BACKGROUND: Local treatment is a crucial element in the standard of care for Ewing sarcoma (EWS). While systemic treatment is improved in randomised clinical trials, local treatment modalities are discussed controversially. We analysed the association between local therapy and event-free survival (EFS), overall survival (OS), and local recurrence (LR) in prospectively collected data of patients with localised EWS. PATIENTS AND METHODS: We analysed data from the international Ewing 2008 study registered between 2009 and 2019 in 117 centres. After induction chemotherapy, patients received surgery, radiotherapy, or a combination thereof. We performed Cox regression, conducted propensity score-weighted sensitivity analysis, and performed subgroup analyses. Hazard ratios (HRs) and 95% confidence intervals are reported. RESULTS: We included 863 patients with localised EWS (surgery alone: 331, combination therapy: 358, definitive radiotherapy: 174). In patients treated with combination therapy compared to surgery alone, EFS HR was 0.84 (0.57-1.24; p = 0.38), OS HR was 0.84 (0.57-1.23; p = 0.41), and LR HR was 0.58 (0.26-1.31; p = 0.19). Hazards of any event were increased in patients treated with definitive radiotherapy compared to surgery only, HR 1.53 (1.02-2.31; p = 0.04). Patients with poor responses to chemotherapy benefitted from combination therapy over definitive surgery with an EFS HR 0.49 (0.27-0.89; p = 0.02). Patients with pelvic tumours benefitted from combination therapy over surgery only regarding LR, HR 0.12 (0.02-0.72; p = 0.02). CONCLUSION: Patients with poor responses to chemotherapy benefitted from radiotherapy added to surgery. In the whole group, radiotherapy alone as opposed to surgery alone increased the hazards of any event.

Center for Pediatric Oncology and Hematology Vilnius University Hospital Santaros Klinikos Vilnius University Santariškių g 2 08661 Vilnius Lithuania

Charles University Motol Children's Hospital 5 Uvalu 84 150 06 Prague 5 Czech Republic

Childhood Cancer Center Queen Silvia Children's Hospital Behandlingsvägen 7 416 50 Gothenburg Sweden

Chris O´ Brien Lifehouse Camperdown Australia; Health University of Sydney Camperdown New South Wales 2006 Australia

Department of Medical Oncology Leiden University Medical Center Albinusdreef 2 2333 ZA Leiden Netherlands

Department of Oncology Haematology University Children's Hospital Basel Spitalstrasse 33 4056 Basel Switzerland

Department of Orthopedics and Trauma Medical University of Graz Auenbruggerpl 2 8036 Graz Austria

Department of Pediatric Haematology and Oncology Cliniques Universitaires Saint Luc Université Catholique de Louvain Av Hippocrate 10 1200 Brussels Belgium

Department of Pediatric Hematology and Oncology University Children's Hospital Münster West German Cancer Center Network Albert Schweitzer Campus 1 48149 Muenster Germany

Department of Solid Tumors Princess Máxima Center for Pediatric Oncology Heidelberglaan 25 3584 CS Utrecht the Netherlands

Gerhard Domagk Institute for Pathology University Hospital Muenster West German Cancer Center Network Albert Schweitzer Campus 1 48149 Muenster Germany

German Cancer Consortium Hufelandstrasse 55 45147 Essen Germany

German Cancer Consortium Partnersite Essen Essen Germany; Clinic of Orthopedics University Hospital Essen West German Cancer Centre Hufelandstrasse 55 45147 Essen Germany

German Cancer Consortium Partnersite Essen Essen Germany; Department of Solid Tumors Princess Máxima Center for Pediatric Oncology Heidelberglaan 25 3584 CS Utrecht the Netherlands

German Cancer Consortium Partnersite Essen Essen Germany; Department of Thoracic Surgery Ruhrlandklinik University Hospital Essen West German Cancer Center Tüschener Weg 40 45239 Essen Germany

HUS Helsinki University Hospital New Children's Hospital Div Hematology and Stem Cell Transplantation Stenbäckinkatu 9 Hallintokeskus rakennus 5 00290 Helsinki Finnland

Mother and Child Institute Department of Oncology and Surgical Oncology for Children and Youth Marcina Kasprzaka 17a 01 211 Warszawa Poland

Patient Representative St Josefs Hospital Bochum University Hospital Gudrunstraße 56 44791 Bochum Germany

Pediatrics 3 West German Cancer Center University Hospital Essen University Duisburg Essen Hufelandstrasse 55 45147 Essen Germany

Pediatrics 3 West German Cancer Center University Hospital Essen University Duisburg Essen Hufelandstrasse 55 45147 Essen Germany; German Cancer Consortium Partnersite Essen Essen Germany

Pediatrics 3 West German Cancer Center University Hospital Essen University Duisburg Essen Hufelandstrasse 55 45147 Essen Germany; University of Zurich Raemistrasse 71 8006 Zurich Switzerland

Radiotherapy and Radiooncology University Hospital Muenster West German Cancer Center Network Albert Schweitzer Campus 1 48149 Muenster Germany

Velkey László Child's Health Center Borsod Abaúj Zemplén County University Teaching Hospital Miskolc Hungary

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Factors Influencing the Outcome of Patients with Primary Ewing Sarcoma of the Sacrum