PURPOSE:Local therapy (LT) is a critical component of curative treatment for Ewing sarcoma (ES). This analysis evaluated clinical and treatment variables associated with local failure (LF) risk for nonmetastatic patients with ES. METHODS AND MATERIALS:AEWS1031 was a phase 3 randomized trial comparing 2 interval-compressed chemotherapy regimens. Patients who completed induction chemotherapy and started LT of the primary tumor site were analyzed. LT was surgery alone (S), definitive radiation therapy (RT), or surgery and RT (S+RT), and was determined by the treating investigator. The primary endpoint was the cumulative incidence of LF estimated from the time LT was started. Elastic net penalization was used to identify predictors associated with the cause-specific hazard rates of LF. RESULTS:Five hundred eighty-eight patients started LT. Tumor sites were extremity (40%), axial (27%), pelvis (18%), and extraosseous (15%). LT was S (54%), RT (27%), and S+RT (18%). With a median follow-up of 67.6 months, the 5-year cumulative incidence of LF for all patients was 6%. LF incidence was 5% for S, 8.4% for RT, and 5.6% for S+RT (P = .47). LF incidence was 3.5% for extremity, 8.7% for pelvis, 7.7% for axial, and 6.3% for extraosseous (P = .09). LF incidence was higher for tumors ≥200 mL (11.3%) compared with tumors <200 mL (3.9%; P < .01). On multivariable modeling, increasing age at enrollment (cause-specific relative hazard ratio [csRHR] 1.04/y) and increasing maximum tumor dimension (csRHR 1.08/cm) were suggestive of a higher incidence of LF. By tumor subsite, axial tumors were associated with the highest risk of LF (csRHR 1.17) and extremity tumors with the lowest risk (csRHR 0.50). CONCLUSIONS:We report the lowest LF incidence to date for prospective ES trials. Large tumors, older age, and axial tumor subsite were associated with higher LF incidence, indicating further efforts are needed to identify the highest-risk subset most likely to benefit from improved LT strategies.
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