michael stahl on behalf of the german oesophageal cancer study group
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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. - PowerPoint PPT PresentationTRANSCRIPT
Michael Stahlon behalf of the
German Oesophageal Cancer Study Group
Long term results of a phase III study investigating chemoradiation with and
without surgery in locally advanced squamous cell carcinoma of the
esophagus
Abstract No 4530, Poster No 18
Participating CentersParticipating CentersGerman Oesophageal Cancer Study GroupGerman Oesophageal Cancer Study Group
Essen (KEM, AKK, University, EKK)Essen (KEM, AKK, University, EKK)Düsseldorf (University)Düsseldorf (University)Tübingen (University)Tübingen (University)Marburg (University)Marburg (University)Duisburg (St.J., Städt.)Duisburg (St.J., Städt.)Trier (KB)Trier (KB)Berlin (RRK)Berlin (RRK)Göttingen (University)Göttingen (University)Mönchengladbach (Franz.)Mönchengladbach (Franz.)
Eligibility CriteriaEligibility Criteria
SCC of the intrathoracic SCC of the intrathoracic esophagusesophagusStage T3-4 N0-1 M0 according Stage T3-4 N0-1 M0 according to CT und EUSto CT und EUSMedically fit for surgery, PS 0-1Medically fit for surgery, PS 0-1Age up to 70 yearsAge up to 70 yearsWritten informed consentWritten informed consent
Flow Diagram of Patients Flow Diagram of Patients includedincludedAssessed
for eligibilityn = 189
Randomisedn = 172
Refusedrandomisation
n = 12
Excluded(not meeting
inclusion criteria)n = 5
Allocated toArm An = 86
Allocated toArm Bn = 86
Treated An = 7
Treated Bn = 5
Treated n = 86 Treated n = 85
Stahl M, et alJCO 23:2310-7,2005
Stratification CriteriaStratification Criteria
CenterCenterGenderGenderWeight loss (up to vs. above Weight loss (up to vs. above 10% of BW)10% of BW)Complete EUSComplete EUSStage (T3N0 vs. T3N+ vs. T4)Stage (T3N0 vs. T3N+ vs. T4)
EndpointsEndpoints
Primary endpointPrimary endpoint- Overall survivalOverall survival
Secondary endpointsSecondary endpoints- Rate of R0-ResectionRate of R0-Resection- Rate of PCRRate of PCR- Postoperative MortalityPostoperative Mortality- Local tumor controlLocal tumor control
POETGOeCSG
Statistical designStatistical design
Test for equivalence between arms ITest for equivalence between arms I<15%I <15%I
- H0: 35% 2y-survival in Arm A; >20% Arm B- H0: 35% 2y-survival in Arm A; >20% Arm B
N= 175 , power of 80%, N= 175 , power of 80%, =0.05 =0.05
Results at SurgeryResults at Surgery
SurgerySurgery 62 patients62 patientsResectionResection 55 / 62 (89%)55 / 62 (89%)R0R0 51 / 62 (82%)51 / 62 (82%)
ypT0 N0 M0ypT0 N0 M0 18 / 51 (35%)18 / 51 (35%)ypT1-3 N0 M0ypT1-3 N0 M0 17 / 51 (33%)17 / 51 (33%)ypT1-3 N1 M0ypT1-3 N1 M0 9 / 51 (18%) 9 / 51 (18%)ypT1-3 N0-1 M1ypT1-3 N0-1 M1 7 / 51 (14%) 7 / 51 (14%)
Surgical ProceduresSurgical Procedures
ExplorationExploration 7 /62 7 /62ResectionResection 55/62 (89%)55/62 (89%)
TTETTE 49/55 (89%)49/55 (89%)THETHE 4/55 4/55OtherOther 1/55 1/55UnknownUnknown 1/55 1/55
Treatment Related MortalityTreatment Related Mortality
CTXCTX CRTX CRTX Surgery Surgery
Arm AArm A 2/86(2.2%) 2/86(2.2%) 0 0 7/57(12.3%) 7/57(12.3%) Arm BArm B 2/85(2.3%) 2/85(2.3%) 0 0 0/5 0/5 allall 4/171(2.3%) 4/171(2.3%) 0 0 7/62(11.3%) 7/62(11.3%)
Overall 8.2%, including 3 pts. with late toxicity
Patterns of FailurePatterns of Failure (treatment according to protocol)(treatment according to protocol)
Arm A*Arm A* Arm B*Arm B*
Any failureAny failure 31/56 (55%)31/56 (55%) 57/83 (69%)57/83 (69%)
Local+regional 14/31 (45%)Local+regional 14/31 (45%) 41/57 (72%)41/57 (72%)Distant (only)Distant (only) 16/31 (52%)16/31 (52%) 14/57 (25%)14/57 (25%)UnknownUnknown 1/31 ( 3%) 1/31 ( 3%) 2/57 ( 3%) 2/57 ( 3%)
* Arm A: CRTX (at least 36 Gy) + Resection, Arm B: CRTX (at least 59 Gy)
Overall Survival (JCO 2005)Overall Survival (JCO 2005)
Log-rank for equivalenceLog-rank for equivalencep = 0.04p = 0.04
2-YSR38.8% vs. 35.4%
Overall Survival (December 2007)Overall Survival (December 2007)
5-YSR27.9% vs. 17.0%Calculated 10-YSR19.2% vs 12.2%Logrank p=0.36HR 1.15 (0.82-1.61)
- CRTX with Surgery- CRTX alone
Survival as treated (no crossover)Survival as treated (no crossover)
5-YSR28.0% vs. 17.0%Calculated 10-YSR19.8% vs 12.9%Logrank p=0.48HR 1.13 (0.79-1.61)
Cox Regression AnalysisCox Regression Analysis
Progn. FactorProgn. Factor HR HR (95%CI)(95%CI) p-value p-value
CTX-Response (y/n)CTX-Response (y/n) 0.300.30 0.19-0.480.19-0.48 <0.0001 <0.0001
Treatment group (A/B)Treatment group (A/B) 1.191.19 0.80-1.760.80-1.76 0.390.39
Gender (m/f)Gender (m/f) 1.061.06 0.65-1.730.65-1.73 0.820.82
EUS complete (y/n)EUS complete (y/n) 0.910.91 0.61-1.350.61-1.35 0.640.64
Weight loss (</>10%)Weight loss (</>10%) 1.191.19 0.76-1.850.76-1.85 0.450.45
Stage (T3N1/T3N0)Stage (T3N1/T3N0) 1.021.02 0.61-1.700.61-1.70 0.940.94
StageStage (T4NX/T3N0)(T4NX/T3N0)1.011.01 0.52-1.970.52-1.97 0.970.97