Michael Stahl on behalf of the German Oesophageal Cancer Study Group Abstract No 4530, Poster No 18 Long term results of a phase III study investigating chemoradiation with and without surgery in locally advanced squamous cell carcinoma of the esophagus Michael Stahl on behalf of the German Oesophageal Cancer Study Group

Participating Centers German Oesophageal Cancer Study Group Essen (KEM, AKK, University, EKK) Düsseldorf (University) Tübingen (University) Marburg (University) Duisburg (St.J., Städt.) Trier (KB) Berlin (RRK) Göttingen (University) Mönchengladbach (Franz.)

Eligibility Criteria SCC of the intrathoracic esophagus Stage T3-4 N0-1 M0 according to CT und EUS Medically fit for surgery, PS 0-1 Age up to 70 years Written informed consent

Flow Diagram of Patients included Excluded (not meeting inclusion criteria) n = 5 Assessed for eligibility n = 189 Refused randomisation n = 12 Treated A n = 7 Treated B n = 5 Randomised n = 172 Allocated to Arm A n = 86 Allocated to Arm B n = 86 Stahl M, et al JCO 23:2310-7, 2005 Treated n = 86 Treated n = 85

Stratification Criteria Center Gender Weight loss (up to vs. above 10% of BW) Complete EUS Stage (T3N0 vs. T3N+ vs. T4)

Endpoints Primary endpoint Overall survival Secondary endpoints POET GOeCSG Primary endpoint Overall survival Secondary endpoints Rate of R0-Resection Rate of PCR Postoperative Mortality Local tumor control

Statistical design Test for equivalence between arms Id<15%I - H0: 35% 2y-survival in Arm A; >20% Arm B N= 175 , power of 80%, a=0.05

Results at Surgery Surgery 62 patients Resection 55 / 62 (89%) ypT0 N0 M0 18 / 51 (35%) ypT1-3 N0 M0 17 / 51 (33%) ypT1-3 N1 M0 9 / 51 (18%) ypT1-3 N0-1 M1 7 / 51 (14%)

Surgical Procedures Exploration 7 /62 Resection 55/62 (89%) TTE 49/55 (89%) THE 4/55 Other 1/55 Unknown 1/55

Treatment Related Mortality CTX CRTX Surgery Arm A 2/86(2.2%) 0 7/57(12.3%) Arm B 2/85(2.3%) 0 0/5 all 4/171(2.3%) 0 7/62(11.3%) Overall 8.2%, including 3 pts. with late toxicity

Patterns of Failure (treatment according to protocol) Arm A* Arm B* Any failure 31/56 (55%) 57/83 (69%) Local+regional 14/31 (45%) 41/57 (72%) Distant (only) 16/31 (52%) 14/57 (25%) Unknown 1/31 ( 3%) 2/57 ( 3%) * Arm A: CRTX (at least 36 Gy) + Resection, Arm B: CRTX (at least 59 Gy)

Overall Survival (JCO 2005) Log-rank for equivalence p = 0.04 2-YSR 38.8% vs. 35.4%

Overall Survival (December 2007) 5-YSR 27.9% vs. 17.0% Calculated 10-YSR 19.2% vs 12.2% Logrank p=0.36 HR 1.15 (0.82-1.61) CRTX with Surgery CRTX alone

Survival as treated (no crossover) 5-YSR 28.0% vs. 17.0% Calculated 10-YSR 19.8% vs 12.9% Logrank p=0.48 HR 1.13 (0.79-1.61)

Cox Regression Analysis Progn. Factor HR (95%CI) p-value CTX-Response (y/n) 0.30 0.19-0.48 <0.0001 Treatment group (A/B) 1.19 0.80-1.76 0.39 Gender (m/f) 1.06 0.65-1.73 0.82 EUS complete (y/n) 0.91 0.61-1.35 0.64 Weight loss (</>10%) 1.19 0.76-1.85 0.45 Stage (T3N1/T3N0) 1.02 0.61-1.70 0.94 Stage (T4NX/T3N0) 1.01 0.52-1.97 0.97