Esophageal cancer - mucosalimmunology.ch

Transcrição

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
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.
3
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
4
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)
Why is the diagnosis of a locally advanced carcinoma
so common?
5
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)
6
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
7
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
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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
Endoscopic resection
Surgery + perioperative RTx/CTx
Palliative treatment
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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
10
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
11
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
12
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.
13
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.
14
Therapy of limited/ locally advanced disease
Stahl et al: Annals of Oncology 21 (Supplement 5): v46–v49, 2010
15
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
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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
17
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
18
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
19
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
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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
21

Esophageal cancer - mucosalimmunology.ch

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