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Background  Two national clinical trial groups, United Kingdom Children’s Cancer and Leukaemia Group (CCLG) and the German Paediatric Oncology and Haematology Group (GPOH) together undertook a randomised trial, EICESS-92, which addressed chemotherapy options for Ewing’s sarcoma. We sought the causes of unexpected survival differences between the study groups.    Methods  647 patients were randomised. Cox regression analyses were used to compare event-free survival (EFS) and overall survival (OS) between the two study groups.    Results  5-year EFS rates were 43% (95% CI 36–50%) and 57% (95% CI 52–62) in the CCLG and GPOH patients, respectively; corresponding 5-year OS rates were 52% (95% CI 45–59%) and 66% (95% CI 61–71). CCLG patients were less likely to have both surgery and radiotherapy (18 vs. 59%), and more likely to have a single local therapy modality compared to the GPOH patients (72 vs. 35%). Forty-five percent of GPOH patients had pre-operative radiotherapy compared to 3% of CCLG patients. In the CCLG group local recurrence (either with or without metastases) was the first event in 22% of patients compared with 7% in the GPOH group. After allowing for the effects of age, metastases, primary site, histology and local treatment modality, the risk of an EFS event was 44% greater in the CCLG cohort (95% CI 10–89%, p = 0.009), and the risk of dying was 30% greater, but not statistically significant (95% CI 3–74%, p = 0.08).    Conclusions  Unexpected differences in EFS and OS occurred between two patient cohorts recruited within an international randomised trial. Failure to select or deliver appropriate local treatment modalities for Ewing’s sarcoma may compromise chances of cure.   Trial registration  Supported by Deutsche Krebshilfe (Grants No. DKH M43/92/Jü2 and DKH 70-2551 Jü3), and European Union Biomedicine and Health Programme (Grants No. BMH1-CT92-1341 and BMH4-983956), and Cancer Research United Kingdom. Clinical trial information can be found for the following: NCT0000251

Survival is influenced by approaches to local treatment of Ewing sarcoma within an international randomised controlled trial: analysis of EICESS-92