Newly Diagnosed Cases Cancer Related Death NCI 2006 Data

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1 Multi-Disciplinary Management of Esophageal Cancer: Surgical and Medical Steps Forward Alarming Thoracic Twin Towers UCSF UCD Thoracic Oncology Conference November 21, Lung Pierre R. Theodore Van Auken Endowed Chair in Thoracic Oncology Division of Thoracic Surgery University of California at San Francisco Newly Diagnosed Cases Cancer Related Death NCI 2006 Data Esophagus Esophageal Cancer Widespread 6 th most common cause of cancer death worldwide 16,500 new cases expected per year in the U.S. Increasing Incidence of esophageal adenoca has increased >3 fold since 1975, Deadly 5-year survival historically < 10% 14,300 deaths expected per year in the U.S. Van Soest et al. Increasing incidence of Barrett s oesophagus in the general population Gut August; 54(8): Source: Sources: Mariette et al. Lancet 2007, Khushalani Mayo Clin Proc

2 Anatomy Designed for Metastasis Hofstetter et al. Proposed Modification of Nodal Status in AJCC Esophageal Cancer Staging System. Ann. Thor. Surg 2007 Balance in Approach to the Esophagus Chemoradiation Surgery Adopted with Permission from Harrison: Is Esophageal Cancer a Surgical Disease? Journal of Surgical Oncology (2000) EUS can Predict Survival in Patients Treated with Neoadjuvant ChemoXRT (Chak et al, Cancer 2000) 59 patients with resectable esoph. ca treated with neoadjuvant chemoradiation EUS performed at baseline and again after chemorads prior to planned surgical resection EUS responders defined as those with > 50% reduction in cross- sectional area (MAX) = 34/59 (58%) 2

3 Competing Approaches? Regardless of Stage, Number of Nodes Resected Influences Survival Peyre et al. The Number of Lymph Nodes Removed Predicts Survival in Esophageal Cancer: An International Study on the Impact of Extent of Surgical Resection. Ann. Surg 2008 Novel Surgical Reconstruction Techniques Thirty-five patients Three patients had stricture at 14, 21 and 25 days post-operatively, operatively, and were successfully treated with endoscopic dilation No leaks or perioperative mortality Adjuvant Therapies in Esophagus Cancer A SAFE AND REPRODUCIBLE ANASTOMOTIC TECHNIQUE FOR MINIMALLY INVASIVE IVOR LEWIS OESOPHAGECTOMY: THE CIRCULAR STAPLED ANASTOMOSIS WITH THE TRANS-ORAL ANVIL G. Campos, D. Jablons, C. Rabl, R. Ramirez, S. Peeva, P. Theodore Eur Journal of Cardiothoracic Surgery (2009) 3

4 Esophageal Adenocarcinoma: Consensus on Adjuvant Therapy Something more than surgery alone should be done Preoperative chemotherapy ECF, CF improves overall survival MAGIC: 13% improvement at 5 yr (25% pts esoph) MRC 0E0-2: 9% improvement at 2 yr (66% adeno) 5 year update: 6% improvement (7% adeno, 5% squamous) No clear impact on rate of R0 resection MRC Lancet 359: 1727; 2002 Cunningham NEJM 355: 11; 2006 Esophageal Cancer: Preop Chemotherapy Positive trials U.K. MRC OEO-2 (n=802) 2 preop cycles of 5-FU + Cisplatin Adeno 66%, Squamous 31% 6% increase 5 yr OS U.K. MAGIC: pre and post op ECF in gastric cancer (n=503) Adeno only 11% GE junction 15% distal esophageal adeno No improvement in R0 resection rate, 13% increase in 5 year OS No Path CRs MRC Lancet 359: 1727; 2002 Cunningham NEJM 355: 11; 2006 Met Analysis Preop Chemo in Esophageal Cancer: Thirion et al, Abs 4512 (2007) Individual patient data from preop chemo trials: esophageal squamous and adenocarcinoma 9 trials OS: 2102 pts 2 dominant trials: U.S. INT 113 (467 pts) U.K. MRC OEO-2 (802 pts) Preop Chemo: Overall survival improvement with a HR of 0.87 (p = ) Translates into 4.3% improvement in OS at 5 yrs Primary End-point: Overall Survival Survival Absolute benefit at 5 years: 4.3 % Time (years) Patients at risk Control Chemo pre-op Squamous: 4% Adeno: 7% 4

5 Induction Chemoradiotherapy 64 Gy /32 fractions (in follow up Int 0123) Addition of RT to chemotherapy Improves rates of curative resection in some trials Achieves pathologic complete responses in 10-30% Phase III: small, inconclusive (< patients) Curative Resection rates increased RT + chemo in some trials Local Recurrence reduced Trends toward Survival Path CR: Survival Only 2 of 5 Randomized Trials indicate survival benefit Preop ChemoRT: Phase III Trial FFCD Therapy Patients % Adeno %R0 Resection Path CR OS / Med Survival Surgery 282 0% 69% -- 26% 5 yr Poet Trial Chemoradiotherapy Fig. 1 versus Chemo Induction Walsh* CRT 81% 26% 26% Surgery % NS -- 6% 3 yr* Urba Burmeister Tepper (CALGB) CRT NS 25% 32%* Surgery % 90% -- 16% 3 yr CRT 88% 28% 32% Surgery % 59% mos CRT 80% 16% 22 mos Surgery 56: 475 planned CRT 75% NS yr NS 33% 4.5 yr Metanalysis Translates into 19% mortality risk reduction with neoadjuvant CRT of 30 Gy was given at 2.0 Gy per fraction, 5 fractions per week Stahl, M. et al. J Clin Oncol; 27: Gy Photon radiotherapy in 5 fractions per week 5

6 Overall survival Who Responds, Lives. Fig % 27.7% Stahl, M. et al. J Clin Oncol; 27: Stahl, M. et al. J Clin Oncol; 27: small Surgery needed at all? Fédération Francophone de Cancérologie Digestive 9102 Overall survival No discernible difference SCC Responders 25% CR Bedenne, L. et al. J Clin Oncol; 25: Bedenne, L. et al. J Clin Oncol; 25:

7 Esophageal Cancer: Preop Chemo, or ChemoRT? Conclusions Conclusions Esophageal Adeno Preop Chemo improves survival RT + Chemo: trends toward improved OS, more path CR s At the cost of greater toxicity? Esophageal Squamous RT + Chemo: As primary therapy without surgery is acceptable 20-25% 25% 5 year survival Surgery after chemo rt: in selected patients Improved local control no improvement in survivalval No Clearly Demonstrated Advantage of Post-operative operative Chemotherapy Who Responds, Wins (better post induction assessments) More Nodes in Resection, Improved Overall Survival 7

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