik Köln, CIO Köln Bonn, Institut für Nuklearmedizin, Köln, Deutschland 4 VU Amsterdam, Amsterdam, Deutschland 5 Uniklinik Köln, Köln, Deutschland 6 Uniklinik Köln, CIO Köln Bonn, Institut für Pathologie, Köln, Deutschland 7 Kliniken der Stadt Köln, Lungenklinik Merheim, Köln, Deutschland 8 Max-Planck-Institute for Neurological Research, Radiochemistry, Köln, Deutschland 1 Background: Molecular imaging tools gain in importance for assessment of efficacy in patients with advanced NSCLC treated with targeted therapy. We set up a prospective clinical trial in order to assess the predictive value of early changes in FDG-PET, FLT-PET, and DCE-MRI during therapy with erlotinib and bevacizumab in untreated patients with advanced non-squamous cell NSCLC and to identify a subgroup of patients with clinical benefit from the combination therapy. Methods: Patients with non-squamous NSCLC stage IV without prior systemic therapy received at least six weeks of combined erlotinib and bevacizumab. FLT and FDG-PET scans as well as DCE-MRI-scans were performed at baseline, after one week of therapy and after six weeks of therapy. Standard uptake values (SUVs) of the PET scans and vascularization parameters of the DCE-MRI scans were analyzed. Tumor specimens were analyzed in accordance with guidelines of a network screening panel. The primary objective of this trial was to evaluate the accuracy of FDG-/FLT-PET and DCE-MRI for early prediction of nonprogression and PFS and its association with molecular markers. Results: 40 patients were enrolled. Preliminary results regarding the predictive value of FDG-PET, FLT-PET and DCE-MRI in patients with advanced NSCLC treated first-line with erlotinib and bevacizumab as well as the association with mutational status will be presented. Conclusions/Perspective: Imaging-based predictive biomarkers to identify the subpopulation of patients with pronounced benefit of the combination of erlotinib with bevacizumab (FDG-, FLT- PET and DCE-MRI) were successfully implemented in the treatment plan of a prospective phase II trial. 92 Oncol Res Treat 2014;37(suppl 1):1–133 Lymphoma and Plasma Cell Disorders ID 436 Nodal reactive and neoplastic proliferation of monocytoid and marginal zone B cells: An immunoarchitectural and molecular study highlighting the relevance of IRTA1 and T-bet as positive markers. R. Bob1, H. Stein1, B. Falini2 Pathodiagnostik Berlin, Referenzzentrum für Lymphom- und hämatopathologie, Berlin, Deutschland 2 University of Perugia, Ospedale S. Maria della Misericordia,, Institute of Hematology, Perugia, Italien 1 Aims: Marginal zone B cells (MZCs) and monocytoid B cells (MBCs) appear to be related lymphoid cells that take part in reactive and neoplastic marginal zone proliferations. These lesions are not yet well characterized, and the aim of this study was to find better diagnostic criteria for them. Methods and results: We analysed 60 nodal lesions with MBC and/or MZC proliferation for their morphological, immunophenotypic, molecular genetic and IG gene rearrangement features. On the basis of the results of the rearrangement assay and immunoglobulin light chain restriction, the lesions were divided into reactive and neoplastic groups. Among the neoplastic lesions, polymorphic and monomorphic subgroups emerged. All reactive lesions had morphological features of the polymorphic subgroup. By immunohistochemistry, IRTA1 and/or T-bet expression was found in all reactive lesions and in 90% of neoplastic lesions. Conclusions: IRTA1 and T-bet are positive markers for the identification of MZC/MBC proliferations, and thus for the diagnosis of nodal marginal zone lymphoma (NMZL). Polymorphic and monomorphic subgroups of NMZL could be distinguished. Most morphological and immunophenotypic patterns in reactive and neoplastic nodal expansions of MZCs and MBCs overlapped. Therefore, PCR clonality assay of the immunoglobulin heavy and light chain gene loci is the most reliable method for their differentiation. Miscellaneous ID 168 Potentials of Computer-aided Decision Support Systems in Medicine D. Andrzejewski1, I. Boersch1, T. Schrader1, P. Ledwon2, N. Haeusler2, E. Beck1 Fachhochschule Brandenburg, Fachbereich Informatik und Medien, Brandenburg, Deutschland 2 Städtisches Klinikum Brandenburg GmbH, Frauenheilkunde und Geburtshilfe, Brandenburg, Deutschland 1 Introduction: According to the principles of Evidence based medicine, physicians’ decisions should be based on currently best available external. However, it is a well know phenomenon that in the overwhelming majority decisions in medicine are made rather heuristic than based on defined decision rules. This may be one of the reasons why only up to 70% of patients with breast cancer are treated in accordance with the national S3 Guideline. It is therefore tempting to speculate if this could be improved by computer aided decision support systems. Methods: For this pilot study, data sets of 165 patients of the Brandenburgisches Brustzentrum were analyzed concerning the decision categories «adjuvant chemo- and/or hormonal therapy», applying methods of descriptive statistics (SPSS Version 19) and data mining. Tumor attributes analyzed and most relevant for the above mentioned clinical decisions are according to the S3 guideline: Patient’s age, menopausal status, hormone receptor (HR) expression, HER-2/neu expression, TNM classification, grading, and Nottingham Prognosis Index. Abstracts Inhalt Index Results: Whereas descriptive analysis showed clear cut correlations between some attributes and the aforementioned categories (e.g. HR expression and anti-hormonal therapy), most results were rather difficult to interpret. E.g. concerning grading we found that 10/41 patients with G1 tumors received adjuvant chemotherapy compared to 30/37 with G3 tumors. We then constructed a (still human readable) C4.5 decision tree to predict physicians’ decisions resulting in a test error of 75%. Conclusion: Using a limited number of tumor associated attributes already enables a good prognosis regarding the decision categories adjuvant chemo- and/or hormone therapy. ID 178 Organ specific tumor conference for hepato-biliar diseases – first results after 2 years R. Kleinert1, R. Wahba1, D. Waldschmidt1,2, A. Hölscher1,2, D. Stippel1,2 Universitätsklinikum Köln, Klinik für Allgemein-, Viszeral-, und Tumorchirurgie, Köln, Deutschland 2 Universitätsklinikum Köln, Klinik für Gastroenterolgie, Köln, Deutschland 1 Background: The established tumor conferences are nowadays often supported by organ specific conferences. The requirements on these meetings in particular on multidisciplinary are similar. The specific focus promises a very efficient meeting as there is usually a smaller but even more specialized expert round. Although the benefit of tumor conferences is undisputable but there is little evidence about the measurable benefit for the patient. However it may be characterized by the comparison of the board recommendations with the therapies and specialized recommendations like inclusion in studies. Therefore it was our aim to test our tumor conference for hepato- biliar diseases according to the criteria quoted above. Method: Retrospective analyses of the patients that were included in the organ specific tumor conference between 09/2011 up to 09/2013. Results: A total of 326 cases were discussed. Recommendations were available in the intranet after 24 h. Recommendations were followed in 94%. Reasons for deviations were worsening of health status or rapid progress. 6% were included in studies. 38% underwent surgery, interval between recommendation and surgery was 10 days. 5% were telemedical consultations over the internet. In 24% a combined therapy was recommended. Conclusion: The potential of a hepato-biliar organ specific tumor lies in discussion of specialized problems in close cooperation between oncologists, gastroenterologists and surgeons. The recommendations show a high percentage of surgical therapies with high technical demands and high amount of multimodal therapies. ID 330 Characteristics, course and outcome of critically ill patients with malignant diseases in a medical intensive care unit in a community hospital with cancer center K. Schulte1, M. Krakau1, P. Schellongowski2, A. Dormann1 Kliniken der Stadt Köln, Krankenhaus Holweide, Mediznische Klinik, Köln, Deutschland 2 Medizinische Universität Wien, Universitätsklinik für Innere Medizin I, Wien, Oesterreich 1 Purpose: Patients (pts.) with a malignant disease may require medical critical care treatment due to the increasingly chronic courses of malignant illnesses. We report characteristics and outcomes of pts. with malignant conditions treated in the medical intensive care unit of a community cancer center. Methods: Characteristics, reasons for admission, interventions and outcomes of all pts. with active malignant diseases admitted to the medical intensive care unit (MICU) of the Krankenhaus Holweide from 10/10 to 9/12 are reported retrospectively. Abstracts Results: Of 175 pts. (median age: 69.6 +/–10.8 years; female/male: 72/103; hematologic: n = 57 (32.6%); oncologic: n = 118 (67.4%)) 61 pts. (34.9%) had curative and 114 (65.1%) had palliative oncologic treatment options. Reasons for admission were acute respiratory failure (n = 49; 28%), sepsis, acute renal failure (both n = 21; 12%) and bleeding (n = 18; 10.3%). 72 pts. (41%) received life saving interventions. Curative pts. had more often a ‘fullcode’ status than palliative pts. (n = 57; 93.4% vs. n = 43; 37.7%; ≤0,0001) and were ventilated more often (n = 16; 26.2% vs. n = 23; 20.2%; ≤0,01). The rates of catecholamine-therapy (n = 21; 34.5% vs. n = 31; 27.2%; p = 0,74), non-invasive ventilation (n = 12; 19.7% vs. n = 15; 13.2%; p = 0,28), and hemofiltration (n = 3; 4.9% vs. n = 3; 2.6%; p = 0,42) did not differ significantly. Survival was equal in palliative and curative pts. (ICU: 78,7/68.4%; p = 0,16; hospital 68.9/ 57.0%; p = 0,15; 6-months 54.1/36.8%; p = 0,24). Conclusion: Two thirds of the pts. admitted to the MICU had a palliative oncological concept. Their treatment in the ICU did not differ from that of curative pts.. There was no significant survival-difference at discharge from MICU or hospital and at 6 months. ID 356 The Freiburg Bio-Databanking combines automaticly updated pathological and clinical information with research data. P. Bronsert1,2, F. Makowiec3, S. Schmid1, E. Stickeler4, V. Drendel1, K. Aumann1, C. Jilg5, M. Werner1,2,6 Department für Pathologie, Institut für Klinische Pathologie, Freiburg, Deutschland 2 Comprehenisve Cancer Center Freiburg, Tumorbank, Freiburg, Deutschland 3 Chirurgische Klinik der Universität Freiburg, Allgemein- und Viszeralchirurgie, Freiburg, Deutschland 4 Chirurgische Klinik der Universität Freiburg, Gynäkologie und gynäkologische Onkologie, Freiburg, Deutschland 5 Chirurgische Klinik der Universität Freiburg, Urologie, Freiburg, Deutschland 6 German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Deutschland 1 Aims: Biobanking in Comprehensive Cancer Centers aims to combine pathologically well characterized and quality controlled tissue specimens with and correlating clinical data and follow-up of the patients. Fundamental for functioning is a standardized acquisition of pathological diagnosis of tumor tissue and the linkage to clinical data. To guarantee sustainability, an automatical, flexible, expandable and restricted accessible database is needed, to link new generated research data to tissue specimens. Certainly, strictly rules of admission, concerning patients data privacy has to be ensured. Here we describe the development and the features of our Biobank linked database Material and Methods: The database was developed in MySQL 5.1, a programming language designed for managing data in relational database management systems on Windows XP Professional PC with the development environment Eclipse Hellios and the database development assistant Toad for MySQL. It runs on a Suse Linux Enterprise server, a virtual server at the central IT facility of the University of Freiburg. Furthermore programs for data import from our intranet application for comprehensive tumor documentation called CARAT established for the entry of all cancer data elements as well as from excel sheets were performed. Data integrity is evaluated by random checks of patients by the IT officer and a physician. Results: We developed a flexible, expandable and restricted accessible database on the fundament of open-source software. Clinical and research data can be updated and/or changed either automatically or manually from our facility and/or extern clinical partners. Patients personal data are electronical protected according to current guide lines. Access for pseudonymized clinic-pathological and research data is only admitted for accredited persons. Oncol Res Treat 2014;37(suppl 1):1–133 93 Inhalt Index ID 366 Consortial Data- and Biobanking P. Bronsert1,2, E. Stickeler3, K. Aumann1, S. Schmid1, T. Fehm4, C. Röcken5, F. Fend6, C. Mundhenke 7, N. Aumann7, U. Vogel6, A. Stäbler6, M. Werner1,2,8 Department für Pathologie, Institut für Klinische Pathologie, Freiburg, Deutschland 2 Comprehenisve Cancer Center Freiburg, Tumorbank, Freiburg, Deutschland 3 Chirurgische Klinik der Universität Freiburg, Gynäkologie und gynäkologische Onkologie, Freiburg, Deutschland 4 Chirurgische Klinik der Universität Düsseldorf, Gynäkologie, Düsseldorf, Deutschland 5 Department für Pathologie, Institut für Klinische Pathologie, Kiel, Deutschland 6 Department für Pathologie, Institut für Klinische Pathologie, Tübingen, Deutschland 7 Chirurgische Klinik der Universität Kiel, Gynäkologie, Kiel, Deutschland 8 German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Deutschland 1 Aims: Essential for a consortial high quality tumor bank is a standardized implementation of clinical and pathological information. By combining three independent breast cancer biobanks from the University Hostpitals Freiburg, Tübingen and Kiel, working procedures has to be synchronized, harmonized and standard operating procedures (SOP) and datasets have to be established. Furthermore, to ensure sustainability, an automatical data transfer has to be implemented. Material and Methods: All three facilities defined SOPs and established Shared Resources Advisory. Datasets for pathological and clinical diagnoses were established. A periodically updating secured database with an automated combination of all consortial data was programmed by an experienced software engineer based on an open source and web accessible platform. Results: Together from 2001 through 2013, the consortial breast cancer tissue bank contains 3900 fresh frozen, prospectively collected and immunohistochemically classified breast cancer samples from all three facilities. The median age is 61 years. Nearly half of the patients were diagnosed with a ductal carcinoma in situ. The major pT category was T1c, the most frequently pN category was pN0 followed by pN2, pN1 and pN3 After written request, access for researchers to the consortial internet accessible breast cancer database can be granted. Conclusions: A well planed clinico-pathological and IT linked infrastructure is the fundament of a consortial database and the basic principle for multicentric translational research. For testing and proving a successful multicentric research approach, several national and international projects were initiated. ID 458 8 years patient navigators in the interdisciplinary tumor ambulance of CIO Köln Bonn – a role model for other cancer centers?! I. Bey1, B. Bergatt-Kuhl1, S. Arndt1, S. Treppner1, I. Schmidt-Wolf2, M. Hallek1, J. Wolf1 Universitätsklinikum Köln, Centrum für Integrierte Onkologie, Köln, Deutschland 2 Universitätsklinikum Bonn, Centrum für Integrierte Onkologie, Bonn, Deutschland 1 Introduction: In 2005 the «Center for Integrated Oncology Köln Bonn» has started to install patient navigators in the central interdisciplinary tumor ambulance. Today these patient navigators («CIO-Lotsen») have become a trade mark of the CIO. They are in the focus of the management of cancer patients by ensuring the continuity of care. The patient navigator’s responsibility is to guide the patient through the complex process of diagnostics and treatment. This unique concept of patient guidance has quickly gained an excellent acceptance amongst our cancer patients. The Patient Navigator 94 Oncol Res Treat 2014;37(suppl 1):1–133 –– is the first and continuous contact for outpatients and their relatives –– organizes appointments, reminds physicians and nurses about upcoming procedures –– joins the patient in the interdisciplinary consultation hours –– literally takes the patient by the hand and helps to make the multi pitstop process of medical diagnostics as convenient as possible –– evaluates the possible inclusion into clinical trials with the medical oncologist –– inform and arrange supplementary services such as psycho-oncology, palliative care, or physical excercise therapy Currently, in Cologne there are 3 Patient Navigators, all certified nurses, working in an office adjacent to the CIO outpatient unit. At the ambulance in Bonn are 2 nurses on duty. The teams will be expanded continuously. Aim: CIO Köln Bonn wants to present its successful navigator concept to other german cancer centers very hands-on and comprehensively. The goal is to supply decision-making-support and give advice and ideas to develop own patient navigator models in their tumor anbulances.. Methods: PR and communication measures 2014: full-time event, information brochure, press work. ID 461 A benchmark study of cancer patient outcome in two Comprehensive Cancer Centers in the US and Germany F. Kron1, J.P. Glossmann1, M. Lotze2, M. Barsoum 1, S. Winters2, D. Normolle2, M. Boyiadzis2, M. Socinski2, A. Bernschein1, I. Schmidt-Wolf3, B. Funke3, M. Meyer1, C. von Levetzow1, S. Leitzke1, M. Hellmich1, C. Scheid1, K.-A. Kreuzer1, A. Kostenko1, D. Waldschmidt1, L. Heukamp1, T. Zander1, M. Scheffler1, M. Hallek1, J. Wolf1 Universitätsklinikum Köln, Centrum für Integrierte Onkologie, Köln, Deutschland 2 University of Pittsburgh, Cancer Institute and Centers, Pittsburgh, Vereinigte Staaten Von Amerika 3 Universitätsklinikum Bonn, Centrum für Integrierte Onkologie, Bonn, Deutschland 1 Introduction: International studies have shown significant differences in population-based cancer survival. Those results have activated an ongoing health-policy debate on optimal cancer care. Aim: Based on three high mortality cancers: lung cancer (C34), pancreatic cancer (C25) and acute myeloid leukemia (C92.00), we propose a pilot comparative effectiveness study in two large Comprehensive Cancer Centers (CCC) in the United States (University of Pittsburgh Cancer Institute) and Germany (Center for Integrated Oncology – Köln and Bonn, CIO) to identify factors and reasons for inequalities in outcome, incidence, stage at presentation, and/or treatment regimens and cost. Methods: The study population will include patients with primary tumors diagnosed and treated between 2009 and 2013. We will analyze data retrospectively from the Clinical Cancer Registries of Cologne, Bonn and Pittsburgh. Additionally we will complete our data by merging special hospital management data with data from the federal cancer registry of North Rhine-Westphalia. We will develop hypotheses regarding patient-related, institutional, health care and other factors that influence early outcome. Data analysis contains statistical methods including Kaplan-Meier, Cox-Regression and other multivariate models. Results:In a first step we have shown the technical feasibility of comparing complex cancer patient information from both sides of the Atlantic. So far we have identified 723 lung cancer cases, 160 pancreatic cancers and 192 leukemias at the CIO. Further we have assigned median survival of CIO lung cancer patients (age, stage, mutation and treatment with platinum based chemotherapy). Pittsburgh data will be available by the end of 2013. Conclusion: Outcome research is a relatively new approach in improving cancer care in Germany. This first transatlantic CCC benchmarking project will activate a variety of quality improvement initiatives. Abstracts Inhalt Index Molecular Pathology ID 275 HS3ST2 modulates breast cancer cell invasiveness and chemosensitivity via MAP kinase- and TCF7L2/ TCF4-dependent regulation of protease and cadherin expression A. Vijaya Kumar1, E. Salem Gassar1, D. Spillmann2, C. Hülsewig1, L. Kiesel1, C. Stock3, G.W. Yip4, M. Götte1 Universitätsklinikum Münster, Klinik für Frauenheilkunde und Geburtshilfe, Münster, Deutschland 2 Uppsala University, Department of Medical Biochemistry and Microbiology, Uppsala, Schweden 3 University of Münster, Institut of Physiology II, Münster, Deutschland 4 National University of Singapore, Department of Anatomy, Singapore, Singapur 1 Aim of Study: HS3ST2, an enzyme mediating 3-O-sulfation of heparan sulfate, is silenced by hyper-methylation in breast cancer. As heparan sulfate has an important co-receptor function for numerous signal transduction pathways, the phenotypical changes due to HS3ST2 re-expression were investigated in vitro using high and low invasive breast cancer cell lines. Methods: MDA-MB-231 and MCF-7 cells were stably transfected with a plasmid encoding HS3ST2, or a control vector. Cell behaviour was studied by chemosensitivity assay, matrigel invasion chamber and endothelial transmigration assay. Molecular analysis was performed by Affymetrix gene array screening, qPCR, Western blotting, Zymography and ratiometric pH measurements. Results: HS3ST2-expressing MDA-MB-231 cells showed enhanced invasiveness and transendothelial migration. Expression of several matrix metalloproteinases, cadherin-11, E-cadherin and CEACAM-1 was increased, while protease inhibitor expression was decreased. Low invasive HS3ST2-over-expressing MCF-7 cells became even less invasive, with no change in MMP activity. HS3ST2 increased HS-dependent basal and FGF2-specific signaling through the constitutively active p44/42 MAPK pathway in MDA-MB-231 cells. Increased MAPK activation was accompanied by upregulation of TCF7L2/TCF4. Dysregulation of TCF4-dependent ion transporters and increased cytosolic acidification were observed in HS3ST2-expressing MDA-MB-231 cells, being a possible cause of increased chemosensitivity towards doxorubicine and paclitaxel in these cells. Conlusions: This study provides the first in vitro evidence of the involvement of HS3ST2 in breast cancer cell invasion and chemosensitivity. ID 277 Severe cancer phenotypes associated with CHEK2 mutations: More risk factors to be identified K. Rhiem1, B. Wappenschmidt1, J. Hauke1, K. Klaschik1, A. Baasner1, B. Blümcke1, A. Meindl2, E. Hahnen1, R. Schmutzler1 Zentrum für Familiären Brust- und Eierstockkrebs, Köln, Deutschland Klinikum rechts der Isar, Klinik für Gynäkologie und Geburtshilfe, München, Deutschland 1 2 CHEK2 is an integral part of the BRCA1-associated genome surveillance complex and monoallelic mutations were found in up to 5% of BRCA1/2 negative breast cancer (BC) and/or ovarian cancer (OC) families. Though with varying frequencies, several studies confirmed the recurrent CHEK2 1100delC frameshift mutation as the most frequent in northern Europe. The breast cancer risk for a female CHEK2 1100delC mutation carrier increases up to 3fold, confirming CHEK2 as a moderately penetrant risk gene. Meanwhile, the search for germline mutations in CHEK2 has been implemented in a routine diagnostic setting, some laboratories focus on recurrent CHEK2 mutations only via a non-quantitative MLPA assay. In the course of a pilot study, we analyzed three CHEK2-positive families with remarkably severe phenotypes. In the first family, the index patient Abstracts (bilateral BC, 29y, 32y) carried a CHEK2 1100delC frameshift. In the second, the index patient (BC, 35y) carried a deletion of CHEK2 exon 9, and in the third family, the index patient (BC, 41y) carried a p.I157T missense mutation associated with a 1,85fold increased risk only (95% CI=1.51-2.26, p < 0.00001). We hypothesized that these CHEK2 alterations alone are not sufficient to cause the severe phenotypes (e.g. sarcoma) observed and searched for further exonic germline alterations by next generation sequencing (NSG). Indeed, the first index patient carried the CHEK2 1100delC frameshift mutation homozygously, the second shows an additional ATM p.G2772R mutation previously described as disease causing and the third patient additionally shows a known pathogenic alteration in a Fanconi anaemia gene. These data warrant i) the search for further pathogenic alterations in CHEK2-positive families with unusually severe phenotypes and potential impact for screening measures, ii) the necessity to evaluate whether CHEK2 alterations occur in a homozygous or heterozygous state. ID 316 Development of the Cancer Genome Scanner (CAGE), a single tube cancer assay for deep genomic analysis of point mutations, insertions and deletions, copy number alterations and gene fusions. J. Heuckmann1, F. Leenders2, R. Thomas2 Blackfield AG, Köln, Deutschland Universität Köln, Department of translational genomics, Köln, Deutschland 1 2 The discovery of activating EGFR mutations in NSCLC patients responding to the EGFR kinase inhibitors erlotinib and gefinitib changed the landscape of personalized oncology dramatically. Today, several additional genomic alterations predicting responsiveness to certain targeted drugs are known (e.g., KIT and BRAF mutations, ABL, ALK, ROS1 and RET fusions, FGFR1 and HER2 amplifications etc.). However, due to the genomic nature of these alterations, each of those is currently diagnosed by an alteration specified assay, ranging from dideoxy amplicon sequencing to Fluorescence In Situ Hybridisation (FISH). Taking time and tumor material consumption into account, analyzing the current spectrum of mutations might not be feasible for all patients. Therefore, we developed an all-in-one assay which allows the parallel detection of point mutations, insertions and deletions, copy number alterations and gene fusions in a broad spectrum of genes on a nucleotide to nucleotide resolution. Alterations in several of those clinically relevant genes are targetable with currently approved drugs. Based on the targeted in-solution hybrid capture technology, followed by massively parallel sequencing, the Cancer Genome Scanner (CAGE) allows a parallel, accurate and comprehensive analysis of all genomic regions relevant for clinical oncology, even for mutations occurring at low allele frequencies. ID 452 RAD51C deletion screening identifies a recurrent gross deletion in breast and ovarian cancer families J. Hauke1, A. Becker1, G. Schnurbein1, G. Neidhardt1, N. Weber-Lassalle1, B. Wappenschmidt1, E. Hahnen1, A. Meindl2, R. Schmutzler1 Uniklinik, Zentrum für familiären Brust- und Eierstockkrebs, Köln, Deutschland 2 Klinikum rechts der Isar, Frauenheilkunde und Geburtshilfe, München, Deutschland 1 RAD51C is an integral part of the DNA double-strand repair through homologous recombination and monoallelic mutations were found in ~1.3% of BRCA1/2 negative breast cancer (BC) and/or ovarian cancer (OC) families. Though with varying frequencies, several studies confirmed the occurrence of RAD51C mutations predominantly in BC and/or OC families, clearly establishing RAD51C as a cancer predisposing gene. There is an ongoing debate whether pathogenic RAD51C alterations increase Oncol Res Treat 2014;37(suppl 1):1–133 95 Inhalt Index the relative risk (RR) for BC in addition to that for OC, which was estimated to be 5.88 (95% CI=2.91-11.88; P=7.65x10-7). Elucidating the role of RAD51C in BC pathogenesis is hampered by the low frequency of clearly truncating RAD51C mutations. In this study, we screened for gross genomic alterations within the RAD51C gene in BRCA1/2-negative familial BC index cases, 500 of which showing a BC only and 325 a BC/ OC family history. We identified a large heterozygous RAD51C deletion encompassing the exons 5 to 9 in two independent families In the first, remarkably a BC only family the mutation carrier was affected by early onset and bilateral BC (33y, 39y). In the second, a BC/OC family, the mutation was identified in dizygotic twins, one of which affected by early onset BC (42y) and one by early onset OC (43y). The 36,637 base pair (bp) deletion appears to be rare as we identified no further case in another large cohort by junction fragment PCR (BC only: 1,011; BC/OC: 203). The early onset of BC in both families, the occurrence of bilateral BC and the triple-negative tumor phenotype resemble features closely associated with hereditary BC and thus, the presence of a clearly truncating mutation is supportive for a pathogenic role of RAD51C. Molecular Targets ID 052 Identification of mitochondrial and PI3K-Akt-mTOR pathways as targets of naphtoquinones in cancer cells by pharmacogenomics B. Wiench1, Y.-R. Chen2, T. Eichhorn1, M. Paulsen3, R. Hamm1, N.-S. Yang2, T. Efferth1 Johannes Gutenberg-Universität, Abteilung für Pharmazeutische Biologie, Mainz, Deutschland 2 Agricultural Biotechnology Research Center, Taipei, Taiwan 3 Institut für Molekulare Biologie, Mainz, Deutschland 1 The development of drug resistance and severe side effects of current cancer chemotherapy necessitates the development of novel anticancer drugs with improved pharmacological features. Shikonin is a naphtoquinone derived from Lithospermum erythrorhizon, which is used for the treatment of inflammatory and other diseases. We analyzed shikonin in 15 cell lines, including multidrug-resistant cell lines. Microarray profiling showed that shikonin affects cellular pathways regulating cell cycle, mitochondrial function, reactive oxygen species (ROS), and cytoskeleton formation. Uptake measurements of shikonin in living cells using flow cytometry and confocal microscopy showed that shikonin’s accumulation in mitochondria was associated with deregulation of cellular calcium and ROS levels followed by disturbed mitochondrial membrane potential, dysfunctional microtubules, cell cycle arrest and apoptosis. In addition to the targeting of mitochondria, we investigated the particular sensitivity of shikonin towards leukemia cells. A «multi-omics» approach using mRNA and miRNA microarrays as well as stable-isotope dimethyl labeling for quantitative proteomics was applied. Bioinformatical integration of all data revealed that the PI3K-Akt-mTOR pathway was affected by shikonin. Deregulations in this pathway are frequently associated with cancerogenesis, especially in a wide range of hematological malignancies. Shikonin’s effect on the PI3K-Akt-mTOR pathway was validated by the determination of decreased Akt phosphorylation and inhibition of the IGF1R kinase activity after shikonin treatment. We conclude that inhibition of IGF1R-Akt-mTOR signaling represents a new cellular mechanism of shikonin strengthening its potential for the treatment of hematological malignancies. 96 Oncol Res Treat 2014;37(suppl 1):1–133 ID 073 Therapeutic targeting of a robust non-oncogene addiction to PRKDC in DNA repair-defective tumors L. Thelen, S. Chen, A. Riabinska, M. Daheim, M. Jokic, R. Thomas, C. Reinhardt University Hospital Cologne, Medical Clinic I, Köln, Deutschland In response to DNA damage, cells activate a complex, kinase-based signaling network to arrest the cell cycle, initiate DNA repair, or, if the extend of damage is beyond repair capacity, induce apoptotic cell death. ATM lies at the heart of this signaling network, which is collectively referred to as the DNA damage response (DDR). Disabling ATM mutations occur frequently in various human tumor entities. Here we show that ATM-deficiency protects human and murine cancer cells from apoptosis induced by genotoxic chemoptherapy. Using genetic and pharmacological approaches we demonstrate in vitro and in vivo that ATM-defective murine and human cells display a strong non-oncogene addiction to DNA-PKcs signaling. We further show that this dependence of ATM-defective cells on DNA-PKcs offers a window for therapeutic intervention. We show that pharmacological or genetic abrogation of DNA-PKcs in ATM-defective settings leads to the accumulation of DNA double-strand breaks and the subsequent CtIP-dependent generation of large single-stranded DNA (ssDNA) repair intermediates. These ssDNA structures trigger the activation of pro-apoptotic signaling through the RPA/ATRIP/ATR/Chk1/p53/Puma axis, ultimately leading to the apoptotic demise of ATM-defective cells exposed to DNA-PKcs inhibitors. Lastly, we demonstrate that DNA-PKcs inhibitors show remarkable preclinical activity as single agents against ATM-defective lymphomas in vivo. Together, our data implicate DNA-PKcs as a novel drug target for the treatment of ATM-defective malignancies. In an extension of this work, we performed a cell line-based screen with the aim to identify additional mutations that are associated with DNA-PKcs dependence. This screen reveals that not only mutations in genes that are involved in homologous recombination-based DNA repair, but also mutations in mismatch repair genes produce DNA-PKcs dependnece. ID 076 Novel alternatively spliced isoform of synuclein gamma M. Hirschfeld, K. Schaal, M. Jäger, E. Stickeler Universitätsfrauenklinik Freiburg, Molekulare Onkologie, Freiburg, Deutschland Introduction: Since Synuclein γ (SNCG) is found highly expressed in advanced breast cancer it was initially described as breast-cancer specific gene (BCSG1). Clinical studies demonstrate the correlation of high SNCG expression with advanced stages, metastasis and poor prognosis in breast and ovarian carcinomas, i.e. reduced relapse-free and overall survival periods. In vitro analyses revealed a SNCG-dependent stimulation of ligand-dependent transcriptional activity of ERα. So far, four mRNA isoforms of SNCG were described, but only isoforms 1 and 2 code for active proteins. For the first time, we analyzed expression levels of SNCG mRNA isoforms in regard to hypoxia or acidosis, in vitro in endometrial cancer cells. Methods: In vitro tests under hypoxic, acidic or control conditions with consecutive RNA and protein analysis. Results: In comparison to the reference breast cancer cell line, endometrial cancer cell lines displayed a general significantly reduced expression of SNCG isoform 1, 2, 3 and 4. In contrast, a novel, shortened mRNA variant of isoform 2 was identified in endometrial cancer cells. Hypoxia and acidosis triggered a marked up-regulation of the novel isoform 2 short, while the expression of constitutive isoform 2 did not significantly change under altered conditions. Immunohistochemistry and Western blot revealed a hypoxia- and acidosis- dependent increase in SNCG protein expression. Conclusion: We hypothesize, that the novel SNCG isoform 2 short bears a specific oncogenic potential in endometrial cancer, since it occurred in elevated levels under typical epiphenomena of solid tumors in vitro. Furthermore we postulate that this novel isoform is capable to code for a biologically active protein isoform. Abstracts Inhalt Index ID 077 Endoxifen and hTra2-beta1 regulate estrogen receptor α alternative splicing pattern in breast cancer cells M. Hirschfeld, C. Zheng, M. Jäger, E. Stickeler ID 173 Clostridium perfringens enterotoxin (CPE) gene therapy for selective treatment of claudin-3- and -4 expressing pancreatic tumors Universitätsfrauenklinik Freiburg, Molekulare Onkologie, Freiburg, Deutschland J. Pahle1, D. Kobelt2, D. Behrens2, M. Rivera Markelova2, J. Aumann1, W. Walther2,1 Background: Endoxifen acts as a selective estrogen receptor modulator by blocking ERα transcriptional activity. Alternatively spliced ERα mRNA variants are present in normal and malignant breast tissues, possessing the potential for increased estrogen activities. Human Tra2-β1 is a splicing factor regulating splicing processes in a sequence-specific and concentration-dependent manner. hTra2-β1 intracellular localization may vary during cancer progression or is changed by exogenic stimuli, e.g. therapeutic drugs. Here we analyzed the potential impacts of endoxifen and hTra2-β1 on ERα expression pattern and the effect of endoxifen on hTra2-β splicing. Methods: In vitro tests under endoxifen and/or hTra2-β1 knock-down with consecutive analysis of mRNA and protein expression. Results: Endoxifen induced a significant reduction of ERα protein expression. As a feedback effect, the ERα mRNA levels markedly increased. Endoxifen treatment triggered a shift in ERα splicing toward the ERα Δ7 variant. hTra2-β1 knock-down created a similar impact on ERα splicing. In addition, a novel isoform of hTra2-β1 occurred under endoxifen treatment. Interestingly, endoxifen also triggers an intracellular translocation of hTra2-β1 characterized by decreased nuclear protein and increased accumulation in cytoplasm. Conclusion: We hypothesize that endoxifen exerts a regulatory impact on hTra2-β1 alternative mRNA splicing pattern and intracellular protein localization. hTra2-β1 is most likely involved in ERα-dependent regulation of breast cancer by triggering aberrant ERα alternative splicing. ERα Δ7 might serve as an auspicious novel prognostic indicator for evaluation of human breast cancer endocrine therapy efficacy. 1 ID 139 Potential early diagnosis of GI cancers by using a CPE derivative specifically targeting CLDN-4 S. Bobersky , S. Hahn , N. Metzler-Nolte 1 2 1 Ruhr Universität Bochum, Anorganische Chemie I / Molekulare Gastroenterologische Onkologie, Bochum, Deutschland 2 Ruhr Universität Bochum, Molekulare Gastroenterologische Onkologie, Bochum, Deutschland 1 Among the gastrointestinal cancers, pancreatic ductal adenocarcinoma (PDAC) is the most aggressive. Clinically, distinguishing between benign biliary structures and pancreatic masses and pancreatic cancer as well as other periampullary malignancies is a challenge. Resectability is present if the primary tumor has the «magic» size of 2–3 cm diameter and no detectable metastasis. Detectability is flawed for all tumors below this «magic» size. Tumors smaller than 1 cm are not traceable to date. The focus here lies in using peptide-metal-bioconjugates to find novel binding partners for bioimaging gastrointestinal tumors, starting with PDAC, because of the need for early detection of the disease. The Claudin-4 (CLDN-4) protein is one marker of ductal differentiation in pancreatic tissue but, even in early lesions, the primary tumor and late metastasis show a sufficient overexpression. CLDN-4 is an integral constituent of tight junctions. Clostridium perfringens Enterotoxin’s C-terminal binding sequence of 29 amino acids is supposedly adequate for targeting, binding and sequential internalization of itself and its interacting binding partner: CLDN-4. The primary focus lies in optimizing this binding sequence in length as well as regarding its affinity to CLDN-4 leading to a medically needed tool to detect even early lesions of GI cancers. Attaching a metal complex feasible for PET imaging, this will become a diagnosis tool. By combining other modules to the final binding sequence, even theranostic tools can be possible. Abstracts Experimental and Clinical Research Center, Charité, Berlin, Deutschland Max-Delbrück-Center for Molecular Medicine Berlin-Buch, Berlin, Deutschland 2 Bacterial toxins represent an effective therapeutic option for cancer therapy. Several studies showed their antitumoral potential. The Clostridium perfringens Enterotoxin (CPE) is a pore forming toxin with a selective, receptor dependent cytotoxicity. The transmembrane tight junction proteins claudin-3 and claudin-4 are known high-affine CPE receptors and are often highly overexpressed in human epithelial tumors such as breast, colon, ovarian and pancreatic cancer. CPE binding to its receptor triggers formation of membrane pore complexes, which lead to cell death. Our approach aimed at evaluation of an efficient and selective cancer therapy of claudin-3- and/or claudin-4-expressing pancreatic carcinoma by using a non viral translation optimized CPE vector (optCPE) in vitro and in vivo. We investigated the sensitivity of selected human pancreatic carcinoma cell lines for treatment with recombinant CPE (recCPE) as well as by optCPE gene transfer. Claudin-3 and -4 high expressing pancreas carcinoma lines showed high sensitivity towards recombinant, and transfected CPE. Here an up to 100% toxicity was observed 72 h after gene transfer. We demonstrated a correlation between CPE cytotoxicity and the level of claudin-3 and/or -4 expression. The claudin-negative human control cell line SkMel-5 did not show any sensitivity toward recombinant CPE treatment or CPE gene transfer. The intratumoral in vivo gene transfer of optCPE led to reduced tumor viability in Panc 9662 patient derived xenograft bearing mice compared to the control group. This study shows that CPE gene transfer is a promising and efficient option for a targeted suicide gene therapy of claudin-3- and/or claudin-4-overexpressing pancreatic tumors in vitro and in vivo. ID 217 K-Ras exon 2 mutations impact on regorafenib-activity in an isogenic disease model of colorectal cancer P. Camaj1, S. Primo1, V. Heinemann2, Y. Zhao1, Y. Wang1, R. Laubender3, B. Schwarz2, C. Haertl1, S. Gamba1, C.J. Bruns1, D.P. Modest2 Medizinische Faultät LMU München, Exp. Forschung: Chirurgie, München, Deutschland 2 Klinikum Großhadern, Medizinische Klinik III, München, Deutschland 3 Medizinische Fakultät LMU München, Institut für medizinische Infrometionsverarbeitung, Biometrie und Epidemiologie, München, Deutschland 1 Purpose: To investigate the impact of different KRAS mutations on treatment with the tyrosine kinase inhibitor regorafenib in SW48 colorectal cancer cell line variants. Materials and methods: Isogenic SW48 KRAS wt, G12A, G12C, G12D, G12R, G12S, G12 V, and G13D cells were tested for the effect of regorafenib on B-RAF, ERK/ELK phosphorylation, cell cycle, and cytotoxicity. Results: Compared to KRAS wt cells, all KRAS mutant variants were associated with resistance to regorafenib treatment. In the MTT chemosensitivity assay, the grade of resistance was less pronounced in G13D and highest in G12C, G12A, G12S and G12V mutant cells. The reduction in B-RAF phosphorylation due to treatment with regorafenib was highest in G12V and G13D mutant cells and lowest in G12C and G12R. The mutant G12V exhibit strongest and mutant G12D weakest inhibition of ERK-activation upon regorafenib treatment. ELK phosphorylation was less decreased in all KRAS mutant variants with exception of G12D, compared to KRAS wt cells following regorafenib treatment. Conclusion: Our isogenic cell culture model suggests that KRAS mutations in SW48 colorectal cancer cells are linked to resistance to the multityrosine kinase inhibitor regorafenib. KRAS G13D mutant SW48 cells Oncol Res Treat 2014;37(suppl 1):1–133 97 Inhalt Index represented the KRAS subspecies with the lowest grade of resistance and mutants G12C and G12A highest. Future studies will have to clarify whether KRAS can be used to guide sunitinib treatment or – in general – a treatment with a multityrosine kinase inhibitor in mCRC. ID 246 Is there an association of Single-NucleotidePolymorphisms in the MDR1-gene with paclitaxel sensitivity in human renal cell carcinoma? P. Reinecke, N. Jallal, H.-E. Gabbert Universitätsklinikum Düsseldorf, Institut für Pathologie, Düsseldorf, Deutschland Objective: Renal cell carcinomas (RCCs) are highly resistant to conventional chemotherapy. The Single-Nucleotide-Polymorphisms (SNPs) in the MDR1-gene represent one possible drug resistance mechanisms. Therefore to elucidate the response to antineoplastic agents we defined the SNPs HAPLO and TAK in the MDR1-gene in a model with ‘intrinsic paclitaxel resistance’ cell lines (chrompho-A and -B) and with ‘acquired paclitaxel resistance’ cell lines (clearCa-21sens and clearCa-21res) before and after exposure to paclitaxel. Methods: MTT-assay, RT-PCR, DNA-sequencing. Results: 1. In all cell lines P-glycoprotein (P-gp) was expressed on mRNA-level. 2. Furthermore the intrinsic resistance model showed an IC50 of 0.08 μM in the paclitaxel-sensitive chrompho-A and an IC50 of 387.5 μM in the paclitaxel-resistant chrompho-B after exposure to paclitaxel whereas in the acquired model an IC50 of 0.38 μM in clearCa-21sens and >1000 μM in clearCa-21res was detected by MTT-assay. 3. Defining the SNPs HAPLO and TAK in the MDR1-gene in untreated cells of the intrinsic model both SNPs were observed in the paclitaxel-resistant cell line chrompho-B by DNA sequencing. 4. In comparison the TAK-SNP became evident in both cell lines of the acquired resistance model however the HAPLO-SNP only in the resistant cell line clearCa-21res. 5. After exposure to paclitaxel the HAPLO-SNP was detected in the cell line clearCa-21sens. Conclusion: Obviously our results indicate that there is an association of SNPs in the MDR1-gene with paclitaxel sensitivity in human RCCs in a model of ‘intrinsic’ and ‘acquired’ paclitaxel resistance. Thus further aims should be to elucidate the mechanisms between SNPs in the MDR1-gene and paclitaxel sensitivity in human RCCs. ID 278 Syndecan-1 (CD138) modulates breast cancer stem cell properties via regulation of IL-6-mediated STAT3 signaling S.A. Ibrahim1, H. Hassan1, L. Vilardo2, H.T. Eich3, L. Kiesel4, R. Reinbold2, B. Greve3, M. Götte4 University of Cairo, Department of Zoology, Faculty of Science, Giza, Aegypten 2 ITB-CNR Segrate, Milan, Italien 3 Universitätsklinikum Münster, Department of Radiotherapy –Radiooncology, Münster, Deutschland 4 Universitätsklinikum Münster, Klinik für Frauenheilkunde und Geburtshilfe, Münster, Deutschland 1 Aim of Study: Syndecan-1 (SDC1), a heparan sulfate proteoglycan, acts as a coreceptor for growth factors and chemokines and is a molecular marker associated with epithelial-mesenchymal transition during development and carcinogenesis. Resistance of SDC1-deficient mice to induced tumorigenesis has been linked to altered Wnt-responsive precursor cell pools. Here, we analyze the molecular contribution of SDC1 to a breast cancer stem cell phenotype in human breast cancer cells in vitro. Methods: MDA-MB-231 and MCF-7 cells were transiently transfected with SDC1 or control siRNA. Stemness-related parameters were analyzed by flow cytometry and sphere formation assays. Molecular analyses were performed by PCR and Western blotting. 98 Oncol Res Treat 2014;37(suppl 1):1–133 Results: Side population measurement by Hoechst dye exclusion and ALDH1 activity revealed that SDC-1 knockdown reduced putative cancer stem cell pools by 60 and 27%, respectively, compared to controls. Intriguingly, IL-6, its receptor sIL-6R, and the chemokine CCL20, implicated in regulating stemness-associated pathways, were downregulated by >40% in Syndecan-1-silenced cells, which showed a dysregulated response to IL-6-induced epithelial-to-mesenchymal transition. Activation of STAT-3 and NFkB transcription factors and expression the Wnt coreceptor LRP6, were reduced by >45% in SDC1-depleted cells compared to controls. SDC1 siRNA reduced the formation of spheres and cysts in MCF-7 cells grown in suspension culture. Conclusion: As Syndecan-1 modulates the breast cancer stem cell phenotype via regulation of the IL-6/STAT3 and Wnt signaling pathways, it emerges as a promising novel target for therapeutic approaches. ID 321 Targeting STAT3 as a therapeutic strategy to sensitize colorectal cancer to chemoradiotherapy M. Grade1, M. Spitzner1, B. Roesler1, C. Bielfeld1, J. Gaedcke1, H. Wolff2, T. Beissbarth3, J. Wienands4, M. Ghadimi1 Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Göttingen, Deutschland 2 Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie, Göttingen, Deutschland 3 Universitätsmedizin Göttingen, Institut für Medizinische Statistik, Göttingen, Deutschland 4 Universitätsmedizin Göttingen, Institut für Zelluläre und Molekulare Immunologie, Göttingen, Deutschland 1 Problem: Increased activity of STAT3 is common in human malignancies, including colorectal cancers (CRC). We have recently reported that STAT3 gene expression correlates with resistance to 5-FU-based chemoradiotherapy (CT/RT). This is of considerable clinical importance, because a large proportion of rectal cancers are resistant to preoperative multimodal treatment. Methods: To test whether STAT3 contributes to CT/RT-resistance, STAT3 protein expression was measured in 12 CRC cell lines. STAT3 was inhibited in vitro in SW480 and SW837 using siRNA, shRNA, and a small-molecule inhibitor (STATTIC). Silencing or inhibition of phosphorylation was confirmed using Western blot analysis and a luciferase reporter assay. Following exposure to 3 µM of 5-FU and irradiation, sensitivity to CT/RT was assessed using standard colony formation assays. Growth delay assay was used to determine the effect of STAT3 inhibition on treatment sensitivity in vivo. Results: STAT3 protein expression correlated positively with increasing CT/RT-resistance. While STAT3 was not constitutively active, stimulation with IL-6 resulted in remarkably higher expression levels of phosphorylated STAT3 in CT/RT-resistant cell lines. A similar result was observed when IL-6-induced expression of phosphorylated STAT3 was determined after irradiation. RNAi- and STATTIC-mediated inhibition of STAT3 resulted in significantly decreased clonogenic survival. In vivo, STAT3 inhibition led to a profound CT/RT-sensitization in a subcutaneous xenograft model. Conclusions: These results highlight a potential role of STAT3 in mediating CT/RT-resistance of CRC cells, and provide first proof of concept that STAT3 represents a promising molecular target. Abstracts Inhalt Index ID 333 CXCR4 over-expression is associated with Cisplatin resistance in esophageal carcinoma Y. Zhao1, Y. Wang1, L. Zhao1, S. Gros2, J. Mysliwietz3, J. Ellwart3, H. Nieß1, C. Betzler4, K.-W. Jauch1, P. Nelson5, C. Bruns4 LMU Klinikum Grosshadern, Department of Surgery, München, Deutschland University of Hamburg-Eppendorf, Department of Surgery, Hamburg, Deutschland 3 Helmholtz Center for Environment and Health, Institute of Molecular Immunology, München, Deutschland 4 Otto-von-Guericke University, Department of Surgery, Magdeburg, Deutschland 5 LMU Medizinische Klinik und Policlinic IV, Clinical Biochemistry Group, München, Deutschland 1 2 Introduction: CXC chemokine receptor 4 was found dys-regulated in many different types of human cancers and generally correlate with poor prognosis, metastasis, and resistance to chemotherapy. Limited data show the influence of CXCR4 on esophageal carcinoma cells especially following chemotherapy with cisplatin. Methods:CXCR4 was detected by FACs analysis in esophageal cell lines OE19, OE21, OE33, PT1590, and LN1590. Corresponding cisplatin resistant cells were established following longterm selection under cisplatin treatment and further confirmation by IC50 and ERCC1 expression. SDF-1α and AMD3100 were used for stimulation or inhibition of CXCR4 in vitro. A subcutanous tumor model of OE19 cell injection in Balb/c nude mice was established, followed by treatment with cisplatin twice a week via i.p injection. Tumors were collected for further molecular biology analysis. Results: The esophageal cell lines OE19, PT1590, and LN1590 have detectable amount of CXCR4+ subpopulations as high as 2.8%±0.9, 0.7%± 0.9, and 1.0%±0.6, respectively. The OE19, PT1590, and LN1590 cisplatin resistant sublines displayed an increased IC50 value after 48h treatment with cisplatin from 6.0±1.3 to 12.2±1.0, 1.4±0.7 to 9.1±0.7, and 1.4±0.6 to 7.2±0.6 ug/ml along with a significant overexpression of ERCC1. Interestingly, only OE19 and LN1590 cisplatin resistant cell lines showed a significant enrichment of CXCR4+ cells (12.1%± 2.5 vs. 2.8%±0.9; 4.2%± 1.1 vs. 1.0%±0.6, pin vivo. The relative expression of CXCR4 will be further evaluated by realtime PCR and immunohistochemistry. Conclusion:Overexpression of CXCR4 is significantly associated with cisplatin-based chemotherapy resistance and might be a prognostic factor in esophageal cancer. Inhibition of CXCR4 might be a strategy to address chemoresistance of EAC cell lines. ID 338 PDGF influences tumor proliferation like VEGF in colon cancer R. Mönch1, T. Grimmig1, V. Kannen2, M. Kim3, C.-T. Germer3, M. Gasser3, A. M. Waaga-Gasser1 Universitätsklinikum Würzburg, Chirurgische Klinik I, Molekulare OnkoImmunologie, Würzburg, Deutschland 2 Universitätsklinikum Würzburg, Institut für Pharmakologie und Toxikologie, Würzburg, Deutschland 3 Universitätsklinikum Würzburg, Chirurgische Klinik I, Würzburg, Deutschland 1 Background: The platelet derived growth factor (PDGF) and Vascular Endothelial Growth Factor (VEGF) are known to play a crucial role in different tumor entities. Involved in cell migration and proliferation of stromal cells in cancer tissue they represent key targets in cancer therapy. The aim of the study was to analyse the specific role of PDGF and VEGF stimulation on tumor cell proliferation and metabolism in colorectal cancer (CRC). Methods: The human colon cancer cell line HT-29 and Caco-2 were cultured and stimulated with PDGF and VEGF in a time-dependent manner. Whole cell extracts and RNA extracts were analyzed by Western Blot and RT-q-PCR for PDGF- and VEGF receptors and for components of cellular metabolism. To discover effects of PDGF and VEGF on proliferation MTS proliferation assays were performed. Abstracts Results: Western Blot analysis and RT-qPCR showed no relevant PDGF-receptor α and β expression in HT-29 cells but varying expression in Caco-2 cells. Stimulation with PDGF or VEGF resulted in increased proliferation compared to untreated controls while simultaneous stimulation with both growth factors did not result in intensified proliferation. Additionally, under stimulation altered expression of various metabolic components was detected. Conclusion: Our results demonstrate a promoting effect on tumor cell proliferation of both growth factors PDGF and VEGF. Simultaneous stimulation did not show synergistic effects. PDGF in HT-29 cells resulted in proliferation in the absence of PDGF receptors with changes in tumor cell metabolism after stimulation. In conclusion, our data give evidence for direct receptor/ligand signalling of PDGF not only on stromal cells but also on colon cancer cells even in the absence of the PDGF receptor. ID 358 Negative Selection In Vivo RNAi Screening Identifies a Ribosomal Protein as a New Therapeutic Target in Liver Cancer M. Pesic1, K. Wolter1, T. Wuestefeld1, T.-W. Kang1, R. Chawla1, R. Geffers2, F. Klawonn3, N. Malek4, P. Schirmacher5, P.K. Premsrirut 6, T. Longerich5, L. Zender1 University Hospital Tuebingen, Division of Translational Gastrointestinal Oncology, Dept. of Internal Medicine I, Tuebingen, Deutschland 2 Helmholtz Centre for Infection Research, Genome Analytics Group, Braunschweig, Deutschland 3 Helmholtz Centre for Infection Research, Bioinformatics and Statistics, Braunschweig, Deutschland 4 University Hospital Tuebingen, Internal Medicine I, Tuebingen, Deutschland 5 University Hospital Heidelberg, Institute for Pathology, Heidelberg, Deutschland 6 Mirimus, Inc., Cold Spring Harbor, New York, Vereinigte Staaten Von Amerika 1 Due to the lack of treatment options hepatocellular carcinoma (HCC) represents the third most frequent cause of cancer related death. The major obstacle in HCC treatment is resistance to chemotherapy and new therapeutic targets, to overcome the treatment resistance, are urgently needed. We devised a system that allows conducting negative selection in vivo RNAi screens to identify new therapeutic target genes in murine HCCs. Multilocular invasive HCCs develop after short latency when oncogenic Nras is stably delivered into p19-/- mouse livers via transposable elements. As a proof of principle that RNAi mediated knockdown of target genes can cause lethality of Nras driven HCCs, we showed that stable expression of shRNA targeting a cell essential DNA replication protein 3 completely blocked Nras driven tumorigenesis and that shRNA against Ras downstream target B-Raf reduced the tumor burden of injected mice. To identify vulnerabilities of Nras driven murine HCCs that may be exploited as new therapeutic targets, transposable elements co-expressing Nras and a focused shRNA library were stably delivered into p19-/- mouse livers. The frequency of each shRNA in the library before delivery into hepatocytes and after hepatocarcinogenesis was quantified via deep sequencing and a comparison of obtained profiles identified hairpins against a ribosomal protein as top depleted. Functional validation experiments with different hairpins show that knockdown of our candidate gene strongly suppress Nras driven tumorigenesis in p19-/- mice. Inhibition of expression of ribosomal candidate gene via RNAi drives the murine hepatoma cells into irreversible cell cycle arrest that has features of senescence. Interestingly, the cells upregulate cytokines involved in activation of immune cells that mediate their clearance. ID 359 Ipilimumab therapy seems to induce CD28 antibodies with inhibitory effect on T cells of melanoma patients C. Pföhler, K.-D. Preuss, E. Janssen, R. Koerner, C. Müller, T. Vogt Universitätsklinikum des Saarlandes, Klinik für Dermatolgie, Homburg, Deutschland CD28 antibodies (abs) may have immunostimulatory effects by acting as superagonists on the CD28 receptor of T cells followed by induction Oncol Res Treat 2014;37(suppl 1):1–133 99 Inhalt Index of T effector cells. On the other hand they may have immunosuppressive effects by activating regulatory T cells or by blocking of the T cell receptor in its proper function. We constructed an ELISA assay to measure CD28 abs in the serum of melanoma patients. We could show that 42/230 (18.3%) of all melanoma patients had CD28 serum antibodies while only 2/140 (1.4%) healthy blood donors were positive. In further experiments we could show that CD28 abs of melanoma patients lead to reduced stimulation of Jurkat cells in vitro. This effect was titer-dependent as high titers resulted in a stronger inhibition than a low titer. First prospective investigations in a small group of patients receiving ipilimumab in stage IV melanoma showed a seroconversion in about one fourth of the patients meaning no prove of CD28 abs at the beginning of therapy followed by production and detection of CD28 antibodies during therapy with ipilimumab. First analyses showed that titers of CD28 abs increased over time, in some patients titers declined after stopping therapy with ipilimumab. CD28 abs positive patients showed a progression of disease in all cases. Further T cells assays are required to investigate the impact of CD28 abs on T cells of melanoma patients. In addition we need to prove whether ipilimumab therapy is able to induce the production of blocking CD28 abs. If our first observations can be confirmed discontinuation of ipilimumab therapy should critically be discussed after detection of CD28 abs. Potentially, CD28 abs could serve as a relevant biomarker during immunotherapies with e.g. ipilimumab or anti-PD1 antibodies. ID 375 Targeting mTORC2 component RICTOR impairs tumor growth in an experimental pancreatic cancer model K. Schmidt, C. Wagner, J. Redekopf, H.J. Schlitt, E.K. Geissler, S. A. Lang University of Regensburg, Surgery, Regensburg, Deutschland Background: The serine/threonine kinase mTOR (mammalian target of rapamycin) is active in two distinct complexes, called mTORC1 and mTORC2. mTOR inhibitors that have recently gained increasing interest for the treatment of human pancreatic cancer, usually only affect mTORC1. Since mTORC2 is a major regulator of Akt activity which in turn plays a pivotal role in the development of human pancreatic cancer, we assessed the effects of targeting RICTOR, an essential component of mTORC2, on growth of pancreatic cancer cells. Methods: The human pancreatic cancer cell line HPAF-II was stable transfected with an shRNA plasmid targeting RICTOR including the respective control (Invitrogen). Knock-down was verified via Western blotting and/or PCR. In vitro effects of RICTOR inhibition on growth of cancer cells were assessed using MTT and cell count assays. Subsequently, migration assays were employed to determine potential effects on cancer cell motility. Tumor growth was finally evaluated in an orthotopic pancreatic cancer model in vivo. Results: Stable transfection with the shRNA plasmid efficiently impaired RICTOR expression in human pancreatic cancer cell line HPAF-II as determined by Western blotting. In MTT assays, only minor effects on growth of tumor cells were observed. In contrast, a significant inhibition of cancer cell motility was found upon RICTOR blockade in vitro (≤0.05). In vivo, RICTOR knock-down led to significant impairment of tumor growth as determined by final tumor weight (≤0.05). Moreover, the incidence of liver and lymph node metastases was strongly reduced upon RICTOR inhibition. Conclusion: Inhibition of mTORC2 component RICTOR impairs tumor growth and metastases in vivo. Although the exact mechanism of these effects remains to elucidated, therapies targeting RICTOR may be a promising approach to improve current treatment concepts in pancreatic cancer patients. 100 Oncol Res Treat 2014;37(suppl 1):1–133 Oncological Pharmacy ID 237 Cumulative bisphosphonate dosages increase the risk of bisphosphonate associated osteonecrosis of the jaws – analysis of 67 patients with prostate cancer and bisphosphonate therapy C. Walter1, C. Engel1, C. Thomas2 1 2 Universität Mainz, MKG-Chirurgie, Mainz, Deutschland Universität Mainz, Urologie, Mainz, Deutschland Introduction: Bisphosphonates (BP) are associated with the occurrence of osteonecrosis of the jaws (BP-ONJ). Nitrogen-containing bisphosphonates (N-BP) such as zoledronate and pamidronate are more often associated with BP-ONJ compared to non N-BPs such as clodronate. The aim of this study was to analyze the effect of bisphosphonate treatment duration on the likelihood of developing BP-ONJ. Material and Methods: Patients from two cross-sectional studies performed in the Urologic Department at the University Medical Center of the Johannes Gutenberg-University were analyzed regarding the duration of BP intake before a BP-ONJ developed. Results: The studies were performed in 2011 and 2007. All together 67 patients had been treated due to prostate cancer; 10 of the 67 patients had developed a BP-ONJ. There were no differences in between the two groups. The average time of BP-intake was 18 (±14 standard deviation) months for the entire group and 16±14 months for the patients without and 27±11 months for the patients with BP-ONJ (p = 0,026). Conclusion: The occurrence of BP-ONJ is correlated to the time of BP-administration most probably due to the cumulative effect of the N-BP. Similar side effects can be seen in patients receiving new medications such as antibodies against Rankl or tyrosine kinase inhibitors. In cases where the primary disease allows it it might be feasible to either reduce the frequency of BP administration or use medications that are less often associated with osteonecrosis such as clodronate. ID 289 Antineoplastic activity of alkylphosphocholines in cell lines of B- and T-cell origin Y. Ilieva1,2, S. Konstantinov1, M. Berger2 Medical University – Sofia, Department of Pharmacology, Pharmacotherapy and Toxicology, Bulgarien 2 DKFZ, Unit of Toxicology and Chemotherapy, Heidelberg, Deutschland 1 Miltefosine, perifosine and erufosine are representatives of the three generations of alkylphosphocholines. Certain agents of this class of compounds have recently become known as inhibitors of AKT phosphorylation. Nevertheless, the differences in chain length, saturation of the carbon chain, and position of the cis-double bond are associated with variations in their mechanism of action, cytotoxicity, route of administration and side effects. Initial investigations of their cytotoxicity in tumor derived cell lines of B-cell and T-cell origin were performed by the MTT-dye reduction assay. Our results showed a well pronounced dose – response inhibition and the lowest observed IC50 values ranged from 2.2 µM for perifosine (B cell lymphoma cell line DOHH-2, 48 h incubation) to 5.7 µM for erufosine (T cell lymphoma cell line HuT-78, 72 h incubation) and to 8.8 µM for miltefosine (T cell lymphoma cell line HH, 48 h incubation). The lowest sensitivity to erufosine (IC50 = 108 µM, 24 h incubation) and perifosine (IC50 = 92.0 µM, 24 h incubation) showed the B cell lymphoma cell line REH and the cell line DOHH-2 was the least sensitive to miltefosine (IC50 = 44.4 µM, 24 h incubation). The mean IC50 values for the three compounds were as follows: miltefosine - 21 µM, perifosine - 23 µM and erufosine - 50 µM. Compared to solid tumor derived cell lines, like MCF-7 and MDA-MB-231 which show IC50 values of about 40 µM, the variation in sensitivity to alkylphosphocholines between B- and T-cell lymphoma derived cell lines is apparently greater. Future experiments Abstracts Inhalt Index will therefore concentrate on the reason of this variation in sensitivity including an analysis of the expression of apoptosis related genes and of signaling pathways based on AKT. ID 315 Oncology Competence Pharmacy – a German approach to improve quality in oncology pharmacy K. Meier1, K. Ohlinger2, S.-O. Nissen2, E.-M. Schöning2 Deutsche Gesellschaft für Onkologische Pharmazie, Hamburg, Deutschland medac, Wedel, Deutschland testine. Toxicology studies carried out in transgenic mice have shown that i.v. injection of JO-1 is safe. In vivo studies have demonstrated that JO-1 remains active in the presence of anti-JO-1 antibodies. Taken together, these findings offer preclinical proof of concept to employ JO-1 treatment prior to mAb therapy or chemotherapy for cancer patients. Paediatric Cancer 1 2 Introduction: Nowadays oral chemotherapy occurs more often in treatment of cancer patients. This demands a lot of knowledge regarding safe handling of oral chemotherapy agents. Community pharmacy staff needs special education and expert knowledge in order to counsel oncology patients and for the communication with other healthcare professionals. The same expert advice of high quality must be ensured regardless which pharmacy staff member is providing the advice. Therefore every staff member needs the same level of education. To ensure this standard we developed the project ‘Oncology Competence Pharmacy’ (OCP). Material and Method: German society of oncology pharmacy (DGOP) in cooperation with medac developed the concept of OCP to verify the special cytotoxic drug knowledge of pharmacy employees. The project is based on an online tool for continuing education in oncology pharmacy. Therefore every staff member gets an individual access to an e-learning online platform where he has to pass through different trainings provided as online presentations and proof his educational success by a multiple choice test. Currently 61 pharmacies with more than 700 members take part. Results and Discussion: The online tool enables every staff member to study whenever it is possible for the individual. Team studies are not necessary so that the daily work flow is not impaired and everyone may take the time he needs to gain qualifications in certain fields of oncology pharmacy. The main target to ensure that every staff member has the same level of education is locked by a multiple choice test. Conclusion: The concept of OCP improves the quality in oncology pharmacy and helps oncology patients to find a specialized pharmacy. ID 224 JO-1, an epithelial junction opener for the improvement of cancer therapy I. Beyer1, J. Persson2, H. Song2, H. Cao2, Q. Feng2, R. Yumul2, R. van Rensburg 2, Z. Li2, C. Drescher2, A. Lieber2 Heinrich Heine Universitaet Duesseldorf, Frauenklinik, Duesseldorf, Deutschland 2 University of Washington, Medical Genetics, Seattle, Vereinigte Staaten Von Amerika 1 Epithelial cancers maintain intercellular junctions that link cancer cells together and prevent the penetration of therapeutics into the cancer. Several studies demonstrated that the upregulation of epithelial junction proteins correlated with increased resistance to therapy, e.g. monoclonal antibodies (mAb) and chemotherapeutics. One of the epithelial junction proteins is desmoglein 2 (DSG2). Recently, we demonstrated that a group of human adenoviruses (Ad) use DSG2 as a primary attachment receptor for the infection of cells. DSG2 is overexpressed in epithelial malignancies. We have created a small recombinant protein derived from Ad serotype 3, which binds to DSG2 and triggers transient opening of epithelial junctions. We therefore named the protein JO-1 (junction opener -1). In several xenograft tumor models, we have shown that i.v. injection of JO-1 increased the efficacy of mAb therapy. Many chemotherapy drugs are larger than 500 Da, the upper limit of molecules that are able to pass through tight junctions. We have demonstrated that the therapeutic effects of several of these drugs, including paclitaxel, nab-paclitaxel and liposomal doxorubicin are increased by co-therapy with JO-1. Furthermore, we have shown that JO-1 leads to accumulation of drugs in the tumor. This resulted in the decrease of chemotherapy-related toxicities to bone marrow, liver, and in- Abstracts ID 118 The Rehabilitation of Adolescents and Young Adults (AYA): Co-operation between Pediatric and Adult Oncologists results in a successful Transition – the Bad Oexen Experience as a Model K. A. Krauth1, V. König2 Klinik Bad Oexen, Pädiatrie/Kinderhämatologie und Onkologie, Bad Oeynhausen, Deutschland 2 Klinik Bad Oexen, Onkologie, Bad Oeynhausen, Deutschland 1 Over the last decades the number of pediatric cancer patients reaching adulthood has increased significantly. In order to ensure a good long-term quality of life a successful transition from pediatric to adult oncology is essential. How can the knowledge and experience of pediatric oncology be successfully transferred into adult oncology? While many former pediatric oncologic patients can lead a normal adult life, a significant number of them must be regarded as chronically ill. So far many of these patients, e.g. suffering from long-term sequelae of brain or bone tumors and their treatments, are not adequately taken care of, as soon as they leave pediatric oncology. Therefore, to ensure a smooth transition the combined efforts of pediatric and adult oncologists are needed in order support the development of AYA units in oncologic centers. More than 25 years of oncologic inpatient rehabilitation of adolescents and young adults in Bad Oexen have proven that a team consisting of: pediatric and adult oncologists, pediatric and adult nurses, physical therapists, ergotherapists, social workers, speech therapists and dietitians experienced in the treatment of adolescents and young adults ensure asuccessful rehabilitation in most patients. Adolescents and young adults are rehabilitated in differentiated age groups ranging from 14 to 18 and 18 to 32 years. Close co-operation of pediatric and adult oncologists and their teams leads to this success. Thus the rehabilitation concept of the oncologic rehab center of Bad Oexen/Bad Oeynhausen, Germany, represents a unique, innovative and well-established model for the successful transition from pediatric to adult oncology through close co-operation of pediatric and adult oncologists and their teams Palliative Care ID 026 The health insurance companies (HIC) practice of accepting or reviewing prescriptions (PR) for specialized outpatient palliative care service (SAPV) in Hesse F.K. Tauchert1, M. Ruppert1, E. Jäger1 Krankenhaus Nordwest, Klinik für Onkologie, Frankfurt am Main, Deutschland 1 Background: SAPV in Hesse has been established in January 2010 to provide professional care for patients in the last phase of life in their homes. The increasing number of patients in SAPV lead to more reviewing of the prescriptions by the HIC. The Aim of this study was to explore possible problems with prescriptions leading to reviews. Methods: All SAPV-PR of our outpatient palliative care team in the period from april to June 2013 (n = 129) were analyzed for various factors whether the HIC did a review or not. Oncol Res Treat 2014;37(suppl 1):1–133 101 Inhalt Index Results: The biggest HIC did 29.4% reviews vs. 5.3% for the rest (p < 0.001). 2.0% of f1st-PR vs. 17.7% following-PR were reviewed (p = 0.007). 7.7% of short-time-PR vs. 13.3% of long-time-PR were reviewed (n.s.). 10.6% of PR for cancer-patients vs. 18.8% of PR for non-cancer-patients were reviewed (n.s.) Conclusions: The health insurance companies focus on reviewing following-PR. 93.3% of the reviews were initiated by only two HIC representing 30.2% of the patients. These findings should be verified by a multicenter survey with a bigger sample to show whether this leads to disadvantages for the patients. ID 030 The mobile oncology service – a project for rural cancer patients U. Vehling-Kaiser , T. Sternfeld , F. Kaiser 1 2 1 Onkologisches und Palliativmedizinisches Netzwerk Landshut, Landshut, Deutschland 2 Praxis für Innere Medizin, Landshut, Deutschland 1 Intravenous chemotherapies are more and more replaced by oral and subcutaneous drugs. These therapies are more convenient as they can be taken by the patients at home. Nevertheless side effects can occur and therefore regular follow up examinations are mandatory. For severely ill or otherwise handicapped patients in rural areas the transport to the ambulatory cancer centre can be stressful and exhausting. Rural regions are often characterised by long-distances, an insufficient public transport system and a low number of specialised cancer centres. To reduce the frequency of necessary patients’ visits to the centre during an oral or subcutaneous cancer therapy, a mobile oncology service (MOD: Mobiler Onkologischer Dienst) was initiated. This service is offered to the described subgroup of handicapped or severely ill patients only. Doctor’s assistants trained in the field of tumour therapy visit the patients on a regular basis. The compliance with the oral therapy is checked and patients are asked and examined for side effects. Relevant changes are discussed with the oncologist immediately. The MOD pilot project is sponsored by the Bavarian State Ministry of the Environment and Public Health. ID 170 Experience of a monoinstitution of a geriatric-oncology department in treatment of advanced head and neck and bronchogenic cancer ID 266 Inhouse training of palliative medicine and its effects and evaluation in a breast and gynecological center of a CCC: Palliative treatment in clinical routine R. Würstlein1,2, B. Haberland3,2, K. Ulbach1, K. Friese4,2, V. Heinemann5,2, N. Harbeck1,2, C. Bausewein3,2 Klinikum der Universität München, Brustzentrum, München, Deutschland Klinikum der Universität München, CCC of LMU, München, Deutschland 3 Klinikum der Universität München, Palliativmedizin, München, Deutschland 4 Klinikum der Universität München, Frauenheilkunde und Geburtshilfe, München, Deutschland 5 Klinikum der Universität München, CCC, Med. Klinik III, München, Deutschland 1 2 Background: Early integration of palliative medicine in the treatment of oncological patient is highly recommended. Control of symptoms in a metastasized stage is an immense interdisciplinary challenge for doctors and nurses. In cooperation with the clinic for palliative medicine a training in the setting of a pilot scheme was developed. The focus was on communication, control of symptoms and structures of treatment. The Inhouse trainining of palliative medicine in gynecological hospital (ITPG) was evaluated by three questionnaires (before, directly after and three month after the ITPG). Results: Questions involved the motivation to participate, differences between the specialized groups and palliative care including the treatment of complex symptoms. 78% of the participants had background in palliative care. Suggestions for improvement of the cooperation were seen in the management of transferring and external specialists. Before ITPG 5% of the participants assessed their skills in palliative care as not good, 32% as very low, 42% as low, 11% as good and none as very good prepared. After ITPG, 5% assessed their skills as low, 75% as good and 16% as very good prepared. Conclusion: The goal of ITPG is the improvement of personal skills and the optimization of palliative care in the breast center and gynecological centers of cancer CCCLMU in cooperation with the clinic for palliative medicine. The great acceptance to participate as an interdisciplinary team in the ITPG induced an improved communication and amplified skills in gynecological palliative care. A short and intensive advanced educational training period shows an immense improvement of the participants’ skills in palliative treatment. Therefore, the pilot scheme establishes the basis to transfer this dynamic training of palliative medicine on other oncological areas of the clinical center. M. Schroeder1, F. Diab2, C. Noack3, U. Schäfer3 HELIOS Klinikum Duisburg, Medizinische Klinik 2 u. 7, Duisburg, Deutschland 2 RNR an HELIOS St. Johannes Klinik, Duisburg, Deutschland 3 HELIOS Klinikum Duisburg, Medizinische Klink 7, Duisburg, Deutschland 1 Head and neck and bronchogenic cancer are most frequently diagnosed in elderly pts with a rate of 60–80% in age more than 65 years. Therefore cancer is in essential an old age cancer. Studies of old aged pts over 75 years don´t exist in theses tumorentities. We report our experience with 34 pts with BC and H+N aged 70+ years (median 76 years). All pts have been classified as incurable by an interdisciplinary tumor-board. Pretreatment investigation included geriatric assessment, social evaluation, investigation of physical organ function, comorbidities, comedication and reduction of functional status. 19 pts with H+N (f=9 / m=10) and 15 pts with BC (f=8 / m=7). All pts suffered from deficit of 1 ADL and 1 iADL. 28/34 pts suffered from cognitive deficit. Treatment procedures will be reported in details. Survival data are remarkable but not comparable with younger pts < 70 years. Conclusion: Even geriatric multimorbid pts with H+N+BC have a profit of a moderate antitumour therapy. Combined RX / CTX should be done as hospitalized pts. Intensive supportive care has to be done. Remarkable survival times are achievable, even more than 2 years. There is no standard therapy – individual treatment is necessary 102 Oncol Res Treat 2014;37(suppl 1):1–133 Patient Care ID 020 Patient satisfaction with oncologic care – an assessment of the key sectors: Primary care physicians, specialist physicians, hospitals and health insurance providers C. Degen1,2, D. Möller2, C. Schlechter3 Deutsches Krankenhausinstitut, Universitäre Forschung und angewandte Wissenschaft, Düsseldorf, Deutschland 2 Universität zu Köln, Seminar für Allgemeine BWL und Management im Gesundheitswesen, Köln, Deutschland 3 megapharm GmbH, Herstellermanagement, Sankt Augustin, Deutschland 1 Objective: The following study examines the influencing factors on the satisfaction of oncologic patients with their primary care physician, specialist physician, hospital and health insurance. Patient satisfaction with cross-sectoral collaboration is examined based on the satisfaction with these sectors. Method: 12 specialist practices from 8 federal states participated in the patient survey during the period 2011–2012. The satisfaction of 516 patients was investigated by multiple regression analysis. Results: The results show that patients are content with cross-sectoral collaboration if they are satisfied with their health insurance and specialist Abstracts Inhalt Index physician. For the satisfaction with the primary care physician and specialist physician, trust is perceived to be the most important influencing factor. For hospitals, the most significant influencing factor is interest in and time for patients. Regarding health insurance providing patients with information leads to a greater degree of satisfaction. Conclusion: Psychosocial factors are of key importance for patients’ perceptions of satisfaction with the different sectors. This contains factors like to ‘putting confidence in physicians’ or ‘talking about patients’ fears’. Oncologic care sectors should give more consideration to these factors during patient care. A health insurance provider can take the role of a competent point of contact, providing quality-assured information in the context of oncologic diseases. ID 041 Presentation and findings of a pilot project from the «Bayerische Krebsgesellschaft» (BKG): «Special consultation hour for patients suffering from cancerrelated fatigue» I. Fischer1, D. Salzmann2, J.U. Rüffer3, J. Lennert2, S. Petsch4, M. Besseler2 Institut für Tumor-Fatigue-Forschung, Emskirchen, Deutschland Bayerische Krebsgesellschaft, München, Deutschland 3 Deutsche Fatigue Gesellschaft, Köln, Deutschland 4 Tumorzentrum der Universität Erlangen-Nürnberg, Erlangen, Deutschland formation, and an algorithm illustrating the care process. Among others, the effectiveness of the model is evaluated using the patient-reported outcome (PRO) version of the CTCAE criteria. The newly developed instrument was tested in a pilot study. Results: Care modules were developed for medication review and interaction check, malnutrition, adherence and for the management of four common adverse events: nausea/emesis, mucositis, fatigue, and pain. They can be applied individually for each patient according to medication and anticipated toxicity. In the pilot study 30 outpatients with solid tumors were surveyed. Results show that approximately 73% of the patients suffered from severe or very severe toxicity according to PRO-CTCAE. Fatigue was the most frequent adverse event (87%) followed by sleep disorders (70%) and nausea (57%). Outlook: The feasibility of the model is currently being evaluated in a randomised two-arm interventional trial at the Johanniter-Hospital, Bonn. About 50 patients are allocated either to the control group or to the intervention group. Endpoints of the study are the frequency and severity of toxicity according to PRO-CTCAE and health-related quality of life. Moreover, the acceptance of the model among health care professionals and patients will be evaluated. The model is currently being adapted to the conditions at the university hospital of Cologne. 1 2 Cancer-related fatigue (CRF) is defined as a persistent, subjective sense of tiredness related to cancer or cancer treatment. It can significantly impair normal physical and psychological functioning and -as a consequence of this- also every day life and quality of life. Although lots of patients are affected and although evidence-based treatment options are available, there is a lack of qualified counseling institutions inGermany. As to date there is no ICD-code for cancer-related fatigue, the care-gap most suitable can be closed by a nonprofit organization like the BKG. Thus, together with the «Institut für Tumor-Fatigue-Forschung» the BKG established in its psycho-social advice center in Nuremberg a free-of-cost consultation hour for patients. It is comprised of diagnosis, individual consultancy, education and the offer to take part in training courses, being appropriate for patients with cancer-related fatigue and being orientated on the current available evidence-based treatment options. This would provide the first consultation for cancer-related fatigue of its kind under the umbrella of the «Deutsche Krebsgesellschaft» (DKG). The consultation hour is connected with a project in health services research. The intent of this research project is to identify the realistic need for such a consultation hour and to evaluate their concept and their benefit. It is our aim initially to develop a consultation hour so that it could be taken on by other consultation centers as needed. The project will be performed in co-operation with the «Deutsche Fatigue Gesellschaft» (DFaG) and the «Tumorzentrum der Universität Erlangen-Nürnberg». The pilot project ends in December 2013; findings of the pilot phase will be presented. ID 171 Evaluation of a best-practice model for multiprofessional cancer medication management A. Wilmer1, A. Tasar2, K. Fleckenstein3, C. Hack3, H. Beck4, A. Liekweg4, K. Ruberg2, Y.D. Ko3, U. Jaehde1 Universität Bonn, Klinische Pharmazie, Bonn, Deutschland Kronen-Apotheke Marxen, Wesseling, Deutschland 3 Johanniter-Krankenhaus, Bonn, Deutschland 4 Uniklinik Köln, Apotheke der Uniklinik, Köln, Deutschland ID 261 Ten years of successful oncologic quality assurance in certified breast centres in Germany S. Brucker1, M. Wallwiener2, M. Bamberg3, D. Wallwiener1, C. Steering4 University Women’s Hospital, Tübingen, Deutschland University Women’s Hospital, Heidelberg, Deutschland 3 University Medical Centre, Tübingen, Deutschland 4 Participating breast centres, Germany, Deutschland 1 2 Purpose: The German Society of Senology (DGS) and the German Cancer Society (DKG) developed and implemented a multimodal system on the certification of breast centres. Aim was to establish a nationwide cooperation network between breast centres and an independent external analysis institute to allow the proof of existing differences in quality of care and the verifiability of quality assurance by an extensive benchmarking and thus to improve overall quality of care. Methods: An own developed generic XML-based data set was used for data collection from the hospitals and the annual analysis by an independent external benchmarking centre (Westdeutsches Brustcentrum (WBC)). Annual conferences on the screening of the quality indicators attended this process. By this the quality, structures, processes and results should be assured in terms of the diagnosis and treatment of breast cancer. Results: Overall 21 quality indicators (QIs) and sub-quality indicators were developed. Three QIs have been abandoned, since they were stable after a few years. 11 out of 14 QIs with defined DGK/DGS guidelines could fulfill these by more than 90%, 6 were even over-fulfilled. Especially QIs on therapeutic recommendations, very important for the outcome quality, could be crucially improved. Conclusion: Specialization, guideline-concordant procedures as well as certification and recertification of breast centres remain essential to achieve further improvements in quality of breast cancer care and to stabilize and enhance the nationwide provision of high-quality breast cancer care. Thereby national and international harmonization of the efforts has to be pursued. 1 2 Objectives: This project aims at enhancing patient safety by structured and standardized cancer care in a multiprofessional best-practice model. Methods: The module-based model was developed in a multiprofessional quality circle to define ‘best practice’. All care modules include evidence-based recommendations for supportive care, written patient in- Abstracts ID 265 What does it means, when my pathology report says... I. Klempert, M. Dietel Charité Universitätsmedizin Berlin, Institut für Pathologie, Berlin, Deutschland Aims: Patients often have problems understanding the information given in pathology reports. Inspired by Jonathan I. Epstein’s «The FAQ Ini- Oncol Res Treat 2014;37(suppl 1):1–133 103 Inhalt Index tiative Explaining Pathology Reports to Patients» (http://www.adasp.org/ FAQs/faqs.htm), we have started the development of an internetbased free access platform, answering the most frequently asked question in connection with pathology reports in German. Methods: We used the existing contents of the website as a guideline and translated the questions and answers into German. To provide a better orientation for patients, we designed a colour-coded layout. A brown background is used for fundamental knowledge, green stands for «healthy», red for «malignant» and yellow for everything in between. Additionally we added new topics for example «cervix», based on often asked questions by patients in Germany. Results: We have built a free access internet-based platform which provides useful and easy-to-understand information for uncertain patients, but also for physicians and medical students. Additionally it is planed to connect the pathology-platform to other similar platforms of different medical disciplines such as surgery to provide a broader range of information. Conclusions: The free access internet platform for uncertain patients,who want to understand their pathology reports or find out more about pathology is a firm start, but it is necessary to update the website’s content regular and add new topics. We believe that our website offers a helpful and fast assistance for unsettled patients. ID 302 Cancer Survivorship – First experiences of the L.O.T.S.E. – Project of the University Cancer Center Hamburg (UCCH) D. Becker, M. Trepel, C. Bokemeyer, G. Schilling UKE, Universitäres Cancer Center, Hamburg, Deutschland L.O.T.S.E. – Living Without Tumor – Strategies and Education is the name of the newly established Cancer Survivor Program at the UCCH. One part of this huge project is a special consultation, tailored towards cancer survivors. Between February and August 2013 we have seen a total of 75 patients. Eighty-five percent were female, 15% male, with an average age of 62 and 63 years, respectively. The time since first diagnosis of a malignant disease was 13.7 years for the female group and 8.9 years for the male collective. Whereas different hematological and solid tumors were well balanced in the male group, in the female group almost 60% had breast cancer. To learn more about the needs and concerns of these patients, we used a short questionnaire (4-level Likert scale), asking about current psychosocial and physical burdens, as well as about supportive care needs. The gravest psychosocial burdens reported by both genders concerned fears -, which was followed by sorrows in the female group. The highest rated physical burdens the patients reported were pain, fatigue, sleep disorders, polyneuropathic complaints, cognitive deficits, sexual dysfunctions and nausea. The survey revealed that the highest supportive care needs, regardless of gender, was to cope with uncertainty about the future, fears, physical deficits and, a need for better information concerning the course of their disease. The most important concern was the need for a permanent available contact person. Women also rated as high a need for support to better cope with sadness and depression. Our pilot study clearly shows a requirement to establish so called survivorship centers, which fill the current void of unmet care needs for this rapidly growing group of patients. 104 Oncol Res Treat 2014;37(suppl 1):1–133 ID 304 Disabled oncological patients represent the main target group for a sectoral-independent support through the social service – evaluation of a survey at the University Cancer Center Hamburg (UCCH) S. Prange1, M. Frese2, C. Bokemeyer3, G. Schilling3 Universitätsklinikum Hamburg-Eppendorf, Patient Care Management, Department of Social Work, Hamburg, Deutschland 2 Universitätsklinikum Hamburg-Eppendorf, Quality Management, Hamburg, Deutschland 3 Universitätsklinikum Hamburg-Eppendorf, Universitäres Cancer Center Hamburg, Hamburg, Deutschland 1 In a representative survey of cancer patients in an in- and outpatient setting conducted at the UCCH between February and March 2013, a total of 1624 patients were evaluated in respect to their satisfaction with the social service and their further needs. More than 60% of all participants stated to be of working-age. Twenty percent of this subgroup was disabled at the time of the survey. Forty-five percent of these patients never had contact with the social service. In respect to both, physical as well as mental demands of work life in general, the group of disabled patients voiced a low score of their ability to work. Sixty-four percent considered themselves not employable within the coming next two years and two-thirds did not believe to be able at all to resume employment before retirement. Thirty percent planned to apply for early retirement and 20% had already done so before taking part in the survey. The survey revealed that disabled patients were the group with the strongest needs for further social encouragement beyond the support they currently received. Only 36% reported satisfactory support after discharge. In consideration of general demographic developments and regarding the rapidly growing number of cancer survivors, participation in working life is of great importance. Achieving, improving or (re-)establishing the working capacity should be the ultimate ambition for every patient in working-age after successful cancer treatment. As all steps and interventions concerning return to work are usually taken after completion of oncological treatment, social service within a cancer center should be aligned to accompany disabled patients independently of the sectors in an optimal way during their process of vocational integration. ID 343 Central Clinical Cancer Registry of Mecklenburg-West Pomerania – concept and first experiences S. Ulrike, C. Sell, P.H. Lahmann, W. Hoffmann Institut für Community Medicine, Universitätsmedizin Greifswald, Zentrales Klinisches Krebsregister M-V, Greifswald, Deutschland Introduction: The Clinical Cancer Registry Law of Mecklenburg-West Pomerania mandates that all physicians, dentists and pathologists involved in the diagnostic and treatment of cancer patients report information on diagnosis, treatment and disease progress to regional Clinical Cancer Registries. The patients are asked to give informed consent to the reporting and have the right to refuse further processing of their data. The regional Cancer Registries should send the patients’ identifying data to the so called «Treuhandstelle» (trusted third party) to obtain a pseudonym for each cancer patient. The de-identified clinical information and information on reporting physicians and hospitals is sent to the Central Clinical Cancer Registry. The Central Registry will perform a record linkage of the obtained information on each individual patient from the four regional registries and different time periods. Concept and First Real Life Experiences: We will present the concept for implementing the Clinical Cancer Registry Law in Mecklenburg-West Pomerania and report on experiences from the pilot test of the data exchange. Abstracts Inhalt Index The data of the four regional Cancer Registries in Mecklenburg-West Pomerania will be linked and evaluated in the Central Registry to improve the oncological care. Based on the evaluations, tumour-specific expert working groups will give feedback to the physicians and dentists treating cancer patients about the quality of their treatment. Conclusion: The internal process of quality assurance of clinical data on cancer diagnosis, treatment and progression will lead to improved health care for cancer patients in the state of Mecklenburg-West Pomerania. ID 365 «Ohne geht’s nicht»: Evaluation einer Radioonkologischen Pflegeberatungsambulanz F. Papendorf1, M. Mascia2, H. John3, H. Christiansen3, I. Meyenburg-Altwarg2, B. Günther1 MH Hannover, Tumorzentrum, Hannover, Deutschland MH Hannover, Geschäftsführung Pflege, Hannover, Deutschland MH Hannover, Klinik für Strahlentherapie und Spezielle Onkologie, Hannover, Deutschland 1 2 3 Fragestellung: In der Klinik für Strahlentherapie und Spezielle Onkologie der Medizinischen Hochschule Hannover wurde im Jahre 2012 eine Pflegeberatungsambulanz für ambulant bestrahlte Patienten etabliert. Methoden: Im Rahmen einer Evaluation wurden alle Beratungskontakte über einen Zeitraum von 5 Monaten dokumentiert und ausgewertet. Ergebnisse: In einer Zwischenauswertung konnten die Daten von 306 Patienten evaluiert werden. Eine Erstberatung dauerte durchschnittlich 30 Minuten. 31,4% der Patienten hatten das Angebot einer Folgeberatung in Anspruch genommen – 21,9% dieser Patienten nahmen sogar mehr als vier pflegerische Beratungen in Anspruch. Diese Daten zum Beratungsaufwand können im Zusammenhang mit Angaben zu Diagnosen, Bestrahlungsintention, Beschwerdespektrum sowie sozialen Parametern relevante Aussagen liefern. Beispielsweise wurden für 24,6% der Patienten stärkere Beschwerden mit CTC-Grad >=3 dokumentiert, sowie für 23% Schmerzen mit WHO-Grad >=4. Patienten mit Kopf-/Halstumoren oder gynäkologischem Tumor zeigten einen deutlich erhöhten Beratungsbedarf. In einer abschließenden, anonymen Befragung gaben über 80% der Patienten an, dass die Pflegeberatung zu einer Verminderung ihrer seelischen und körperlichen Belastungen beigetragen habe. Fast alle Patienten fanden das Angebot hilfreich und würden es weiterempfehlen. Schlussfolgerungen: Eine differenzierte Evaluation kann dazu beitragen, Patientengruppen mit höherem Beratungsbedarf zu identifizieren, um das Angebot zielgerichtet zu verbessern. Die hohe Zahl der auf freiwilliger Basis durchgeführten Beratungsgespräche, die Häufigkeit auftretender Beschwerden sowie das positive Feedback sollte dazu führen, dieses Angebot in die Routineversorgung zu übernehmen. ID 460 How tumor board recommendations influence patient care: Adherence to clinical decisions made in multidisciplinary teams A. Frangenberg, A. Bernschein, M. Gardizi, M. Meyer, U. Schnittner, R. Hatwig, J. Wolf Universitätsklinikum Köln, Centrum für Integrierte Onkologie, Köln, Deutschland Introduction: The Center for Integrated Oncology (CIO) Cologne Bonn has started to implement a hospital-wide standardized, quality-oriented auditing system to investigate adherence to interdisciplinary tumor board (ITB) recommendations. First results of a pilot project at the University Hospital of Cologne (UHC) are available. Aim: The aim of the first evaluation project was to investigate the implementation of ITB recommendations to patient care in lung cancer (LC) and colorectal cancer (CRC) patients with initial diagnosis in 2011 and to identify causes of non-adherence in terms of a feedback-loop. Abstracts Methods: ITB records were retrospectively collected. Recommendations were compared with actually implemented therapies/diagnostics by studying electronic patient files. Causes of non-adherence were identified. Results: 108 ITB recommendations of 73 LC patients and 96 ITB recommendations of 58 CRC patients were analyzed. The recommendations given by the ITB included for LC patients: 59% active antitumoral therapy (ATT), 18% further diagnostic procedures (DP), 8% ATT and further DP, 6% clinical trials, 5% follow up, 4% other / for CRC patients: 62% ATT, 18% no treatment, 14% ATT and further DP, 5% further DP, 1% other therapies. Regarding overall adherence, 82 of 108 (76%) respectively 82 of 96 (85%) recommendations were completely implemented. Causes of non-adherence: course of disease made treatment-/diagnostic-change necessary (35%), patient’s condition was worse/different than described in the ITB (30%), patient refused the recommendation (25%), non-adherence due to the physician (10%). Conclusion: Decisions made in multidisciplinary teams of experts have a high potential of subsequently being realized and thereby influence patient care. What we do not know, however, is whether the implementation of ITB recommendations in patient care is associated with better clinical outcomes. Appropriate studies should follow. Phase I Studies ID 194 Phase I/II, open label, dose escalating study to investigate safety, tolerability, and preliminary efficacy of the trifunctional anti-HER2/neu x anti-CD3 antibody ertumaxomab in patients with HER2/neu (1+/SISH positive, 2+ and 3+) expressing solid tumors progressing after standard therapy N. Hänse1, M. Jäger2, D. Klunker3, W. Hozaeel1, M.-R. Rafiyan1, D. Sorgius1, H. Lindhofer2,3, S.-E. Al-Batran1 Institut für Klinisch-Onkologische Forschung, Krankenhaus Nordwest, Frankfurt/Main, Deutschland 2 TRION Pharma, München, Deutschland 3 TRION Pharma, Martinsried, Deutschland 1 Purpose: Ertumaxomab (ertu) is a bispecific, trifunctional antibody (ab) targeting HER2/neu, CD3 and the Fcγ-receptors I, IIa, and III forming a tri-cell complex between tumor cell, T cell and accessory cells. Patients (pts) with HER2/neu expressing tumors progressing after standard therapy are treated to investigate safety, tolerability and preliminary efficacy. Methods: In this ongoing investigator driven, non-randomized study, ertu is applied i.v. in 2 cycles. Each cycle consists of 5 ascending doses (10–500 µg) applied weekly within 28 days with a 21 day treatment-free interval. If 2 pts experience a DLT at a given dose level, the MTD will have been exceeded. Results: So far 10 heavily pretreated pts (e.g. breast, rectal, gastric cancer) have been enrolled. 1 (10%) pt had a PR at end of study (EoS), 2 (20%) pts had a SD after the first cycle and a PD at EoS. 6 (60%) pts had a PD after the first cycle and were not further treated. 1 (10%) pt had to be replaced. So far, no therapy related SAE was detected and consequently the MTD is not yet reached. All AEs (e.g. headache, fever, chills) were transient and completely reversible. To date, single doses up to 300 µg were well tolerated in this dose scheme (total dose up to 670 µg per cycle). All pts showed a transient decrease of the CD3+lymphocyte count 24 h after infusion. 3/5 analyzed pts developed an anti tumor immune response demonstrated by the induction of either anti-HER2/neu-abs (3/3) or anti-EpCAM-abs (1/3). Conclusions: In this study, doses up to 300µg can be safely administered in an escalating dose scheme. First signs of efficacy with only mild and reversible AEs warrant further increasing of dosing. The development of anti-HER2/neu and anti-EpCAM abs suggests the promotion of an immunologic memory. Oncol Res Treat 2014;37(suppl 1):1–133 105 Inhalt Index Psychooncology ID 004 Is there an influence of prostate cancer diagnosis on distress and quality of life one year after biopsy? A. Ihrig1, A. Brechtel1, L. Willmann1, H.-C. Friederich1, T. Kuru2, J. Seidenader2, B. Hadaschik2, J. Huber2,3 University Hospital, National Center of Tumor Diseases, Section of Psychooncology, Heidelberg, Deutschland 2 University Hospital Heidelberg, Department of Urology, Heidelberg, Deutschland 3 University Hospital «Carl Gustav Carus», Department of Urology, Dresden, Deutschland 1 Research Question: As a matter of course having cancer is supposed to worsen quality of life (QoL). The aim of our study was to compare QoL and distress in men with or without proven prostate cancer one year after prostate biopsy. Methods: At the University Hospital of Heidelberg 411 men (age 42–85 years) underwent transperineal MRI-fusion biopsy of the prostate to clarify the suspicion of prostate cancer. One year later patients received a follow-up questionnaire via mail covering distress, QoL (EORTC-C30), and the further course of treatment. Results: The response rate was 78% and 295 questionnaires were analyzed. In 103 patients (35%) the biopsy result was benign, and in 192 (65%) prostate cancer was found. The majority decided for active treatment with radical prostatectomy (125) or radiotherapy (18) while 26 chose active surveillance. QoL did not vary between patients with or without the diagnosis of prostate cancer. Counterintuitively, QoL was even slightly superior in the prostate cancer group (EORTC 75 vs 74). Scores in both groups were higher than normal in prostate cancer patients and the general population. The distress thermometer showed the same tendency (3.0 vs 3.2). Only treatment related symptoms and social, role, and sexual functioning showed poorer values in the prostate cancer group. Conclusions: One year after the initial diagnosis of prostate cancer and subsequent treatment QoL is not deteriorated. There might be a psychologic burden in the control group, because cancer suspicion can persist despite a benign biopsy result. Since QoL was even superior to the general population, a paradoxical effect due to the diagnostic measures appears to be likely. ID 043 Electronic Psychooncological Screening of Cancer Patients (ePOS): Diagnostics and Clinical Pathways N. Schäffeler1,2, M. Wickert1,2, D. Wallwiener3,2, S. Zipfel1,2, M. Teufel1,2 Universitätsklinikum Tübingen, Psychosomatische Medizin und Psychotherapie, Tübingen, Deutschland 2 Universitätsklinikum Tübingen, Südwestdeutsches Tumorzentrum (CCC), Tübingen, Deutschland 3 Universitäts-Frauenklinik, Tübingen, Deutschland Questionnaire-2» (PHQ-2), and «EORTC QLQ-C30» have been used. Furthermore we asked the patients to indicate their subjective need. Results: Out of N=245 patients who underwent the routine screening n = 206 have been included in the study. There is no significant difference between computer- and paper-pencil-version in all instruments. The maximal accordance of indications has been 88.5% (HADS depression and PHQ-2), the minimal 36.6% (HADS depression and DT). There have been small correlations between subjective need and screening indications. Discussion: This study first reviews the accordance of 5 recommended screening instruments which is quite low. They seem to focus on different aspects of distress in cancer patients. Nevertheless psychooncological distress screening considering the subjective need seems to be a feasible way to route psychooncological clinical pathways. Patients acceptance of computer-based screening was high. ID 046 Job related behavioral and experiential patterns of employable cancer patients before and after inpatient oncological rehabilitation M. Reuss-Borst, E. Steckelberg Rehaklinik Am Kurpark, Bad Kissingen, Deutschland With an increasingly positive outlook for many tumor diseases as well as general societal developments such as the increase in retirement age and emerging lack of specialized workforce, the occupational reintegration of cancer patients is becoming more important. The AVEM-questionnaire provides an analysis of participants’ motivation to work, their resistance to occupational stressors and their emotional states associated with the working environment. Four coping patterns (cluster-analysis) are distinguished: High risk pattern A (high commitment, excessive demands of oneself), high risk pattern B (‘burnout’, tendency to give up quickly, low ability to deal with problems, no experiences of success), protection pattern S (very low motivation and ambition to work, high ability to distance oneself from problems) as well as the pattern G, which is a healthy, balanced and ambitious behavioral pattern in relation to the working environment. A study with 136 cancer patients (70 female, 66 male) between the ages of 19–60 years was conducted at the beginning and end of an inpatient rehabilitation program which included an intensive psychosocial training. A significant increase of patterns beneficial to health (G and S) and decrease of the high risk patterns (A and B) was found (F(2.6, 353.9) = 25.9, p < 0.001, partial h2 = 0.16). In contrast to males (21.9%), females (11.4%) had much less pattern G but a significantly higher amount of the risk pattern B at the beginning of the rehabilitation (p = 0.002). Working related themes should take a high priority in rehabilitation following a serious illness in order to assist the reintegration into the working environment as well as contribute to a long-term employability. 1 Background: About 1/3 of cancer patients develop distress related mental illnesses requiring treatment. Because of shortening inpatient treatment periods as well as brief personal resources psychooncology has to face the challenge to reliably identify patients in need and offer prompt treatment. Current S3-guidelines recommend a psychooncological routine screening as it is already required for certification of organ cancer centres. Methods: Patients with breast cancer have been randomly assigned to a paper-pencil and a tablet-computer questionnaire. To evaluate the accordance of indication for psychooncological treatment the instruments «Hornheider Screening Instrument» (HSI), «Distress Thermometer» (DT), «Hospital Anxiety and Depression Scale» (HADS), «Patient Health 106 Oncol Res Treat 2014;37(suppl 1):1–133 ID 117 Psychooncology on the internet – chance or risk? A. Winkel Prosper-Hospital Recklinghausen, Klinik für Urologie, Recklinghausen, Deutschland Background: From the medical point of view, the internet is seen with skepticism concerning the professional benefit. Nevertheless, new online-offers for psychooncological counseling arise on a regular basis. Psychooncologic assistance demonstrably lessens fear, depression and stress and helps to establish potent coping strategies. The chances of an internet-based supervision consist of spatial independence, usefulness without taking into consideration social standing, a high level of patient-held self-determination and lower influence of geographically disadvantageous locations, sense of shame and challenging family aspects. Abstracts Inhalt Index Methods: The web pagewww.projekt-koni.deaims at giving the opportunity for mutual exchange to children suffering from cancer as well as to their relatives. Users of the website have the option to ask medical experts questions. In a chat group accompanied by professionals a first contact is arranged, initializing a continuative supervision without allowing inspection to other users. The questions asked to the psychooncologists are inspected and evaluated. Results: The analysis of the results in the frame of the web page directed at patients suffering from cancer indicate the patients’ strong desire for continuative supervision not in real life only, but also on the internet. Approximately 70% of the participants of the mentioned survey expressed a strong wish for a chat supervised by a health professional. Conclusion: The given data strongly suggests an immense usefulness of psychooncologic supervision for selected target groups. A successful online supervision requires: an adequate ability to communicate in written form and effortlessness concerning the handling of the internet. ID 124 Psychooncological burden in tumor patients receiving chemotherapy in an outpatient setting K. Heinig1, A. Lück2, J. Wierecky3, U.-M. Mattner4, V. Schulz5, H.-J. Hurtz6, F. Breuer7, F. Upleger8, M. Holländer9, B. Adhami10, B. Otremba11, C. Kurbacher12, P. Schmidt-Rhode13, P. Herschbach14, R. Reichelt15 SP Gynäkologische Onkologie, Spremberg, Deutschland Zentrum für Urologie & Onkologie, Rostock, Deutschland 3 Gemeinschaftspraxis mit Schwerpunkt Onkologie & Hämatologie, Hamburg, Deutschland 4 Gynäkologische Praxisklinik, Hamburg-Harburg, Deutschland 5 Brustzentrum Kiel Mitte, Kiel, Deutschland 6 Gemeinschaftspraxis & Tagesklinik, Halle/Saale, Deutschland 7 PIOH, Frechen, Deutschland 8 Frauenarztpraxis am Klosterstern, Hamburg, Deutschland 9 Frauenärztliche Gemeinschaftspraxis, Pirmasens, Deutschland 10 Praxis Dr. Adhami, Erkelenz, Deutschland 11 Onkologische Praxis, Oldenburg, Deutschland 12 Fraunärztliche Gemeinschaftspraxis, Bonn, Deutschland 13 Frauenarztpraxis, Hamburg, Deutschland 14 Roman-Herzog Krebszentrum, München, Deutschland 15 Onkotrakt AG, Hamburg, Deutschland 1 2 Background. Cancer of any type is frequently associated with a psychooncological burden for the affected patients. However, the extent of this burden often is not readily assessable, as many patients do not express their need for psychooncological counseling. Materials and Methods. To assess the patients’ burden of disease, a standardized self-rating questionnaire, termed FBK-R10 (Questionnaire for Psycho-Oncological Burden of Cancer Patients, 10 items) was to be answered by each patient at least once throughout the course of therapy. Patients with a minimum of 1 item scoring 5 or 3 items scoring 4 were referred to as most heavily burdened. A multidimensional burden was defined for patients not fulfilling these criteria but with a total score of >14. Results. According to the FBK-R10, 43.7% (n = 652) of the male and 48.0% (n = 1,474) of the female patients suffered from psychooncological distress due to the disease. Merely 10.5% and 18.3% (male vs. female) out of these patients already received or expressed their wish to receive psychooncological support. In contrast, 1 out of 4 patients with psychooncological burden were unsure whether psychooncological support would be beneficial. Furthermore, 2.8% and 12.8% of the male and female patients wanted to get in touch or already were in contact with a patient support group. Conclusions. Due to the high uncertainty concerning the demand for psychooncological support, the identification of burdened patients and timely initiation of appropriate measures are of particular importance. In addition, long-term monitoring of patients is recommended. In this context, the FBK-R10 has proven to be an appropriate instrument to identify the need for psychooncological support in cancer patients. Abstracts ID 137 Sektorenübergreifende Psychosoziale Versorgung (PSV) onkologischer Patienten im Rahmen des §116b SGB V A. von Kries HSK, Dr. Horst Schmidt Kliniken GmbH, Psycho-Onkologischer Dienst (POD), Wiesbaden, Deutschland Die vom Psycho-Onkologischen Dienst (POD) der HSK, Dr. Horst Schmidt Kliniken GmbH Wiesbaden entwickelten praxistauglichen Versorgungsstrukturen und -abläufe und der notwendige Versorgungsumfang werden vorgestellt. Die Indikationsstellung wird beschrieben (Screening, Klinisches Urteil). Die Dokumentation erfolgt edv-gestützt (ICD, OPS, EBM, Leistungsart + Umfang, mit wem und Inhalte. Dies ermöglicht die Analyse der Versorgungswirklichkeit (Statistiken). Kooperationsverträge mit ärztlichen Praxen wurden gestaltet (patientennahe Versorgung, Interdisziplinarität). Die Abrechnung erfolgt dierekt mit der GKV. Fazit: In dem vorgegebenen Rahmen des bisherigen §116b SGB V ist eine PSV umsetzbar. Die im neuen §116b SGB V geforderten Kooperationsverträge wurden schon umgesetzt. Die Auswertung der realen Versorgungszahlen ergab einen durchschnittlichen Versorgungsbedarf von 10–12 Sitzungen á 50 Min pro Patient in 70–80% der Fälle ( N 200 / 2011). Die Angehörigen sind in diesem Rahmen leider nicht eingebunden. Mit dieser PSV konnte die nachstationäre Versorgungslücke geschlossen werden und die Wartezeit für die ambulante Psychotherapie überbrückt werden. Zum Erhalt dieser PSV im neuen §116b SGB V (spezialärztliche Versorgung) wurde mit der Fachgesellschaft PSO/DKG eine Stellungnahme an den G- BA verfasst. ID 175 Dyadic communication and distress in cancer patients and their caregivers H. Sklenarova1, M. Haun1, A. Brechtel1, J. Huber2, M. Thomas3, E. Winkler4, W. Herzog1, M. Hartmann1 Universitätsklinikum Heidelberg, Klinik für Allgemeine Innere Medizin und Psychosomatik, Heidelberg, Deutschland 2 Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Klinik und Poliklinik für Urologie, Dresden, Deutschland 3 Thoraxklinik am Universitätsklinikum Heidelberg, Onkologie Innere Medizin, Heidelberg, Deutschland 4 Nationales Centrum für Tumorerkrankungen Heidelberg, Medizinische Onkologie, Heidelberg, Deutschland 1 Problem: Establishing and maintaining open and coherent communication during the trajectory of a cancer disease constitutes a major challenge for affected families. We examined how cancer patients’ disease-related communication affects their own well-being and that of their relatives. Methods: A cross-sectional survey on N = 189 pairs of cancer patients from mixed cancer type and their closest caregivers was conducted at the National Centre for Tumour Diseases in Heidelberg, Germany. To determine how patients communicate with caregivers or hospital staff, we used the 5-item ‘Communication’ subscale of the Cancer Communication Assessment Tool for Patients and Families (CCAT-PF). In addition, generalized anxiety and depression (GAD-2 and PHQ-2) as well as strain of patients and their relatives were assessed (QSC-R10). Results: Communication about the disease was not associated with depression, neither for caregivers nor for patients. However, significant associations were found for caregiver’s communication score and caregiver’s anxiety (GAD-2: r = .31 p < .001). In contrast, only modest correlation coefficients were found for patient-specific communication scores (GAD-2: r = .18; PHQ-2: r = .09; QSC-R10: r = .30). Conclusion: These results demonstrate that patient’s degree of communication about the disease is related to dyadic affective adjustment, with higher importance for the caregiver than for the patient. Therefore, targeting cancer-specific communication of the patient in psycho-oncological interventions may help to improve emotional well-being not only of patients but especially also of caregivers. Oncol Res Treat 2014;37(suppl 1):1–133 107 Inhalt Index ID 205 How do nurses and physicians perceive age and need oriented education of children of parents with cancer? An explorative study at the university clinic in Munich A. Beraldi1, S. Tari2, M. Erlbeck1, E. Hoster3, W. Hiddemann3, P. Heußner1 Klinikum Großhadern, LMU, Psycho-Onkologie der Med III, München, Deutschland 2 lebensmut e.V., München, Deutschland 3 Klinikum Großhadern, LMU, Med III, München, Deutschland 1 Background: Parents are often uncertain, if and how to talk about their cancer disease to their children. The better all involved professionals are informed about how to deal with children of parents with cancer the better parents can be supported. The clinical experience however shows that professionals too, are often uncertain and ambivalent regarding the children’s involvement in the disease management. The aim of the study was to explore the perception, attitudes and cognitions of the different staff members dealing with children (up to 21 years) of parents with a tumour. The following questions were investigated: - Which knowledge, perceptions, attitudes and cognitions regarding age and need oriented education of children exist? - How do doctors and nurses perceive the contact with children of cancer patients in ordinary day in hospital? Method: We conducted a cross sectional study with 1 time point. Data collection was carried out from december 2012 until march 2013. Population consisted of nurses and physicians of the haematological clinic at the university hospital Großhadern inMunich. A self-designed questionnaire was administrated. Results: 112 nurses and 65 physicians participated in the study. Return rate was of 83%. Preliminary results show that over all attitudes concerning the handling of children of cancer patients correspond to the recommendations of the current literature. However there exists incertitude concerning specific situations (e.g. premorbid distress, age, severity of the illness). 78% of the sample show experiences in and 45% of them agree to be distressed by handling with children of cancer parents. Staff members that are parents are more distressed than participants without children, but would more frequently take the opportunity to talk to children of cancer patients. ID 207 Which questionnaire is most suitable for the detection of depressive disorders in haemato-oncological patients? Comparison between HADS, CES-D and PHQ-9. A. Beraldi1, A. Baklayan1, E. Hoster2, W. Hiddemann2, P. Heußner1 Klinikum Großhadern, LMU, Psycho-Onkologie der Med III, München, Deutschland 2 Klinikum Großhadern, LMU, Med III, München, Deutschland 1 Introduction: Depressive disorders often remain unrecognised in oncological patients (Ford et al., 1994, Mc Donald et al., 1999, Passik et al., 1998, 2000). The aim of this study was to implement a diagnostic tool that is suitable for the identification of depressive disorders in haemato-oncological patients. We therefore compared three questionnaires with a gold standard to define which instrument allows the best to recognise a depressive disorder in haemato-oncological patients. Methods: We conducted a cross-sectional study with consecutive patient accrual. The patients completed a questionnaire about socio-demographic and medical information as well as the Hospital Anxiety and Depression Scale (HADS-D, Zigmond & Snaith, 1983, Herrmann et al., 1995), the 9-item Patient Health Questionnaire (PHQ-9, Löwe et al., 2010) and the Center for Epidemiologic Studies Depression Scale (CES-D) (Radloff, 1977, 1991). The Structured Clinical Interview for DSM-IV (SCID, Wittchen, Zaudig & Fydrich, 1997) served as gold standard. Results: 128 patients were included. The SCID identified 11 cases with a depressive disorder. The CES-D found 13 and the HADS-D found 17 108 Oncol Res Treat 2014;37(suppl 1):1–133 depressive patients. The PHQ-9 found a depression in 8 cases. The sensitivity and specificity were as follows: CES-D: 0.82 / 0.97, HADS-D: 0.82 / 0.93 and PHQ-9: 0.36/ 0.97. The areas under the curve (AUC) of the corresponding ROC-curves were significant (p < .001): CES-D = 0.965, HADS-D = 0.931 and PHQ-9 = 0.868. Conclusion: The HADS-D and the CES-D showed the best sensitivity and similar specificity and AUC-values. The diagnostic power of the HADS-D and the CES-D was superior to the PHQ-9. Both seem to be suitable to identify depressive disorders in haemato-oncological patients. ID 214 How do long-term survivors of breast cancer remember their course of illness 6–7 years after therapy onset? Qualitative analysis of worst and positive experiences of participants of a randomized trial P. Lindberg1, M. Koller2, B. Steinger1, P. Netter3, W. Lorenz1, M. Klinkhammer-Schalke1 Tumorzentrum Regensburg e.V., An-Institut der Universität Regensburg, Regensburg, Deutschland 2 Zentrum für Klinische Studien, Universitätsklinikum Regensburg, Regensburg, Deutschland 3 Universität Gießen, Fachbereich Psychologie, Gießen, Deutschland 1 Background: Survivorship has become an important field in cancer research. But little is known about how breast cancer survivors remember their course of disease. Methods: A follow-up study with survivors, diagnosed with primary breast cancer in 2004–2006, was conducted. 2×100 women were initially part of a randomized trial with a quality of life diagnosis and therapy pathway. More than 6 years after diagnosis, 166 survivors were asked by questionnaire about their worst experience and positive aspects during cancer (multiple answers possible). Qualitative data were categorized by 2 independent raters. Divergent cases were discussed with a third expert. Results: 133 women with mean age of 64.2 years (SD = 10.8) and mean time since surgery of 84.9 months (range 74–96) participated in follow-up (response rate 80%). Qualitative questions were answered by 118 participants. As worst experience regarding breast cancer 38% reported psychological distress (e.g. fear of recurrence), followed by chemotherapy with side-effects (25%), diagnosis (12%), mastectomy (8%), social burden (7%), fact of having cancer (6%) and additional diseases (6%). Positive aspects of illness were reported by 53% of survivors: 50% mentioned new preferences in life (e.g. living more consciously, relaxed), followed by social support (22%), favorable course of illness (15%), support by health care staff (10%) and deep gratitude (9%). Conclusion: Breast cancer survivors remembered psychological distress and chemotherapy as most stressing during illness. Supportive interventions need to focus on these aspects. The fact, that the majority of women also found some benefit in suffering from cancer needs to be communicated to newly diagnosed patients for better coping with disease. ID 223 Effects of socioeconomic status on health-related quality of life in prostate cancer patients A. Ullrich1, H.M. Rath1, U. Otto2, C. Kerschgens3, M. Raida4, C. Hagen-Aukamp5, U. Koch1, C. Bergelt1 Universitätsklinikum Hamburg-Eppendorf, Institut und Poliklinik für Medizinische Psychologie, Hamburg, Deutschland 2 Klinik Quellental, Bad Wildungen, Deutschland 3 Vivantes Rehabilitation, Berlin, Deutschland 4 HELIOS Klinik Bergisch-Land, Wuppertal, Deutschland 5 Niederrhein-Klinik, Korschenbroich, Deutschland 1 Objectives: This study aimed to investigate the effects of socioeconomic status (SES) on health-related quality of life (HRQOL) in prostate cancer patients who took part in a medical rehabilitation program. Abstracts Inhalt Index Methods: In this prospective multicenter study 837 patients completed the quality of life questionnaire EORTC QLQ-C30 (15 domains) and its prostate cancer module PR25 (six domains) at the beginning (t1) and the end (t2) of rehabilitation. To assess SES, we used a composite social class indicator on basis of education, occupation and income (Winkler Index). For pre-post-comparisons of HRQOL in SES groups, ANCOVAS were modelled at t2-outcome with adjustment for differences among groups at t1. Results: Patient’s mean age was 57 years and average time since diagnosis was 2.8 months. Twenty percent of patients were of lower, 53% of middle and 27% of upper social class. After controlling for HRQOL at t1, we found significant main effects of SES on HRQOL in 4 out of 6 functional and 6 out of 9 symptom scales of the QLQ-C30 (p-values <.001–.012), and in all 4 symptom scales of the PR25 (p-values .004– .040). Planned contrasts revealed that compared to lower class membership, upper class membership was accountable for significantly increased HRQOL in 10 domains. In the domains of emotional functioning and financial problems, both middle and upper class patients showed significantly better HRQOL. Conclusions: There were substantial social differences in HRQOL at the end of rehabilitation. Our results indicate HRQOL at t2 to be least favourable for patients of lower social class. To maximize health outcomes for this patient group, special counselling from health care professionals and social workers during rehabilitation might be helping, i.e. on financial issues. eases of the kidney, the testes and the bladder, psychooncology is still treated as a stepchild. Patients suffering from the named maladies encounter tremendous problems coping with the psychological aftermath. Patients undergoing corporal changes due to their therapy (e.g. urostomy, loss of a testicle, scars) face a high risk of suffering mentally. Methods: Patients definitely contracted a cancerous disease and either assigned a surgical therapy or a chemotherapeutic treatment obtain a distress-questionnaire prior to their inpatient-therapy in order to determine their need for psychooncological supervision. According to their requirements, the patients already receive support by a psychooncologist during their first hospital attendance. Following the medical intervention, the patients were asked to answer the questionnaire anew. Results: After two months of treatment, an average of 40 per cent of the patients suffering from the diseases express a wish for psychooncological supervision. 70 per cent of those patients were supported sufficiently by a short intervention of not more than four or less consultations only. Following the psychoogological supervision, all patients declared to feel a decrease concerning their distress. Conclusion: Psychooncology is of high significance not only as additional therapy in breast, bowel and prostate cancer treatment, but also in patients contracted with other cancerous urological diseases. Therefore, further investigation of this topic in future is more than desirable. ID 247 ID 239 Coping with medical information is related to nocebo effects in patients with breast cancer S. Heisig, M. Shedden Mora, Y. Nestoriuc Universität Hamburg, Arbeitsbereich Klinische Psychologie und Psychotherapie, Hamburg, Deutschland Introduction. Patients with cancer differ in coping with medical information. Informational coping styles have been shown to relate to psychological and physiological well-being. Unspecific side effects and the nocebo phenomenon are influenced by psychological variables, but have not been subject of research on informational coping styles. This study aims to show that informational coping styles are associated with anxiety, unspecific side effects and quality of life in patients with breast cancer. Methods: Within a cross-sectional survey, n = 102 women with breast cancer (mean age: 46.7±9.0, mean time since first diagnosis: 2.36±3.0 years), who were currently in medical treatment, were recruited through the internet. Relations between informational coping styles (TMSI-D), anxiety (HADS-D), future perspective, quality of life (EORTC-QLQ), and unspecific side effects (GASE) were analyzed using a path analysis. Results: Information seeking behavior was more frequent than avoiding or distracting from information. Patients were more anxious than healthy women. The path analysis showed that patients who were more anxious reported more unspecific side effects and lower quality of life. Patients who sought information and had a low future perspective were more anxious. Patients who avoided information showed less anxiety. Discussion: Women with breast cancer who seek medical information need special support because they tend to develop unspecific side effects when being anxious. In clinical routine, often nonsufficient treatment information is given to patients with breast cancer, although most patients seek information. Information provision should be adapted to individual needs to prevent anxiousness and nocebo effects. ID 245 Psychooncology in urology A. Winkel, D. Kusche Evaluation of the cancer consultation by the SachsenAnhalt Cancer Society A.-T. Nietzschmann1, S. Weise2, D. Vordermark3, Y. Paelecke-Habermann4 MLU Halle-Wittenberg, Klinik für Strahlentherapie, Halle (Saale), Deutschland 2 Sachsen-Anhaltische Krebsgesellschaft e.V., Halle (Saale), Deutschland 3 MLU Halle-Wittenberg, Universitätsklinik und Poliklinik für Strahlentherapie, Halle (Saale), Deutschland 4 Universität Würzburg, Psychologie, Würzburg, Deutschland 1 Background: The diagnosis cancer results in severe changes for those affected, including disease-related problems and crises. How well patients handle the occuring psychosocial demands also depends on the professional und psychological help available. The Sachsen-Anhalt Cancer Society cares for patients and their families during the individual phases of the disease with various information services and counseling. We aimed to evaluate whether this counselling increases satisfaction with the level of information. Methods: Consulters of the Sachsen-Anhalt Cancer Society in the branch Halle/Saale were interviewed from December 2010 to December 2012 before (t1) and after (t2) a consultation using a questionnaire on awareness about the disease, the treatment, the social and financial impact and coping with every-day life (from «0» = no to «10» = very good). Statistical analysis was effects via t-test, Wilcoxon-test or sign-test for dependent samples. Results: 52 of 85 subjects approached participated in t1 and 42 of 85 in t2 (response rates 61.1% and 49.4%). There was a significant increase in satisfaction with the amount of information, the type of information, the information being helpful so far, level of information about the cancer, the treatment, the social and financial impact, and coping with every-day life. Satisfaction with the comprehensibility of the information showed no significant increase. Summary: Counseling by the Sachsen-Anhalt Cancer Society led to an increase in satisfaction with information on many aspects of cancer. This could contribute to higher self-efficacy and thus to a better management of the disease and higher quality of life. Prosper-Hospital Recklinghausen, Klinik für Urologie, Recklinghausen, Deutschland Background: The value of psychooncological care is beyond controversy and therefore well-established, especially as additional therapy in breast, bowel and prostate cancer treatment. Concerning cancerous dis- Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 109 Inhalt Index ID 308 Communication between nurses and patients in oncology: Discrepancy between expectation and reality – a single center study at a German university hospital N. Birninger, F. Gieseler University Hospital Schleswig-Holstein, Medical Department I, Lübeck, Deutschland Background: The appropriate communication with cancer patients is a key factor in the quality of care. However, the implementation in daily life often reveals a discrepancy between expectations and reality, as well for doctors as for nurses. The intensification of workload combined with consistently high standards is often portrayed as an ethical problem. Yet there are very few studies that could be used as a basis for specific training to improve this calamity and avoid burn-out situations. Here we present first results of a study exploring the problems in communication between doctors, patients and nurses at the UKSH Campus Lübeck. Results: As part of the training for nursing in oncology 15 participants (12 female, 3 male) were interviewed. The percentage of communication within the triangle doctor-patient-nurse and the appraisal of the «actual situation» and a «should be» situation were asked. Actual situation: nursing / patient 70%, physician / nursing 55%, physician / patient 56%. Should be: nursing / patient 89%, physician / nursing 96%, physician / patient 94%. Conclusion: As assessed by the nurses for the actual situation, the low values for physician / nursing communication (55%) and physician / patient communication (56%) are disturbing. The nursing staff often sees himself as a mediator between doctor and patient – a role that they cannot cope in the current work situation. The goal of the ongoing study is an improvement and coordination of education and training for doctors and nurses with subsequent implementation and integration of knowledge into the daily workflow. The goal is to improve the quality of care and to reduce the ethical burden both for the nursing staff, as well as for the doctors. ID 314 Factors that influence posttraumatic growth following breast cancer: A controlled study trial Y. Gottschlik1, K. Brückner1, P. Erz1, L. Graf1, B. Leplow1, C. Thomssen2, U. Berndt2 Martin-Luther-Universität, Psychologie, Halle-Wittenberg, Deutschland Universitätsklinik und Poliklinik für Gynäkologie, Halle (Saale), Deutschland 1 ience» and «positive emotions» were significant predictors of PTG, accounting for 36% and 38% of PTG variance, respectively. Conclusions: Positive emotions and resilience represent important indicators for PTG in breast cancer patients. Supportive psychological treatment strategies related to these two factors might be helpful for breast cancer patients. ID 334 The first results of targeted screening with a Distress Thermometer and initiation of psycho-oncological care of cancer patients. M. Angerer-Shpilenya, A. Heidenreich RWTH Uniklinikum Aachen, Urologie, Aachen, Deutschland Introduction: Tumor disease has not only somatic but also psychological impact on patients with complete change of life dimension. This resonates not only to the patients and their relatives, but also to the therapy. A precise screening helps to determine the stress factor and to initiate an psycho-social care. Patients: 230 patients with various tumors got since 2011 in the Urological Clinic of Aachen Univ. Hospital screening using a Distress Thermometer (DT). 23 of the 40 questions of the DT depend on somatic complaints of patients. The other 17 questions cover the psycho-social problems. Results: 82 of the 230 patients reported to have a low stress level by the tumor. 75 patients showed an average and 73 patients significantly higher stress level. This means that 148 of the 230 patients need a psycho-oncological counseling and possibly even further treatment. The most common entered symptoms were fears, nervousness, fatigue & worry. Depending on the wishes of the patient the psycho-oncological consultation was initiated. Only completing the DT helps the patient to face their problems & worries and makes perhaps the first great step in the perception of the disease. Since 1/2012 a new component was inserted into the discharge reports of the tumor patients. This component contains the recommendation, depending on the result of the DT, to start if necessary the professional psycho-oncological support. That gives the patients a sense of security and a feeling not to fight alone against the disease. Abstract: A targeted screening and an interdisciplinary, together with psycho-oncologists, care to cancer patients support them and their families at all stages of the disease, helps to deal with the new life situation and can possibly also increase the patient’s compliance and the therapeutic response. 2 Objectives: Psychological distress in cancer and its effect on anxiety and depresssion has been assessed among several studies. Only recently researchers have begun to examine positive outcomes such as posttraumatic growth (PTG) in cancer empirically. This study compared self-reported PTG from women with breast cancer with those of an age- and education-matched control group and investigated the impact of personality traits (resilience, optimism, self-efficacy) and positive emotions on PTG in breast cancer survivors. Methods: Participants were 64 breast cancer patients and 61 patients with gynecological, not oncological surgery (control group). Patients completed self-report measures of PTG, resilience, optimism, self-efficacy and positive emotions approximately six months after primary cancer treatment. Sociodemographic and clinical characteristics from participants were recorded. Results: Breast cancer patients showed a pattern of greater PTG compared to controls with respect to «relating to others» (t = 3.03, df = 123, p < .01), «appreciation of life» (t = 3.48, df = 123, p < .01) and «personal strength» (t = 2.54, df = 123, p < .05), respectively. «Resilience» (r = .60, p < .01), «optimism» (r = .36, p < .01), «self-efficacy» (r = .49, p < .01) and «positive emotions» (r = .61, p < .01) were positively correlated with self-reported PTG levels in women with breast cancer. Moreover, «resil- 110 Oncol Res Treat 2014;37(suppl 1):1–133 ID 407 Psychosocial Factors Relating to the Decision Against or in Favour for Prophylactic Surgery K. Wassermann, K. Rhiem, R. Schmutzler Uniklinik Köln, Zentrum f. Familiären Brust- und Eierstockkrebs, Köln, Deutschland BRCA-Mutations are related to an increased risk for breast and ovarian cancer. The breast cancer risk ranges from 30-80% and can be reduced to approx. 3% by prophylactic mastectomy. Therefore women with a BRCA-mutation often deal with the question whether a prophylactic surgery or the intensified surveillance programme is a reasonable solution. The decision does not only affect health, cancer incidence and survival, but is entangled with everyday life. Data for side effects and the long term outcome of a mastectomy are still poor. To elucidate the psychological implications of such a decision we have initiated a research project supported by the BMG (Bundesministerium für Gesundheit). We offer psychological counselling and testing to mutation carriers in addition to the medical non-directive risk consulting. The goal is to support a sustainable decision that considers all aspects of the woman’s individual situation. The women get validated questionnaires to analyse mental state, personality aspects and life events and are asked about their decision process and the support needed. Abstracts Inhalt Index Preliminary Results: From 68 participants about 48% consider prophylactic mastectomy independent from their current health status and independent of their cancer risk situation. 28% of women with breast cancer and 21% of the healthy women reveal increased anxiety scores (HADS >8) before the medical consulting. 68% of the women with an increased HADS-anxiety score tend to pMTX to reduce their fear. After consultation 92% of women feel well informed (n = 39) and 85% feel they can make a well-considered decision. 92% feel very satisfied/ satisfied with the support. 80% recommend other mutation carriers to undergo psychological counselling before making a decision. Quality-of-Life Management ID 028 Demands from patients completed primary treatment of breast or gynaecological cancer G. Sprossmann-Günther1, H.-R. Metelmann2, J. Potenberg1 Ev. Waldkrankenhaus, Oncological Centre, Berlin-Spandau, Deutschland Universität Greifswald, Mund-Kiefer-Gesichtschirurgie, Greifswald, Deutschland 1 2 Introduction: Completing primary treatment patients enter the follow-up period. Technical procedures such as computer tomography, magnetic resonance tomography or tumour markers could not improve the overall survival. Patients often have symptoms caused by treatment or the disease itself and wish to speak about their complaints. Methods: To evaluate the wishes of the patients a specialized questionnaire was developed. Here questions were asked concerning the ideas suffering from breast or gynaecological cancer completed primary treatment. Results: 150 questionnaires were distributed and 120 were returned (80% response rate). 40% of patients got physiotherapy, 25% took advantage of psychology and 17% asked for the pharmacists advice. This support was needed in 55% occasionally and in 20% regularly. 40% spoke not with the pharmacist over the entire prescription. Further points of interest were drug interactions, adverse events and effects of the medicine. 39% of the patients said they would discontinue taking drugs if adverse effects are occurring. The majority could ask all the questions to the physician, but 24% of the patients had not this opportunity. The cause for not asking was lacking of privacy or trust. The majority would like technical procedures such as computer tomography or magnetic resonance tomography and further laboratory tests. Further demands concerned more psychological support. 57% of the patients expect the covering of all expenses by the insurance company, only 21% were ready to participate in the costs. Conclusions: After completion of the primary treatment of breast or gynaecological cancer there is more demand for after-care including technical procedures and laboratory tests. Approximately 40% of patients will discontinue the taking of cancer medicine if adverse events are occurring. Health professionals are requested to offer more structured help in the period of after-care. ID 053 Normative data of the EORTC QLQ-C30 in Germany: A population-based survey Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), in a random sample of the population of Northern Germany. Methods: Population-based survey of a random sample of 10,000 persons aged 16 years or older. The questionnaire addressed lifetime prevalence of common diseases and QoL. Differences in QLQ-C30 scores (scored according to standard procedures) of>10 points between subgroups were considered as clinically relevant. Results: The questionnaire was completed by 47%. Participants’ mean age was 51.7 years (SD: 18.5 years); 57% were females. Missing data across QLQ-C30 scales and items were sparse (min. 0.2%, max. 1.5%). QoL varied by age and sex. Generally, men reported better functioning and fewer symptoms than women. With increasing age function declined and symptoms increased. Most frequently reported symptoms were fatigue, pain, and insomnia (Mean (SD): 31 (26), 28 (31), 28 (33)). Of all 4,684 respondents 27% did not report any disease; most frequently reported were hypertension (36%), hyperlipidemia (26%), and arthritis (30%). Lifetime prevalence of depression was high (women: 16%; men: 11%). Prevalence of at least one disease increased with age (16–19 years: 30% vs. 85+ years: 91%), showing a significant impact on self-reported QoL. Conclusion: Study participants are representative for the German general population with regard to age, sex, and education. A high proportion of participants reported depression which is also mirrored by the fatigue, pain, and insomnia scores that are more than 10 points higher than in the Schwarz and Hinz data (2001). This normative data should be used as reference data when evaluating QoL in German cancer patients. ID 096 Long term effects of the INOP-intervention on physical activity and health following oncological rehabilitation H. Kähnert1, A.-K. Exner1, B. Leibbrand2 Institut für Rehabilitationsforschung, Norderney, Abt. Bad Salzuflen, Bad Salzuflen, Deutschland 2 Salzetalklinik, Abt. Onkologie, Bad Salzuflen, Deutschland 1 Background: A healthier lifestyle including regular physical activity (PA) plays a major role in the rehabilitation of breast cancer patients. Although oncological rehabilitation programs focus on a healthier lifestyle of their patients, long-term success is only modest. The study investigates the effectiveness of the INOP-intervention focusing on volitional strategies to change PA and thus improve health-related quality of life (QL), functional capability in workaday (FCW) as well as occupational (FCO) over 12 months. Methods: Breast cancer patients (n = 386) who underwent a rehabilitation were randomly assigned to the control (CG) or intervention group (IG) and were interviewed at the beginning (t1), 6 (t3) and 12 month (t4) after discharge. While the CG received the usual care, the IG additionally received the INOP-intervention. Analysis of covariance was applied to investigate differences between CG and IG regarding the PA, QL, FCW and FCO. Results: At the 12 month follow-up, level of PA in the IG was on average 120 min./week higher than in the CG (p < 0.05, d = 0.63). Moreover, from the primarily inactive participants 92% of the IG were exercising at t4, but only 60% of the CG (p < 0.001, d = 0.37). During the 12 months after clinic discharge, IG patients were also considerably less limited in their FCW (p < 0.001, d = 0.44) and FCO (p < 0.05, d = 0.27) than CG patients. Furthermore, the QL is noticeably more increased in IG than CG patients (p < 0.001, d = 0.53). Conclusion: The study provides evidence that INOP is a useful intervention to enhance physical activity, quality of life and thus functional capability of breast cancer patients at least 12 months after discharge. The INOP-intervention is brief and can be implemented in a clinical setting and post-rehabilitation support. A. Waldmann1, D. Schubert1, A. Katalinic1,2 Universität zu Lübeck, Institut für Sozialmedizin und Epidemiologie, Lübeck, Deutschland 2 Universität zu Lübeck, Institut für Krebsepidemiologie e.V., Lübeck, Deutschland 1 Aims: Generating up-to-date normative data for quality of life (QoL), as measured by the European Organization for Research and Treatment of Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 111 Inhalt Index ID 172 Quality of Patients’ Information – What Kind of Information Is Looked for by Cancer Patients? M. Liefold, G. Dathe, J. Wilhelm, T. Feustel, B. Wincheringer, R. Grohs, M. Theuer, D. Wagner, E. Beck Fachhochschule Brandenburg, Fachbereich Informatik und Medien, Brandenburg, Deutschland Introduction: Shared decision making is one of the central demands of patients’ representatives. However, before decisions can be made, patients need all relevant information concerning the subjects under discussion. Besides the fact that information nowadays is readily available via the internet, it is difficult for the average person to judge relevance, validity and reliability of the provided information. Moreover it is still unclear what kind of information is searched for by patients and to what extend and granularity this information should be provided. Methods: In order to get first impressions on patients’ needs regarding information on malignant diseases, we asked the members of a local selfhelp sports group to formulate as many queries as possible dealing with all their disease related concerns. We then choose a limited number of these questions, discussed them within our group, searched for relevant information available on the internet and prepared then short presentations. Finally these presentations were held and discussed with the members of the self-help group. Results: More than two thirds of the patients questions (34/46) where dealing with organizational or rather common «every day» problems. Only 12 questions were related to disease specific topics (e.g. kind of treatment, complementary methods). Most of the questions however, where formulated in rather global forms and where thus not really answerable, which was one of the major topics discussed with the patients. Granularity of the information should not be to detailed, no tables, graphs, statistics or any technical terms are to be used. Conclusion: In order to improve quality of information portals patients should be invited to be members of the allocation teams. ID 211 Novel care conception for cancer patients in Germany ID 269 eHealth in modern patient-caregiver-communication: Use of modern media in breast cancer patients and their physicians R. Würstlein1,2, T. Kirkovits1, C. Drewes1, I. Bauerfeind3, U. Goldmann-Posch4, D. Schiltz1, N. Harbeck1,2, T. Schinköthe1 Klinikum der Universität München, Brustzentrum, München, Deutschland Klinikum der Universität München, CCC of LMU, München, Deutschland 3 Tumorzentrum München, Projektgruppe Mammakarzinom, München, Deutschland 4 mamazone, Augsburg, Deutschland 1 2 Introduction:Implementation of oral and s.c. medications for breast cancer (BC) led to new challenges for patients and physicians regarding optimal and continuous communication. New ways of communication, including eHealth and web-based programs, may thus be useful. The objective of our investigation is to evaluate actual use of internet and modern media (e.g. smartphones) in BC patients and their healthcare professionals. Methods: We designed questionnaires for patients and physicians and analyze frequency and behavior of use of internet and modern media, available equipment and opinions on future eHealth tools. Patients were asked to answer the questionnaire before consultations and at a BC patient conference (mamazone). Health care specialists were asked to complete the questionnaire at several regional BC meetings. Results: In an interim analysis 80% patients had been diagnosed with BC at time of investigation, 29% with advanced stage. 89% of patients use internet for health related issues. Even above age 70, more than the half use internet for health related purposes. Among doctors, 98% use internet for medical issues. Implementation of potential future eHealth tools would be highly accepted in both groups (f.e. registration of side effects via electronic devices: patients 41.1%; physicians 71.2%). Discussion: This survey shows a high rate of internet and modern media use among BC physicians and their patients. In both groups, the additional possibility to regularly record side effects and manage them without face to face meetings is favored. The routine use of modern media and trust in new interactive communication tools may enable improvement in doctor-patient-relationship, compliance and adherence in oncology. T. Klose, M. Putzker Sonnenschein Apotheke Koblenz, Koblenz, Deutschland Subject: Diagnosis, therapy and monitoring of outpatients in Germany usually are performed at different locations with probably elevated waiting periods each. Small cancer practices may lack actual scientific knowledge. Supplying pharmacies do not employ a «Qualified Person» according to § 15 of the German Drug Act in order to release medically prescribed but non-approved effective components. Methods: Five oncologists with high university reputation co-operate in a day clinic in Koblenz/Rhineland-Palatinate (~ 3,000 patients per year; > 30 types of cancer), added by a scientific investigation unit. The health care center further includes a radiologic institute and a public pharmacy certified to ISO 9001:2008 with a GMP-cleanroom at its disposal for the production of cytostatic drugs and two «Qualified Persons» available. Results: The patient profits from this comprehensive care conception. Morning arrival via cab with outward and return journey being refunded by the health insurance is followed by a medical check-up including a hemogram and if necessary a radiological examination. Based upon these data, the oncologist lays down the actual treatment. The pharmacy immediately produces the sterile solution (>10,000 individual formulations anually) reaching the clinic by an in-house material lift. Venous infusion of the patient is directly started and he is allowed to leave the clinic after a few hours highly facilitating his independence and mobilty. Conclusions: The novel care conception offers minimum stress for the affected person, highest medico-pharmaceutical level of treatment, and maximum cost saving for the health insurance company. 112 Oncol Res Treat 2014;37(suppl 1):1–133 ID 306 Younger cancer patients are much more affected in quality of life than older patients L. Distel1, W. Losensky1, S. Weiss1, R. Fietkau1, M. Weiling1 1 Strahlenklinik, Strahlenbiologie, Erlangen, Deutschland Objective: Maintaining the quality of life during and after a cancer therapy is of great importance for a successful therapy outcome. The aim of the study was to evaluate whether there are age related differences in a cancer patients collective compared to the general German population*? Methods: The study collective consists of 257 recruited patients and lead to a total of 793 data sets. 44% of patients suffered from colorectal cancer and 23% of patients from head and neck cancer. All patients were treated with concurrent radiochemotherapy. The median age was 62 years with a range of 24 to 86 years. Patients were classified into divisions of 10 years age. The EORTC QLQ-C30 questionnaire was used and functional and symptom scores were calculated. On average, each patient filled out 3.1 questionnaires. Results: In the general German population functional scores decrease with age and symptom scores increase with age. In contrary in the cancer patients collective the functional score somewhat increase and the symptoms scores slightly decrease with age. Though in patients younger than 60 years there is a distinct difference between the German population and cancer patients, while in patients older than 70 years there is only a marginal difference. Conclusion: Younger patients are much more affected in all quality of life domains by a cancer therapy treatment than older patients. Older pa- Abstracts Inhalt Index ID 396 Cortical activity during exercise in B-Non-Hotgkinlymphoma (B-NHL) patients and healthy controls T. Hülsdünker1, A. Mierau1, F. Baumann2, T. Elter3, M. Hallek3, W. Bloch2, P. Zimmer2 Deutsche Sporthochschule Köln, Institut für Bewegungs- und Neurowissenschaft, Köln, Deutschland 2 Deutsche Sporthochschule Köln, Institut für Kreislaufforschung und Sportmedizin, Abteilung für molekulare und zelluläre Sportmedizin, Köln, Deutschland 3 Universitätsklinikum Köln, Med. Klinik 1, Köln, Deutschland ID 401 Quality of life in Lynch Syndrome patients with colon cancer is not impaired after extended (prophylactic) colonic resection C. Schneider1, R. Schneider2, G. Möslein1 1 2 HELIOS St. Josefs-Hospital, Chirurgie, Bochum, Deutschland Universitätsklinik Marburg, Chirurgie, Marburg, Deutschland Objectives: Lynch Syndrome (LS) is associated with a substantial risk for metachronous cancers following segmental oncologic resection of the initial cancer. The aim of this study was to compare the quality of life (QoL) after segmental or extended colonic resection in patients with a hereditary predisposition to colorectal cancer. Design: QoL was assessed with EORTC QLQ-C30 and CR38 questionnaires. Patients were recruited from the German HNPCC Consortium, the New Zealand Familial Gastrointestinal Cancer Registry and the database ofthe Hôpital Saint Antoine in Pariswith the following inclusion criteria:Colonic resection for colon cancer; hereditary cancer according to Amsterdam II Criteria and/or mismatchrepair deficient tumour;age at operation < 60y; surgery >6 months before study; no ostomy. Results: 51% of questionnaires were returned, 587 eligible (503 segmental, 84 extended). Patients with limited resections were significantly younger at the time of surgery, whereas age at the time of survey was comparable. Patients with subtotal colectomy, reporting more frequent nocturnal bowel movements, demonstrated an improved outcome regarding fatigue/weakness, role functioning and constipation, but after adjustment for multiple testing, there was no significant difference. Conclusion: This large, international study has demonstrated that when compared with segmental resections, extended colonic resection is associated with an equivalent QoL. In view of the risk reduction for metachronous cancers, patients with LS should undergo more extensive surgery at the time of their primary colon cancer. This finding highlights the importance of preoperative diagnosis in patients with hereditary predisposition to cancer. n Aim: Does Quality of life assessment prior to the initial transarterial chemoembolisation using the HCC-specific questionaire validated by the EORTC help to improve patient selection for repetitive interventions? Methods: Ouality of life (Qol) -assessment was performed in 66 patients (14female/52male, median age: 66.4 years) undergoing initial transarterial chemoembolisation (TACE) for treatment of intermediate-stage hepatocellular carcinoma (HCC). Doxorubicin and cisplatin or mitomycin were used as chemotherapeutic agents in combination with lipiodol. Qol evaluation was performed before (66 patients: 100%) and 2 weeks after TACE (52 patients: 78.8%) as well as prior to the second TACE (26 patients: 39.4%). The combined questionnaire consists of 48 questions, divided in 24 functional/symptom scales and single items. Global health status scores at the individual timepoints were correlated to imaging parameters: 1) Sum of target lesion diameters 2) enhancement pattern of the largest target lesion 3) RECIST tumor response. Results: There was a significant correlation between Patients presenting with large target lesion (TL) diameter (TL1 + TL2 > 6.1 cm) before 1st TACE and low global health status one day before 2nd TACE (p < 0,01). Enhancement pattern did also show a significant correlation to low global health status before second TACE (p = 0,021). Tumor response (RECIST 1.1): 7.9% partial response, 84.6% stable disease, 11.5% progressive disease. RECIST tumor response did not show a significant correlation to global health status. Conclusion: Large Target Lesions as well as Target Lesions showing heterogeneous enhancement pattern prior to the initial TACE do show significant correlation to a low global health status one day before 2nd TACE. These findings can help to decide about the continuation of TACE treatment. ge Medizinische Hochschule Hannover, Institut für Diagnostische und Interventionelle Radiologie, Hannover, Deutschland 2 Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Hannover, Deutschland 1 zo D.B. Hasdemir1, M.W. Nordlohne1, H. Rosenthal1, N. Schweitzer2, A. Vogel2, F. Wacker1, B.C. Meyer1, T. Rodt1 ge Pre-treatment imaging parameters predicting low quality of life after initial transarterial chemoembolisation in treatment of intermediate-stage hepatocellular carcinoma ck ID 309 rü *Schwarz R, Hinz A. Eur J Cancer 2001 37 1345. locations during eyes-closed resting state as well as at the beginning, half way through and at the end of exercise. Spectral power in the theta, alpha, beta and gamma frequency bands was calculated in the frontal, central, parietal and occipital regions of the cortex. T-test for unpaired samples indicates lower occipital alpha power in the B-NHL patients compared to controls during rest with eyes closed. Further, repeated measures analysis of variance revealed a group x time interaction for theta and alpha power during exercise. Both, theta and alpha power increased from the beginning to the end of exercise in N-BHL patients while there were no effects in the control group. The results indicate a decreased arousal level in the course of exercise in N-BHL patients represented by increased alpha and theta power values. Increases in these frequency bands have further been proposed to be related to improved cognitive performance. Therefore, our results suggest that physical activity might be beneficial for oncologic patients as reflected by the positive effects on cortical activity. zu tients have probably developed strategies in their course of life to cope better with the side effects and problems of a cancer therapy. 1 Cancer-related fatigue (CRF) is accompanied by reduced cognitive abilities and altered cortical activity suggesting an effect on the central nervous system. From many studies it is known that acute physical exercise induces changes in the cortical state and positively affects cognitive performance even though, exclusively tested on healthy subjects. Therefore, the aim of the present study was to investigate cortical activity during exercise in B-Non-Hodgkin-lymphoma (B-NHL) patients and age-matched healthy controls. 16 subjects (9 B-NHL patients, 7 controls) exercised for 25min on a cycle ergometer. Electroencephalography (EEG) was recorded from 16 scalp Abstracts ID 434 Physical Activity Navigator – successful example for motivation in physical activity against cancer. 3-yearsresults of a project with exercise programs with in- and outpatients from acute therapy to aftercare during the chemotherapy and radiotherapy S. Michelis1, M. Wöge2, F. Merten2, D. Nürnberg1 Onkologischer Schwerpunkt Brandenburg NW e.V., Neuruppin, Deutschland 2 OGD GmbH, Reha-Zentrum, Neuruppin, Deutschland 1 Presentation of a patient-centred care Project – called Physical Activity Navigator. Hereby, are to describe the relevant interfaces for this care pathway, show the stage specific methodology, and introduce the stake- Oncol Res Treat 2014;37(suppl 1):1–133 113 Inhalt Index holders. The foundation, «Leben mit Krebs» has enabled us to appoint a sports therapist designing activity programs and coordinating physical activities patients with cancer diagnosis. The Physical Activity Navigator supports patients (1) in the Hospital, (2) in rehabilitation centre, and (3) in special outpatient. We have established a personalized sports therapy, offering patients in our cancer wards to practice sports during primary treatment. The benefits of positive physical experience through individualized motor activity are part of treatment concept during on-going inpatient chemotherapy or radiotherapy. Following the hospitalization, we offer established outpatient exercise schemes for endurance training, adapted strength training, or gymnastics. These motor activity offers are recommended by our ambulatory cancer healthcare centre. The rehabilitation Centre with its specific possibilities for physical activity and sports links up all parts of the program, from acute therapy to aftercare. In addition, we encourage individual medical fitness training, advise recreational sports activities in sport clubs, and introduce patients to an active daily living. Results: We started the project Physical Activity Navigator in January 2011. A total of 280 in- and outpatients have been supervised in our program up to date. Currently, 30 outpatients per week are participating in the special motor activity offers. We succeeded to integrate patients in our care project, starting at the time of cancer diagnosis. This early intervention is the key to success of our physical activity pathway for cancer patients. Radiation Biology ID 021 Individual differences in chromosomal aberrations in a rectum cancer collective and cancer patients with assumed increased radiosensitivity A. Ellmann, B. Soppa, M. Haderlein, R. Fietkau, L. Distel Strahlenklinik der Universität Erlangen-Nürnberg, Erlangen, Deutschland Objective: The knowledge of patients’ individual radiosensitivity could be the key to a more individual and specific therapy for cancer patients. Side effects could be avoided from the healthy tissue and the tumour still could be controlled. The aim was to identify sensitive individuals among our collective. Materials and Methods: Peripheral blood samples from 66 individuals were analysed. The 57 rectum carcinoma patients got into this survey in the context of a rectum carcinoma study, the other 9 patients got in due to more intense side effects after a radiotherapeutic treatment. The blood samples were parted, one half got irradiated with 2.0 Gy, the other half served as unirradiated control. The chromosomes 1, 2 and 4 were painted with the three colour FISH-painting technique to analyse chromosomal aberations. These events were quantified as breaks per metaphase. Results: The 66 individuals had a mean of 0.455 breaks per metaphase. Gaussian fits were performed and breaks per metaphase in both collectives were found to be normally distributed. The 2.0 Gy sample corrected for the 0 Gy control data showed that 5 individuals are above double standard deviation range (0.716), 2 of them even above triple standard deviation range (0.857). Discussion: In this collective are 3% patients with a distinct increased radiosensitivity and about 7% with increased radiosensitivity. Adopting that malignant tissue has a corresponding sensitivity to radiation as normal tissue, single and total doses of radiation therapy should be adapted to patient´s individual. Especially individuals with a low radiosensitivity could benefit from a dose escalation and an increased tumour control rate. 114 Oncol Res Treat 2014;37(suppl 1):1–133 ID 087 Flattening-filter-free intensity modulated breath-hold image-guided SABR (Stereotactic ABlative Radiotherapy) can be applied in a 15-min treatment slot J. Boda-Heggemann1, S. Mai1, J. Fleckenstein1, K. Siebenlist1, A. Simeonova1, M. Ehmann1, V. Steil1, F. Wenz1, F. Lohr1, F. Stieler1 Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie, Mannheim, Deutschland 1 Introduction: Hypofractionated image-guided stereotactic ablative radiotherapy (igSABR) in breath-hold is an effective non-invasive treatment modality for stage I-II NSCLC and lung metastases. In the past, daily fraction duration with IMRT was >> 15 min. Flattening filters have been used to compensate for variation in the integral fluence and were integral parts of linear accelerators in the last decades. FFF (flattening-filter-free) mode reduces treatment duration by increasing dose rate. We analyzed the impact on treatment slot time in the first cohort treated with FFF breathhold igSABR. Patients/ Methods: 9 PTVs of 8 patients have been treated with FFF beams on a Versa HD linear accelerator (Elekta) with 60Gy in 12 or 5 Gy single fraction doses in breath-hold with Active Breathing Coordinator (ABC®, Elekta). IMRT plans for dMLC or VMAT delivery were generated with Monaco 3.3 (Elekta). Non-FFF breath-hold igSABR treatment times were evaluated in a subgroup of 8 patients of previously published patient populations. Total on-couch time, net treatment times and net beam-on times were measured. Results: One 12 Gy fraction of a non-FFF hypofractionated breath-hold lung SABR had a fraction duration of 27±5 min. On-couch time for the first fraction of FFF igSABR (including image guidance) was 15,77±8,58 min. Net treatment time (including beam-off free breathing phases) was 7.3±4.8 min. Net beam on time was 4,56±0,50 min (dMLC) and 3,15±1,71 min (VMAT). Conclusion: For lung SABR with VMAT or an 8 field IMRT using a breath hold technique, FFF reduces beam-on time sufficiently to enable each beam/VMAT sector to be delivered in a single breath hold, greatly improving the duty cycle and consequently halving overall fraction time from ~30 min to ~15 min, making this method available for more patients. ID 192 Reduced side effects by proton microchannel irradiation – study in a human skin model T.E. Schmid1, S. Girst2, O. Zlobinskaya1, C. Greubel2, J. Seel2, C. Siebenwirth2, C. Marx1, J. Wilkens1, G. Multhoff1, G. Dollinger2 Klinikum Rechts der Isar, TU München, Strahlentherapie und radiologische Onkologie, München, Deutschland 2 Universität der Bundeswehr München, Neubiberg, Deutschland 1 We propose a novel strategy to reduce the known side effects of radiotherapy by using proton microchannel irradiation. In order to prove the hypothesis of reduced side effects in normal tissue through microchannel proton irradiation, we report on a comparative study of microchannel and broad beam irradiation of artificial skin tissue. 20 MeV protons were administered to human skin models (EpidermFTTM) in 10 to 180 µm wide irradiation channels on a quadratic raster with distances of 500 to 1800 µm between each channel applying an average dose of 2 Gy. For comparison, other samples were irradiated homogeneously by protons at the same average dose. Widened channels as in deeper lying tissues were investigated in skin tissues as well. Normal tissue viability was significantly enhanced after microchannel proton irradiation compared to homogenous irradiation (80 vs. 40% compared to unirradiated control. Levels of inflammatory markers, such as cytokines and chemokines, were significantly lower in the supernatant after microchannel irradiation than after homogeneous irradiation. Furthermore, genetic damage as determined by the measurement of micronuclei in keratinocytes was also significantly reduced after microchannel irradiation compared to homogeneous irra- Abstracts Inhalt Index diation (0.015–0.030 micronuclei per divided cell for microchannel vs. 0.070 ± 0.007 MN/divided cell for homogeneous irradiation). Our data show that proton microchannel irradiation maintains cell viability while significantly reducing inflammatory responses and genetic damage compared to homogenous irradiation, and thus might improve normal tissue protection after radiation therapy. Supported by the DFG Cluster of Excellence: Munich-Centre for Advanced Photonics. ID 397 The motility of irradiated glioblastoma cells is modulated by the axon-guidance system Slit2/ROBO1 P. Nguemgo-Kouam1, I. Pisarenko1, B. Priesch-Grzeszkowiak1, H. Bühler1, I. Adamietz2 Universitätsklinikum Marienhospital, Institut für Molekulare Onkologie, Strahlenbiologie und Experimentelle Strahlentherapie, Herne, Deutschland 2 Universitätsklinikum Marienhospital, Klinik für Strahlentherapie und Radio-Onkologie, Herne, Deutschland 1 Background: Glioblastoma is a highly invasive brain tumor with poor prognosis. Recent data indicate that irradiation might enhance the motility of glioblastoma cells and thereby promote local recurrences. In this study we investigated whether or not slit2/ROBO1 signaling has an impact on cellular migration following radio-therapy. Methods: The experiments were performed on the human glioma cell lines U87 and U373. Slit2 or ROBO1 over-expressing clones were established by transfection of the respective gene. The cells were irradiated with 0, 0.5, 2, or 8 Gy photons. Expression of slit2 and ROBO1 was determined by western blotting and qRT-PCR. The motility parameters velocity, accumulated, and Euclidean distance were obtained by time-laps videography. Results: Wild type expression of slit2 was moderate in U373 and very low in U87 cells. In contrast ROBO1 was high in U87 and low in U373 cells. The expression was markedly affected by irradiation, however differently in both cell lines. The migration of both cell lines was enhanced after irradiation, particularly after low doses. After transfection the migration was reduced by 50% for all clones. Similar to the wild type cells irradiation enhanced the motility of both U373 clones slightly. In contrast the motility of the U87 clones was decreased significantly after irradiation. Conclusions: Slit2 and ROBO1 are differently expressed in glioblastoma cells and can be influenced by irradiation. Slit2/ROBO1 are involved in the cellular motility as shown by the transfected clones. Irradiation in the range of a fractionated radio therapy enhances the migration of glioblastoma cells, however strengthened Slit2/ROBO1 signaling might counteract this potentially malignant side effect. Sarcoma ID 005 Outcome after local recurrence of soft tissue sarcoma: A retrospective analysis of factors predictive of survival in 135 patients with local recurrent soft tissue sarcoma A. Daigeler1, I. Zmarsly1, O. Goertz1, T. Hirsch1, H.-U. Steinau1, M. Lehnhardt1, K. Harati1 Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil Bochum, Klinik für Plastische Chirurgie und Schwerbrandverletzte, Handchirurgiezentrum, Operatives Referenzzentrum für Gliedmaßentumore, Bochum, Deutschland 1 Aim: The aim of this study was to identify prognostic indicators of survival in patients with locally recurring soft tissue sarcoma (STS) through a long-term follow-up at our institution. Patients und Methods: We retrospectively assessed the relationship between post-recurrence survival (PRS) and factors related to demography, disease and treatment in 135 patients who had experienced local recur- Abstracts rence after surgical treatment. The median follow-up time after initial recurrence was 12.3 years (95% confidence interval [CI]: 10.4–14.2). Results: The 5-year estimate of the PRS rate was 53.1% (95% CI: 44.3– 61.2) for the entire series. In a univariate analysis, initial recurrence, which occurred ≥2 years from primary diagnosis, was found to be a predictor of a better outcome (5-year PRS of 68.1%; 95% CI: 53.3–79.1) compared with earlier recurrence (5-year PRS of 45.2%; 95% CI: 34.4– 55.5) (P=0.042). Synovial sarcoma and fibrosarcoma were associated with a significantly worse post-recurrence outcome compared with other STS histotypes. Patients with negative margins after the final surgery experienced improved survival compared with patients with positive margins (5-year survival: 46.7% [35.2–57.5] vs. 35.5% [23.4–47.8]; P=0.01). In a multivariate analysis, the significant prognostic factors for PRS were histologic grade, tumour site, the time to initial recurrence, the number of recurrences and the surgical margin status attained at the last resection. Schlussfolgerungen: Complete surgical resection with microscopically clear margins is desirable in patients with local recurrent STS. However, when the goal of achieving clear surgical margins would require major functional impairment of the extremity, a radical surgical approach should be weighed for the patient in each case. ID 062 A non-comparative phase II study of dose intensive chemotherapy with doxorubicin and ifosfamide followed by high dose ICE consolidation with PBSCT in nonresectable, high grade, adult type soft tissue sarcomas (STS) J. Hartmann1, M. Horger2, T. Kluba3, A. Königsrainer4, P. de Zwart5, C. Hann von Weyhern6, F. Eckert7, W. Budach8, C. Bokemeyer9 Universitätsklinikum Schleswig-Holstein, Internistische Onkologie, Kiel, Deutschland 2 Universitätsklinikum Tübingen, Diagnostische und Interventionelle Radiologie, Tübingen, Deutschland 3 Universitätsklinikum Tübingen, Orthopädie, Tübingen, Deutschland 4 Universitätsklinikum Tübingen, Allgemeine,Viszeral- und Transplantationschirurgie, Tübingen, Deutschland 5 BG Klinik, Unfall- und Wiederherstellungschirurgie, Tübingen, Deutschland 6 Klinikum München, Pathologie, München, Deutschland 7 Universitätsklinikum Tübingen, Radioonkologie, Tübingen, Deutschland 8 Universitätsklinikum Düsseldorf, Strahlentherapie und Radioonkologie, Düsseldorf, Deutschland 9 9Universitätsklinikum Hamburg-Eppendorf, Onkologie, Hämatologie mit der Sektion Pneumologie, Hamburg, Deutschland 1 Background: To determine the feasibility and effectivity of dose intensive induction chemotherapy (CTh) in patients (pts) with STS. Methods: Treatment consisted of at least 2 cycles of DOX IFO. In responding and stable pts, this was followed by one cycle of HD-ICE), ETO 500 mg/m2, Carbo 500 mg/m2 and IFO 4 g/m2 (days –4 to –2, PBSC support on day 0. Pts with a single distant metastasis deemed resectable were allowed. Results: 30 out of 631 consecutive pts, age 46 years (range, 21–62), were included, 5 of whom had a single lung (4) or liver (1) metastasis. 29 pts completed at least 2 cycles of DOX/IFO. While 16 pts (55%) remained stable, 7 pts (24%) showed a PR, 1 pt (3%) a CR, and 5 pts (17%) progressed. HD-ICE was withheld because of PD in 5 pts, neurotoxicity in 6, insufficient PBSC mobilization, CR and refusal in 1 pt each. 16 pts received HD-ICE, which was associated with non-hematological grade III toxicity including emesis, mucositis, fever, neurotoxicity, and transaminase level elevation. Two pts attained a PR after HD-ICE. 24 of 30 (80%) pts underwent surgery, with complete resections in 19 pts (63% of all pts, 79% of the operated subgroup); however, 2 of whom required amputation. After a follow up period of 50 mos in surviving pts (range, 26–120) 5-yr DFS and OS rates were 39 and 48%, respectively. Pts with shrinking STS becoming resectable after pretreatment had a markedly improved DFS (median, 50 vs. 3.5 mos; HR: 7.2 (95% CI, 1.5–34.3), p < 0.01) and survival (median, 73 vs. 9 mos; HR: 9.1 (95% CI 1.8–45.6), p < 0.007). Oncol Res Treat 2014;37(suppl 1):1–133 115 Inhalt Index Conclusions: Induction chemotherapy plus consolidation HD-ICE is generally feasible, but is associated with significant neurotoxicity. The advantage of HD-ICE over conventional dose CTh plus EBRT in non-resectable disease remains unproven. ID 282 Population-based survival of adult patients with bone cancer and soft tissue sarcoma – a comparison between Germany and the United States B. Holleczek1, L. Jansen2, C. Hamann3, A. Eberle4, K. Emrich5, A. Gondos2, A. Katalinic6, H. Brenner2 Saarland Cancer Registry, Saarbrücken, Deutschland Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Deutschland 3 Technical University Medical Center, Department of Orthopedics, Dresden, Deutschland 4 Cancer Registry of Bremen, Bremen, Deutschland 5 Cancer Registry of Rhineland-Palatinate, Mainz, Deutschland 6 Cancer Registry of Schleswig-Holstein, Lübeck, Deutschland 1 2 Background: Up-to-now, population-based survival studies of rare cancers from Germany were hampered by insufficient national coverage by cancer registries. Using data from 11 German regions and US data from the SEER program, this study aims at providing a detailed comparison of survival of adult patients with bone cancer (BC) and soft and connective tissue sarcoma (SCTS) in Germany and the US. Methods: The analysis included 5526 patients with BC (ICD-10: C40+C41) and 18,107 patients with SCTS (ICD-10: C47 and C49) over 15 years of age at diagnosis with diagnosis and follow-up between 1997 and 2006 from both countries. Five-year relative survival (RS) was derived overall and according to age, sex, tumor site and morphology by period analysis. Results: Overall age standardized 5-year RS of patients with BC and SCTS was 54% and 60% in Germany and 63% and 66% in the US, respectively. Survival of sarcoma patients generally decreased with age. Higher RS was observed for tumors of the limbs and the head region, but survival was substantially lower for BC of the pelvic bones, and SCTS of the trunk. BC patients with chondrosarcoma had highest survival, and those with Ewing sarcoma had lowest survival. Among SCTS patients, those with liposarcoma had highest survival, whereas survival was lowest for those with rhabdomyosarcoma. For both BC and SCTS, analyses consistently revealed inferior survival of German patients. Conclusions: Based on two large datasets, this population-based study provided detailed survival data for patients with rare cancers from Germany and the US for the first time. It further revealed consistently lower survival of these patients in Germany compared to the US that should be further investigated. ID 297 Hyperthermia combined with Trabectedin prolongs G2 cell cycle arrest and reduces cellular survival in human tumor cells D. Harnicek1, E. Kampmann2, A. Tanović3, A.S. Cardoso Martins1, Y. Guo4, E. Gallmeier4, R. Kanaar4,5, K. Lauber6, T. Knösel7, L. Lindner2, R. Issels2,1 Helmholtz Zentrum, München, Deutschland Klinikum der LMU, Medizinische Klinik III, München, Deutschland 3 PharmaMar, Medical Affairs, Barcelona, Spanien 4 Klinikum der LMU, Medizinische Klnik II, München, Niederlande 5 Erasmus Medical Center, Department of Cell Biology & Genetics, Rotterdam, Niederlande 6 Klinikum der LMU, Institut für Strahlentherapie, München, Deutschland 7 Klinikum der LMU, Pathologisches Institut, München, Deutschland 1 2 py improves the treatment of patients with high-risk STS (Issels, Lancet Oncol 2010). The rational for combining both treatments is that HT induces degradation of BRCA2 which is crucial for DSB-repair by Rad51 (Krawczyk, PNAS 2011). Methods: Four different human cell lines were analyzed: osteosarcoma (U2Os), liposarcoma (SW872), synovial sarcoma (SW982) and colorectal cancer (DLD1). For investigation of BRCA2 deficient cells, DLD1 mutant (-/-BRCA2) cells and siRNA knock-down were used. TR (0.5–4 nM) was applied for 3 h with 1.5 h HT (41.8°C and43°C). Cell cycle arrest was analyzed by Nicoletti-staining and cytotoxicity was assessed by clonogenic survival. Expression of BRCA2, the amount of γH2AX positive DSB-repair-foci and recruitment of Rad51 were analyzed by immunostaining. Results: Treatment with Tr enhanced G2 arrest and reduced clonogenic survival, both was significantly augmented by HT. After HT, BRCA2 expression was strongly reduced and recruitment of Rad 51 to DSBs was diminished (41.8°C) or even abolished (43°C). Combined treatment increased the amount of DNA damaged cells. In BRCA2 deficient cells, HT-dependent enhancement of TR toxicity in terms of G2 arrest and reduced survival was significantly reduced. Conclusion: Treatment with TR and HT resulted in enhanced toxicity, which was accompanied by elevated DNA-damage and G2-arrest. HT-mediated BRCA2-degradation and impairment of DSB-repair seem to be related mechanisms. ID 325 Uterine leiomyosarcomas: A single-center cohort with a favorable outcome in advanced disease E. Hartmann1, S. Buettner2, F. Menge1, P. Hohenberger1, B. Kasper1 Universität Heidelberg, Mannheimer Fakultät, Interdisziplinäres Tumorzentrum, Mannheim, Deutschland 2 Universität Heidelberg, Mannheimer Fakultät, Abteilung für Medizinische Statistik, Biomathematik und Informationsverarbeitung, Mannheim, Deutschland 1 This analysis examines treatment and survival characteristics of our cohort with advanced uterine leiomyosarcoma (uLMS). Out of a series of 48 patients presenting with uterine sarcomas between 2007 and 2012, we analyzed all evaluable patients with uLMS, mainly with locally recurrent or metastatic disease. 21 women were recorded with a median age of 47 years (range: 28–74) at initial diagnosis. Hysterectomy had been previously performed for all patients. 57% (12/21) of the women presented with locally advanced uLMS but limited to the uterus, whereas 43% (9/21) had already metastatic disease at initial diagnosis. In the first cohort, in 3 of 12 women, there was no necessity for further treatment after hysterectomy; one patient received adjuvant radiotherapy. However, 8 of 12 patients either developed metastases or never were tumor free (R1 resection) and subsequently presented distant metastases. Surgical therapy (metastasectomy for solitary lesions, multivisceral resection of local recurrence) was performed in 6 of 12 patients, chemotherapy in another 5 of 12 and radiotherapy in 4 of 12 patients. In the second cohort of patients with M1 disease the women were treated with surgical therapy (5/9), chemotherapy (7/9) and radiotherapy (3/9). 4 of 9 patients never reached remission; 5 of 9 patients experienced a limited period of response. The median relapse-free survival in the cohort of 21 patients was 17 months (range, 2–57 months). The 5-year survival rate was 60% and the median overall survival was 26 months (range, 4–172 months). Despite a negative patient selection in our cohort of advanced locally recurrent or metastatic uLMS, we observed a rather favorable outcome with a median overall survival of 26 months and a 5-year survival rate of 60%. Background: Trabectedin (TR) is approved in Europe for advanced soft tissue sarcoma (STS) after failure of anthracyclines and ifosfamide. Its cytotoxicity is associated with the induction of DNA double-strand breaks (DSB). Regional hyperthermia (HT) combined with chemothera- 116 Oncol Res Treat 2014;37(suppl 1):1–133 Abstracts Inhalt Index ID 350 Impact of gender on efficacy of alkylating agents and their acute toxicity in patients with standard risk localized Ewing sarcomas (EWS-R1) in the EURO-Ewing99(EE99)-R1 trial U. Dirksen1,2, H. van den Berg3,4, B. Brennan5, P. Marec Berard6, R. Ladenstein7, I. Judson8, L. Hjorth9, J. Kruseova10, M.C. LeDeley11, A. Ranft2,9, I. Lewis12, O. Oberlin13, A. Craft14, H. Jürgens1,2 Westfälische Wilhelms Universität Münster, Pädiatrische Hämatologie und Onkologie, Münster, Deutschland 2 Universitätsklinikum Münster, Münster, Deutschland 3 Academic Medical Centre / University of Amsterdam, Amsterdam, Niederlande 4 - Emma Children Hospital AMC, Dept. of Paediatric Oncology, Amsterdam, Niederlande 5 University Hospital, Royal Manchester Children‘s Hospital, Manchester, Großbritannien 6 Centre Berard, Institut d‘Hémato-Oncologie Pédiatrique, Frankreich 7 Universität Wien, St. Anna Kinderspital, Wien, Oesterreich 8 Royal Cancer Hospital, Institute of Cancer Research, London, Großbritannien 9 Clinical Sciences Lund University, Skåne University Hospital, Department of Paediatrics, Schweden 10 University Prague, University Hospital Motol, Pediatric hematology and Oncology, Prague, Tschechische Republik 11 Institut Gustave-Roussy, Service de Biostatistique et d‘Epidémiologie, Paris, Frankreich 12 Alder Hey Children‘s NHS Foundation Trust, Liverpool, Großbritannien 13 Institute Gustave- Roussy, Hèmato-Oncologie Pédiatrique, Paris, Frankreich 14 Institute of Child Health, University of Newcastle upon Tyne, Newcastle upon Tyne, Großbritannien 1 Background: Patients were randomized for cyclophosphamide vs. ifosfamide-based consolidation (VAC vs. VAI) in the Euro-EWING99-R1 trial. Overall, the efficacy of the two agents was similar [PBC, 57, p710;2011). Abstracts Long-term outcome of desmoid tumors treated with highdose antiestrogen and NSAID therapy C. Schneider1, D. Quast1, R. Schneider2, G. Möslein1 1 2 HELIOS St. Josefs-Hospital, Chirurgie, Bochum, Deutschland Universitätsklinik Marburg, Chirurgie, Marburg, Deutschland en *Supported by Deutsche Krebshilfe and the BMBF. ID 399 Introduction: Desmoid tumors are generally rare, but frequently occur in patients with familial adenomatous polyposis (FAP) and are prone to recurrence. The treatment is discussed controversely. We prospectively evaluated the outcome of antiestrogens in combination with sulindac. Material and Methods: Patients with symptomatic desmoids, either spontanous or FAP-associated were treated with high-dose antiestrogen and sulindac for more than 1 year. Development of disease was measured via CT and/or MRI scan. Stable disease and tumor regression were regarded as response. Results: 134 patients (64 spontaneous, 70 FAP-associated) with a mean follow up of 7.1 years were included. Male:female ratio was 90:44 (p < 0.5), the location was predominantly intraabdominal in FAP-patients while spontaneous desmoids developed extraabdominal. FAP-patients were significantly younger (39,7±13,6 y vs. 44,6±14,3 y). The response rate was 85.1%, with 3 desmoid-associated deaths. Mean time to response was 14.9 ± 9.1 months, only 1 recurrence occurred after cessation of the medication and only 3 patients died from their desmoid. No stop of the medication due to side effects was necessary. Patients after surgical resection demonstrated a significantly higher rate of progressive diseases (p = 0.03) Conclusions: The treatment of desmoids with high- dose antiestrogens and sulindac is characterized by a relatively long time to response, but a high rate of success and low recurrences with excellent tolerance and very low mortality, compared with other therapies. og The event free survival (EFS) in patients with relapsedEwingsarcoma (ES) remains poor with a 5 year- EFS of 13%. We analysed the value of high dose chemotherapy (HDtx) in relapsed ES and compared the most frequently used high dose regimens versus no HDtx in terms of outcome. Methods: Data from 239 patients with first relapse of ES registered from 2003–2009 into the ES relapse registry database of the German Society of Pediatric Hematology and Oncology were analyzed. Outcome was analyzed descriptively by event-free-survival (EFS) and overall-survival (OS) controlled for risk factors by multivariate regression analysis. Results:Amongst 73 pts who received HDtx; 15 received busulfan-melphalan (bu-mel), 38 treosulfan-melphalan (treo-mel) and 20 other regimens. Status prior to HDtx was remission in 25 pts, stable disease in 3 pts, progressive disease in 1pt and not known in 15 pts. The 3- year overall survival (3y-OAS) was 14% (SE= .03) in patients treated without HDtx, 47% (SE=.13) in patients treated with bu-mel and 48% (SE=.1) with treomel HDtx. The 3-yOAS in pts with early relapse was 6% (SE .02) without HDtx and 42 (SE= .14) or 31% (SE= .14) after bu-mel and treo-mel HDTx, respectively. The 3-yOAS in pts with late relapse was 33% (SE .08) without HDtx and 67 (SE= .27) or 67% (SE= .14) after bu-mel and treo-mel respectively. Conclusion: The results demonstrate a significant benefit from HDtx in patients with relapsed ES. There was no significant difference between the HDtx regimens in terms of outcome. Detailed analysis excluding the patients who did not receive HDtx due to early progression and the impact of different standard relapse regimen will be provided. ez Westfälische Wilhelms Universität Münster, Pädiatrische Hämatologie und Onkologie, Münster, Deutschland 2 Universitätsklinikum Münster, Münster, Deutschland 1 kg U. Dirksen1,2, S. Jabar2, A. Ranft2, H. Jürgens1,2, M. Rasper2 Based on the EE99R1 gender-stratified randomization, gender impact on efficacy and acute toxicity was explored. Methods: Gender impact on EFS and acute toxicity by course, switches between treatment arms, and cumulative dose of alkylating agents was evaluated in multivariable models on the intention-to-treat population, including tests for heterogeneity of treatment effect due to gender. Results: 856 patients (347 females) were randomized between 2000 and 2010: 425 VAI and 431 VAC. Overall EFS was not gender dependent. (p = 0.33). Marginal variation was seen between treatment and gender (p = 0.083): In males VAC exhibited poorer EFS than VAI, HR(VAC/ VAI) = 1.34 [0.96–1.86]. In females, VAC was slightly better than VAI, HR = 0.83 [0.54–1.28]. Equivalently, males had poorer EFS than females with VAC, HR(M/F) = 1.42 [0.97–2.08]. Results by gender were similar with VAI, HR = 0.91 [0.62–1.33]. Severe hematological toxicity was more frequent with VAC. Tubular renal impairment was more frequent with VAI. Severe toxicity was more frequent in females, independent of the type of toxicity, with no significant treatment-gender interaction. Thirty patients switched from VAI to VAC (21 F, 9 M), mostly due to renal toxicity, and 3 from VAC to VAI (1 F, 2 M). A reduction of either alkylating agents` cumulative dose >20% was more frequent in females (15% vs. 9%, p = 0.01 Conclusions: Gender impact on EFS and acute toxicity from an alkylating agent requires further study. Effects of gender-dependent polymorphism/activity of metabolic enzymes (e.g. CYP2B6) of ifosfamide vs. cyclophosphamide should be explored. rü c The value of high dose chemotherapy in relapsed Ewing sarcoma patients zu ID 336 ID 445 Risk stratification by number of metastatic sites in nonlocalized Ewing sarcomas* A. Ranft, U. Dirksen, H. Jürgens University Hospital, Pediatric Hematology and Oncology, Muenster, Deutschland Objective: The outcome variation in subgroups of Ewing sarcoma patients with metastases at initial diagnosis is high. A major current criterion Oncol Res Treat 2014;37(suppl 1):1–133 117 Inhalt Index is to stratify treatment according to the site of metastases, e.g., patients with pulmonary disease only are distinguished from patients with other metastatic sites. In this project outcome was analyzed according to the number of metastatic sites. Methods: Five-hundred Ewing sarcoma patients with metastases at diagnosis were analyzed. All patients were included in the GPOH Ewing sarcoma registry from 1998 to 2009 and received similar treatment strategies with standard and/or high-dose chemotherapy. The median follow-up was 2.62 years (range 0.20–14). Outcome by event-free-survival (EFS) was analyzed by univariate and multivariate analyses. Results: 3y-EFS in patients with isolated pulmonary metastatic disease was 0.46 (SE=.03; n = 268), compared to 0.27 (SE=.03; n = 232) in patients with dissemination to sites other than lung alone (R3) (p < .001). In R3 patients, 3y-EFS with one metastatic site was 0.39 (SE=.07; n = 52), compared to 0.28 (SE=.04; n = 120) with two, and 0.14 (SE=.05; n = 60) with three or more metastatic sites (p < .001). In multivariate analysis, the number of metastatic sites persisted as the major significant risk factor (Hazard ratio (HR): 1.45 (2 vs. 1); 2.38 (>2 vs. 1); p < .001), whereas the risk group affiliation did not (HR: 1.21; p = .302), even if the model was controlled for treatment intensification with high-dose chemotherapy (HR: 1.82-2.70; p < .001 vs. 1.63; p = .025; n = 432). Conclusion: Stratification by virtue of the quantity of metastatic sites appears to discriminate for prognosis in non-localized Ewing sarcoma patients. *Supported by Deutsche Krebshilfe. TRAIL-induced apoptosis remained largely elusive. Here, sensitization of melanoma cells for TRAIL by the PI3-kinase inhibitor wortmannin correlated to activation of mitochondrial apoptosis pathways. Apoptosis was dependent on Bax and abrogated by Bcl-2 overexpression. The synergistic enhancement was explained by Bax activation through wortmannin, which tightly correlated to characteristic Bax phosphorylation patterns. Thus, wortmannin resulted in early reduction of the Bax-inactivating phosphorylation at serine-184, whereas the Bax-activating phosphorylation at threonine-167 was enhanced. Proving the responsibility of the pathway, comparable effects were obtained with an Akt inhibitor (MK2206). While suppressed phosphorylation of serine-184 may be attributed to reduced Akt activity itself, the causes of enhanced threonine-167 phosphorylation were addressed here. Characteristically, production of ROS was seen early in response to wortmannin and MK-2206. Providing the link between ROS and Bax, we show that abrogated ROS production by a-tocopherol or by NADPH oxidase 4 (NOX4) siRNA suppressed apoptosis and Bax activation. This correlated with reduced Bax phosphorylation at threonine-167. The data unravel a mechanism by which NOX4-dependent ROS production controls apoptosis via Bax phosphorylation. The pathway may be considered for proapoptotic, anticancer strategies. ID 154 Variationen zur Defektabdeckung durch regionäre Lappen bei ambulanter Tumorchirurgie im Gesicht L. Tischendorf Skin Cancer including Melanoma ID 018 RAF inhibition overcomes resistance to TRAIL-induced apoptosis in melanoma cells A. Berger, S.-A. Quast, P. Michael, N.-F. Kuhn, U. Trefzer, J. Eberle Charité-Berlin, Klinik für Dermatologie, HTCC, Berlin, Deutschland Mutated BRAF represents a critical oncogene in melanoma, and selective inhibitors have been approved for melanoma therapy. However, the molecular consequences of RAF inhibition in melanoma cells remained largely elusive. Here, we investigated the effects of the pan-RAF inhibitor L-779,450, which inhibited cell proliferation both in BRAF-mutated and WT melanoma cell lines. It furthermore enhanced apoptosis in combination with the death ligand TRAIL (TNF-related apoptosis-inducing ligand) and overcame TRAIL resistance in melanoma cells. Enhanced apoptosis coincided with activation of mitochondrial pathways, seen by loss of mitochondrial membrane potential and release of cytochrome c, SMAC and AIF. Subsequently, caspases-9 and -3 were activated. Apoptosis induction by L-779,450/TRAIL was prevented by Bcl-2 overexpression and was dependent on Bax. Thus, activation of Bax by L-779,450 alone was demonstrated by Bax conformational changes, whereas Bak was not activated. Furthermore, the BH3-only protein Bim was upregulated in response to L-779,450. The significant roles of Smac, Bax and Bim in this setting were proven by si-RNA-mediated knockdown experiments. L-779,450 also resulted in morphological changes indicating autophagy confirmed by the autophagy marker LC3-II. The proapoptotic effects of L-779,450 may explain the antitumor effects of RAF inhibition and may be considered when evaluating RAF inhibitors for melanoma therapy. ID 063 ROS-dependent phosphorylation of Bax by wortmannin sensitizes melanoma cells for TRAIL-induced apoptosis A. Quast, A. Berger, J. Eberle Charité Universitätsmedizin, klinik für Dermatologie, HTCC, Berlin, Deutschland The pathways of reactive oxygen species (ROS)-mediated apoptosis induction, of Bax activation and the sensitization of tumor cells for 118 Oncol Res Treat 2014;37(suppl 1):1–133 Praxis MKG Chirurgie, Halle, Deutschland Die Spezifik ambulanter Operationen an der Gesichtshaut erfordert die Auswahl geeigneter Methoden zur Defektdeckung, die onkologischen und ästhetischen Ansprüchen genügen. Wir stellen die Erfahrungen aus den Jahren 1993 bis 2013 an 1450 ambulanten Tumorbehandlungen in ihrem zeitlichen Wandel vor. Besprochen werden Variationen, Vor- und Nachteile sowie eigene Modifikationen von regionären Lappen:Transpositionslappen, Rotationslappen, Glabellalappen, Gleitlappen sowie Deckungen von Ober- und Unterlippendefekten. Grenzen der ambulanten Chirurgie an der Gesichtshaut werden eher durch Transportprobleme, Blutungsübel sowie Compliancefragen als durch Tumorcharakteristika bestimmt. ID 218 Systemic treatment of metastatic uveal melanoma – a silver lining on the horizon? H. Richly, M.E. Scheulen, M. Wiesweg, A. Abendroth, M. Schuler, S. Bauer Uniklinikum Essen, Tumorklinik, Essen, Deutschland Background: Uveal melanoma (UM) is the most common ocular tumor but accounts for only 0.1% of overall cancer mortality. Classical chemotherapeutic drugs, given systemically or as perfusion treatment, may delay progression but have a minor impact on the general course of disease. Thus, clinical trials have been considered the standard of care in these patients (pts). Recently, mutations in GNAQ/GNA have been shown to affect most pts with metastastic uveal melanoma, that lead to activation of protein kinase C (PKC) and the Raf/MEK/ERK signalling pathway. We aim to present updates of ongoing clinical trials in order to facilitate access to treatment for this rare disease. Methods and Results: We have initiated three clinical trials that focus on uveal melanoma or genetic pathways relevant for the disease. These trials may have a major clinical impact for patients and trial design and preliminary results (STREAM-trial) will be presented. The STREAM trial is a multicenter randomized discontinuation, blinded, placebo-controlled, phase II study of sorafenib in patients with chemonaïve metastatic uveal melanoma. To date, 60 patients have been enrolled of whom 26 have entered randomization on day 56. The results of a planned interims analysis of the STREAM trial will be presented. Abstracts Inhalt Index A phase I trial investigates the combination of a MEK-inhibitor (MEK162, fix-dose) and a PKC-inhibitor (AEB071, escalating doses) in patients with UM. A novel c-MET inhibitor (INC280) investigates clinical activity in c-MET-dependent solid tumors which has been found in up to 20% of UM pts. Conclusions: Novel insights into the genetic evolution of metastatic uveal melanomas may trigger substantial therapeutic progress. Patients should be directed towards clinical trials that inhibit these targets. ID 447 Validation of a fresh-frozen tissue-based prognostic gene signature in formalin-fixed, paraffin-embedded melanomas G. Brunner1, A. Heinecke2, L. Suter1, C. Berking3, H.-J. Schulze4, J. Atzpodien5 Skin Cancer Center Hornheide-Münster, Cancer Research, Münster, Deutschland 2 Westfälische Wilhelms University Münster, Medical Informatics and Bio informatics, Münster, Deutschland 3 Maximilians University Munich, Dermatology and Allergology, Munich, Deutschland 4 Skin Cancer Center Hornheide-Münster, Dermatology, Münster, Deutschland 5 Niels-Stensen-Kliniken, Oncology, Georgsmarienhütte, Deutschland 1 Current melanoma staging is limited in predicting outcome, and complementary molecular markers are not available for routine prognostic assessment. We have recently identified a prognostic nine-gene signature expressed in fresh-frozen primary cutaneous melanomas (training cohort n = 91; validation cohort n = 44). A signature-based risk score predicts patient survival independently of AJCC staging (multivariate analysis p = 0.0004; hazard ratio 3.8). The purpose of this study was to establish signature expression analysis in formalin-fixed, paraffin-embedded (FFPE) melanomas. From FFPE melanomas matching the training and validation cohorts of the above study (n = 125), RNA was prepared and transcribed into cDNA. Following cDNA pre-amplification, expression of the 9 signature genes, 2 additional candidate genes, and 3 housekeeping genes was quantified by real-time PCR. Correlation of gene expression with overall survival was evaluated using Cox regression analysis. Expression of a signature of 8 genes was associated with overall survival in univariate analysis. A signature-based risk score predicted survival independently of AJCC staging (multivariate analysis p = 0.0059, hazard ratio 3.09). The misclassification rates were 20% overall, 13.8% for low risk, and 5.7% for double low-risk (combined with AJCC staging). The risk score significantly refined conventional AJCC staging. Thus, the fresh-frozen tissue based prognostic gene signature was successfully validated in FFPE melanomas. Our quantitative prognostic score, based on FFPE melanomas, is complementary to AJCC in predicting outcome. This increases clinical applicability and allows retrospective assessment of melanomas. The score identifies patients at low risk, not identified by AJCC staging, and defines high-risk patients in need of adjuvant therapy. Stem Cells in Cancer ID 162 Evaluation of stem cell markers and different stemness genes in glioblastoma cell lines markers are still inadequate to specifically identify glioma stem cells. Therefore, we aimed to investigate a set of key stemness – and progenitor genes in established glioblastoma cell lines. RNA was isolated from 5 cell lines: U87 as a commercially available established glioblastoma cell line, Gl36 as a tumor derived primary glioblastoma cell line, human embryonic stem cells, neuronal progenitor cells as positive control and fibroblasts as a negative control. After cDNA synthesis PCR was performed in order to investigate a set of stemness genes (Nanog, Oct4, Klf4, Lin28 and cMyc) as well as neuronal progenitor genes (Sox1, Pax6, Olig2, CD133). Protein expression was confirmed by Western blot analysis and cell stainings. A subset of stemness and progenitor genes is differentially expressed in both investigated tumor cell lines. GI36 cells showed expression of Oct4, Klf4, and Lin28, whereas Oct4 and Pax6 were identified in U87 cells. Overall, Pax6 was the only detectable neuronal progenitor marker in both tumor cell lines. Furthermore, cMyc was expressed in both tumor cell lines, while neither of them showed any signs of CD133. Our results show the expression of a subset of stemness and neuronal progenitor genes in two glioblastoma cell lines. Interestingly, we found a distinct expression pattern in an established glioblastoma cell line compared to a primary cell line, emphasizing the caution necessary when extrapolating results derived from established cell lines. ID 208 Plasticity of CD133 and OCT4A-expressing melanoma cells could account for treatment failure in malignant melanomas Y. Welte1, D. Behrens2, I. Fichtner2, R. Schäfer1,3, C. Regenbrecht1,4 Institut für Pathologie/Charité – Universitätsmedizin Berlin, Berlin, Deutschland 2 EPO Berlin-Buch GmbH, Berlin, Deutschland 3 German Cancer Consortium (DKTK) / DKFZ, Heidelberg, Deutschland 4 Comprehensive Cancer Center Charité, Berlin, Deutschland 1 Malignant melanoma is the most severe type of skin cancer. To study the biology and clinical impact of melanoma stem cells, we have established patient-specific cell lines and identified two distinct subpopulations of cells that express CD133, which is correlated with asymmetric cell division and OCT4A the master regulator of pluripotency. An overlap of both putative CSC populations was indicated by the overexpression of OCT4A in the CD133+ subpopulation compared to CD133- melanoma cells and vice versa. We enriched CD133+ as well as OCT4A+ cells from the bulk and found crucial pathways related to oncogenesis and stemness such as Wnt and FGF/MAPK activated in the respective positive populations. In vivo experiments showed increased tumorigenic capabilities of CD133+ and OCT4A+ melanoma cells compared to their negative counterparts. Analysis of the robustness of the CD133+ subpopulation revealed a plasticity of CD133+ and CD133- phenotypes. This plasticity may have tremendous implications for the therapeutic intervention in malignant melanomas. In vitro cytotoxicity assays with FGFR1- and PI3K-inhibitors significantly increased the CD133+ melanoma subpopulation within 48 h. Our results indicate small melanoma subpopulations with cancer stem cell characteristics, which are neither statically nor hierarchically organized. Instead, a dynamic plasticity between both CSC and bulk tumor populations exists, which facilitates rapid adaption to environmental stress and could therefore substantially hamper a successful therapeutic intervention. L. Dreher1, M. Perrech1, G. Röhn1, R. Goldbrunner1, T. Saric1, M. Timmer1 1 Uniklinik Köln, Allgemeine Neurochirurgie, Köln, Deutschland The cancer stem cell hypothesis postulates that a small population of cancer cells possess self-renewal characteristics and is responsible for initiating and maintaining tumour growth. The so far described stem cell Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 119 Inhalt Index ID 300 Characterization of colon cancer stem cells at the single cell level for target identification in diagnosis and therapy P. Malkomes1, N. Haetscher2,3, T. Oellerich3, T. Schroeder4, K. Holzer1, H. Serve3, W.O. Bechstein1, M. Rieger2,3 Universitätsklinikum Frankfurt, Allgemein- und Viszeralchirurgie, Frankfurt, Deutschland 2 Georg-Speyer-Haus, onkologische Forschung, Frankfurt, Deutschland 3 Universitätsklinikum Frankfurt, Hämatologie und Onkologie, Frankfurt, Deutschland 4 Helmholtz Zentrum München, Stem Cell Dynamics Research Unit, Neuherberg, München, Deutschland 1 Introduction: Colorectal cancer is the second leading cause of cancer related death in Germany. Current understanding suggests that colorectal cancer is a stem cell-driven disease, in which only a small population of cells, referred to as cancer stem cells (CSCs), are capable to initiate and sustain tumor growth. Despite the description of some surface markers, the identity of CSCs and thereby their biology remains largely undefined. Our purpose is to identify CSCs by their distinct cell behavior in order to detect new targets for a CSC-directed therapy. Methods: We applied time-lapse microscopy and single cell tracking to continuously study the behavior of individual colon cancer SW480 cells and their progeny over many generations. Cell fates as division, death or generation time were recorded in pedigrees and analyzed to identify functionally different subpopulations. We prospectively purified these subpopulations by FACS and performed proliferation and colonosphere assays, in vivo transplantations as well as SILCAC-based proteomics. Results: Continuous cell tracking enabled the link of surface marker expression with distinct cell behavior and thus the discrimination of functionally different subsets. Sorted subpopulations showed differences concerning proliferation and their stemness to form colonospheres and to initiate tumor growth. Proteomics detected potential target proteins, which are now functionally analyzed in cell lines and primary patient material. Conclusion: Continuous single cell tracking yields new insights in individual cell behavior in heterogenous cell populations and provides great potential in the identification of CSCs in colon cancer. Quantitative proteomics revealed new CSC-related targets. was strongly reduced by 48% or by 73% in the presence of 1 µM or 10 µM ZOL respectively. The remaining cellular motility led to very little change in distance, with cellular activity appearing more as a ‘stepping on the spot’. A ZOL gradient dislocated the center of mass of migrating cells towards lower concentrations. Conclusions: The suppression of cancer stem cell motility could potentially contribute to the clinical benefits that recent studies have described following the adjuvant administration of zoledronic acid in breast cancer. Supportive Care ID 031 Network kids – a support project for the children of cancer affected families U. Vehling-Kaiser1, M. Flieser-Hartl1,2, T. Sternfeld3, B. Betz1, F. Kaiser1 Onkologisches und Palliativmedizinisches Netzwerk Landshut, Landshut, Deutschland 2 Landshuter Kommunalunternehmen für Medizinische Versorgung, Landshut, Deutschland 3 Praxis für Innere Medizin, Landshut, Deutschland 1 Children are often psychologically and socially affected when a family member, e.g. the parents, are diagnosed with cancer. The illness of parents can cause fears and depressions in children. Family and leisure time activities can be severely affected by the treatment of one family member. Furthermore problems at school or at the apprenticeship can follow. There are no established support programs for these children. Therefore the «Netzwerkinder» project for the support of these affected families was initiated. The project co-operates with local social workers, school psychologists, child psychologist and cram schools. Leisure group activities as excursions and garden parties, private lessons and family weekends are organised and financed. Monetary support in selected situations of acute misery due to the disease is offered. ID 042 Physical Activity and Exercise after Treatment for Childhood Cancer ID 370 The motility of cultured breast cancer stem-like cells is severely restricted by zoledronic acid. S. Kesting1, M. Götte1, C. Winter2, D. Rosenbaum2, J. Boos1 C. Hoberg , P. Nguemgo-Kouam , A. Kochanneck , K. Fakhrian , H. Bühler1, I. Adamietz2 1 1 1 2 Universitätsklinikum Marienhospital, Institut für Molekulare Onkologie, Strahlenbiologie und Experimentelle Strahlentherapie, Herne, Deutschland 2 Universitätsklinikum Marienhospital, Klinik für Strahlentherapie und Radio-Onkologie, Herne, Deutschland 1 Background: Various effects on tumor cells have been described for zoledronic acid (ZOL). However, only limited data exist regarding its influence on the motility of tumor cells. Since migration is a decisive step in metastasis, we examined whether ZOL reduces the motility of tumor cells, which may lead to less aggressive metastasis. Methods: The hypothesis of tumor stem cells postulates that recurrences may occur from cancer stem cells rather than from ‘normal’, somatic tumor cells. Therefore, we investigated the effects of ZOL on stem-like progenitor cells obtained via the formation of spheroids from the human breast cancer cell line MDA-MB 231. The motility parameters velocity, accumulated and Euclidean distance were obtained by time-resolved videography. The effect of a ZOL gradient on the direction of migration was determined in ibidi µ-slides. Results: The videography showed that ZOL strongly reduced the migration of cancer stem cells. The cellular velocity was reduced by 61% following exposure to 1 µM ZOL, and by 82% after exposure to 10 µM ZOL. The accumulated distance traveled by the cells was reduced by 60% or by 79% after exposure to 1 µM or 10 µM ZOL. The Euclidean distance 120 Oncol Res Treat 2014;37(suppl 1):1–133 University Hospital of Muenster, Department of Pediatric Hematology and Oncology, Muenster, Germany, Deutschland 2 University Hospital of Muenster, Movement Analysis Lab, Institute for Experimental Musculoskeletal Medicine, Muenster, Germany, Deutschland 1 Background: It is not clear whether children and adolescents achieve a satisfactory level of physical activity (PA) following cancer treatment that matches reference values and whether patients return to physical education (PE) at school, club and leisure-time sports activities. This study aimed at analyzing the status of integration into sport structures and assessing self-reported PA. Method: A standardized questionnaire of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) assessed PA and exercise, supplemented by questions related to PE, specific aspects of disease and therapy. Applying this instrument enables comparison with a healthy reference population (n = 4529). Results: 85 patients (13.5±3.7 years; 48 male) during maintenance therapy and aftercare of childhood cancer (4.6±3.6 years post-diagnosis) were included. Overall, the status of PA and integration into club and leisure-time sports activities was comparable to the reference population. However, 25% of the sample was exempted from PE at school. 21% (KiGGS: 15%) met the PA recommendations in childhood (60 min/day). Especially brain tumor patients showed a reduced level of PA. Both brain and bone tumor patients revealed a status of integration below-average and a high proportion of exemptions from PE. Abstracts Inhalt Index Conclusion: In general, the observed sample showed an adequate status of integration into sport structures and a level of PA appropriate for their age. However, this positive result should not mask problems occurring in brain and bone tumor patients regarding their limited activity and insufficient integration. This emphasizes the need of individually-tailored support and strategies for the promotion of a long-term active lifestyle. ID 069 Different Doses of Micafungin for Prophylaxis of Invasive Fungal Diseases: A Web-based Non-Interventional Trial in Four Large University Hospitals in Germany S. Heimann1, O.A. Cornely1, L. Meintker2, W. Heinz3, T. Schroeder4, M. Vehreschild1, H. Wisplinghoff1, M. von Bergwelt-Baildon1, J. Vehreschild1 University Hospital of Cologne, Cologne, Deutschland University Hospital of Erlangen, Erlangen, Deutschland University Hospital of Würzburg, Würzburg, Deutschland 4 University Hospital of Düsseldorf, Düsseldorf, Deutschland 1 2 3 Background: Treatment indications of new antifungals in clinical practice often deviate from the strict criteria used in controlled clinical trials. Aim of this study was to describe customary prescription and treatment strategies of micafungin (MIC). Methods: A registry was set up on ClinicalSurveys.net and physicians were invited to provide retrospective information on cases they had treated with MIC. Documentation comprised demographics, underlying disease, efficacy, safety, and tolerability of MIC. Results: A total of 125 episodes of patients (PTS) hospitalized between 10/09 and 01/12 were documented, of which seven had to be excluded due to incomplete documentation. The most common underlying disease and risk factor was hematological malignancy (116, 98.3%) and antibiotic treatment > 3 days (115, 97.5%). Micafungin was administered as prophylaxis (PPX) in 106 (89.9%) and for treatment of possible, probable or proven IFD in 12 PTS (10.1%). In the group of antifungal PPX, mean duration of MIC treatment was 22.8 days (d) (95% CI: 20.4–25.3); 53 of the PTS (50%) received a dosage of 50mg, while the other 53 (50%) received 100mg/d. For the different doses, prophylactic outcome was rated as success in 42 (79.2%) vs. 52 PTS (98.1%; p = 0.004); 55 PTS (51.9%) were treated with posaconazole (POS) before initiation of MIC. Four PTS (3.8%) developed a proven IFD while being treated with 50mg/d, compared to no PTS treated with 100mg/d. At the end of MIC PPX, 24 PTS (22.6%) were switched to fluconazole, 63 PTS (59.4%) to POS. Conclusions: Clinical effectiveness of MIC PPX in high risk PTS was demonstrated. In most cases, MIC was part of a multi-modal antifungal PPX strategy. Investigators reported better outcomes in PTS receiving therapeutic doses of MIC for PPX. ID 071 Factors that influence participation in physical activities and exercise in pediatric cancer patients during treatment: A qualitative study M. Götte, S. Kesting, C. Winter2, D. Rosenbaum2, J. Boos University Hospital of Muenster, 1Department of Pediatric Hematology and Oncology, Muenster, Deutschland 2 Movement Analysis Lab, Institute for Experimental Musculoskeletal Medicine, Muenster, Deutschland Purpose: Due to growing evidence about the value of exercise in pediatric cancer patients, the purpose of this study was to determine barriers and motivations for physical activities during treatment. Methods: This qualitative study included semi-structured guideline interviews, transcription and coding based on grounded theory with 40 pediatric cancer patients (5.5 ± 2.3 months since diagnosis). Four major topics were discussed: 1) values and beliefs, 2) barriers to exercise, 3) motivations to exercise and 4) encouragement from parents and physicians. All participants were treated at the Department of Pediatric Oncology in Muenster where a supervised exercise program has been implemented for hospital stays. Abstracts Results: Patients reported mainly positive attitudes towards physical activities during treatment and the local exercise program was desired and valued as essential for engaging in exercise during in-patient stays. Identified barriers included physical, psychological and organizational aspects. Motivational aspects were based on improvements in physical fitness and mental well-being. Parents’ behavior related to physical activities of their children differed between being supportive, inhibiting and inert. Few patients received information about exercise by their physicians. Conclusions: Interventions that are aimed at maintaining physical activities during treatment and eliminating barriers to exercise are required due to the patients´ positive attitudes and multiple motivations towards exercise. These interventions need to be supervised and should include health-counseling programs for patients, parents and physicians to underline the importance of physical activities in pediatric cancer patients. ID 075 A multicenter cohort study on colonization and infection with extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) in high-risk patients with hematological malignancies M.J.G. Vehreschild1, L. Peterson2, S. Schubert3, W. Vogel4, S. Peter5, P. Schafhausen6, H. Rohde7, M. v. Lilienfeld-Toal8, I. Bekeredjian-Ding9, O.A. Cornely1,10,11,12, H. Seifert13 Uniklinik Köln, Klinik I für Innere Medizine, Köln, Deutschland University of Munich, Med. Klinik III, Munich, Deutschland 3 University of Munich, Max von Pettenkofer Institut, Munich, Deutschland 4 University Hospital Tübingen, Internal Medicine II, Tübingen, Deutschland 5 University of Tübingen, Institute of Medical Microbiology and Hygiene, Tübingen, Deutschland 6 University Medical Center Hamburg-Eppendorf, Department of Oncology and Hematology, Hubertus Wald Tumorzentrum, Hamburg, Deutschland 7 University Medical Center Hamburg-Eppendorf, Institute for Medical Microbiology, Virology and Hygiene, Hamburg, Deutschland 8 Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I, Bonn, Deutschland 9 Universitätsklinikum Bonn, Institut für Medizinische Mikrobiologie, Immunologie und Parasitologie, Bonn, Deutschland 10 University of Cologne, Clinical Trials Center Cologne, ZKS Köln, BMBF 01KN1106, Cologne, Deutschland 11 University of Cologne, Center for Integrated Oncology CIO Köln/Bonn, Cologne, Deutschland 12 University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Deutschland 13 University of Cologne, Institute for Medical Microbiology, Immunology and Hygiene, Cologne, Deutschland 1 2 Introduction: Bloodstream infections (BSI) remain the leading cause of mortality in patients with chemotherapy-induced neutropenia. The rate and type of ESBL-E colonization, infection and transmission in German cancer centers is largely unknown. Methods: We performed a prospective, observational multicentre study at five German university-based haematology departments. Participating sites screened for intestinal ESBL-E colonization within 72h of admission. Additional samples were collected every 10 +/– 2 days and before discharge from hospital. Two blood culture sets were drawn in case of neutropenic fever. Anonymous data of all patients were entered into webbased electronic case report forms. Resistance gene amplification and typing of isolates by rep-PCR or PFGE was performed to assess transmission between patients. Results: Between Nov 2011 and Dec 2012, 736 hospitalizations of 496 patients were documented; 287 patients (57.9%) received intensive chemotherapy for acute leukemia, 108 (21.8%) autologous and 220 (44.4%) allogeneic stem cell transplantation. Median duration of stay was 36.1d (range 5-159d). ESBL-E was identified from screening samples (83.8% E. coli and 13.2% K. pneumoniae) in 49/496 (9.9%; range by center: 5.9–22.6%) patients and 68/736 (9.2%) hospitalizations, and 7 (1.4%) ESBL-E BSI were observed. The relative risk of BSI with ESBL-E was 13.1 in patients previously found to be colonized. Oncol Res Treat 2014;37(suppl 1):1–133 121 Inhalt Index Discussion: Even though BSI with ESBL-E is still rare in this high-risk population, colonization rates are substantial and vary considerably between centers. ID 148 Cardiorespiratory fitness in breast cancer patients undergoing adjuvant therapy O. Klassen1, M. Schmidt1,2, F. Scharhag-Rosenberger1,3, M. Sorkin4, C. Ulrich1,5, A. Schneeweiss6, K. Potthoff7, K. Steindorf1,2, J. Wiskemann1,3 German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Preventive Oncology, Heidelberg, Deutschland 2 German Cancer Research Center (DKFZ), Environmental Epidemiology, Heidelberg, Deutschland 3 University Hospital, Medical Oncology, Heidelberg, Deutschland 4 Yale University, Chronic Disease Epidemiology, New Haven, Vereinigte Staaten Von Amerika 5 Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Seattle, Vereinigte Staaten von Amerika 6 University Hospital, Obstetrics and Gynecology, Heidelberg, Deutschland 7 University Hospital, Radiation Oncology, Heidelberg, Deutschland # Shared last authorship. 1 Aim: To investigate cardiorespiratory fitness (CF) level in breast cancer patients at different stages of adjuvant therapy. Patients and Methods: Women with breast cancer, stage 0-III (n = 222), were categorized according to their current treatment status (neo-adjuvant chemotherapy (CT)/adjuvant CT/started CT/surgery only). Cardiopulmonary exercise testing was used to measure the patient’s CF. Maximal oxygen uptake (VO2peak) was measured to represent cardiovascular and pulmonary functions. Heart rate during exercise at 50 watts (HR50) was assessed as a cardiocirculatory parameter and ventilatory threshold (VT) was used as an indicator of O2 supply to muscle. Analysis of covariance was used to investigate the determinates of CF. Results: The mean age of our study population was 55±9 years. The mean VO2peak was 20.6±6.7 ml/kg/min, mean VT 10.7±2.9 ml/min/kg and mean HR50 112±16 beats/min. CT was significantly associated with decreased VO2peak, with significantly lower adjusted mean VO2peak among patients post adjuvant CT compared to patients with no CT or just started CT regime (all p < .01). Patients post adjuvant CT reached only 63% of the VO2peak level expected for their age- and BMI-category (mean VO2peak 15.5±4.8 ml/kg/min). Similarly, HR50 was significantly associated, but VT was not associated with treatment. Conclusion: Breast cancer patients have marked impaired cardiopulmonary function during and after CT. Hereby, CT seems to impair CF by influencing the oxygen delivery system rather than impacting metabolic muscle function. However, the exact mechanisms need further investigations. Our results underline the need of exercise training in breast cancer patients to counteract the loss of CF during the adjuvant therapy. Physical activity is mentioned to be able to influence epigenetic modifications in various tissues including NK-cells. In the present study we try to find out if physical activity induced epigenetic modifications also affect NK-cells of cancer patients. To investigate the influence of physical activity on epigenetic modifications in NK-cells, 8 female breast cancer patients in follow-up care perform endurance training for 5 months. Before and after the intervention, blood is taken and NK-cells are isolated using magnetic beads. Changes in global DNA metyhylation and histone acetylation (H4K5) are detected by immunocytochemistry, followed by optic density analysis (ImmageJ). Data collection will be finished in October. We expect a lower DNA methylation and a higher histone acetylation. Their impact on transcription is oppositional and this result would promote a higher transcription. A higher level of transcription could enhance the NK-cell activity by increasing the receptor density. If we can show a change in epigenetic modifications by enhanced physical activity, a next step would be to investigate more precisely where these changes are and how they influence the NK-cell activity in detail. ID 238 Effect of bisphosphonates on vascular cells A.M. Pabst1, T. Ziebart1, M. Ackermann2, M.A. Konerding2, C. Walter1 1 2 Universität Mainz, MKG-Chirurgie, Mainz, Deutschland Universität Mainz, Anatomie, Mainz, Deutschland Introduction: Bisphosphonate-associated osteonecrosis of the jaw (BPONJ) can occur in long-term bisphosphonate treatment. In addition to the impact the bone remodeling, bisphosphonates have a negative impact on angiogenesis. In an in vivo study, the effects of bisphosphonates on angiogenesis in a 3D Matrigel assay were analysed. Material and Methods: Matrigel was injected into 6 to 8-week old female nude mice (n = 50). Five groups (n = 10) were treated either with clodronate, ibandronate, pamidronate, zoledronate, or the carrier solution as a control. Immunohistological stainings were performed to determine the microvessel density (MVD), microvessel area (MVA), and microvessel size (MVS) in the Matrigel plugs after 3 weeks of treatment. Results: MVD was decreased for all bisphosphonates tested (p each <0.001). The nitrogen-containing bisphosphonates (N-BPs) had a stronger negative impact than the non-nitrogen containing (NN-BP) clodronate (control 166, clodronate 99, ibandronate 48, pamidronate 47, zoledronate 35 microvessels/mm2). Results for MVA were similar. Especially ibandronate increased MVS compared to control group (p < 0.001). Conclusion: Clodronate’s impact on MVD and MVA is less strong compared to the N-BPs, which might explain why no BP-ONJ occur after treatment with NN-BPs. Ibandronate increased MVS compared to all other bisphosphonates, which may be a compensation for reduced perfusion since MVD and MVA were significantly decreased. This might be a possible explanation for the lower incidences of BP-ONJ after ibandronate treatment. ID 221 Changes of epigenetic modifications in natural killer cells of breast cancer patients in follow-up care by enhanced physical activity A. Schenk1, F. Baumann1, C. Koliamitra1, W. Bloch1, F. Schollmayer1, J. Beulertz1, P. Zimmer1 Deutsche Sporthochschule Köln, Molekulare und zelluläre Sportmedizin, Köln, Deutschland 1 Natural killer cells (NK-cells) are able to recognize and kill tumor cells. With different germ-line encoded receptors, they recognize tumor cells and kill them by promoting cell lysation and apoptosis. A higher expression of receptors on the surface of NK-cells could imply a higher sensitivity to target cells. Besides genetically settings, gene expression is also based on epigenetic modifications. Whereas DNA methylation seems to have a repressive effect on transcription, histone acetylation seems to have activating potential. 122 Oncol Res Treat 2014;37(suppl 1):1–133 ID 253 Effects of a six-month sports therapy intervention for childhood cancer patients: Preliminary results of the ESCiMo Study. V. Rustler1, F. Baumann1, W. Bloch1, A. Prokop2, J. Beulertz1 Deutsche Sporthochschule Köln, Institut für Kreislaufforschung und Sportmedizin, Abteilung Molekulare und Zelluläre Sportmedizin, Köln, Deutschland 2 Kliniken der Stadt Köln gGmbH, Kinderkrankenhaus Amsterdamer Straße, Klinik für Kinder- und Jugendmedizin, Pädiatrische Onkologie/Hämatologie, Köln, Deutschland 1 Background: Recently, several studies in pediatric oncology have emerged finding positive effects of exercise programs on activity behavior, as well as different physiological and psychosocial outcome measures. However, research to date has mainly focused on ALL-patients Abstracts Inhalt Index during medical treatment. Future research must therefore focus on cancer diagnoses other than ALL, as well as on patients during survivorship. Methods: The ESCiMo Study is a controlled trial, designed to evaluate the effect of a group-based sports therapy program on motor performance (primary outcome), quality of life and level of activity in a mixed childhood cancer population. Within a six-month period, childhood cancer patients (post-inpatient medical treatment) aged 4–17 years will exercise once a week for 60 minutes (intervention group). Healthy children in the control group do not receive any specific sports therapy. Results: Study recruitment started in May 2012. First findings suggest that motor performance of participating childhood cancer patients may improve substantially. Preliminary results regarding the effect of the exercise intervention on motor performance and quality of life in the IG (n = 15) compared to the CG (n = 15) will be available at the time of the congress. Conclusion: The ESCiMo Study aims to explore the potential benefits of a unique sports therapy program for a mixed childhood cancer population after cessation of their inpatient medical treatment. The results may help to develop recommendations for exercise programs with childhood cancer survivors and therefore improve the care structure in pediatric oncology. ID 353 Evaluation of the impact of a three month resistance training on fatigue and biomarkers of breast cancer patients during chemotherapy L. Gerland1, S. Frisse2, S. Latta3, W. Bloch1, N. Harbeck4, F.T. Baumann1 Deutsche Sporthochschule Köln, Institut für Kreislaufforschung und Sportmedizin, Abt. für molekulare und zelluläre Sportmedizin, Köln, Deutschland 2 Unifrauenklinik, Brustzentrum, Köln, Deutschland 3 Frauenarztpraxis Latta, Brühl, Deutschland 4 Universität, Brustzentrum, München, Deutschland 1 ID 361 Evaluation of the physical demand of cancer patients while cross-country skiing K. Gutekunst1, L. Vogt1, K. Schmidt1, A. Bernardi1, E. Jäger2, W. Banzer1 Goethe-Universität Frankfurt, Sportmedizin, Frankfurt am Main, Deutschland Krankenhaus Nordwest, Frankfurt am Main, Deutschland 1 2 Leisure and adventure orientated journeys for cancer patients are increasingly promoted. Focusing on specific aerobic activities, some offers also encourage patients to become physically active. However, there is lack of objective data and evaluation. Therefore the present study monitored objective and subjective parameters of the relative physical demand of cancer patients during a one week cross-country skiing (CCS) excursion. Thirteen cancer patients (63 ± 9.8 years; 9 ♀, 4 ♂) underwent baseline (T0) cardiopulmonary exercise testing (treadmill) with continuous registration of oxygen uptake (VO2peak) and heart rate (HR). Subjective mood state was assessed using the Profile of Mood States questionnaire (POMS) at baseline, day 1 (T1) and day 3 (T2) of the excursion. HR was monitored during the guided CCS sessions and perceived exertion (sRPE, Borg scale 6-20) was recorded immediately afterwards. The individual physical demand during CCS was categorized in reference to VO2peak and corresponding HR intensities. The average physical demand during CCS sessions (1.5±0.5h) was 13.1% moderate, 65.7% vigorous and 17.3% near-maximal. Average sRPE was 12.3±1.5. Nonparametric testing (Friedman-test, post-hoc-comparisons) revealed a reduction in the POMS subscale dejection from T0 to T2 (6.5±5.4 vs. 2.3±3.3; p = .015). Considering the detected changes of dejection and the subjective perception of a moderate physical demand, CCS seems to be feasible for cancer patients. However, due to the vigorous to near-maximal exercise intensities in more than 80% of the sessions medical testing and exercise counseling prior to participation is recommended. Background: 80–96% of breast cancer patients suffer from cancer related fatigue during acute therapy. Numerous studies showed positive effects of exercise on CRF, but the number of studies implementing resistance training in rehabilitation is insufficient. Trials produced some evidence that physical activity may result in beneficial changes in biomarkers in breast cancer survivors. However, studies in this field are rare. Goals: The study aims at analyzing the development of Fatigue and biomarkers of breast cancer patients executing resistance training during chemotherapy. Methods: The study was organized as a prospectively randomized and controlled preference study. 40 breast cancer patients in adjuvant chemotherapy were involved 6–12 weeks after surgery for 12 weeks: 20 probands each were assigned to the intervention and control group. Resistance training was executed twice per week for about 60 minutes, consisting of 7 routines in 3 sets of 8–12 dynamic repetitions. Training was supervised. Subjective intensity was controlled during exercise by modified RPE-scale, aiming at local muscular exhaustion. The following parameters of both control and intervention group were analyzed in the beginning, after 6 and after 12 weeks: Fatigue (MFI-Questionnaire), biomarkers. Results: General (–10,6%) and physical Fatigue (–14,7%, p = 0,04) could be lowered significantly in the IG whereas both increased in the CG (GF=+6,2%, PF=+12,1%). The examination of all results is scheduled for November 2013. Discussion: General (n = 40) and therapy-matched (n = 27) results show strong positive effects on GF and PF. Preliminary results suggest the integration of intense resistance training into the rehabilitation of mastocarcinoma patients. ID 374 Abstracts Oncol Res Treat 2014;37(suppl 1):1–133 MeMa Study – exercise program for patients with metastatic breast cancer P. Wirtz1,2, P. Mallmann2,3, W. Malter2,3, W. Bloch1,2, F.T. Baumann1,2 German Sports University Cologne, Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, Cologne, Deutschland 2 CIO Center for Integrated Oncology Cologne Bonn, Cologne, Deutschland 3 Gynecological Clinic of the University of Cologne, Breast Center, Cologne, Deutschland 1 Background: The importance of being physically active is known to reduce disease- and treatment-related side effects, as the fatigue syndrome, and therefore positively influence quality of life in cancer patients. Recently, many studies have focused on the influence of physical activity during and after medical treatment in breast cancer patients. These findings may lead to examine the feasibility and effects of an exercise program for patients with advanced breast cancer. The aim of the project is to examine the influence of an exercise program on reduction of fatigue syndrome in women with advanced breast cancer. Methods: Twenty women with advanced breast cancer (age ≥ 18) in any medical treatment take part in a 12 week supervised training intervention. Patients with bone metastases affected more than 50% of bone density are excluded. Participants exercise twice a week on medical exercise machines for 60 minutes or alternatively absolve twice a week a relaxation training program for 45 minutes. Physical performance (spiroergometry), muscle strength (h1RM), physical activity (GPAQ, KAS-O), anxiety and depression (HADS), pain (BPI), quality of life (EORTC QLQ-C30, BR 23) and fatigue (MFI 20) are assessed before and after the intervention. Perspective: Final outcomes about fatigue syndrome and the results of the spiroergometry and the h1RM-test will be available at the time of the congress. Based on the results and conclusions of the study a program with 123 Inhalt Index larger sample size could be developed. Further studies should examine possible effects of exercise programs on the progressions status and they should improve supportive care for patients with advanced breast cancer. ID 420 Perceived functional ability relates to laboratory and field measures of exercise capacity in cancer patients K. Schmidt, L. Vogt, C. Thiel, W. Banzer Goethe-Universität, Abteilung Sportmedizin, Frankfurt, Deutschland Although objective cardiopulmonary exercise testing (CPET) is considered as gold standard for exercise capacity evaluation, subjective instruments (e.g. self-rating scales) may be more economic to estimate fitness in the everyday clinical setting. However, in cancer patients it is unknown how such instruments relate to results derived from objective tests. Therefore this study in cancer patients compared a self-rating instrument to assess perceived functional ability (PFA) with the gold standard in both, laboratory and field exercise testing. Methods: 50 cancer patients (57.4 ± 10.2 yrs.; during/after (56%/44%) treatment) rated their PFA on a 13-point scale by estimating the walking/ running velocity they could keep up for 1.6 kilometers (4x400 m track). Subjects also performed a CPET to assess peak oxygen consumption (VO2peak) and a 6-minute walking test (6MWT) to determine 6MWT distance (6MWD). PFA reproducibility was evaluated in a subsample (n = 27) within 2-7 days. Results: Participants’ VO2peak was 21.2 ± 4.8 ml·kg-1·min-1, mean 6MWD 594 ± 81m, and average PFA 6.9 ± 2.7 points. PFA was significantly correlated (p < .001) with VO2peak (r = .62) and 6MWD (r = .63). Grouped for PFA estimated walking or running velocity (≤5; >5-7; >7 km·h-1) statistical testing revealed significant differences in VO2peak and 6MWD. The ICC (2,1) for PFA test-retest reliability was .858 (95%CI: .713; .933) (p < .001). Conclusions: The present findings revealed linear relationships between PFA and VO2peak/6MWD which are almost comparable to the correlations established between field and laboratory outcome measures. From subgroup analyses it emerged that different grades of PFA seem to be able to distinguish between varying levels of exercise capacity. Surgical Oncology ID 227 Certification of biobanks: Adaption of the DIN EN ISO 9001:2008 norm to implement a quality management system for the North German Tumorbank of Colorectal Cancer. M. Oberländer, R. Kaatz, J.K. Habermann Universität zu Lübeck, Sektion für Translationale Chirurgische Onkologie und Biomaterialbanken, Lübeck, Deutschland Introduction: Standardization between biobanks is an essential factor to guarantee high-quality human biospecimens for translational research projects and clinical studies. So far, no international norm exists to promote common standards between biobanks. However, the DIN EN ISO 9001 norm is increasingly being adopted by biobanks in Europe since it reflects many aspects of biobanking management and quality improvement. Methods and Results: For the North German Tumorbank of Colorectal Cancer (ColoNet) a quality management (QM-) system according to DIN EN ISO 9001 was first implemented at the ColoNet site at the University Medical Center Lübeck. Here, the different biobanking steps (e.g. patient’s recruitment, sample collection and processing) have been categorized into major «processes» which include associated Standard Operating Procedures (SOPs), form sheets and check lists. Over a period of 7 months, one study nurse, one research associate and one QM-consultant 124 Oncol Res Treat 2014;37(suppl 1):1–133 were dedicated to create a QM-handbook which comprises the overall quality criteria and aims that had been defined by the biobank and will regularly be checked by internal and external audits. The implementation of the QM-system resulted in certification in November 2011. Summary: Preparing a biobank for certification according to DIN EN ISO 9001 is possible within a 7 months’ time period if dedicated personal and funding is available. The certification has improved the overall QM-performance assuring high-quality sampling and processing of biospecimens in Lübeck. This certification will further serve as basis for the expansion of the QM-system to other ColoNet sites thus enabling highest compatibility among all ColoNet sites. ID 288 Kombination aus Schädeltrepanation und Vakuumtherapie zur Granulationsinduktion bei großen Skalpdefekten E. Valesky, R. Kaufmann, M. Meissner Universitätsklinik Frankfurt, Klinik für Dermatologie, Venerologie und Allergologie, Frankfurt, Deutschland Große Skalpdefekte, die sämtliche Schichten einschließlich des Periosts umfassen, stellen eine Herausforderung dar. Häufig bleiben nur sehr aufwendige Lappenplastiken oder aber die freie Lappenplastik mit mikrovaskulärem Gefäßanschluss, um die Defekte zu verschließen. Diese Operationen sind vielen Patienten aufgrund ihres hohen Alters, ihren Begleiterkrankungen und Ihrer Prognose nicht zuzumuten. Eine einfach durchzuführende Spalthauttransplantation ist aufgrund des fehlenden Periosts nicht möglich. Hier empfiehlt sich eine Trepanation der Tabula externa, um die gefäßführende Diploe zu eröffnen und eine Granulation zu induzieren. Die Bildung des Granulationsgewebes kann sich jedoch über viele Wochen bis Monate hinziehen. Die Gefahr des Austrocknens der Trepanationslöcher besteht trotz regelmäßiger Verbandswechsel. Um den Prozess wesentlich zu beschleunigen und ein Austrocknen zu verhindern, kombinieren wir die Trepanation mit einer Vakuumtherapie. Am Beispiel einer Patientin mit einem großen Angiosarkom des Capillitiums, wird das Vorgehen beschrieben und dargestellt. Nach schnittrandkontrollierter Exzision des Tumors bis auf die Schädelkalotte, wurden im Bereich des 15×17 cm großen Defekts, multiple Trepanationsbohrungen mit dem Rosenbohrer angelegt. Direkt im Anschluss wurde eine Vakuumversiegelung durchgeführt. In 3 Wochen konnte ein flächiges Granulationsgewebe über der Schädelkalotte erreicht und die Patientin erfolgreich Spalthaut transplantiert werden. Die Kombination aus Trepanation und Vakuumtherapie stellt eine effektive Methode der Defektdeckung von großen, alle Schichten umfassenden Skalpdefekten dar, bei denen ein Verschluß mittels Lappenplastiken nicht in Frage kommt. ID 292 New aspects in the development of Bisphosphonaterelated jaw necorsis W. Reich1, M.H.W. Lautner1, D. Wilhems1,2, A.W. Eckert1 Martin-Luther-Universität Halle-Wittenberg, Universitätsklinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie, Halle (Saale), Deutschland 2 Marti-Luther-University Halle-Wittenberg, Institute of Medical Microbiology, Halle (Saale), Deutschland 1 Introduction: Bisphosphonate-related osteonecrosis of the jaws [BRONJ] is a serious side-effect of bisphosphonate treatment. The mechanism behind BRONJ remains unclear. In literature several origins are suggested. An important role play presence of the teeth in the jaw, the other lesions spontaneously develop due to dental prosthesis. Therefore in this study 63 patients were analyzed retrospectively. Materials and methods: A total of 63 patients with a clinical manifest BRONJ were analyzed during 2005 and 2013. The following clinical and histological parameters were collected to a database [SPSS 17.5]: primary diagnosis, treatment and complications, kind of bisphosphonate adminis- Abstracts Inhalt Index tration. Additionally, in 19 cases swabs were taken from acute BRONJ. All microbiological material was collected under standardized conditions (Stuart medium, transport within 4 hours to the laboratory). Results: We found 84 clinical manifest BRONJ lesions. Most of them were localized at the mandibular bone (n = 70), only 14 cases developed at the maxilla. The mean time of bisphosphonate administration was 38 month. Most of them developed after tooth extraction or other dental surgical procedures. We found 95 different bacteria [4.3 strains per specimen]. The predominant bacterial genera were: Streptococci (18x), Neisseria (8x) and members of the family Enterobacteriaceae (7x). The most frequent anaerobes were Prevotella (16x), Fusobacterium (14x) and Peptostreptococcus (8x). Discussion: The mean factors influencing a BRONJ are dental surgical procedures and insufficient prosthetical rehabilitation. In our opinion, other predictors should be suggested for the risk to develop BRONJ. The bacterial contamination is underestimated. As a consequence, an administration with Bisphosphonates will induce a bony necrosis. But only the subsequent bacterial contamination results in the typical clinical manifest BRONJ. ID 357 Vascular anomalies in patients undergoing retroperitoneal lymph node dissection A.K. Thissen, D. Pfister, D. Porres, C. Piper, A. Heidenreich Uniklinikum Aachen, Urlogie, Aachen, Deutschland Anomalies of the renal vessels are clinically silent and might be depicted during CT scanning of the abdomen for staging purposes of urological malignancies. Awareness of these rare anomalies is crucial especially in patients undergoing staging for germ cell tumors to avoid overstaging and unnecessary therapy. We report on the incidence of renal vessel anomalies of patients undergoing RPLND for testis cancer. 245 patients with testicular germ cell tumors underwent primary or secondary RPLND following inductive chemotherapy. Prior to RPLND, all patients underwent abdominal staging by CT scans or by MRI in selected cases. CT scans were reviewed with regard to the detection of vascular anomalies of the vena cava inf., renal veins, renal arteries and iliac vessels. CT findings were correlated with intraoperative findings. Overall, vascular anomalies were encountered in 39 patients (15.9%): retroaortic left renal vein in 10 (4.1%), circumaortic left renal vein in 2 (0.8%), reduplication of the common iliac vein in 1 (0.4%), accessory renal arteries in 14 (5.7%), thrombosis of the inferior vena cava in 12 (4.9%) patients with IIC disease. Anomalies of the renal vein were detected in 10/12 (83%), in 2 cases venous anomalies were falsely diagnosed as lymph node disease in stage I NSGCT. All arterial anomalies were identified preoperatively. CT scan identified caval thrombosis in only 8 cases (68%), 4 cases were identified by an additional MRI of the abdomen. Vascular anomalies are frequently encountered in pts with RPLND for testis cancer and have to be acknowledged during surgery even with negative imaging studies. Retroaortic renal veins represent a potential pitfall of CT imaging resulting in unnecessary therapy; it should be considered in pts with CT suspicious lymph nodes caudal to the renal hilus. IVC thrombosis is associated with advanced disease and is best diagnosed by MRI of the abdomen. ID 387 Lung parenchyma sparing surgery – retrospective study of laser segmental resection for pulmonary malignancies A. Pereszlenyi, S. Eggeling, R.-L. Morgen, J. Strasburg, S. Sklenar Vivantes Lungenkrebszentrum, Thoraxchirurgie, Berlin, Deutschland Objective: Is to prove the feasibility of laser segmental lung resection for primary/secondary pulmonary tumors within the retrospective study. Patients and Methods: Between 02/2009 and 08/2012, 31 patients (18 males, 13 females, mean age 69.7, range 54–85 yrs) underwent Laser Abstracts Segmental Resection (LSR) in our Clinic. The indications for LSR were: non-small cell lung carcinoma (NSCLC) in 19 and pulmonary metastases in 12 patients. The most detected histologic type of NSCLC was adenocarcinoma (n = 11), followed by squamous-cell (n = 6) and large-cell carcinoma (n = 2). The lung metastases of the colorectal-carcinoma (n = 8) was the main indication for pulmonary metastasectomy. The metastases of breast cancer (n = 2), melanoma and anal-carcinoma (one in each) completed this indication group. All LSR were performed by the new Nd YAG laser system of 1318 nm wavelength and up 120 W power output. Results: No intraoperative mortality was recorded. The most common complications after the LSR were prolonged air leakage in 5 and prolonged pleural effusion in 3 patients. Postoperative pneumonia occurred in 3, atrial fibrillation in 2 pts. In none of these patients a bronchial stump insufficiency/ fistula was recorded. Follow-up was completed for all patients with median of 15 Months (0.2–39 Mo). Survival was analyzed according to Kaplan-Meier method with 10 Months 82.5%, 20 Mo 66.7% and 30 Mo 48.2% overall survival. Conclusion: Radical surgical resection is still the therapy of choice in NSCLC treatment. However, laser segmental lung resection represents an optimal treatment eventuality especially for those high risk patients in whom the standard resection – lobectomy is not feasible or performable. ID 393 Basal cell carcinoma of facial skin A.W. Eckert, W. Reich, K. Scheller Martin-Luther-Universität Halle-Wittenberg, Universitätsklinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie, Halle (Saale), Deutschland Basal cell carcinoma is the most frequent human malignancy. Surgical therapy is the common goldstandard. The classic surgical therapy is controversially discussed. A one-stage treatment is favorized by maxillofacial surgeons, whereas dermatologists suggest the two-stage approach including micrographic surgery. We evaluated the recurrence rates in facial skin basal cell carcinomas Based on the clinical courses of more than 7 decades. We analyzed more than 1400 primary basal cell carcinomas and determined the risk to develop a recurrence as a function of tumor size, histological subtype and R-status. The recurrence rate of all primary basal cell carcinomas was 4%. The predesinating factors for developing a recurrence were tumor localization, tumor size and histological subtype, respectively. Significant more reccurences were observed in tumor diameters more than 14 mm. On the other hand, also histological subtype had an influence. Solid forms showed a recurrence of only 1.9%, whereas sclerodermiformic basal cell carcinoma and metatypic subtype had an increased risk of 4.3 and 7.4%. As a consequence, more than 97% of all primary basal cell carcinoma can be treated by surgical removal without any recurrence. It was observed that size, incomplete excision, deep margin involvement, the presence of sclerodermiform or metatypic basal cell carcinoma related to an increase in the probability of recurrence.The following safety distances for successful surgical resection should be considered: 5 mm to remove solid types and 10 mm for surgical removal of sclerodermiformic/metatypic basal cell carcinoma, large or recurrent tumors. We recommend the surgical removal of basal cell carcinoma and direct closure of the defect instead of the more cost-effective micrographic surgery. ID 398 Vaskuläre Dimension onkochirurgischer Interventionen – repräsentative Fallbeispiele des ergänzenden gefäßchirurgischren Managements Z. Halloul1, A. Udelnow1, F. Meyer1 Universitätsklinikum Magdeburg A.ö.R., Arbeitsbereich Gefäßchirurgie, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Magdeburg, Deutschland 1 Einleitung: In der alltäglichen Praxis trifft jeder Chirurg immer wieder auf vaskuläre Probleme, insbesondere im Rahmen ausgedehnter onkochi- Oncol Res Treat 2014;37(suppl 1):1–133 125 Inhalt Index rurgischer oder multiviszeraler Resektionen. Diese erfordern Kenntnisse der speziellen und teils variablen Gefäßanatomie, der gefäßchirurgischen Operationszugänge, aussichtsreicher operationstaktischer Vorgehensvarianten und der speziellen Gefäßersatzmöglichkeiten. Patienten & Methode: Anhand exemplarischer Krankheitsbilder und operativer Situationen werden operationstaktische Entscheidungen und das gefäßchirurgisch- technische Vorgehen demonstriert. Ergebnisse: Traumatische und iatrogene intraabdominelle Gefäßläsionen, spontane intra-abdominelle Blutungen, tumorassoziierte Gefäßinfiltration sowie perivaskuläre Infektionen gehören zu den häufigsten intraund perioperativen Konstellationen. In einem 4-Jahreszeitraum wurden insgesamt 63 Tumor-assoziierte-Operationen durchgeführt (u.a. V. cava: n = 16; Pfortader/Konfluenz: n = 12; A. mesenterica superior n = 2; A. hepatica: n = 3; Truncus coeliacus: n = 2; Aorta/Beckenarterien: n = 7; Halsgefäße: n = 4). Die Eingriffe verliefen gefäßchirurgisch weitestgehend komplikationsarm. Das Grundleiden bestimmte die Prognose. Schlussfolgerungen: In Zentren mit multiviszeralen Rekonstruktionen ist eine spezialisierte Gefäßchirurgie unabdingbar. Ein breites Spektrum der interdisziplinären Zusammenarbeit bei der Operationsplanung und Durchführung kann in indizierten Fällen die Resektabilität mit real erreichbarem R0-Status sichern und die Prognose verbessern helfen. ID 402 Lung-sparing Radical Pleurectomy for Malignant Pleural Mesothelioma: 11-year Single-Center Experience S. Bölükbas1, M. Eberlein2, A. Fisseler-Eckhoff3, J. Schirren1 HSK Wiesbaden, Klinik für Thoraxchirurgie, Wiesbaden, Deutschland Carver College of Medicine, University of Iowa, Division of Pulmonary, Critical Care and Occupational Medicine, Iowa, Vereinigte Staaten von Amerika 3 HSK Wiesbaden, Institut für Pathologie und Zytologie, Wiesbaden, Deutschland 1 2 Objective: To report our 11-year single center experience of malignant pleural mesothelioma (MPM) treated with radical pleurectomy (RP) as surgical arm within a multiimodality approach. Methods: In a prospective, non-randomized study, all patients with histologically proven MPM, clinical stage cT1-3 cN0-2 and without prior treatment for MPM were evaluated for multimodality therapy from 2002 to 2012: Lung-sparing RP followed by 4 cycles of Cisplatin/Pemetrexed. Prophylactic radiation of the chest wall was only performed between 2002 and 2010. Results: One-hundred-two out of 231 consecutive patients underwent RP. 84 out of 102 patients (82%) completed the therapy. Surgical morbidity and mortality were 29.4% and 2.9%. Median survival and 5-year-survival were 26.3 months and 28%, respectively. Progression-free-survival was 13 Mo. The sites of failure were locoregional in 44.1%, distant in 9.8% and both in 13.7%, respectively. Macroscopic complete resection, T1/T2, N0, IMIG stage I/II and age < 70 years were associated with significant prolonged survival in the univariate analyses. Non-epitheloid histology (p = 0.089) and tumor spread at the resected previous incision sites (p = 0.058) showed a trend towards inferior survival. Histology, age ≥ 70 years, T3/T4, IMIG-stage III/ IV and tumor spread at the resected previous incision sites remained independent significant prognostic factors in the multivariate analysis. Conclusions: Lung-sparing RP within a multimodality therapy concept is associated with promising long-term survival. Tumor biology in terms of type of histology, stage and tumor spread at the resected previous incision sites are independent prognostic factors. Patients aged ≥ 70 years should be selected very carefully for multimodality therapy. 126 Oncol Res Treat 2014;37(suppl 1):1–133 ID 410 En-Bloc Resection of pulmonary metastases with infiltration of the spine S. Bölükbas1, T. Dönges1, M. Eberlein2, J. Schirren1 HSK Wiesbaden, Klinik für Thoraxchirurgie, Wiesbaden, Deutschland Carver College of Medicine, University of Iowa, Division of Pulmonary, Critical Care and Occupational Medicine, Iowa, Vereinigte Staaten von Amerika 1 2 Objective: Pulmonary metastases from extrathoracic carcinoma with infiltration of the spine are very uncommon. There is a lack of data with regard tothe benefit of extended pulmonary metastasectomy. The purpose of this study is to describe our surgical en bloc approach and to assess the outcome and survival. Methods: We retrospectively analyzed all patients, who underwent pulmonary resection for metastatic disease from extrathoracic carcinoma with en bloc hemivertebrectomy or total vertebrectomy between January 2003 and December 2012. Survival was estimated by the Kaplan-Meier method. Log-rank analyses were used to compare groups. Results: Location of the primary cancer in 12 patients (age 51.8 ± 18.9 years, 8 males) were testicular (n = 3), renal (n = 3) and other (n = 6), respectively. Median time interval between therapy of the primary cancer and metastasectomy was 31.6 ± 1.9 months. Seven patients (58%) had induction therapy before surgery. Indications for metastasectomy were curative intend in nine and palliative intend (neurologic impairment, instable spine) in three patients, respectively. Resections were complete in 9 patients (75%). Morbidity and mortality were 33% and 0%. Median, 1and 5-year survivals were 48.0 ± 14.0 months (CI 95% 20.6-75.4), 83% and 35%, respectively. Surgeries with palliative intend (p = 0.003) and age ≥ 65 years (p = 0.003) were associated with inferior survival. Conclusions: Pulmonary metastasectomy with en bloc hemivertebrectomy or total vertebrectomy can be performed safely. These extended resections in curative intend offer promising long-term survival in highly selected patients. Patients aged ≥ 65 years should be selected very carefully for surgery. ID 415 Are chemotherapy and radiotherapy risk factors for postoperative delirium in elderly cancer patients undergoing elective surgery? Observational study in two tertiary university hospitals. B. Neuner1, M. Schmidt1, E. Weiss-Gerlach1, V. von Dossow-Hanfstingl2, K. Hartmann1, C. Spies1 Charité – Universitatsmedizin Berlin, Klinik für Anästhesiologie mit Schwerpunkt operative Intensivmedizin, Berlin, Deutschland 2 LMU München, Dept. of Anesthesiology, München 1 Introduction: Many elderly cancer patients undergo surgery. Age and impaired physical status are risk factors for post-operative delirium (POD), a cognitive disorder with disorientation, hallucinations and disturbance of vigilance. Objectives: To evaluate the independent association of pre-operative chemotherapy and radiotherapy on POD in ≥ 65 year old cancer patients. Methods: Between 02- 2011 and 09-2012 and after ethical committee approval and written informed consent the study was conducted in 2 tertiary university hospitals in Germany. Patients were categorized according to the American Society of Anesthesiologists physical status classification system (ASA PS) score. Post-operatively patients were screened for POD using the Nursing Delirium Screening Scale (Nu-DESC) respectively the Confusion Assessment Method for the ICU (CAM-ICU) within 7 days post-operative. Multivariate analysis was by logistic regression analysis. Results: Overall 658 patients (mean age 71.8 years, 68.4% males) with prostate cancers (38.8%), ovarian cancers (13.7%), other cancers of the genito-urinary tract (16.0%), upper gastroinstestinal tract (21.1%) and colorectal cancers (10.5%) were included. Preoperatively 77 patients (11.7%) had received chemotherapy and 27 (4.1%) radiotherapy. Within the first 7 days after operation 61 patients (9.3%) developed POD. In Abstracts Inhalt Index multivariate analysis adjusted for age, gender, ASA PS score and tumor site, study participants after preoperative chemotherapy were at decreased risk for POD, Odds Ratio = 0.23 (95%-confidence interval (0.07–0.73)), p = 0.012 while study participants after radiotherapy showed a tendency for increased POD: OR = 3.1 (95%-CI (0.9–10.3)), p = 0.07. Conclusion: Pre-operative chemotherapy in cancer patients is associated with post-operative delirium. Tumor and Cell Biology cells, this effect was almost completely abrogated by Nrf2. Accordingly, p38- and Smad3-phosphorylation was diminished whereas p42/ p44-phosphorylation was enhanced under these conditions. Moreover, Nrf2 induces a migratory phenotype in HPDE cells though inhibiting TGF-b1 associated EMT-characteristics. Interestingly, krasG12V expression is dispensable for these effects in HPDE cells. Our data show that Nrf2 is induced under inflammatory conditions and counteracts the anti-proliferative function of TGF-b1 already in non-malignant pancreatic ductal epithelial cells. This could be a mechanism by which the anti-tumorigenic function of TGF-b1 is suppressed, also underscoring the pro-tumorigenic role of Nrf2 that can manifest already in early stages of pancreatic ductal adenocarcinoma development. ID 081 Interlude of cGMP and cGMP/protein kinase G type I in pancreatic adenocarcinoma cells S. Karakhanova, J. Werner, A. Bazhin Chirurgische Uniklinik Heidelberg, Heidelberg, Deutschland cAMP and cGMP signaling is important both for normal and cancer cells. This signaling is controlled by adenylyl and guanylyl cyclases (GC) and cyclic nucleotide phosphodiesterases (PDE). One of the direct targets for cGMP is protein kinase G (PKG). The main aim of this work was to investigate cGMP and PKG signaling in pancreatic adenocarcinoma (PDAC) cells. PKG activity, cGMP and calcium level were measured with the CycLex Cyclic GMP dependent protein kinase (cGK) Assay Kit, with the DetectX® Cyclic GMP Colorimetric EIA Kit, and with the Fluo-4 NW Calcium Assay Kit, correspondingly. Proteome ProfilerTM Array was done using Human Phospho-Kinase Array and Human Phospho-MAPK Array Kits. Here, we show for the first time that functional PKGI is expressed in PDAC cells. We demonstrate that the specific PKGI inhibitorDT3 induces cytotoxicity through necrosis and reduces proliferation and migration of PDAC cells. Besides, ERK1/2 and p38 can be considered as potential targets for PKGI in PDAC cells. Furthermore, we show that PDE and NO-GC regulate the cGMP level in PDAC cells affecting proliferation of the cells. cGMP and PKG signaling may be a target for developing new therapeutical approaches for PDAC. ID 127 The anti-oxidative transcription factor Nuclear factor E2 related factor-2 (Nrf2) counteracts the effect of TGF-b1 on proliferation in pancreatic ductal epithelial cells – a protumorigenic function of Nrf2? M. Kruppa1, S. Arfmann-Knübel2, R. Simon3, G. Sauter3, J.R. Izbicki4, H. Schäfer2, S. Sebens1 UKSH Campus Kiel, Institut für Experimentelle Medizin, AG Inflammatorische Karzinogenese, Kiel, Deutschland 2 UKSH Campus Kiel, Klinik für Innere Medizin I, Labor für Molekulare Gastroenterologie & Hepatologie, Kiel, Deutschland 3 Universitätsklinikum Hamburg-Eppendorf, Institut für Pathologie, Hamburg, Deutschland 4 Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Hamburg, Deutschland 1 Nuclear factor E2 related factor-2 (Nrf2) is an oxidative stress inducible transcription factor mediating cytoprotective responses. Thereby, Nrf2 protects e.g. epithelial cells exposed to inflammation from oxidative cell damage and mutagenesis supporting an anti-tumorigenic effect of Nrf2. However, Nrf2 is deregulated in many tumors and confers therapy resistance, thus pointing to a pro-tumorigenic role. A similar duality in tumorigenesis is known for the Transforming Growth Factor-beta 1 (TGF-b1). Based on the observation that activated Nrf2 (phospho-Nrf2) is present in pancreatic ductal epithelium during chronic pancreatitis (CP) and in precursor lesions of PDAC (IPMNs), this study aimed at elucidating the combined effects of Nrf2 and TGF-b1 on proliferation of HPDE pancreatic ductal epithelial cells as well as the underlying signalling pathways. While TGF-b1 treatment markedly reduced the proliferation of HPDE Abstracts ID 128 Regulatory T-cells and CD4+T-effector cells both mediate epithelial-mesenchymal transition in pancreatic ductal epithelial cells E. Grage-Griebenow1, L. Goebel1, A. Gorys1, O. Helm1, R. Mennrich1, S. Freitag-Wolf2, I. Vogel3, T. Becker4, M. Ebsen5, C. Röcken6, D. Kabelitz7, H. Schäfer8, S. Sebens1 Institute für Experimentelle Medizin, UKSH Campus Kiel, AG Inflammatorische Karzinogenese, Kiel, Deutschland 2 UKSH Campus Kiel, Institut für Medizinische Informatik und Statistik, Kiel, Deutschland 3 Städtisches Krankenhaus, Chirurgische Klinik, Kiel, Deutschland 4 UKSH Campus Kiel, Klinik für Allgemeine Chirurgie und Thoraxchirurgie, Kiel, Deutschland 5 Städtisches Krankenhaus, Institut für Pathologie, Kiel, Deutschland 6 UKSH Campus Kiel, Institut für Pathologie, Kiel, Deutschland 7 UKSH Campus Kiel, Institut für Immunologie, Kiel, Deutschland 8 UKSH Campus Kiel, Klinik für Innere Medizin I, Labor für Molekulare Gastroenterologie & Hepatologie, Kiel, Deutschland 1 Progression of pancreatic ductal adenocarcinoma (PDAC) is characterized by an accumulation of CD4+ T-cells in the tumoral stroma. Regulatory T-cells (Tregs) and effector T-cells (Teffs) are the most prominent CD4+ T-cell subsets being abundant already in chronic pancreatitis (CP). Recent reports indicate that epithelial-mesenchymal transition (EMT) might be induced in the ductal epithelium already during chronic inflammation promoting PDAC development. This study aimed to investigate the impact of CD4+ T-cells on EMT induction in human pancreatic ductal epithelial (HPDE) cells in vitro and to correlate these data with findings from immunohistochemical analysis of pancreatic tissues from CP and PDAC patients. [CD4+CD25+CD127-CD49d-FoxP3+]Tregs and [CD4+CD25-CD127+ CD49d+FoxP3-]effector T-cells (Teffs) isolated from leukocyte concentrates of healthy donors by magnetic bead separation were directly co-cultured for 72 hours with HPDE cells. Compared to HPDE cells cultured alone, not only Treg co-cultured but also Teff co-cultured HPDE cells exhibited a markedly upregulated expression of the mesenchymal marker proteins vimentin and L1CAM, whereas no alteration in the expression of the epithelial marker e-cadherin was noted. In line with this finding, the expression level of both mesenchymal marker proteins in the pancreatic ductal epithelium was greater in PDAC than in CP tissues correlating with elevated numbers of CD4+ T-cells. In summary, these data point to a common role of Tregs and CD4+ Teffs in EMT induction in pancreatic ductal epithelial cells already in CP. This supports the view that EMT commences early during inflammation paving the way for PDAC development. Oncol Res Treat 2014;37(suppl 1):1–133 127 Inhalt Index ID 166 Expression of human aryl hydrocarbon receptor and ARNT is upregulated after chemotherapy in recurrent glioblastoma multiforme M. Timmer, R. Tjiong, G. Röhn, R. Goldbrunner Uniklinik Köln, Allgemeine Neurochirurgie, Köln, Deutschland The aryl hydrocarbon receptor (AhR) is a transcription factor, which has been attributed a role in human cancerogenesis and TGF-b signaling. The endogenous tumor-promoting ligand of the human AhR kynurenine was discovered recently. It is constitutively generated by tumor cells via tryptophan-2, 3-dioxygenase (TDO), a neuron-derived tryptophan-degrading enzyme. We used real-time RT-PCR to quantify the expression of AhR, TDO, the AhR nuclear translocator (ARNT), and the repressor of AhR (AHRR). We examined a set of 70 human glioma samples representing the differences between the three degrees of malignancy (WHO grade II-IV), primary and recurrent gliomas, pure and mixed astrocytic tumors, and with and without radio- and/or chemotherapy. We also studied whether the expression profile changes as the same tumor progresses in 20 individual patients. Both, the expression of AhR and ARNT were significantly increased after chemotherapy (CTx). The AhR was upregulated from 0.69 before CTx to 3.49 after CTx in secondary GBM and from 0.76 to 1.51 in primary GBM respectively (p = 0.003). The mRNA expression of ARNT was increased from 1.37 before CTx to 2.7 after CTx in secondary- and from 0.86 to 1.68 in primary GBM (p = 0.009). In contrast, TDO expression was downregulated during temozolomide CTx in GBM from 0.77 to 0.35 (p = 0.03). Moreover, ARNT was significantly upregulated in grade II and grade III astrocytomas compared to peritumoral tissue (p < 0.0001). These results provide evidence for an important pathophysiological role of the AhR with profound implications for cancer and immune biology and could have broad implications for potential targeted therapies. ID 189 Isolation of circulating tumor cells in vivo by the CellCollector™ technology S. Herold1, R. Hoda2, L. Gasiorowski3, P. Nowaczyk4, K. Haubold1, W. Dyszkiewicz5, D. Murawa4, G. Theil2, B. Długaszewska1, K. Lücke1 GILUPI GmbH, Potsdam, Deutschland Martin Luther University, Halle, Deutschland 3 Medical University Poznan, Department of Thoracic Surgery, Poznan, Polen 4 Wielkopolska Cancer Centre, Poznan, Polen 5 Medical University Poznan, Poznan, Polen 1 2 Background: Circulating tumor cells (CTCs) are discussed as a prognostic biomarker. Whereas current methods isolate CTCs in vitro; the novel CellCollector™ is an in vivo technology. The aim was to assess the CellCollector™ system with non-small cell lung cancer (NSCLC), breast cancer (BC), colorectal cancer (CRC) and prostate cancer (PC) patients, and to compare it to the CellSearch® method. Methods: The device was inserted in a cubital vein via a standard cannula for thirty minutes. CTCs were captured by an antibody directed against the epithelial cell adhesion molecule (EpCAM) on the CellCollector™ surface. To confirm the CTCs’ binding, immunohistochemical staining against EpCAM/Cytokeratins and CD45 was performed. More than 450 applications of the CellCollector™ in cancer patients and over 50 controls were performed. Samples of 126 cancer patients and 15 control subjects were also tested in the CellSearch® system. Results: The device was well tolerated in more than 500 applications without side effects. A direct comparison of the CellCollector™ and CellSearch® resulted in detection rates of 74.5% and 18.2%, respectively. Specifity rates were 91% and 93%, respectively. Regardless of the disease 128 Oncol Res Treat 2014;37(suppl 1):1–133 stage, in nearly all compared samples the number of CTCs detected with the CellCollectorTM was higher or equal to CellSearch®. Conclusions: With a detection rate of over 75% this new device overcomes present limitations in CTC-enrichment. Future implementation into clinical practice may improve early detection, prognosis and therapy monitoring of cancer patients. Captured CTCs are ready for molecular characterization and will help to establish personalized treatment regiments. ID 201 microRNA-449 depletion promotes chronic obstructive pulmonary disorders independently of tobacco smoke exposure M. Lizé, A. Klimke, C. Herr, M. Schuldt, R. Bals, M. Kessel, M. Dobbelstein Institut für Molekulare Onkologie, AG Dobbelstein, Göttingen, Deutschland MicroRNA-449 expression is associated with apoptosis (p53 regulation) and ciliated differentiation (notch regulation). It is specifically expressed in the airway epithelia. A knockdown of miR-449 was shown to inhibit ciliogenesis in a frog model. To rigorously assess the function of miR-449 in vivo, we engineered a mouse strain with global deletion of the miR-449 locus. Against all expectations, the genetic ablation of miR-449 did not cause an obvious ciliary phenotype, and this is not due to a compensatory up-regulation of its homologues miR-34abc. The bronchial epithelium is slightly affected with a decrease in Clara cells and an increase in Goblet cells. To evaluate the role of miR-449 in the regeneration of airway epithelia, we exposed the mice to long-term cigarette smoke. Lung function analysis revealed typical chronic obstructive pulmonary disorder (COPD) symptoms in the smoke-exposed mice regardless of their miR-449 status. Surprisingly, the non-exposed miR-449 knockout animals (KO) acquired COPD symptoms with age. A Muc5ac up-regulation was observed in all COPD cohorts, characteristic of Goblet cell hyperplasia and enhanced mucus production. This was accompanied by the induction of genes responsible for regeneration and proliferation: the replication marker Mcm3, the CDK inhibitor p27 and Sox2, a marker for stem cells. Additionnally, the miR-449 depleted control mice have more macrophages in the lungs, indicative of inflammation. To conclude, miR-449 is not required for ciliogenesis in the mouse but its loss promotes COPD probably through Goblet cell hyperplasia, enhanced inflammation and hyperproliferation. ID 215 miR-199b-3p: A novel potential growth inhibitor in PDAC H. Zöllner, A. Maghnouj, S. Hahn Ruhr Universität Bochum, Molekulare Gastroenterologische Onkologie, Bochum, Deutschland Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths worldwide, due to a late detection and lack of specific therapeutic targets and ineffective therapies. Novel strategies for both the diagnosis and treatment of this disease are urgently needed. MicroRNAs (miRNAs) are small (~21–25 nucleotides), endogenous, noncoding RNAs that are involved in varoius biological processes through suppression of target gene expression. Rapidly accumulating evidence indicates that the expression of miRNAs is deregulated in cancer. This provides potential applications for cancer therapy as well as for early tumor detection. Characterization of the ‘pancreatic miRNome’ in normal and in PDAC tissue demonstrated that miR-199b was a downregulated miRNA in this cancer type but not in normal tissue. To elucidate its potential biological role in PDAC, miR-199b-3p was overexpressed via a doxycycline-inducible lentiviral vector system in several PDAC cell lines. This induced growth inhibition in all cell lines, attributable to a cell cycle arrest at the G1 phase. In addition, miR-199b-3p effect on tumor growth was examined by an in Abstracts Inhalt Index vivo nude mouse xenograft model using PDAC cell lines. Mice bearing cells inducibly overexpressing miR-199b-3p developed tumors more slowly compared to control cells after induction with doxycycline. Combining global gene expression analyses of miR-199b-3p xenograft derived from transgenic PDAC line PancTuI with in silico miRNA target expression, we identified potential miRNA-199b-3p targets. However, the functional characterization of these genes and their role in carcinogenesis as well as the underlying mechanism of the G1 cell cycle arrest have yet to be explored. ID 229 Coherence of polarization phenotype of tumor associated macrophages, cytokine levels and progression free survival in ovarian cancer M. Jansen1, S. Reinartz1, R. Müller2, S. Müller-Brüsselbach2, T. Schumann2, F. Finkernagel2, A. Wortmann2, W. Meissner2, M. Krause2, U. Wagner1 Uniklinikum Gießen und Marburg GmbH, Klinik für Gynäkologie, gynäkologische Endokrinologie und Onkologie, Marburg, Deutschland 2 Universität Marburg, Institut für Molekularbiologie und Tumorforschung, Marburg, Deutschland 1 Background: Tumor associated macrophages (TAMs) are present in the ascites fluid of advanced serous ovarian cancer. The anti-inflammatory M2-polarization on TAMs has been thought to be important for development, progression and metastasizing of ovarian carcinoma. We hypothesized that a certain kind of phenotype of TAMs is associated with a worse outcome in primary advanced ovarian cancer. Methods: We analyzed the polarization phenotype of ascites derived TAMs and the cytokine milieu of ascites of 30 women. Ascites fluid was obtained during initial debulking surgery for primary ovarian cancer. Preparation of TAMs, FACS analysis for surface expression markers and gene profiling were described earlier. Cytokine analysis was performed with commercially available ELISAs. The experimental and clinical data (e.g. progression free survival (PFS)) of 20 patients were available for this analysis. Results: Seventeen out of these featured a mixed- polarization phenotype of the M1/M2 classification. The M2- surface marker CD 163 showed an inverse association with PFS (p < 0,01). CD 163 expression was positively correlated with the concentration of the cytokines IL-6 and IL-10 (p < 0,01) is ascites fluid; both cytokines are active to induce CD 163 expression. Consequently, PFS was likewise found to be inverse associated with the concentration of these cytokines (p < 0,01). Conclusion: The presence of TAMs with high CD 163 expression was demonstrated, which correlated positively with IL-6 and IL-10 levels in ascites but inversely with PFS. This results warrant further investigations of TAMs in ovarian cancer. ID 240 CA125 (MUC16) gene silencing suppresses tumour growth through activation of PI3K/Akt signaling pathways of ovarian and breast cancer cells S. Kage, S. Reinartz, U. Wagner Universitätsklinikum Giessen und Marburg GmbH, Klinik für Gynäkologie, Gynäkologische Endokrinologie und Onkologie, Marburg, Deutschland Background: The tumour associated antigen CA125 (MUC16) is commonly expressed in ovarian cancer and can also be detected in other tumour of epithelial origin. The aim of the present study was to investigate the impact of MUC16 gene silencing on the growth properties of ovarian and breast cancer cells. Methods: Four ovarian and one breast cancer cell lines with differential MUC16 expression were transfected with MUC16 shRNA. Successful silencing of MUC16 was detected by quantitative real-time PCR. We analysed the cellular effects linked to oncogenesis, such as proliferation, cell cycle and apoptosis after transient or stable MUC16 knockdown. Signaling pathways influenced by MUC16 were then examined by Western Blot. Abstracts Results: The growth of all tested MUC16+ tumour cells was significantly suppressed by induction of caspase-dependent apoptosis after transient transfection with MUC16 shRNA, irrespective of the initial MUC16 expression level and cancer origin. Growth inhibition could be confirmed in stable MUC16 knockdown clones, albeit caspase-dependent death pathways seemed no longer be activated. Furthermore Akt activation was suppressed in all stable MUC16 knockdown clones, which correlated with translocation of AIF to the nucleus and downregulation of the anti-apoptotic Bcl-2. Conclusion: Our results provide evidence for a central role of MUC16 in cancer cell survival pathways regulated through the PI3K/Akt signaling pathway. ID 341 Chronic inflammation-mediated tumor cell proliferation and chemoresistance is driving tumor progression in pancreatic cancer T. Grimmig1, R. Mönch1, K. Höland1, C.- T. Germer2, A.M. Waaga-Gasser1, M. Gasser2 Universitätsklinikum Würzburg, Chirurgische Klinik I, Molekulare OnkoImmunologie, Würzburg, Deutschland 2 Universitätsklinikum Würzburg, Chirurgische Klinik I, Würzburg, Deutschland 1 Background: Recent data demonstrate chronic inflammation associated with Toll-like receptor (TLR) signalling mediates carcinogenesis and tumor progression. The aim of this study was to determine the role of specifically TLR7 and TLR8 expression and signalling in cell proliferation and chemoresistance for pancreatic cancer. Methods: Gene and protein expression of TLR7, TLR8, NF-kB and COX-2 in pancreatic cancer (UICC stages II and III), chronic pancreatitis and normal pancreatic tissue as well as in the human pancreatic cancer cell line PANC1 was examined. For further in vitro studies TLR7 or TLR8 overexpressing PANC1 cell lines were generated. Effects of TLR overexpression and stimulation on cell proliferation and chemoresistance to 5-FU were analysed by MTS and AlamarBlue assays. Results: Increased TLR expression was found in late stage tumors compared to earlier stages and chronic pancreatitis. No or occasionally low expression was detected in normal pancreatic tissue. Stimulation of TLR7 or TLR8 overexpressing PANC1 cells with R848 resulted in elevated expression levels of NF-kB and COX-2. Additionally, increased cell proliferation and reduced chemosensitivity were demonstrated under TLR stimulation. Conclusion: Our data demonstrate for the first time a stage-dependent increase in TLR7 and TLR8 expression in pancreatic cancer and chronic pancreatitis. Additionally, our findings in TLR7 or TLR8 overexpressing PANC1 cells suggest chronic inflammation-mediated TLR7/8 signalling leading to cancer cell proliferation and chemoresistance. These findings emphasize the particular role of TLR7 and TLR8 in pancreatic cancer and their relevance as potential targets for cancer therapy. ID 348 The functional integrity of c-Myc-specific tumor metabolism is determined by a novel interaction of HIF-1α and Annexin A1 N. Rohwer1, F. Bindel2, C. Grimm3, H. Lehrach3, M. de Graauw4, B. Wiedenmann1, S. Kempa2, T. Cramer1,5 Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Berlin, Deutschland 2 Max-Delbrück-Centrum für Molekulare Medizin, Berlin Institute for Medical Systems Biology, Berlin, Deutschland 3 Max-Planck-Institut für Molekulare Genetik, Berlin, Deutschland 4 Universiteit Leiden, Amsterdam, Niederlande 5 Molekulares Krebsforschungszentrum, Berlin, Deutschland 1 Solid tumors are characterized by robust therapy resistance. Hence, the identification of pathways regulating resistance is a central prerequisite to improve cancer therapy. Our earlier work characterized the hypox- Oncol Res Treat 2014;37(suppl 1):1–133 129 Inhalt Index ia-inducible factor HIF-1α as a pivotal mediator of therapy resistance. We established a stable, shRNA-mediated inhibition of HIF-1α and noted that gastric cancer cells were able to compensate the loss of HIF-1α. To further characterize the underlying mechanisms, we performed transcriptome analyses. We found a group of ~30 genes that were upregulated in HIF-1α-deficient cells and hypothesized that these genes confer survival upon loss of HIF-1α. We further elucidated the role of Annexin A1 (ANXA1), one of the identified genes. Strikingly, simultaneous knockdown of HIF-1α and ANXA1 resulted in a complete growth arrest. Given the importance of HIF-1α for tumor metabolism we characterized the central carbon metabolism. Interestingly, this revealed a robust impairment of both canonical and reductive glutamine metabolism in HIF-1α/ ANXA-deficient cells, reasoning for reduced TCA cycle activity. This notion led us to characterize the expression of the oncogene c-myc. Strikingly, c-myc expression was completely lost upon combined inhibition of HIF-1α and ANXA1. Retroviral transfection of c-myc into HIF-1α/ ANXA1-deficient cells was able to rescue proliferation supporting the involvement of c-myc in the observed growth defect. Taken together, ANXA1 is able to compensate the loss of HIF-1α in cancer cells, a hitherto unrecognized role for ANXA1. Furthermore, this work has identified an interaction between HIF-1α and ANXA1 in the regulation of c-myc with potential importance for cancer pathogenesis and therapy. ID 360 Functional Connection between C/EBPβ and Cyclin D1 in Tumorigenesis J. Schiller, A. Leutz Max-Delbrück-Center for Molecular Medicine, Berlin, Deutschland Overexpression of cyclin D1 is a very frequent event in human tumorigenesis. Cyclin D1 is mainly known as a Cdk-dependent regulator of pRb, catalyzing entry into the cell cycle. Several studies suggest, however, that nuclear gene and chromatin regulatory functions of cyclin D1 are more important in tumor formation than its function in controlling pRb. A previous gene profiling meta-analysis of more than 500 tumor samples revealed consistent co-expression of the transcription factor C/EBPβ with cyclin D1 target genes. C/EBPβ regulates cell differentiation and proliferation and has been shown to be an important factor in cyclin D1-overexpressing malignancies such as multiple myeloma and breast cancer. We set out to unravel the molecular connection between cyclin D1 and C/EBPβ and show that cyclin D1 binds to C/EBPβ via two binding sites. Binding is tightly regulated by structural C/EBPβ alterations that depend on post-translational modifications. The type of interaction has severe impact on cyclin D1 biology: N-terminal C/EBPβ interaction causes cytoplasmic retention and proteasomal degradation of cyclin D1, while C-terminal C/EBPβ binding promotes nuclear localization of cyclin D1.The interaction between both transcription factors also results in altered binding of partner proteins, including Cdk4 and the arginine methyltransferase PRMT5, suggesting modified outcome in gene regulation. Our data suggest a model where C/EBPβ regulates nuclear cyclin D1 function by controlling its sub-cellular localization and stability. When C/ EBPβ functions are deregulated, nuclear cyclin D1 may accumulate and support tumorigenesis. This model also entails a pharmacological potential of altering enzymes that modify the C/EBPβ structure. 130 Oncol Res Treat 2014;37(suppl 1):1–133 ID 386 Novel apoptosis inducers in the acute lymphatic leukemia cell line JM N. van den Höfel1, E. Carosati2, G.M. Randazzo2, A. Abo Houf1, R. Mannhold3, G. Cruciani2, S. Funke1, S. Heikaus1, H.E. Gabbert1, C. Mahotka1 Universitätsklinikum Düsseldorf, Insitut für Pathologie, Düsseldorf, Deutschland 2 University of Perugia, Chemometrics and Cheminformatics, Perugia, Italien 3 Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland 1 Aims: Dysregulation of apoptosis is an early hallmark of cancer. The balance between pro- and anti-apoptotic factors is important for drug responses. The IAPs are – as caspase inhibitors – key factors of the core apoptosis machinery and aberrantly expressed in various tumors. Inhibiting IAPs renders tumor cells potentially responsive for apoptosis inducing signals. Here we report the discovery of novel apoptosis inducers, based on a fast and efficient ligand based virtual screening approach. Methods: Multistep ligand based virtual screening, proliferation and apoptosis assays, flow cytometry, Western Blotting. Results: (1) A ligand based virtual screening approach delivered 31 hit candidates. (2) All compounds were tested for solubility with different solvents in vitro and under cell culture conditions: 7/31 compounds aggregate and show crystal-like structures at approximately 10–100 µM. (3) Time-dependent dose-response-curves reveal 10–40% cell death for 3 compounds, designated LBPS-1, -3, and -5 in a proliferation assay. (4) Enhancement of compounds by death receptor ligand TRAIL does not increase dose-effect relation. (5) Determination of cell death by Nicoletti staining reveals that a predominant part of cell death is due to apoptosis. (6) Analysis of intracellular caspase activity shows an activation of caspase-3 to be correlated with peak levels of apoptosis. (7) Degradation of the cIAP-1 target might hint at the putative molecular mode of action. (8) Tumor type independency of the action of the novel compounds is shown in different tumor cell lines. Conclusion: Virtual screening is a powerful tool to detect new chemotypes of apoptosis promoting agents for the treatment of cancer. Abstracts Inhalt Index Tyrosine Kinase Inhibitors ID 040 Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: The phase 3 DECISION trial. M.S. Brose1, C. Nutting2, B. Jarzab3, R. Elisei4, S. Siena5, L. Bastholt6, C. de la Fourchardiere7, F. Pacini8, R. Paschke9, Y.K. Shong10, S.I. Sherman11, J.W.A. Smit12, J. Chung13, C. Kappeler14, I. Molnar13, M. Schlumberger15 The University of Pennsylvania, Abramson Cancer Center, Philadelphia, Vereinigte Staaten Von Amerika 2 Royal Marsden Hospital, London, Großbritannien 3 Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice, Polen 4 University of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italien 5 Ospedale Niguarda Ca’ Granda, Milan, Italien 6 Odense Universtiy Hospital, Odense, Dänemark 7 Hospices Civils-Centre Anticancereux, Lyon, Frankreich 8 University of Siena, Unit of Endocrinology, Siena, Italien 9 Leipzig University, Department for Endocrinology and Nephrology, Leipzig, Deutschland 10 University of Ulsan College of Medicine, Asan Medicine Center, Seoul, Korea, Republik 11 The University of Texas, MD Anderson Cancer Center, Houston, Vereinigte Staaten Von Amerika 12 Radboud University Nijmegen Medical Center, Department of Internal Medicine, Nijmegen, Niederlande 13 Bayer Healthcare Pharmaceuticals, Montville, Vereinigte Staaten Von Amerika 14 Bayer Pharma AG, Berlin, Deutschland 15 Institut Gustave Roussy, Villejuif, Frankreich 1 Background: Sorafenib, an orally active inhibitor of VEGFR1-3 and Raf kinases, has shown promising clinical activity in single-arm phase 2 studies in radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). The double-blind, randomized, multi-center phase 3 DECISION trial examined sorafenib efficacy and safety vs placebo in patients with progressive RAI-refractory DTC (NCT 00895674). Methods: Patients with locally advanced/metastatic RAI-refractory DTC who progressed in the preceding 14 months were randomized 1:1 to sorafenib 400 mg bid po or placebo. Placebo patients were allowed to receive sorafenib open-label upon progression. The primary endpoint was progression free survival (PFS) assessed every 8 wks by independent radiologic review using modified RECIST 1.0 and analyzed by stratified log-rank statistics at α = 0.01 (one-sided). Secondary endpoints included overall survival (OS), response rate (RR; complete + partial response [PR]), and safety. Results: A total of 417 patients were randomized (207 to sorafenib and 210 to placebo); median age 63 yr, 52% female. Tumor histology by independent assessment was 57% papillary, 25% follicular and 10% poorly differentiated. 96% of patients had metastatic disease; the most common metastatic lesions were lung (86%), lymph node (51%) and bone (27%). The primary endpoint was met: median PFS 10.8 months (sorafenib) vs 5.8 months (placebo); HR 0.587, 95% CI 0.454–0.758, p. Conclusions:Sorafenib significantly improved PFS compared with placebo in patients with progressive RAI-refractory DTC. Tolerability was consistent with the known sorafenib safety profile. Abstracts ID 107 Specific inhbitor of ERK 1/2 AEZS-131: Anticancer activity in models of human cancers with and without overactivation of ERK1/2 J. Engel1, A. Hönig2, S. Meyer2, J. Dietl2, B. Kwok1, O. Ortmann1, J. Hahne2 Medizinische Universität Regensburg, Klinik für Frauenheilkunde und Geburtshilfe, Regensburg, Deutschland 2 Universitätsfrauenklinik Würzburg, Würzburg, Deutschland 1 Introduction: The RAS/RAF/MEK/ERK pathway is activated in more than 30% of human cancers. The current study investigates specific ERK inhibitor AEZS-131 in models of endometrial, ovarian and breast cancer with and without mutations in the MAPK-pathway. Methods: ERK-inhibition was determined by analyzing phosphorylation status of downstream target of ERK1/2 RSK-1. Mode of cell death induced by AEZS-131 was explored by FACS-analysis. Cytoxicity was evaluated by MTT-assay in 3 endometrial, 6 breast and 5 ovarian cancer cell lines. Potential synergy with the host´s tumour immune response was evaluated by NK-cell lysis assay. Results: In MDA-MB-435s cells RSK-1 phosphorylation was reduced by 50% subsequent to treatment with AEZS-131. Treatment with AEZS131 dose-dependently induced necrotic cell death in the majority of the cell lines. Accordingly, in those cells cytotoxicity induced by AEZS-131 could not be inhibited by a pan-caspase inhibitor. AEZS-131 effectively inhibited cell growth with IC50 in the low mM range in 3 ovarian, 5 breast and 3 endometrial cancer cell lines, of which 2 mammary and 2 endometrial harboured mutations in the ERK-pathway. The compound was ineffective in 1 breast and 2 ovarian cancer lines without mutations in the ERK-pathway. Treatment with AEZS-131 dose dependently increased cell lysis by natural killer cells, suggesting potential synergistic effects with the host anti-tumour response. Discussion: We could demonstrate good anti-tumour activity of ERK1/2 inhibitor AEZS-131 in a panel of breast, ovarian and endometrial cancers in -vitro. Cytotoxicity was pronounced in cancers harbouring a mutation in the MAPK-pathway, but did also occur in cancer cell lines negative for such mutations. ID 202 Circulating tumor cell composition and molecular markers in metastasized renal cell carcinoma (mRCC) T. Gauler, I. Nel, K. Bublitz, L. Lazaridis, M. Schuler, A.-C. Hoffmann Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Essen, Deutschland Background: Circulating tumor cell (CTC) numbers have been studied as a timely and minimally invasive tool for monitoring the therapy response in advanced cancers. We recently described a detection method based on multiparameter immunofluorescence microscopy (MPIM) that amongst others includes epithelial markers such as CK or EpCAM, mesenchymal and stem cell-like markers. Here, we have studied different subtypes of CTC in patients with metastatic renal cell cancer (mRCC) and their association with the response and progression-free survival (PFS) to antiangiogenic therapies. Furthermore we evaluated the correlation of angiogenesis related molecular markers with these individual CTC profiles. Methods: Peripheral blood was drawn from 16 consecutive mRCC patients receiving antiangiogenic therapies. Individual CTC profiles were analyzed by MIPIM. The expression of angiogenesis-related genes was studied by quantitative RT-PCR analysis in EpCAM-enriched and depleted CTC fractions. Results were correlated to treatment outcomes. Results: Multiple CTC subtypes with epithelial, mesenchymal, stem celllike or mixed-cell characteristics were detected. The presence and quantity of N-cadherin-positive or CD133-positive CTC was associated with inferior PFS following antiangiogenic therapy. High mRNA expression of HIF1A, VEGFA, KDR1 and FGFR were associated with response to first- Oncol Res Treat 2014;37(suppl 1):1–133 131 Inhalt Index line antiangiogenic therapy. There was an inverse correlation between high expression of HIF1A, VEGFA, KDR1 and FGFR and the presence of N-cadherin-positive and CD133-positive CTC. Conclusions: Patients with mRCC exhibit distinct CTC profiles, which associate with the outcome of antiangiogenic therapies. Prospective evaluation of phenotypic and genetic CTC profiling as prognostic and predictive marker is warranted. ID 422 BARIS: A phase I trial to evaluate the safety and tolerability of combined BIBF 1120 and RAD001 in solid tumors and to determine the maximum tolerated dose (MTD) of the combination M. Scheffler1, M. Gardizi1, M. Bos1, L. Nogova1, I. Papachristou2, T. Persigehl3, F. Dietlein3, T. Zander3, J. Wolf1 Uniklinik Köln, CIO Köln Bonn, Lung Cancer Group Cologne, Klinik I für Innere Medizin, Köln, Deutschland 2 Universität, Zentrum für Klinische Studien, Köln, Deutschland 3 Uniklinik Köln, Köln, Deutschland 1 Background: Simultaneious inhibition of several signalling pathways involved in angiogenesis as well as in tumor cell growth regulation by kinase inhibitor combination therapy may increase therapeutic efficacy. Here we evaluate the combination of the mTOR-inhibitor RAD001 (everolimus) and the triple kinase (FGFR, VEGFR, PDGFR) inhibitor BIBF 1120 (nintedanib). In addition we use DCE-MRI for early identification of patients with benefit from BIBF 1120. Methods: This is a phase I trial with 3 dosage arms in a classical „3+3»-design. Eligible are all patients with relapsed or refractory advanced/metastatic solid tumors for whom no further standard therapies are available. All patients will start with a 2-week run-in phase of BIBF 1120. DCE-MRI scans will be performed at baseline staging, on day 3 and day 14. On day 14, there will be 12 hours-pharmacokinetic (PK) assessment. Combination therapy starts on day 15. After two weeks of combination therapy, on day 29, a DCE-MRI scan and 12-hours PK will be performed. Restaging will be performed on day 57. Results:12 patients have been enrolled so far. In one patient with FGFR-amplified lung cancer, there was a partial response after six weeks of therapy. No DLTs were detected within the first dosage step. Tolerability of the combination was good, as there were no toxicities of CTC-AE grade 3 or greater. In arm B, there has been one DLT (elevation of transaminases), which turned out to be reversibel. Discussion: So far, the combination of BIBF 1120 and RAD001 seems tob e very good tolerated, demonstrating activity in a patient with NSCLC and FGFR1-amplification. Enrollment into the second dosage stage has already started. The trial is registered under NCT01349296 (clinicaltrials.gov). Pflegerische Beiträge ID 132 Demenz – die etwas andere Herausforderung für professionell Pflegende in der Onkologie Pflegenden zunehmend mit Patientinnen und Patienten sowie Angehörigen konfrontiert, die an den verschiedensten Formen von Demenz leiden. Bisher gibt es in Deutschland keine Untersuchungen zu den hieraus resultierenden Belastungen der professionell Pflegenden und zu deren Fortbildungsbedarfen in diesem sehr speziellen Arbeitsbereich. Folglich existieren auch keine Angebote, die das Pflegepersonal für diese besonderen Aufgaben weiterqualifizieren. Methode: Mittels qualitativer Interviews wird onkologisches Pflegepersonal nach seinen Belastungen in der pflegerischen Arbeit mit dementiell Erkrankten befragt. Ergänzende, offen gestellte Fragen des Interviews dienen dazu, die Bewältigungsstrategien herauszufinden, mit denen die Pflegenden versuchen, die Situation zu entlasten. Abschließende Fragen richten sich auf die speziellen Fortbildungsbedarfe der Pflegenden, so dass mit dieser Erhebung eine erste explorative Studie zur spezifischen Belastungs- und Bedarfssituation im onkologischen Pflegeberich vorliegt. Ergebnis: Bisher wurden 100 Fragebögen versandt. Aufgrund der sehr guten Netzwerkarbeit ist eine Rücklaufquote von 60% sehr wahrscheinlich, so dass bei zügiger Auswertung Ergebnisse bis Ende des Jahres 2013 vorliegen werden, die ihrerseits erste Veröffentlichungen im Februar 2014 ermöglichen. ID 165 Haustierbesuch auf der Palliativstation der Universitätsklinik Frankfurt am Main J. Kunze, C. Gog Universitätklinik Frankfurt am Main, Palliativstation – UCT, Frankfurt am Main, Deutschland Haustiere haben einen hohen Stellenwert in der Familie. Durch die Kommunikation zwischen Mensch und Tier entsteht eine tiefe Bindung zueinander. Kommt es zum Fortschreiten einer Erkrankung mit Aufenthalt auf einer Palliativstation, führt dies bei Mensch und Tier zu einem schmerzhaften Verlust und Abbruch der Beziehung. Wir entwickelten deshalb ein Konzept zur Realisierung eines Haustierbesuches auf der Palliativstation an der viele Bereiche der Universitätsklinik Frankfurt am Main (Leitung der Krankenhaushygiene, Ärztliche Leitung der Palliativstation, Betriebsärztliche Leitung, Tierpsychologin, Fachpersonal der Palliativstation) beteiligt waren. Vorbereitungen: Alle notwendigen Impfungen des Haustieres müssen vom Tierarzt durchgeführt werden. Der Klinikbesuch sollte in Begleitung der jetzigen Bezugsperson des Hundes erfolgen. Das Einverständnis des Personals nach Durchführung eines Tierallergentests ist einzuholen. Haustiere, die nicht an der Leine geführt werden, müssen durch andere geeignete Vorkehrungen gesichert werden. Hunde und Katzen sind zuvor zu bürsten und die Pfoten des Tieres müssen vor dem Betreten des Personalaufzuges gesäubert und getrocknet werden. Durchführung: Haustierbesuch ist nur im Einzelzimmer gestattet. Es erfolgt die Abholung am Personalaufzug durch zuständige Pflegekraft. Die Besuchsdauer beschränkt sich auf max. 2 Stunden. Danach Händedesinfektion aller beteiligten Personen. Nachbereitungen: Das Patientenbett komplett frisch beziehen und Desinfektion aller Oberflächen. Zimmer lüften und Bodenreinigung durch Reinigungskraft initiieren. Es konnten in der Zwischenzeit bereits mehrere Haustierbesuche erfolgreich auf der Palliativstation umgesetzt werden. T. Dreischer Carus Akademie am Universitätsklinikum Carl Gustav Carus Dresden, Department CPD, Dresden, Deutschland Fragestellung: Welche Situationen erleben in der Onkologie tätige Pflegende im Umgang mit dementiell Erkrankten als besonders belastend und wie bewältigen sie diese Situationen? Davon ausgehend soll geklärt werden, welche Fortbildungsbedarfe die professionell Pflegenden äußern. Situationsbeschreibung: Der Anteil dementiell Erkrankter nimmt in Deutschland aufgrund der demographischen Entwicklung bekanntermaßen stetig zu. Daher werden auch die in der Onkologie professionell 132 Oncol Res Treat 2014;37(suppl 1):1–133 Abstracts Inhalt Index ID 196 ID 448 Pflegekonzept in der Integrativen Onkologie S. Kuhlmann , O. Langels , P. Voiß , A. Paul , G.J. Dobos , S. Kümmel1 1 2 1,2 2 2 Kliniken Essen-Mitte, Klinik für Senologie / Brustzentrum, Essen, Deutschland 2 Kliniken Essen-Mitte, Klinik für Naturheilkunde und Integrative Medizin, Essen, Deutschland 1 Hintergrund: Die Integrative Onkologie kombiniert konventionelle Schulmedizin mit evidenzbasierten, komplementärmedizinischen Verfahren. Diese umfassen Medizinsysteme (z.B. traditionell chinesische Medizin), Mind-Body-Therapien (z.B. Ernährung, Bewegung, Entspannung), manipulative körperbezogene Praktiken wie Massage sowie den Einsatz von Vitaminen / Mineralien, medizinischen Tees und klinisch bewährten Hausmitteln. Das Ziel der Integrativen Onkologie ist, Nebenwirkungen primärer Tumortherapien zu reduzieren und die gesundheitsbezogene Lebensqualität der Patienten zu steigern. Dieses Konzept wird seit 2010 an den Kliniken Essen-Mitte, gemeinschaftlich durch das Brustzentrum und die Klinik für Naturheilkunde und Integrative Medizin, praktiziert. Diskussion: Unser Pflegekonzept in der Integrativen Onkologie umfasst u.a. regelmäßige, gemeinsame ärztliche und pflegerische Visiten, den Einsatz von medizinischen Auflagen, Akupunktur, Schröpfen, verschiedene Massageformen, Aromatherapie, Fußbäder, Information zu weiteren pflegerischen Anwendungen, Anleitung zu Selbsthilfestrategien aus der Mind-Body-Medizin. Eine Schlüsselfunktion kommt der Breast Care Nurse zu, die die Patientin bereits ab Diagnosemitteilung unterstützend mit Aufklärung, Information, Koordination, seelischer Unterstützung im gesamten Behandlungsablauf begleitet. Sie ist von Anfang an wichtige Ansprechpartnerin für die Patientin und fungiert als Bindeglied zwischen den einzelnen Disziplinen. Fazit: Eine evidenz-basierte, integrativ onkologische Versorgung bietet die Möglichkeit für ein effektives Nebenwirkungsmanagement und eine ganzheitliche Versorgung des onkologischen Patienten. Abstracts «Ohne Pflege geht’s nicht»: Etablierung der Radioonkologischen Pflegeberatungsambulanz H. John1,2 MHH, Radioonkologie, Hannover, Deutschland Med. Hochschule, Radioonkologie- Pflegeberatungsambulanz, Hannover, Deutschland 1 2 Einleitung: Onkologische Erkrankungen gehen mit physischen u. psychischen Belastungen einher. Moderne Behandlungsmöglichkeiten erfordern Umdenken. Es braucht Behandlungskonzepte, welche Selbstpflege und salutogenetisches Verstehen fördern. Frage: Hat eine pflegerische Beratung mit dem Ansatz der Stärkung von Selbstpflegekompetenz Einfluss auf Angst und andere Nebenwirkungen bei ambulanter Radiatio? Methodik: Bedarfsermittlung, Hospitationen, Bildung Projektgruppe, Pflegeempfehlungen wurden nach wissenschaftlichen Kriterien erstellt. Individuelle Copingstrategien werden im obligatorischen pflegerischen Beratungsgespräch entwickelt. Datensammlung und Evaluation folgen. Fallbesprechungen finden statt. Florenze e.V. unterstützt das Projekt. Ergebnis Die Wirksamkeit ist bisher subjektiv zu bewerten. Erfahrungen zeigen, dass patientenorientierte Aufklärung dem Gefühl von Kontrollverlust entgegen wirkt. Fazit: Die Pflegeberatung ist eine Ergänzung und Qualitätssteigerung in der Patientenversorgung mit hoher Akzeptanz .Die Regelversorgung wird angestrebt. Oncol Res Treat 2014;37(suppl 1):1–133 133 Inhalt Index Author Index Oncol Res Treat 2014;37(suppl 1):134–145 A Aaspõllu, A., 195 Abbas, M., 60 Abendroth, A., 92, 218 Abo Houf, A., 386 Abo-Madyan, Y., 248 Abou-Dakn, M., 328 Aboumadian, A. Y., 251 Abraham, J., 32 Abramczyk, M., 92 Abu Jawad, J., 97, 389 Ackermann, M., 238 Adamietz, I., 370, 397, 430 Adenis, A., 6 Adhami, B., 124 Adwan, H., 138, 141, 143, 145 Adzersen, K. -H., 179 Agaimy, A., 56 Ahmadzadehfar, H., 49 Ahrens, M., 38 Aigner, K., 441 Akram, I., 145 Aksnes, A. -K., 36 Aktas, B., 68, 94, 136, 456 Al Ghazal, A., 281 Al-Batran, S. -E., 160, 174, 194 Albers, P., 311, 371 Albert, U. -S., 105 Albrecht, S., 450, 451 Aldabbas, O., 251 Almgren, P., 99, 101, 228 Almstedt, K., 270 Alten, N., 116 Altmann, A., 441 Aminossadati, B., 432 Amit, M., 51 Andergassen, U., 449 Anders, M. P., 198, 210 Andratschke, N., 429 Andrzejewski, D., 168 Angerer-Shpilenya, M., 334 Ansmann, L., 83, 226 Arenz, D., 90 Arfmann-Knübel, S., 127 Arndt, S., 458 Arndt, V., 45 Arnold, D., 429 Arnold, G., 389 Asen, M., 362 Astor, D., 249 Atanackovic, D., 119 Ataseven, B., 395 Attard, G., 195 Atzpodien, J., 447 Augustin, D., 456 Aumann, J., 173 Aumann, K., 356, 366 Aumann, N., 366 Azizian, A., 263, 296 © 2014 S. Karger GmbH, Freiburg Fax +49 761 4 52 07 14 [email protected] www.karger.com Accessible online at: www.karger.com/ort B Baaijens, M., 161 Baasner, A., 277, 453 Baba, H., 38 Baba, H. A., 199 Baccelli, I., 67, 68 Bach, F., 457 Bache, M., 17, 260 Bachinger, A., 116 Bachmann, C., 16 Backes, C., 406 Badalamenti, G., 10, 11 Bahlo, J., 500 Bahra, M., 443 Baklayan, A., 207 Bals, R., 201 Baltin, C. T. H., 364 Bamberg, M., 261 Bani, M. R., 150 Bankfalvi, A., 94 Banys, M., 327, 368 Banzer, W., 361, 420 Baras, N., 258 Barnes, B., 140 Barone, C., 6 Barsoum, M., 461 Bartels, S., 35 Bartmann, C., 167 Bartsch, H., 185, 187 Bastholt, L., 40 Battista, M., 50 Battmann, A., 174 Batzler, U., 317 Bauer, A., 406 Bauer, P., 412 Bauer, S., 12, 13, 85, 218 Bauerfeind, I., 269 Bauerschlag, D., 120 Baum, M., 395 Baum, S., 243 Baumann, F., 221, 253, 364, 396 Baumann, F. T., 353, 374 Baumann, K., 432 Baumann, K., 231, 244, 416 Baumann, K. H., 329 Baumann, K., 153, 454 Baumann, W., 83 Baumgart, S., 163 Baur, F., 125 Bausewein, C., 266 Bayer, C. M., 270, 294 Bayer, C., 280 Bazhin, A., 79, 80, 81 Bechstein, W. O., 300 Beck, E., 168, 172 Beck, H., 171 Becker, A., 452 Becker, C., 95 Becker, D., 302 Becker, M., 58 Becker, N., 121, 131, 179 Becker, S., 262, 327 Becker, T., 128 Beckert, S., 3 Beckmann, K., 352 Beckmann, M., 337 Beckmann, M. W., 150, 270, 294, 352, 385, 449 Bedke, J., 311 Begus-Nahrmann, Y., 37 Behrens, D., 173, 208 Behringer, D. M., 457 Behringer, D., 414 Beissbarth, T., 321 Bekeredjian-Ding, I., 75 Belau, A., 222, 231, 416 Belka, C., 395 Bellen, G., 114 Belova, I., 380, 418 Belting, M., 99, 101, 228 Benndorf, D., 421 Benz-Jansen, C., 454 Benz-Weißer, A., 428 Beraldi, A., 205, 207 Berdel, W., 457 Bergatt-Kuhl, B., 458 Bergelt, C., 223 Berger, A., 18, 63, 169, 241 Berger, M., 135, 289 Berger, M. R., 138, 141, 143, 145 Berger, S., 135 Bergmann, A., 99, 101, 228 Bergmann, C., 97 Berking, C., 447 Bernardi, A., 361 Berndt, U., 314 Bernhardt, C., 93 Bernschein, A., 460, 461, 462 Bersi, H., 220 Bertsch, T., 113 Bertz, H., 34 Bertz, J., 140 Besseler, M., 41 Bettinger, D., 342 Betz, B., 31 Betzler, C., 333 Beulertz, J., 221, 253 Bey, I., 458 Beyer, I., 224 Bichev, D., 74 Biegner, T., 100 Bielfeld, C., 321 Bielow, C., 322 Biersack, H. -J., 49 Biesenbaum, D., 326 Bindel, F., 348 Birkner, B., 382 Birninger, N., 308 Bitzer, E. M., 61, 65 Bitzer, J., 236 Inhalt Index Bitzer, M., 412 Blackstein, M. E., 10, 11 Blassl, C., 182, 190 Blay, J. -Y., 10, 11, 12, 13 Blettner, M., 110 Bloch, W., 221, 253, 291, 353, 364, 374, 396 Blohmer, J. U., 395 Blumenstengel, K., 191 Bläker, H., 88 Blümcke, B., 277, 453 Bob, R., 436 Bobersky, S., 139 Boda-Heggemann, J., 87 Boehnke, K., 299 Boellaard, R., 439 Boersch, I., 168 Bogdahn, U., 310 Bojunga, J., 232 Bokemeyer, C., 62, 302, 304 Bollschweiler, E., 364 Bolt, T. A., 160 Bonacker, J., 400 Bongartz, R., 276, 373, 383 Bonin, M., 185, 187 Boos, J., 42, 71 Bootz, F., 272, 295 Boral, A., 233 Bos, M., 22, 112, 376, 381, 404, 414, 422, 431, 439 Bosserhoff, A. -K., 310 Bouché, O., 6 Boyiadzis, M., 461 Braicu, E. I., 234, 347 Brandi, L., 419 Brandt, H., 95 Braun, S., 328 Brechtel, A., 4, 175 Brehm, B., 385 Brehmer, S., 248 Breitbart, E. W., 198, 210 Breitenbuecher, F., 97 Breitenbücher, F., 85 Bremer, M., 395 Brennan, B., 350 Brenner, H., 44, 45, 88, 282, 283, 382 Breuer, F., 124 Brock, M., 264 Brockhoff, G., 16 Bronsert, P., 356, 366 Brose, M. S., 40 Brucker, S., 261 Bruland, O., 36 Brunel-Geuder, L., 150 Brunner, G., 447 Bruns, C., 333 Bruns, C. J., 217 Brückner, K., 314 Brüggemann, K., 271 Brümmendorf, T. H., 376, 381 Bublitz, K., 202 Bucan, V., 193 Buchholz, M., 391, 394 Buchholz, S., 114, 305 Budach, W., 62 Buderath, P., 94 Buettner, R., 22 Author Index Buettner, S., 325 Bulsara, M., 395 Burfeind, P., 200, 206 Burghaus, S., 352 Burke, T., 14 Burwinkel, B., 67 Busch, C. -J., 119, 301 Busch, C., 403 Busch, R., 219, 500 Buttmann, N., 180 Bölükbas, S., 340, 402, 410, 427 Böttcher, S., 219, 500 Bühler, H., 370, 397, 430 Bürkle, B., 384 Büther, F., 372, 377 Büttner, R., 112, 376, 381, 404, 414, 431, 439 C Cacsire Castillo-Tong, D., 234 Camaj, P., 217 Camara, O., 449 Canon, J. -L., 126 Canzler, U., 231, 244, 250, 329, 416, 432 Cao, H., 224 Cardoso Martins, A. S., 297 Carosati, E., 379, 386 Casali, P. G., 10, 11, 12, 13 Celik, E., 108 Celik, I., 384 Chang, J., 12 Chang-Claude, J., 45, 88 Chawla, R., 358 Chekerov, R., 234, 328, 347 Chen, S., 73 Chen, Y. -R., 52 Choudhury, K., 198 Christgen, M., 455 Christiansen, H., 365, 390 Chromik, A., 391, 394 Chung, J., 40 Cibula, D., 416 Cihon, F., 6, 7, 8 Clauditz, T. S., 119 Clausen, S., 248 Claussen, C. D., 54 Clemens, M., 222, 456 Clement, P., 98 Codo, P., 406 Coleman, R. E., 57, 64 Concin, N., 234 Conradi, L. C., 296 Constantinidou, M., 442 Cornely, O. A., 69, 72, 75, 90 Cortes-Incio, D., 85 Coy, J. F., 100 Craft, A., 350 Cramer, C., 164 Cramer, T., 319, 322, 348 Croner, R., 95, 129 Cross, A., 64 Cruciani, G., 379, 386 D Daheim, M., 73 Dahlmann, M., 268 Dahm, S., 140, 258, 405 Daigeler, A., 5 Dall, P., 176 Dammer, U., 294 Dan Costa, S., 273 Dandekar, G., 125, 152, 220, 235 Daniel, P. T., 169 Danker, H., 109 Dathe, G., 172 Daum, S., 74 Davies, C., 299 De Dosso, S., 457 de Graauw, M., 348 De Gregorio, N., 244, 250, 329, 337, 416 de Hoog, S., 72 de la Fourchardiere, C., 40 de Zwart, P., 62 Dechene, A., 92 Decker, T., 449 deFigueiredo, M., 34 Degel, F., 446 Degen, C., 20 Demetri, G. D., 10, 11, 12, 13 Demidova, O., 322 Denecke, T., 443 Dengler, J., 188 Derks, C., 85, 136 Dexel, S., 413 Diab, F., 170 Dieckmann, K. -P., 311 Diefenbach, K., 6 Dierks, S., 200 Dietel, M., 88, 209, 265 Dieterich, M., 400 Dietl, J., 107, 167 Dietlein, F., 422 Dietlein, M., 439 Dietrich, D., 272, 274 Dietz, A., 109, 362 Dikomey, E., 301 Diller, M., 305 Dirksen, U., 336, 350, 445 Dirnhofer, S., 408 Distel, L., 21, 115, 306 Dittrich, C., 369 Dobbelstein, M., 201 Dobos, G. J., 196 Dold, S., 344 Doll, M., 287, 424, 426 Dollinger, G., 192 Dommach, M., 457 Domschke, C., 67 Donders, G., 114 Donel, E., 122 Dormann, A., 330 Dountsop, P., 212 Drecoll, E., 279 Dreger, P., 500 Dreher, L., 162, 184 Dreischer, T., 132 Drendel, V., 356 Drescher, C., 224 Dressel, R., 206 Drewes, C., 269 Drozdz, S., 367 Du Bois, A., 222, 231, 244, 250, 329, 416, 432 Dubrowinskaja, N., 60 Oncol Res Treat 2014;37(suppl 1):134–145 135 Inhalt Index Duma, M. N., 280 Dunst, J., 429 Dyszkiewicz, W., 189 Döhner, H., 500 Dönges, T., 410 Dörken, B., 443 Dörr, M., 134 Długaszewska, B., 189 E Eberhardt, W. E. 85, 102, 209, 389, 404 Eberle, A., 44, 282 Eberle, J., 18, 63, 241 Eberlein, M., 402, 410, 427 Ebert, M. P., 457 Ebert, A., 328 Ebsen, M., 128 Eckel, R., 147, 293 Eckert, A. W., 260, 292, 393 Eckert, D., 444 Eckert, F., 62 Efferth, T., 52 Eggeling, S., 387 Egger, M., 160 Eggert, J., 176 Ehmann, M., 87 Eich, H. T., 278, 372, 377 Eichhorn, T., 52 Eichhorst, B. F., 90, 219, 500 Eichstaedt, M., 414 Eidt, S., 254 Eigentopf, A., 131 Eisele, A. -C., 98 Eisele, G., 98, 213 Eisenacher, M., 38, 199 Elisei, R., 40 Ellmann, A., 21 Ellwart, J., 333 Elter, T., 396, 439 Eltrop, S., 303 Emons, G., 103, 104, 222, 231 Emrich, K., 44, 282 Engbers, A., 271 Engel, C., 237 Engel, J., 84, 107, 134, 147, 155, 293 Engel-Riedel, W., 102, 116, 431, 439 Engström, G., 99, 101, 228 Erbes, T., 78 Erdmann-Reusch, B., 318 Erlbeck, M., 205 Ernst, I., 372, 377 Ernstmann, N., 83, 226 Erz, P., 314 Eschenburg, H., 35, 48 Eucker, J., 442 Ewald, C., 24, 25 Ewald-Riegler, N., 250 Exner, A. -K., 96 Ezziddin, S., 49 F Fackler-Schwalbe, I., 438 Fahlbusch, M., 371 Fakhrian, K., 370 Falcone, A., 6, 7, 8, 9 Falini, B., 436 Fang, F., 36, 47 136 Farace, F., 195 Farahati, J., 417 Fasching, P. A., 150, 270, 294, 352, 385, 449, 450, 451 Faschingbauer, F., 294 Fasola, G., 126 Fecher, D., 152, 235 Fehm, T., 68, 182, 183, 185, 187, 190, 195, 222, 231, 244, 250, 262, 270, 327, 329, 332, 337, 366, 416, 419, 425, 449, 450, 451 Feisel-Schwickeradi, G., 176, 222 Feiten, S., 130 Fend, F., 366 Feng, Q., 224 Fersis, N., 270 Feustel, T., 172 Feyen, O., 100 Feyer, P., 395 Fichtner, I., 208 Fietkau, R., 21, 56, 115, 306 Fink, A., 219, 500 Finkelmeier, F., 232, 342 Finkernagel, F., 229 Fischer, D., 153, 454 Fischer, I., 41 Fischer, J., 332 Fischer, J., 442 Fischer, K., 219, 500 Fisseler-Eckhoff, A., 402 Fleckenstein, J., 87, 395 Fleckenstein, K., 171 Fleisch, M., 425 Flier, A., 391, 394 Flieser-Hartl, M., 31 Floca, R., 151 Forner, D., 250 Forstbauer, H., 455 Fotopoulou, C., 250, 347 Frangenberg, A., 460 Frank, O., 188, 191 Frechen, S., 414 Frei, K., 324 Freitag, D., 24, 25, 433 Freitag, L., 85 Freitag-Wolf, S., 128 Frese, M., 304 Freytag, M., 119 Fridrich, C., 378 Friederich, H. -C., 4 Friedl, T. W., 449, 450, 451 Friedrich, S., 121, 179 Friese, K., 266, 395 Friesenhahn, V., 130 Frisse, S., 353 Fritzsche, K., 34 Fröhner, M., 106 Fuchs, A., 252 Fuchs, I., 430 Fuhr, U., 404, 414 Funke, B., 459, 461, 462 Funke, S., 386 Fürst, S. T., 244, 329 G Gabbert, H. E., 246, 379, 386 Gabrysiak, T., 191 Oncol Res Treat 2014;37(suppl 1):133–145 Gaedcke, J., 263, 296, 321 Gajda, M., 163 Galle, P., 216 Galle, P. R., 255 Gallmeier, E., 297 Gamba, S., 217 Garcia Vargas, J. E., 39, 47, 64 Gardizi, M., 22, 376, 381, 404, 414, 422, 431, 439, 460 Gasiorowski, L., 189 Gasser, M., 335, 338, 341 Gastinger, I., 409, 411 Gauler, T., 85, 97, 202, 204, 389 Geater, S. L., 242 Gebauer, F., 181 Gebauer, G., 337, 368 Gebauer, K., 60 Gebhard, S., 50 Geffers, R., 355, 358 Gehrmann, M., 50, 280 Geinitz, H., 280 Geisler, K., 150 Geissler, E. K., 375 Geist, T., 414 Gelderblom, H., 10, 11, 13 Georgii, J., 385 Gerber, B., 337, 400, 416 Gerhardt, A., 249 Gerigk, U., 376, 381 Gerken, G., 92, 199 Gerken, M., 298 Gerland, L., 353 Germer, C. -T., 335, 338, 341 Gerstenhauer, M., 307 Gerstner, A., 295 Ghadimi, M., 263, 296, 321 Giedl, J., 405 Gieseler, F., 308 Giger-Pabst, U., 388, 392 Gil, Z., 51 Gillissen, B., 169 Giordano, F. A., 248 Girgert, R., 104 Girst, S., 192 Gittler, A., 243, 428 Glanemann, M., 344 Glatzle, J., 3 Glockzin, G., 298 Gloede, T. D., 83 Glossmann, J. P., 461 Glossmann, J. -P., 459, 462 Gluz, O., 455, 456 Glüer, C., 403 Go, W., 126 Goebel, L., 128 Goepfert, K., 216 Goertz, O., 5 Goettig, T., 440 Goetze, T., 256 Gog, C., 165 Goker, E., 457 Goldbrunner, R., 162, 164, 166, 184 Goldmann-Posch, U., 269 Goldwasser, M., 233 Gondos, A., 44, 282 Gorys, A., 128 Gottschlik, Y., 314 Author Index Inhalt Index Grade, M., 263, 296, 321 Graf, C., 58 Graf, L., 314 Graf, M., 151 Graf von der Schulenburg, J. -M., 209 Grage-Griebenow, E., 128 Gramatzki, D., 324 Gramatzki, M., 324 Gratzke, A. -L., 193 Grehl, S., 389 Greiner, W., 120 Greinert, R., 198, 210 Greubel, C., 192 Greve, B., 278, 372, 377 Griebel, L. -F., 329 Grimm, C., 348 Grimm, D., 303 Grimm, M., 100 Grimmig, T., 335, 338, 341 Grischke, E., 16 Grob, P., 114 Grobe, T., 61, 65 Grohs, R., 172 Grohé, C., 102 Gropp-Meier, M., 231, 416 Gros, S., 333 Grosu, A. L., 111 Grothey, A., 6, 7, 8, 9 Groß, M. -L., 131 Groß, S. E., 83 Grube, S., 24, 25, 433 Gruber, I., 327 Gröne, J., 349 Gründker, C., 103, 104 Gschwend, J., 122 Guckenberger, M., 429 Guo, Y., 297 Gutekunst, K., 361 Göhl, J., 56, 129 Göhler, T., 176 Gölz, T., 34 Göpfert, K., 255 Görgen, P., 462 Götte, M., 42, 71, 271, 275, 278 Göttel, R., 89 Göttlich, C., 235 Götz, C., 279 Günther, B., 365 Güttler, A., 17 Gütz, S., 102 H Haase, M., 103 Haberland, B., 266 Haberland, J., 140, 258 Habermann, A., 244, 329 Habermann, J. K., 227 Hack, C. C., 171, 270 Hadaschik, B., 4 Haderlein, M., 21, 115 Haeberle, L., 294 Haertl, C., 217 Haetscher, N., 300 Haeusler, N., 168 Hagen-Aukamp, C., 223 Hagenbeck, C., 450, 451 Hager, B., 106 Author Index Hahlbohm, U., 197 Hahn, M., 262 Hahn, S., 215, 394 Hahn, S. A., 93, 139 Hahne, A., 82 Hahne, J., 107 Hahnen, E., 277, 452, 453 Hailemariam-Jahn, T., 285 Hallek, M., 219, 346, 396, 458, 459, 461, 462, 500 Halloul, Z., 398 Hamann, C., 282 Hamm, R., 52 Hamprecht, A., 72 Hanenberg, H., 419 Hanker, L. C., 231, 244, 250, 329, 337, 416, 432 Hann von Weyhern, C., 62 Hantschmann, P., 244, 329 Happold, C., 320 Harati, K., 5 Harbeck, N., 266, 267, 269, 353, 455, 456 Hardt, M., 363 Harnicek, D., 297 Harter, P., 231, 244, 329, 337, 416, 432 Hartkopf, A. D., 67, 68, 262, 327 Hartmann, A., 352 Hartmann, E., 325 Hartmann, J., 62 Hartmann, K., 415 Hartmann, M., 175 Hartmann, M., 311 Hartmann, S., 400 Hartmund, L., 200 Hasdemir, D. B., 309 Hasenburg, A., 244, 250, 303, 416 Haslerud, T., 49 Hassan, H., 278 Hassenkamp, P., 212 Hatwig, R., 460 Hau, P., 310 Haubold, K., 189 Hauch, S., 94 Hauke, J., 277, 452, 453 Haun, M., 175 Haus, U., 136 Hautzel, H., 371 Haverkamp, U., 372, 377 Hedblad, B., 99, 101, 228, 299 Hedderich, M., 153 Heiden, E., 363 Heidenreich, A., 284, 286, 311, 313, 334, 354, 357, 423 Heikaus, S., 379, 386 Heil, J., 67 Heilmann, V., 176 Heimann, S., 69 Hein, A., 270, 294, 352 Heinecke, A., 447 Heinemann, V., 217, 266 Heinig, K., 124 Heinrich, A., 153 Heinrich, B., 216 Heinrich, G., 449 Heinrich, M., 234 Heinz, W., 69 Heinzelmann, J., 163 Heinzmann, F., 355 Heisig, S., 239 Heiss, C., 244, 329 Heizmann, C. W., 268 Helle, S. I., 39 Hellmich, M., 383, 461 Hellriegel, M., 244, 250, 329 Hellwig, B., 50 Helm, O., 128 Henderson, D., 299 Hengstler, J., 50 Henke, M., 111 Henkel, T., 112 Hennenlotter, J., 100 Hense, J., 85, 136 Hentschel, M., 417 Hepp, P. G., 449 Herkommer, K., 122 Hermanek, P., 56, 345 Hermann, R., 390 Hermann, S., 121 Hero, B., 90 Herold, N., 276 Herold, S., 189 Herr, C., 201 Herr, D., 323 Herrmann, P., 268 Herschbach, P., 124 Hertrampf, K., 133 Herwig, U., 416 Herz, S., 156, 157 Herzog, W., 175 Heuckmann, J., 316 Heudorfer, F., 310 Heukamp, L., 22, 112, 404, 414, 431, 439, 461 Heukamp, L. C., 346, 376, 381 Heusinger, K., 352 Heußner, P., 205, 207 Heydenreich, M., 159 Heymanns, J., 130 Hiddemann, W., 205, 207 Hildebrandt, B., 88 Hildebrandt, G., 429 Hillemanns, P., 231, 244, 250, 329 Hilpert, F., 244, 250, 329, 337, 416 Hils, R., 337 Hindenburg, H. -J., 146 Hinke, A., 176 Hirsch, T., 5 Hirschfeld, M., 76, 77, 78 Hjorth, L., 350 Hoberg, C., 370 Hoda, R., 189 Hoffarth, S., 97 Hoffmann, A., 38 Hoffmann, A. -C., 199, 202, 204, 212 Hoffmann, G., 50 Hoffmann, O., 136 Hoffmann, T. K., 119 Hoffmann, W., 343 Hoffmeister, M., 45, 88, 382 Hofheinz, R., 457 Hofheinz, R., 160, 429 Hofmann, D., 456 Hofmann, D., 455 Hofmann, H., 100 Oncol Res Treat 2014;37(suppl 1):134–145 137 Inhalt Index Hofstädter, F., 307 Hoheisel, J., 406 Hohenberger, P., 10, 11, 13, 325 Hohenberger, W., 56, 95, 129 Hohenfellner, M., 405 Hohmeyer, A., 355 Holleczek, B., 44, 282, 283 Holländer, M., 124 Holm, P., 279 Holtick, U., 346 Holzer, K., 300 Honisch, E., 332, 419 Hoppe, P., 115 Horger, M., 54, 62 Horn, O., 156 Horsch, L. D., 379 Hoster, E., 205, 207 Hoyer, J., 150 Hozaeel, W., 194 Hrgovic, I., 285, 287, 424, 426 Huber, J., 4, 106, 175, 405 Humblet, Y., 6 Hurtz, H. -J., 124 Häberle, L., 352 Hänse, N., 194 Häring, J., 230 Höland, K., 341 Hölscher, A., 178, 364 Hölzel, D., 84, 147, 293 Hönig, A., 107 Höwner, A., 199 Hübner, J., 270 Hülsdünker, T., 396 Hülsewig, C., 275 Hünerlitürkoglu, A. -N., 381 Hüttner, N. B. M., 270 I Iborra, S., 329 Ibrahim, S. A., 278 Ignatiadis, M., 369 Ignatov, A., 273 Ignatov, T., 273 Ihorst, G., 34 Ihrig, A., 4 Ilieva, Y., 289 Ilm, K., 331 Ilmberger, C., 186 Ingold-Heppner, B., 88 Inwald, E. C., 307 Issels, R., 297 Izbicki, J. R., 127, 181 J Jabar, S., 336 Jacke, C. O., 105 Jackisch, C., 222, 291 Jackson, E. K., 86 Jaehde, U., 171 Jagota, A., 328 Jahn, P., 32 Jallal, N., 246 Janni, W., 68, 110, 190, 270, 369, 449, 450, 451 Jansen, L., 44, 45, 88, 282, 283 Jansen, M., 229 Janssen, E., 359 138 Jarzab, B., 40 Jauch, K. -W., 186, 333 Jeffers, M., 11 Jehn, U., 204 Jilg, C., 356 Jirakova Trnkova, Z., 6 Jo, P., 263, 296 Joensuu, H., 10, 11 Johannessen, D. C., 39 John, H., 365, 448 Joka, M., 186 Jokic, M., 73 Jonat, W., 403 Jones, T., 174 Joseph, D., 395 Jud, S. M., 150, 294, 385 Judson, I., 350 Jueckstock, J., 329 Juhasz-Böss, I., 243, 323, 421 Jung, J., 83 Jung, M. 274 Junginger, T., 345 Junker, K., 163 Junker, S., 412 Jäger, B., 449, 450, 451 Jäger, E., 26, 27, 361 Jäger, M., 76, 77, 78 Jäger, M., 194 Jückstock, J. K., 244, 449 Jürgens, H., 336, 350, 445 K Kaatz, R., 227 Kabelitz, D., 128 Kadhim, K., 138, 141 Kage, S., 240 Kahraman, D., 439 Kaiser, F., 30, 31 Kaiser, G., 92 Kajüter, H., 44 Kalder, M., 105 Kalff, R., 24, 25, 433 Kambartel, K., 381 Kaminski, B., 376, 414 Kaminsky, B., 431 Kampmann, E., 297 Kanaar, R., 297 Kang, T. -W., 355, 358 Kang, Y. -K., 10, 11, 12, 13 Kannen, V., 338 Kappeler, C., 10, 13, 40 Kappler, M., 260 Kapteina, S., 383 Karakhanova, S., 79, 80, 81 Karl, A., 311 Karthaus, M., 6, 7, 126 Kasimir-Bauer, S., 94 Kaskel, P., 14 Kasper, B., 325 Kasper, S., 85, 92, 97, 136 Kasprowicz, N., 195 Kasprowicz, N. S., 332 Katalinic, A., 53, 133, 282, 317 Katay, I., 414 Kates, R., 456 Kates, R. E., 455 Kaufmann, M., 395 Oncol Res Treat 2014;37(suppl 1):133–145 Kaufmann, R., 285, 287, 288, 424, 426 Kaulfuß, S., 200, 206 Keck, B., 106, 405 Keil, E., 328 Keilholz, U., 299 Keller, A., 406 Keller, A., 249 Keller, K., 344 Keller, T., 94 Kemmner, W., 331 Kempa, S., 319, 322, 348 Kemper, B., 271 Kerkhoff, A., 457 Kerschgens, C., 223 Kessel, M., 201 Kesting, M., 279 Kesting, S., 42, 71 Keszte, J., 109, 362 Kettelhake, A., 319, 322 Ketterer, M., 121 Keyver-Paik, M. -D., 250 Khalaf, F., 49 Kiani, A., 444 Kiechle, M., 437 Kiesel, L., 271, 275, 278 Kilger, U., 99 Killing, F., 259 Kim, M., 338 Kimmig, R., 94, 136, 416 Kimminger, A., 84 Kind, M., 326 Kippenberger, S., 424, 426 Kirkovits, T., 269 Kirn, V., 373 Kitz, J., 296 Klaschik, K., 277 Klassen, O., 148 Klaus, B., 250 Klawonn, F., 358 Kleboth, K., 130 Klein, F., 443 Klein, P., 120 Kleinert, R., 178 Klempert, I., 265 Kliesch, S., 311 Klimke, A., 201 Klinkhammer-Schalke, M., 214, 307 Kloor, M., 88 Klose, T., 211 Kluba, T., 62 Klug, S. J., 405 Klunker, D., 194 Kneba, M., 457, 500 Knecht, R., 119, 301 Kneissl, P., 403 Knuth, A., 119 Knösel, T., 297 Ko, Y. D., 113, 171, 381 Kobe, C., 439 Kobelt, D., 173 Koch, J., 369 Koch, M. C., 294 Koch, T., 176 Koch, U., 223 Kochanneck, A., 370 Kocher, M., 108, 257 Koerner, R., 359 Author Index Inhalt Index Kogosov, M., 60 Kohl, M., 136 Koliamitra, C., 221 Kolk, A., 279 Koller, M., 214, 307 Kollmar, O., 312, 344, 428 Kollmeier, J., 102 Konerding, M. A., 238 Kong, A., 369 Konstantinov, S., 289 Korfel, A., 406 Kosian, P., 347 Koslowsky, T., 254 Kosse, J., 231, 244, 329, 337, 416 Kossow, J., 136 Kostenko, A., 461 Kotrba, J., 260 Kotzsch, M., 17 Kovacheva, M., 135 Kowalski, C., 226 Kowalski, F., 252 Krabisch, P., 416, 432, 456 Krakau, M., 330 Krause, M., 229 Krauth, K. A., 118 Krawczyk, N., 327 Kraywinkel, K., 106, 140, 180, 258, 317, 405 Krege, S., 311 Kreienberg, R., 110 Kreipe, H. H., 455 Kreis, M. E., 345, 349 Kreppel, M., 51 Kretzschmar, L., 328 Kreuzeder, J., 291 Kreuzer, K. -A., 219, 461, 500 Krex, D., 98 Kriegs, M., 301 Kristiansen, G., 272, 274 Krombholz, A. S., 24 Kron, F., 461 Kron, M., 122, 462 Kronenberg, C., 328 Kronenberger, B., 232, 342 Kruppa, M., 127 Kruseova, J., 350 Krämer, S., 373, 378, 383 Krüger, S., 376, 381 Kuczyk, M. A., 60, 311 Kudelin, N., 340, 427 Kuhlmann, J. D., 94 Kuhlmann, S., 196 Kuhn, E., 225 Kuhn, N. -F., 18 Kuhn, P., 225 Kunze, J., 165 Kunze, S., 108 Kunzmann, V., 113 Kurbacher, C. M., 124, 156, 157, 413 Kurbacher, J. A., 156, 157, 413 Kurschat, P., 346 Kuru, T., 4 Kurzeder, C., 231, 432 Kusche, D., 245 Kuss, I., 10, 11, 12, 13 Kvasnicka, H. -M., 408 Kwok, B., 107 Author Index Kähnert, H., 96 Kämpfe, D., 259 Kästner, P., 37 Köberle, V., 232, 342 Köhler, A., 390 König, F., 39 König, K., 112, 431 König, K., 100 König, V., 118 Königsrainer, A., 3, 62 Königsrainer, I., 3 Köppler, H., 130 Kümmel, S., 196, 455 L Laban, S., 119, 301 Ladenstein, R., 350 Laffers, W., 295 Lahmann, P. H., 343 Lamb, T., 174 Lammertsma, A., 439 Landenberger, M., 32 Lang, S., 86, 97 Lang, S. A., 298, 375 Lange, M., 299 Lange, N., 378 Langels, O., 196 Langenberg, R., 368 Langenbuch, T., 59 Langer, M., 90 Langhammer, S., 149 Langheinrich, M., 129 Lardinois, D., 408 Laschke, M., 344 Lathan, B., 191 Latta, S., 353 Lattrich, C., 230, 305 Laubender, R., 217 Lauber, K., 297 Laurent, D., 6 Lautner, M. H. W., 292 Lazaridis, L., 202 Le Cesne, A., 10, 11 Le Coutre, P., 188 Leahy, M. G., 10, 11 Lebrecht, A., 50 LeDeley, M. C., 350 Ledwon, P., 168 Lee, B. H., 136 Lee, L. D., 349 Leenders, F., 316 Lehnerdt, C., 136 Lehnerdt, G., 212 Lehnhardt, M., 5 Lehrach, H., 299, 348 Leibbrand, B., 96 Leidinger, P., 406 Leisse, A., 272 Leitzke, S., 461 Lemos, C., 363 Lennert, J., 41 Lenz, H. J., 6, 7, 8, 9 Lenzen, G., 176 Lepique, J., 156, 157, 413 Leplow, B., 314 Leukel, P., 310 Leutz, A., 360 Lewis, J. D., 255 Lewis, I., 350 Li, Z., 224 Lieber, A., 224 Liebl, A., 95 Liebrich, C., 416 Liedtke, B., 456 Liefold, M., 172 Liekweg, A., 171 Lindberg, P., 214 Linde, I., 294, 385 Lindhofer, H., 194 Lindner, L., 297 Link, K., 113 Linnig, M., 216, 255 Lintermans, A., 114 Linthorst, M., 161 Lippert, H., 409, 411 Litiere, S., 369 Lizé, M., 201 Lloyd, A. J., 57 Lohr, F., 87 Longerich, T., 355, 358 Lorence, R., 242 Lorenz, C., 65 Lorenz, W., 214 Lorenz-Salehi, F., 456 Losem, C., 188 Losensky, W., 306 Lotze, C., 318 Lotze, M., 461 Ludwig, C., 116 Lueck, H. -J., 222 Luley, K., 160 Lux, M. P., 150 Luyten, A., 244, 329 Löhberg, C. R., 150 Löppenberg, B., 264 Lück, A., 124 Lück, H. -J., 231, 337 Lücke, K., 189 Lüftner, D., 291 Lütkens, T., 119 M Maass, N., 120, 270 Maderer, A., 255 Madhavan, D., 67 Maghnouj, A., 93, 215 Magnet, F., 116 Mahner, S., 222, 231, 234, 244, 250, 303, 329, 416, 432 Mahnke, E., 430 Mahotka, C., 379, 386 Mai, S., 87 Maier, W., 44 Maisel, T., 444 Majchrzak, B., 93 Maki, R. G., 10, 11 Makowiec, F., 356 Malek, N., 358, 412 Malgorzata, K., 351 Malkomes, P., 300 Mallmann, P., 244, 329, 373, 374, 378, 383 Malter, M., 344 Malter, W., 373, 374, 378, 383 Oncol Res Treat 2014;37(suppl 1):134–145 139 Inhalt Index Mandapathil, M., 86 Manjer, J., 99, 101, 228 Mannhold, R., 379, 386 Mansmann, U., 155 Marcinkowski, P., 268 Marec Berard, P., 350 Markiefka, B., 373, 383 Markowetz, J., 97 Markus, P., 92 Marmé, F., 67, 68, 416 Martin, K., 408 Martin, R., 295 Martinez, M., 174 Marx, C., 192 Mascia, M., 365 Massey, D., 242 Mastrobuoni, G., 319, 322 Mattner, U. -M., 124 Mattonet, C., 376, 414, 439 Matzdorff, A., 252 Maurer, C., 345, 500 Mavroudis, D., 369 Mavrova, R., 243, 323 Mayer, B., 186 Mayer, F., 160 Mayer, J., 500 Mayer, K., 49 Mayer, S., 303 Meese, E., 406 Meier, K., 315 Meier, W., 231, 244, 250, 329, 337, 416, 432 Meier-Stiegen, F., 190 Meiler, J., 85, 92 Meincke, M., 188, 191 Meindl, A., 277, 452 Meintker, L., 69 Meisner, C., 182 Meissner, M., 285, 287, 288, 424, 426 Meissner, W., 229 Meister, E. F., 109 Melander, O., 99, 101, 228 Melcher, C., 419, 450, 451 Menge, F., 325 Menger, M., 312, 344 Menger, M. D., 428 Mennrich, R., 128 Merger, M., 416 Merkel, S., 56, 129, 345 Merkelbach-Bruse, S., 112, 376, 381 Merseburger, A. S., 60 Merten, F., 434 Messina, C., 369 Metelmann, H. -R., 28 Metzler-Nolte, N., 139 Meyenburg-Altwarg, I., 365 Meyer, A., 362 Meyer, A., 390 Meyer, B. C., 309 Meyer, F., 398, 409, 411 Meyer, H., 38 Meyer, H. E., 199 Meyer, J., 206 Meyer, K., 310 Meyer, M., 460 Meyer, M., 461 Meyer, S., 107 140 Michael, P., 18 Michelis, S., 434 Mierau, A., 396 Milanovic, D., 111 Milde-Langosch, K., 167 Mineur, L., 6 Modest, D. P., 217 Modl, S., 273 Modugno, C., 67 Moehler, M., 216 Mohr, C., 389 Mohrmann, S., 332 Mok, T., 242 Molnar, I., 40 Morgen, R. -L., 387 Moritz, B., 113 Motsch, E., 131 Moustakis, C., 372, 377 Muche, T., 252 Mueck, A., 183 Muhs, H. -J., 100 Multhoff, G., 192, 280 Mundhenke, C., 366 Mundt, A., 411 Munz, A., 100 Murawa, D., 189 Mustea, A., 244, 329 Muth, M., 291 Mysliwietz, J., 333 Möckel, S., 310 Mögele, M., 114 Möhler, M., 255 Möller, D., 20 Möller, P., 281 Mönch, R., 335, 338, 341 Möslein, G., 399, 401 Müller, A., 417 Müller, B., 328 Müller, C., 359 Müller, F. H. H., 417 Müller, L., 113 Müller, M. C., 188 Müller, P., 408 Müller, R., 229 Müller, S., 3 Müller, V., 68, 450, 451 Müller-Brüsselbach, S., 229 Müller-Mattheis, V., 371 Münscher, A., 119 Münstedt, K., 250 N Nadtotschi, T., 100 Nagel, W., 157 Nassir, M., 347 Nees, J., 67 Neidhardt, G., 452 Nel, I., 199, 202, 204, 212 Nelson, P., 333 Nennecke, A., 44 Nestoriuc, Y., 239 Netter, P., 214 Neubauer, H., 182, 183, 185, 187, 190, 425 Neugebauer, J. K., 449 Neuhaus, P., 443 Neumaier, B., 439 Oncol Res Treat 2014;37(suppl 1):133–145 Neumann, M., 425 Neumann, M., 83 Neumann, V., 78 Neuner, B., 415, 446 Neureiter, D., 351 Neuser, P., 244, 329 Neusser, S., 61, 65 Neven, P., 114 Neves, R. P., 425 Neyns, B., 98 Nguemgo-Kouam, P., 370, 397 Niederacher, D., 332, 419, 425 Nietzer, S., 125, 152, 220, 235 Nietzschmann, A. -T., 247 Nieß, H., 333 Nikkhah, G., 98 Nils, H., 160 Nilsson, P., 99, 101, 228 Nilsson, S., 36, 57, 64 Nimmrich, I., 102 Nishida, T., 10, 11 Nissen, S. -O., 315 Nitz, U., 455, 456 Nitzsche, A., 83 Nix, O., 151 Nißler, V., 95 Noack, C., 170 Noble-Pyott, C., 197 Nogová, L., 112, 376, 381, 404, 414, 422, 431, 439 Noldus, J., 264 Nordlohne, M. W., 309 Normolle, D., 461 Noureddine, R., 92 Novopashenny, I., 442 Novotny, V., 405 Nowaczyk, P., 189 Nuding, B., 455 Nutting, C., 40 Nymbach, N., 156 Nürnberg, D., 434 O O‘Brien, D., 242 O‘Bryan Tear, C. G., 39, 47, 64 O‘Byrne, K. J., 242 O‘Sullivan, J. M., 39 Ober, A., 449 Oberlin, O., 350 Oberländer, M., 227 Oberthür, R., 206 Ochsenbein, A., 98 Ocker, M., 351 Odom, D., 12 Oellerich, T., 300 Ohlinger, K., 315 Okhrimenko, A., 268 Olbrich, C., 328 Oliner, K., 126 Orho-Melander, M., 99, 101, 228 Ortmann, O., 107, 114, 123, 230, 273, 305, 307 Osburg, S., 83 Osterland, M., 268 Ostermann, H., 120 Ostheimer, C., 17 Otremba, B., 124 Author Index Inhalt Index Ottmann, O. G., 188 Otto, R., 409 Otto, U., 223 Overkamp, F., 457 O’Shannessy, D. J., 347 P Pabst, A. M., 238 Pabst, F., 109 Pabst, U., 260, 384 Pacini, F., 40 Padur, W., 259 Paelecke-Habermann, Y., 247 Pahernik, S., 405 Pahle, J., 173 Palisaar, J., 264 Palmer, M. R., 136 Panse, J., 376, 381, 431 Pantel, K., 67, 68, 449 Paolucci, V., 256 Papachristou, I., 404, 422, 439 Papendorf, F., 365 Park-Simon, T. -W., 222, 395 Parker, C., 36, 39, 57, 64 Parker, C., 47 Paschke, R., 40 Patel, S., 51 Paul, A., 38, 92 Paul, A., 196 Pauligk, C., 160 Paulsen, M., 52 Pawar, V., 8, 9 Pedro Neves, R., 190 Peifer, M., 112 Peipp, M., 324 Pelzer, U., 443 Pereszlenyi, A., 387 Perrakis, A., 95 Perrech, M., 162, 184 Persigehl, T., 422, 439 Persson, J., 224 Pervaiz, A., 143 Pesic, M., 358 Pester, L., 90 Pestka, A., 449 Petat-Dutter, K., 185, 187 Peter, S., 75 Peters, I., 60 Petersen, C., 244, 301, 429 Peterson, L., 75 Petsch, S., 41, 405 Pfaff, H., 83, 226 Pfirrmann, R. W., 394 Pfister, D., 284, 286, 313, 354, 357, 423 Pfisterer, J., 244, 250, 329, 416 Pföhler, C., 359 Pförtner, R., 389 Picard, M., 98 Piccart, M., 369 Pierga, J. -Y., 369 Pietzke, M., 322 Pigorsch, S., 395 Piiper, A., 232, 342 Pinter, A., 285, 424, 426 Piper, C., 284, 284, 286, 313, 354, 357, 423 Pisarenko, I., 397 Author Index Piso, P., 298 Plötner, U., 14 Plötz, M., 169 Pogorzelski, M., 97 Polednik, M., 251 Pollmanns, A., 456 Porres, D., 284, 286, 313, 354, 357, 423 Possinger, K., 120, 442 Potenberg, J., 28, 328, 416 Poths, S., 185, 187 Pottek, T., 311 Potthoff, K., 148 Potzner, M., 102 Prange, S., 304 Prasauskas, V., 114 Premsrirut, P. K., 358 Preuss, K. -D., 359 Priesch-Grzeszkowiak, B., 397 Primo, S., 217 Pritzkuleit, R., 44, 133 Prokop, A., 253 Proschek, D., 58 Ptok, H., 345, 409, 411 Puhl, G., 443 Pujade-Lauraine, E., 337 Putzker, M., 211 Pöttgen, C., 389 Q Quast, A., 63 Quast, D., 399 Quast, S. -A., 18, 169, 241 Quidde, J., 429 Quint, K., 351 R Raabe, E., 294 Rack, B., 68, 195, 369 Rack, B. K., 449, 450, 451 Radicke, M., 385 Radosa, J., 323 Rafiyan, M. -R., 194 Rahimi-Nedjat, R., 236 Rahnenführer, J., 50 Raida, M., 223 Rambow, A. -C., 403 Rammensee, H. -G., 412 Randazzo, G. M., 379, 386 Randerath, W., 431 Randerath, W. J., 376, 381 Ranft, A., 336, 350, 445 Rapp, F., 433 Rasper, M., 336 Rath, H. M., 223 Rau, J., 222, 231, 432 Rauh, C., 270, 385 Rave-Fränk, M., 206 Redekopf, J., 375 Regenbrecht, C., 208, 299, 363 Regierer, A., 442 Reich, W., 292, 393 Reichardt, P., 10, 11, 12, 13 Reichelt, R., 124, 413 Reif, S., 6 Reifenberger, G., 320 Reimer, T., 400, 456 Reimers, K., 193 Reinartz, S., 229, 240 Reinbold, R., 278 Reinecke, P., 246 Reinert, S., 100 Reinhardt, C., 73 Reis, A., 150 Reis, H., 85, 136 Reiser, M., 376 Reiter, W. W., 432 Renner, S. P., 352 Retz, M., 311 Reuss, A., 337, 416 Reuss-Borst, M., 46 Reuter, D., 457 Reuß, A., 250 Rexrodt, P., 29 Reymond, M., 384, 388, 392 Rezai, N., 455 Rhiem, K., 276, 277, 407, 437 Riabinska, A., 73 Richly, H., 85, 136, 218 Richter, B., 222, 231, 244, 250, 329, 416 Richter, G., 197 Richter, R., 234 Richters, L., 437 Ridwelski, K., 409 Rieckmann, T., 301 Rieger, L., 29 Rieger, M., 300 Riemenschneider, M. J., 310 Riess, H., 88, 443 Riess, O., 185, 187 Riethdorf, S., 67, 68 Riethmüller, C., 271 Rieß, O., 412 Rivera, F., 126 Rivera Markelova, M., 173 Rodt, T., 309 Rody, A., 153, 270, 454 Roedel, C., 429 Roesler, B., 321 Roessler, M., 113 Roghmann, F., 264 Rohde, H., 75 Rohr, I., 234 Rohrberg, R., 457 Rohwer, N., 348 Roller, J., 344 Rommens, P. -M., 58 Roos, F., 285 Rosenbaum, D., 42, 71 Rosenthal, H., 309 Rot, S., 260 Roth, P., 406 Roth, W., 88 Rothe, S., 328 Rotmann, A. -R., 177 Rottmann, M., 147 Ruberg, K., 171 Rudolph, I., 319, 322 Rupertus, K., 312 Ruppert, M., 26, 27 Ruppert, R., 345 Rustemeyer, R., 285 Rustler, V., 253 Rutkowski, P., 10, 11, 13 Röcken, C., 128, 366 Oncol Res Treat 2014;37(suppl 1):134–145 141 Inhalt Index Rödel, C., 395 Röhn, G., 162, 164, 166, 184 Rüffer, J. U., 41 Rüssel, J., 326 Rützel, J. D., 250 S Sabet, A., 49 Sage, E. K., 280 Sagheb, K., 236 Salamon, J., 181 Salamone, S., 113 Salem, M., 456 Salem Gassar, E., 275 Salendo, J., 263, 296, 435 Salmen, J. C., 449 Salomo, D., 444 Salzmann, D., 41 Saric, T., 162 Sartor, A. O., 57 Sartor, O., 36, 64 Sasazuki, T., 331 Sauer, A., 188, 191 Sauter, G., 119, 127 Sauvigny, D., 255 Savic, S., 408 Schaal, K., 76 Schaffrin-Nabe, D., 66 Schafhausen, P., 75 Schaller, G., 430 Scharf, J. -G., 206 Scharf, J. -P., 328, 337 Scharhag-Rosenberger, F., 148 Schechtmann, G., 320 Scheer, M., 51 Scheffler, M., 376, 381, 404, 414, 422, 431, 439, 461 Scheid, C., 461 Scheller, K., 393 Schellerer, V., 56, 95, 129 Schellong, G., 276 Schellongowski, P., 330 Schem, C., 403 Schenk, A., 221 Scherer, R., 60 Scherwitz, P., 254 Scheulen, M. E., 136, 218 Schildhaus, H. -U., 376, 381, 404 Schiller, J., 360 Schilling, D., 280 Schilling, G., 302, 304 Schilling, J., 14, 146 Schiltz, D., 269 Schindler, C., 176 Schinköthe, T., 267, 269 Schirmacher, P., 88, 209, 355, 358 Schirra, J., 186 Schirren, J., 340, 402, 410, 427 Schittenhelm, J., 16 Schlaak, J. F., 38, 199 Schlaak, M., 346, 408 Schlag, P. M., 268 Schlechter, C., 20 Schlegel, F., 457 Schlegel, U., 98 Schlegel, W., 151 Schlesinger-Raab, A., 134, 293 142 Schlichting, A., 48 Schlitt, H. J., 298, 375 Schlumberger, M., 40 Schlösser, H., 346 Schlößer, H. A., 254 Schmalenberg, H., 160 Schmalfeldt, B., 222, 231, 244, 250, 329, 416 Schmdit, H., 32 Schmeling, C., 389 Schmelz, H. U., 311 Schmid, K., 136 Schmid, K. W., 85, 92, 97, 404 Schmid, S., 356, 366 Schmid, T. E., 192, 280 Schmidt, W. E., 457 Schmidt, E., 103 Schmidt, K., 361, 375, 420 Schmidt, M., 50 Schmidt, M., 415, 446 Schmidt, M., 148 Schmidt-Rhode, P., 124 Schmidt-Wolf, I., 458, 461, 462 Schmiedek, P., 248 Schmiegel, W., 93 Schmitt, S., 100 Schmitz, S., 381 Schmoll, H. -J., 326 Schmutzler, R., 276, 277, 407, 437, 452, 453 Schneck, H., 182, 183, 190 Schneeweiss, A., 67, 68, 148, 449 Schneeweiss, R., 163 Schneider, A., 379 Schneider, C., 399, 401 Schneider, E. M., 441 Schneider, F., 248 Schneider, M. O., 294 Schneider, R., 399, 401 Schneider-Kappus, W., 188 Schnell, R., 414 Schnittner, U., 460 Schnurbein, G., 452 Schochter, F., 449, 450, 451 Schoffski, P., 10, 11 Schollmayer, F., 221 Scholz, M., 195 Schott, S., 67, 68, 403 Schrader, A. J., 36, 281, 311 Schrader, M., 281, 311 Schrader, T., 168 Schrauder, M. G., 150, 352 Schroeder, C., 412 Schroeder, M., 170 Schroeder, T., 69, 300 Schröck, A., 272 Schröder, C., 167 Schröder, W., 250 Schubert, D., 53 Schubert, S., 75 Schubert-Fritschle, G., 84, 134, 147, 293 Schuette, W., 209 Schuldt, M., 201 Schuler, M., 85, 92, 97, 136, 202, 204, 218, 233, 242, 404 Schulmann, K., 93 Schulte, K., 330 Oncol Res Treat 2014;37(suppl 1):133–145 Schultheis, B., 457 Schultheiß, M., 342 Schultz, S., 182, 185, 187 Schulz, H., 381 Schulz, S., 425 Schulz, V., 124 Schulz-Wendtland, R., 150, 294, 385 Schulze, H. -J., 447 Schumacher, D., 299, 363 Schumacher, U., 167, 181 Schumann, C., 102 Schumann, T., 229 Schwarting, A., 58 Schwartzberg, L., 126 Schwarz, B., 217 Schwedas, M., 367 Schween, U., 413 Schweitzer, C., 156 Schweitzer, N., 309 Schwentner, L., 110 Schwickert, A., 271 Schwinger, U., 188 Schäfer, H., 127, 128 Schäfer, R., 208, 299 Schäfer, U., 170 Schäffeler, N., 43 Schöler, S., 94 Schöning, E. -M., 315 Schüler, S., 230, 305 Schütz, F., 68, 291 Scobioala, S., 372, 377 Sebens, S., 127, 128 Sedelmayr, M., 280 Seeger, H., 182, 183 Seel, J., 192 Seeliger, H., 349 Seemann, H., 206 Seggewiß, J., 271 Sehouli, J., 222, 231, 234, 244, 328, 329, 337, 347, 416, 432 Seidel, C., 60 Seidenader, J., 4 Seifert, H., 75 Seitz, S., 123 Seitz-Rosenhagen, M., 248 Seiz, L., 273 Selbach, J., 176 Sell, C., 343 Semrau, R., 108, 257, 373, 383 Sequist, L. V., 242 Serke, M., 22, 102, 203, 376, 381, 431 Serth, J., 60 Serve, H., 300 Shak, S., 455 Shan, M., 39 Shaw, A. T., 233 Shedden Mora, M., 239 Sherman, S. I., 40 Shimabukuro-Vornhagen, A., 254, 346 Shinde, R., 14 Shirasawa, S., 331 Shong, Y. K., 40 Sicking, I., 50 Siebenlist, K., 87 Siebenwirth, C., 192 Sieber, S., 125 Siena, S., 6, 7, 8, 9, 40 Author Index Inhalt Index Simeonova, A., 87 Simon, M., 98 Simon, R., 127 Singer, S., 109, 110, 362 Sinistra, J., 312 Sinn, M., 443 Sipos, B., 412 Sitek, B., 38, 199 Siveke, J., 457 Sklenar, S., 387 Sklenarova, H., 175 Skottky, S., 85 Slottky, S., 136 Smit, J. W. A., 40 Smith, J., 268 Sobrero, A., 6, 7, 8, 9 Socinski, M., 461 Sohn, C., 67, 68, 403 Solaß, W., 384, 388, 392 Solbach, C., 50 Solomayer, E. F., 68, 243, 262, 323, 395, 421 Somers, E., 347 Song, H., 224 Sonnenschein, U., 113 Soppa, B., 21 Sorgius, D., 194 Sorkin, M., 148 Sos, M., 404, 439 Sotiriou, C., 369 Sotlar, K., 185, 187 Spaeth-Schwalbe, E., 438 Spagnoli, G., 408 Spang, R., 310 Speiser, D. E., 408 Sperk, E., 249, 395 Sperling, J., 344, 428 Spies, C., 415, 446 Spillmann, D., 275 Spitzner, M., 321 Sponholz, S., 427 Sprossmann-Günther, G., 28 Stachs, A., 400 Stadler, R., 346, 408 Staebler, A., 16 Staebler, A., 327 Stamatis, G., 85 Stamm, K., 112 Starbatty, B., 459 Staudacher, K., 57, 64 Staudinger, M., 324 Stausberg, J., 155 Steckelberg, E., 46 Steering, C., 261 Stefek, A., 456 Stegelmann, F., 188 Stegmaier, C., 252 Steguweit, H., 346 Steil, V., 87 Stein, A., 8, 9, 429 Stein, H., 436 Stein, U., 268, 331, 363 Steinau, H. -U., 5 Steindorf, K., 148 Steinert, R., 409 Steinestel, J., 281 Steinestel, K., 281 Author Index Steinger, B., 214 Steinle, A., 213 Steinmetz, T., 457 Steinmetz, K., 174 Steinsiek, L., 303 Stenzl, A., 100 Stern, S., 188 Sternfeld, T., 29, 30, 31 Steuber, T., 57 Stevens, J., 379 Stickeler, E., 76, 77, 78, 356, 366 Stiegler, H., 14 Stieler, F., 87 Stieler, J., 443 Stilgenbauer, S., 219, 500 Stippel, D., 178 Stippel, D. L., 254 Stock, C., 271, 275, 382 Stoecklein, N. H., 332 Stoelben, E., 116, 257, 431, 439 Stoetzer, O., 113 Stojceva, N., 320 Stolzenbach, F., 163 Strasburg, J., 387 Strassburg, J., 345 Straub, M., 279 Strauss, A., 47 Strauss, H. -G., 329 Strauß, H. -G., 244, 250 Streichert, T., 167 Strik, H., 351 Stroeder, J., 323 Strohbach, F., 89 Struck, J., 99, 101, 228 Strumberg, D., 384, 388, 392, 457 Ströbel, P., 296 Strölin, P., 64 Stubert, J., 400 Stupp, R., 98 Sturm, M., 412 Stuschke, M., 389 Stäbler, A., 366 Stöckle, M., 163 Stürzl, M., 95 Suleiman, A., 414 Suter, L., 447 Suttmann, I., 113 Svedman, C., 455 Swoboda, S., 38 Syha, R., 54 Sänger, J., 100 Sörgel, F., 414 Sütterlin, M., 231, 249, 395 Tebbe, S., 191 Temming, S., 257 Tempfer, C., 384 Teriete, P., 100 Terstappen, L., 195 Terszowski, G., 408 Tesch, H., 120, 176, 191, 291 Tessen, H. -W., 35, 48, 89 Teufel, M., 43 Tewes, M., 85, 136 Thangarajah, F., 383 Theil, G., 189 Thelen, L., 73 Theobald, M., 58 Theuer, M., 172 Theurich, S., 346, 408 Thiel, C., 420 Thiel, E., 406 Thiel, F., 244, 329, 352 Thielecke, C., 14 Thies, B., 295 Thill, M., 337, 416 Thissen, A., 284, 286, 313 Thissen, A. K., 354, 357 Thomalla, J., 130 Thomas, C., 237 Thomas, M., 102, 175, 209, 233 Thomas, R., 73, 112, 316, 404 Thomssen, C., 314 Thuß-Patience, P., 74 Timmer, M., 162, 164, 166, 184 Ting, S., 85, 97, 136 Tischendorf, L., 154 Tiwari, S., 403 Tjiong, R., 166 Tobias, J., 395 Tonn, J., 98 Torsten, U., 328 Towers, R., 403 Treeck, O., 230, 305 Treese, C., 74 Trefzer, U., 18 Trepel, M., 302 Treppner, S., 458 Tretter, W., 84 Tribius, S., 301 Trillsch, F., 234, 250, 303 Trippler, M., 38 Tritschler, I., 213 Trojan, J., 232 Trumpp, A., 67, 68 Tummes, D., 414 Töpelt, K., 414, 431, 439 T Tabatabai, G., 98 Tabernero, J., 6 Takacz, S., 243 Tanner, B., 244, 329 Tanovi_, A., 297 Tao, S., 88 Taran, F. -A., 262 Tari, S., 205 Tasar, A., 171 Taubert, H., 260 Tauchert, F. K., 26, 27 Taylor, K. J., 236 U Udelnow, A., 398 Uder, M., 385 Uhl, W., 391, 394 Ulbach, K., 266 Uleer, C., 456 Uleer, C., 337 Ullrich, A., 223 Ulrich, A., 88 Ulrich, C., 148 Ulrich, U., 328 Ulrike, S., 343 Upleger, F., 124 Oncol Res Treat 2014;37(suppl 1):134–145 143 Inhalt Index V v. Lilienfeld-Toal, M., 75 Vaidya, J., 395 Valesky, E., 285, 287, 288, 424, 426 van Cutsem, E., 6, 7, 8, 9 van den Berg, H., 350 van den Höfel, N., 386 van der Zee, J., 161 van Erps, T., 423 Van Ewijk, R., 110 van Geel, A., 161 van Gool, R., 57 Van Gorp, T., 234 van Rensburg, R., 224 van Rhoon, G., 161 van Roye, C., 130 Vanezi, M., 49 Vehling-Kaiser, U., 29, 30, 31, 188 Vehreschild, J., 69, 72 Vehreschild, M. J. G., 69, 72, 75, 90 Velasco, J., 299 Ventola, A., 195 Vestergaard, A., 440 Vettorazzi, E., 250 Vijaya Kumar, A., 275 Vilardo, L., 278 Vizler, C., 195 Vogel, A., 309, 429 Vogel, H. -J., 109 Vogel, I., 128 Vogel, U., 182, 366 Vogel, W., 75 Vogelzang, N. J., 39, 47, 64 Vogt, L., 361, 420 Vogt, P. M., 193 Vogt, T., 359 Voigt, W., 225 Voiß, P., 196 Volgelzang, N., 57 Volkmer, B., 198, 210 Vollmann, A., 310 von Bergwelt-Baildon, M., 69, 254, 346, 408 von Bodman, C., 264 von Dehn-Rotfelser, K., 186 von Dossow-Hanfstingl, V., 415 von Hardenberg, S., 200 von Kries, A., 137 von Levetzow, C., 461 von Mehren, M., 10, 11 von Pawel, J., 102 Von Schumann, R., 456 von Tresckow, J., 90 von Wilucki, J., 294 von Winterfeld, M., 74, 88 Vordermark, D., 17, 247 Vossebein, I., 97 W Waaga-Gasser, A. M., 335, 338, 341 Wachter, D., 352 Wacker, F., 309 Wagner, A., 7, 9 Wagner, C., 375 Wagner, D., 172 Wagner, F., 385 Wagner, S., 150 144 Wagner, U., 105, 229, 240 Wagner, W., 311 Wahba, R., 178 Wahlers, K., 72 Waidmann, O., 232, 342 Waldmann, A., 53, 133, 153, 454 Waldschmidt, D., 178, 461 Walles, H., 125, 152, 220, 235 Wallwiener, D., 16, 43, 185, 187, 261, 262, 270, 327 Wallwiener, M., 67, 68, 261, 262 Walter, B., 405 Walter, C., 37, 236, 237, 238 Walter, J., 24, 25, 433 Walter, M., 185, 187 Walther, W., 173 Wang, Y., 217, 333 Wappenschmidt, B., 277, 437, 452, 453 Wassermann, K., 407 Weber, F., 38, 199 Weber, K., 56, 129 Weber-Lassalle, N., 452 Wedel, B., 454 Weghake, E., 271 Wehler, T., 58 Weide, R., 130 Weigang-Köhler, K., 113 Weigel, A., 442 Weiling, M., 306 Weise, S., 247 Weiss, S., 306 Weiss-Gerlach, E., 415 Weiß, C., 102 Weißbach, L., 311 Weißenborn, C., 273 Wellenberg, N., 38 Weller, M., 98, 213, 320, 324, 406 Weller, P., 212 Welt, A., 85, 136 Welte, Y., 208 Welzel, G., 248, 249, 251 Wendling, J., 136 Wendt, T. G., 367 Wendtner, C., 219, 500 Wenkel, E., 150, 385 Wennhold, K., 346 Wenz, F., 87, 248, 249, 251, 395, 429 Wenz, H. -J., 133 Werner, D., 160, 174 Werner, J., 79, 80, 81 Werner, J. A., 86 Werner, M., 356, 366 Wesselmann, J. S., 219 Wessling, G., 156, 157 Westermann, A., 219 Westermann, S., 295 Wetzel, C., 123 Whiteside, T., 86 Wichmann, H., 260 Wick, A., 98 Wick, W., 98 Wickert, M., 43 Wicklein, D., 167, 181 Wickmann, U., 163 Wiedemann, M., 84 Wiedenmann, B., 348 Wiek, C., 419 Oncol Res Treat 2014;37(suppl 1):133–145 Wienands, J., 321 Wiench, B., 52 Wierecky, J., 124 Wiesweg, M., 85, 92, 136, 218, 404 Wilhelm, J., 172 Wilhelm, M., 113 Wilhems, D., 292 Wilke, J., 176 Wilkens, J., 192 Willinek, W., 49 Willmann, L., 4 Wilmer, A., 171 Wiltfang, J., 133 Wimberger, P., 94, 231, 244, 250, 329, 337, 432 Wincheringer, B., 172 Wind, S., 242 Winkel, A., 117, 245 Winkler, E., 175 Winkler, S., 115 Winter, C., 42, 71 Winter, E., 311 Winters, S., 461 Wirsing, U., 91 Wirth, M., 106, 405 Wirtz, M., 83, 226 Wirtz, P., 374 Wirtz, R., 50 Wischnewsky, M., 442 Wiskemann, J., 148 Wisplinghoff, H., 69 Wittenberg, T., 385 Wittmann, L., 216 Woelber, L., 303 Wohlschläger, J., 85 Wolf, J., 460 Wolf, J., 233 Wolf, J., 22, 112, 376, 381, 404, 414, 422, 431, 439, 458, 459, 461, 462 Wolf, U., 140 Wolff, H., 263, 321 Wolff, H. A., 296 Wolff, K. D., 279 Wolff, S., 409 Wollbrück, D., 362 Wollschlaeger, K., 250 Wolpert, F., 213 Wolter, K., 358 Wolters, R., 442 Worm, K., 85, 136 Wortmann, A., 229 Wu, Y. -L., 12, 242 Wuestefeld, T., 358 Wullich, B., 405 Wurster, I., 182 Wöckel, A., 110 Wöge, M., 434 Wölber, L., 244, 329 Wölke, G., 155 Wömpner, C., 404, 414 Wünsch, A., 34 Würstlein, R., 226, 266, 267, 269, 455 X Xu, J. -M., 10, 11 Author Index Inhalt Index Y Yalcin, S., 457 Yamamoto, N., 242 Yang, J. C., 242 Yang, N. -S., 52 Yaspo, M. -L., 299 Ychou, M., 6, 7, 8, 9 Yeganeh, B., 368 Yip, G. W., 275 Yoshino, T., 6, 7, 8, 9 Yu, H., 126 Yumul, R., 224 Z Zamarchi, R., 195 Zander, T., 422, 431, 439, 461 Author Index Zaun, S., 120, 209 Zeilinger, R., 234 Zeman, F., 307 Zenclussen, A., 273 Zender, L., 355, 358 Zengerling, F., 311 Zermann, D. -H., 159 Zeuzem, S., 232 Zey, A., 219 Zhao, L., 333 Zhao, Y., 217, 333 Zheng, C., 77 Ziebart, T., 238 Zieker, D., 3 Zielberg, D., 441 Ziemann, C., 344, 428 Zieren, J., 384, 388, 392 Zimmer, P., 221, 364, 396 Zipfel, S., 43 Zippelius, A., 408 Zirrgiebel, U., 209 Zlobinskaya, O., 192 Zmarsly, I., 5 Zorr, A., 231 Zou, J., 64 Zwink, N., 382 Zöhrer, F., 385 Zöller, J., 51 Zöllner, H., 215 Oncol Res Treat 2014;37(suppl 1):134–145 145