Esophageal cancer - mucosalimmunology.ch
Transcrição
Esophageal cancer - mucosalimmunology.ch
Esophageal cancer Dr. med. Henrik Csaba Horváth Universitätsklinik für Viszerale Chirurgie und Medizin Epidemiology 8th most common cancer worldwide Male/Female ratio: 3,5-4 Mean age at Dx 64 yrs Epidemiology in Switzerland 500-550 new cases/yr 400-450 deaths/yr Change of incidence in the last decades: US National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) Data base. Oesophageal carcinoma Bundesamt für Statistik Neuchatel 2 Universitätsklinik für Viszerale Chirurgie und Medizin Histological classification Squamous cell carcinoma (SCC) Adenocarcinoma 90% Melanoma Leiomyosarcoma Carcinoid Lymphoma adenocarcinoma SCC others Histology and esophageal cancer incidence (National Cancer Institute US) Oesophageal adenocarcinoma melanoma prostate cancer SCC Adenocarcinoma Ennzinger et al: N Engl J Med 2003;349:2241-52. breast cancer lung cancer colorectal cancer Relative change in the incidence of esophageal adenocarcinoma and other malignancies Pohl et al: J Natl Cancer Inst (2005) 97 (2): 142-146. Oesophageal carcinoma 3 Universitätsklinik für Viszerale Chirurgie und Medizin Histological classification Male to femal ratio Localization Long-term prognosis Risk factors - male gender - long-standing GERD - length of Barrett`s - HGD (59% vs 4%) Adenocarcinoma Squamous cell carcinoma 7:1 3:1 Distal oesophagus Middle (distal) oesophagus better worse GERD Barrett`s oesophagus Smoking Obesity (BMI) Increased age H. pylori (?) Alcohol consumption Smoking Achalasia History of thoracic radiation Low socioeconomic status Poor oral hygiene Increased risk of second primary cancers such as Head and neck Lung Pohl et al: Am J Gastroenterol 2013; 108:200–207 Oesophageal carcinoma 4 Universitätsklinik für Viszerale Chirurgie und Medizin Prognosis and stage at diagnosis 5-year overall survival Stage 0 (T1is) Stage IA (T1a,b N0): IB (T2 N0): Stage IIA (T3, N0): IIB (T1-2, N1): Stage III (T4 N0, T3 N1, T1-2 N2): Stage IV (N3 or M1): 98% 70% 50-55% 15-35% 15-27% 4-15% 0-2% Esophageal cancer stage distribution at diagnosis for the US male and female between 1999 and 2006 (SEER data base) At presentation, 57% patients are Stage III 24% patients are Stage II 5-year survival rates for esophageal cancer by stage at diagnosis for the US male and female between 1999 and 2006 (SEER data base) Oesophageal carcinoma Why is the diagnosis of a locally advanced carcinoma so common? 5 Universitätsklinik für Viszerale Chirurgie und Medizin Diagnosis Clinical presentation Dysphagia (75%) Weight loss (57%) Odynophagia (17%) Hoarseness due to recurrent laryngeal nerve palsy Respiratory symptoms due to esophagotracheal fistules Bleeding Heartburn/history of GERD (Barrett`s carcinoma) History of smoking/alcohol intake Primary diagnostic tools Oesophago-gastroduodenoscopy + biopsy Barium oesophagography Bronchoscopy (for mid-oesophageal tumours) Staging Endoscopic ultrasound (accuracy of overall staging 72%, nodal staging with FNAB 90%) CT scan of the chest and abdomen PET-CT (initial and to determine the response to therapy) – of prognostic value? Minimal invasive staging (laparoscopy/thoracoscopy) Oesophageal carcinoma 6 Universitätsklinik für Viszerale Chirurgie und Medizin Classification of adenocarcinomas in the EGJ Siewert 1996/2000 Localization of tumour center Type I: within 1 to 5 cm above EGJ Type II: within 1 cm above and 2 cm below EGJ Type III: between 2 to 5 cm below EGJ Clinical relevance? Lymphatic spread: Type I (6%) vs type II (22%) and type III (38%) Grading: better in type I tumours vs type II/III Histology: 80% of type I cancers have intestinal type tumour growing pattern, type II/III more agressive Type II/III tumourbiological characteristics of gastric cancer (therapeutic consequences) Surgery: type I transthoracal, type II/III transhiatal Siewert et al: Ann Surg 2000; 232:353–361 Oesophageal carcinoma 7 Universitätsklinik für Viszerale Chirurgie und Medizin Pathology histological type tumour invasion grade (required for staging!) presence/abscence of Barrett`s +++ ++ 0 Role of HER2-neu overexpression? Her2-neu expression in 20-25% of esophageal tumours Higher rate in adenocarcinomas vs SCC Positive correlation with tumour invasion/lymph node metastasis Poorer survival Langer et al.: Mod Pathol 2011; 24, 908-916 Oesophageal carcinoma 8 Universitätsklinik für Viszerale Chirurgie und Medizin Therapy Crucial factors of therapy planning: Tumour stage Histological type Patient`s performance status Major staging groups: Early cancer (Tis, T1a N0) Limited disease (T1-2 N0-1 M0) Locally advanced disease (T3-4 N0-1 M0) Advanced (Tx Nx M1)/recurrent disease Oesophageal carcinoma Endoscopic resection Surgery + perioperative RTx/CTx Palliative treatment 9 Universitätsklinik für Viszerale Chirurgie und Medizin Early cancer - Endoscopic therapy modalities 1. Endoscopic mucosal resection (EMR) 2. Endoscopic ablation procedures (RFA, cryoablation, photodynamic therapy) Endoscopic resection/ablation vs. esophagectomy: Similar median cancer-free survival Less morbidity Precondition: EUS staging is essential (nodularity, lateral spread) Tumour<2cm, G1-2, w/o invasion beyond mucosa and ulceration Limitations of endoscopic therapy: - angiolymphatic invasion irrespective of tumour depth nodal metastases (7% of T1 tumours) positive resection margins in 1/3 of cases recurrent/metachronous lesions in 11% of patients Zehetner et al: J Thorac Cardiovasc Surg 2011;141:39-47. Ell et al: Gastrointest Endosc 2007; 65, 3-10 Oesophageal carcinoma 10 Universitätsklinik für Viszerale Chirurgie und Medizin Surgery Esophagogastrectomy 1. Transthoracic (right thoracotomy+laparotomy±cervical anastomosis) less anastomatic leakage rate 2. Transhiatal (laparotomy+cervical anastomosis) less postoperative morbidity 3. Thoracoabdominal 4. Minimal invasive esophagectomy (laparoscopy/thoracoscopy) shorter hospitalisation, less postop morbidity/mortality, less pulmonary complications, preserves QOL with systematic lymph-node dissection Preconditions for surgical therapy: Tumour is resectable Patient is fit Is surgery alone feasible? No, combined modality therapy is necessary Oesophageal carcinoma 11 Universitätsklinik für Viszerale Chirurgie und Medizin Radiation therapy Definitive: 50 (-60) Gy (for tumours of cervical oesophagus 60-65 Gy) Preoperative: 40-50 Gy Postoperative 45-50 Gy Palliative: individual brachytherapy (local control rate 25-35%) Squamous cell carcinoma - more radiosensitive Preoperative radiation versus surgery alone – no improved survival in long-term randomized trials Post-op radiation versus surgery alone – no improved survival, but higher stricture rate – improved local recurrence rates in node negative mid- to upper-third SCCs – benefit if positive margins/residual tumours Radiotherapy as part of the multimodal therapy with CTx for cancer in the cervical esophagus (no surgery possible) as single therapy for palliation/rescue only Oesophageal carcinoma 12 Universitätsklinik für Viszerale Chirurgie und Medizin Chemotherapy Surgery + neoadjuvant RCTx: CROSS study OS (HR 0.657; 95% CI, 0.495 to 0.871; P = 0.003) Median OS 49,4 vs 24,0 mo R0 92% vs 69% (P<0.001) down staging: complete pathological response (pT0 pN0) and/or size reduction of tumours in 29% of patients van Hagen et al: N Engl J Med 2012;366:2074-84. Oesophageal carcinoma 13 Universitätsklinik für Viszerale Chirurgie und Medizin Chemotherapy Surgery + perioperative CTx for adenocarcinomas: MAGIC study (Epirubicin+Cisplatin+5-FU) Better OS (HR for death, 0.75; 95% CI, 0.60 to 0.93; P = 0.009 Better five-year survival rate: 36 percent vs. 23% Better progression-free survival (HR for progression, 0.66; 95% CI, 0.53 to 0.81; P<0.001) Cunningham et al. N Engl J Med 2006;355:11-20. Oesophageal carcinoma 14 Universitätsklinik für Viszerale Chirurgie und Medizin Therapy of limited/ locally advanced disease Stahl et al: Annals of Oncology 21 (Supplement 5): v46–v49, 2010 Oesophageal carcinoma 15 Universitätsklinik für Viszerale Chirurgie und Medizin Targeted therapies Which targeted terapy modilities may play a role in the treatment of esophageal cancer? EGFR-inhibitors Her2-neu VEGF-inhibitors MET/HGF-pathway inhibitors (crizotinib, rilotumumab) (inhibition of tumour endothelial cells) Aurora kinases A (and B)- inhibitors (centrosome amplification) Heat-shock protein 90-inhibitor Hedgehog-inhibition Mukherjee et al: Dig Dis Sci. 2010; 55(12): 3304–3314 Hong et al: Semin Radiat Oncol 2013 23:31-37 Oesophageal carcinoma 16 Universitätsklinik für Viszerale Chirurgie und Medizin Postoperative treatment of limited/locally advanced disease Which factors have impact on the postop treatment? 1. Histology 2. Surgical margins (shows the best correlation with survival) 3. Preoperative (radio)chemotherapy 4. Nodal status Which patient group(s) do not need a postoperative chemotherapy? Patients who have not received preoperative Tx SCC R0 R1 R2 observation CTx CTx (palliation) CTx CTx (palliation) pTis, pT1 N0 Adenocarcinoma Patients who have received preoperative Tx pT2 N0* pT1-2 N1 pT3-4a Nx R0 R1 R2 SCC obs CTx/ observation CTx/ palliation Adenocarcinoma CTx CTx/ observation CTx/ palliation obs CTx * If age<50yrs, grade>1, lymphovascular/neural invasion Oesophageal carcinoma 17 Universitätsklinik für Viszerale Chirurgie und Medizin Follow-up After endoscopic therapy (EMR) for Tis, T1a cancers: 1st year: 3 mo endoscopy After 1 yr: annual endoscopy After surgery for T1b-4 cancers Physical exam, laboratory, endoscopy First (1-)2 years: 3-6 mo 3-5 years: 6-12 mo After 5 years: annual Oesophageal carcinoma 18 Universitätsklinik für Viszerale Chirurgie und Medizin Treatment of advanced (metastatic, disseminated) disease Palliative chemotherapy SCC: cisplatin+5-FU Adenocc: cisplatin+irinotecan cisplatin+5FU+docetaxel epirubicin+oxaliplatin+capecitabine (±panitimumab) Management of pain Improvement of dysphagia Endoscopy: esophageal stents (also for trecheo-esophageal fistules) brachytherapy (better long-term effects?) photodynamic therapy (for bleeding, better acute tumour response) YAG-laser therapy (for bleeding, more perforations) Adequate nutrition enteral(PEG tube)/parenteral nutrition Oesophageal carcinoma 19 Universitätsklinik für Viszerale Chirurgie und Medizin Prevention Smoking cessation (risk of SCC decreases after one decade) Moderation of alcohol intake Substitution fresh fruits and vegetables for high-salt/ nitrosamine-preserved food Aspirin, selenium, black raspberries No screening for patients with long-term GERD for Barrett`s - high number of people having reflux symptoms - 40% of patients with Barrett`s without reflux symptoms Surveillance for patients with Barrett`s is essential. Why? 100x risk of esophagus cancer vs. general population LGD: 3-4% HGD: 0.5-1% Cancer: 0.3-0.5% of patients with Barrett`s esophagus/yr Wang et al: Am J Gastroenterol. 2008 Mar;103(3):788-97 Wani et al: Clin Gastroenterol Hepatol. 2011;9(3):220-227 Oesophageal carcinoma 20 Universitätsklinik für Viszerale Chirurgie und Medizin Prevention Prevention of esophageal cancer in patients with Barrett`s Barrett`s esophagus No dysplasia 2x 6 mo, then 3yrs (LSB) 4 yrs (SSB) High-grade dysplasia Low-grade dysplasia 2x 6 mo, then annual mucosal irregularity Unifocal/ visible EMR Multifocal/ unvisible Esophagectomy RFA/PDT 3 mo first year 6 mo second year then annual until 5 yrs Wang et al: Am J Gastroenterol. 2008 Mar;103(3):788-97 Oesophageal carcinoma 21