Multi-Institutional Experience of Proton Therapy for Rhabdomyosarcoma and Ewing Sarcoma in the Proton Collaborative Group (PCG) Prospective Registry

Abstract

To report on outcomes, acute toxicities, and the use of dose-escalation with proton therapy (PT) in patients with rhabdomyosarcoma and Ewing sarcoma in a prospective multi-institutional registry (PCG). Data on patients with primary rhabdomyosarcoma and Ewing sarcoma treated with definitive PT (defined as ≥45 Gy) were queried from the PCG registry. A similar query was performed of our institutional database with IRB approval. Overall survival rates were calculated by Kaplan-Meier. Toxicities were scored using CTCAE v4.0. A total of 354 patients across 10 institutions (203 rhabdomyosarcoma, 151 Ewing sarcoma) met the eligibility criteria. Median age was 9 years (Interquartile Range: 5-15). Median dose was 50.4 GyRBE for rhabdomyosarcoma patients (Range: 45-66 GyRBE) and 55.8 GyRBE for Ewing sarcoma patients (Range: 45-66 GyRBE). Median follow-up was 2.4 years (Range 0.3-12.3 years). Two-year overall survival rates were 81.1% (95% CI: 73.7%-88.5%) for rhabdomyosarcoma and 79.1% (95% CI: 71.7%-86.2%) for Ewing sarcoma. The Table lists the prescription doses delivered by tumor histology; 28.1% of rhabdomyosarcoma and 21.9% of Ewing sarcoma patients, respectively, received dose-escalated radiotherapy (defined as >50.4 Gy for rhabdomyosarcoma and >55.8 Gy for Ewing sarcoma). Excluding alopecia and skin desquamation, 153 patients (43.2%) developed any acute grade 2+ non-hematologic toxicity, while 49 patients (13.8%) developed one or more grade 3 toxicities. The most common grade 3 toxicities were anorexia/weight loss (7.3%), pain (7.3%) mucositis/esophagitis (4.8%), and nausea/vomiting (3.1%). One grade 4 toxicity (esophagitis) and no deaths were reported during treatment. In this multi-institutional prospective registry, 28.1% of rhabdomyosarcoma and 21.9% of Ewing sarcoma patients received dose-escalated PT, with 13.8% of patients developing grade 3 toxicities. Long-term outcomes for disease control and late toxicity and anticipated cooperative group trial results are needed to fully assess the benefits and risks of dose-escalated radiotherapy for these tumors.