Comprehensive Radiotherapy for Pediatric Ewing Sarcoma: Outcomes of a Prospective Proton Study

Abstract

<h3>Purpose/Objective(s)</h3> Patients with Ewing Sarcoma (EWS) are treated with multimodal therapy, with radiation therapy (RT) as an option for local control. We report on the efficacy after proton radiation therapy (PRT) for localized and metastatic EWS. <h3>Materials/Methods</h3> Fifty children with EWS (39 localized, 11 metastatic) treated between 2007 and 2020 were enrolled on a prospective IRB-approved protocol for pediatric patients undergoing PRT. Median age at time of PRT was 11.5 years (range 0.9-19.6 years); 62% were male. Median tumor size was 6.4cm (range 2.5-21cm). All patients received induction chemotherapy prior to PRT; 38 patients had definitive PRT and 12 had surgery followed by PRT. PRT was delivered by passive scatter (74%), pencil-beam scanning (12%) or mixed technique (14%). Treated sites included the spine (40%), pelvis/sacrum (26%), skull (18%), extraosseous (10%), and axial-skeleton (6%). Median radiation dose was 54Gy-RBE (range 36.9-55.8Gy-RBE). All patients with metastatic disease (n=11) received consolidative RT to metastatic sites (5 at the time of local control [LC], 6 after completion of chemotherapy). Long-term follow-up data was available for 41 patients which comprise the subjects included in this report. Local failures were classified as in-field (>80% of relapse volume within the 95% isodose line [IDL]), marginal (>20% to ≤80% within the 95% IDL), or out-of-field (≤20% within the 95% IDL). Median follow-up time was 47 months after PRT. <h3>Results</h3> The 4-year LC, progression-free survival (PFS), and overall survival (OS) rates were 83.2%, 71.4%, and 86.3%, respectively. All local failures (n=6) were in-field failures. Tumor size ≥8cm predicted both inferior 4-year LC and PFS (69% vs 95%, p=0.04; 55% vs 86%, p=0.03, respectively). The 4-year PFS and OS rates were not statistically different in patients with localized versus metastatic disease (72% vs 67%, p=0.70; 89% vs 78%, p=0.38, respectively). Long-term toxicity included a grade 3 esophageal stricture in 1 patient. <h3>Conclusion</h3> We report one of the largest series of pediatric patients with EWS treated with PRT. LC was comparable to that of historical patients who received photon-RT and there were no marginal failures. Larger initial tumor size predicted increased risk of local failure and disease progression, which supports current efforts to dose-escalate treatment of tumors ≥8cm. Finally, patients with metastatic disease received radiation therapy to all metastatic sites and had survival outcomes comparable to those of patients with localized disease, suggesting a benefit to using RT for consolidation in metastatic EWS.