Definitive Radiation Therapy for Ewing Sarcoma: Outcomes Based on Tumor Volume, Dose, and Fractionation

Objective Dose escalation for definitive radiation therapy (DE-RT) in larger Ewing sarcomas (ES) is associated with a lower risk of local recurrence. We report treatment and toxicity outcomes in ES tumors treated with DE-RT, including hypofractionated approaches and size stratification of analysis. Methods A retrospective review of ES patients treated with definitive RT to doses ≥55.8 Gy was performed. Local failure with death as a competing risk (LF) was assessed. Maximally selected rank statistics were used to determine the optimal stratification of patients by survival using tumor size measurements. Results 47 patients were analyzed. Twenty-eight patients (59.6%) received DE-RT, of which 6 received hypofractionation. For DE-RT, median EQD2 α/β=10 was 60 Gy (range: 56.2-62) with conventional fractionation and 62.2 Gy (range: 56.5-67.1) with hypofractionation. Empirically derived size cutoffs identified a subgroup of ultra-large tumors at higher risk of LF defined as greater than 11.8 cm in longest direction, 569.2 cm 3 prechemotherapy volume, or 288.9 cm 3 postchemotherapy volume.5-year cumulative incidence of LF was lower in patients treated with DE-RT at 11.7% (95% CI, 3.16%-43.6%) versus 35.6% for non-DE-RT (95% CI, 17.4%-72.61%, p=0.098). Multivariate analysis showed trends toward DE-RT benefiting tumors of all sizes and stages. Conclusions DE-RT was associated with a trend toward better LF in all tumors without toxicity or plan quality changes. Ultra-large tumors demonstrated poor LF rates and necessitate further study.