Multi-Institutional Experience of Proton Therapy for Osteosarcoma in the Proton Collaborative Group (PCG) Prospective Registry

Abstract

To report on the utilization of dose-escalated radiotherapy, acute toxicities, and survival following definitive proton therapy (PT) for osteosarcoma patients in a prospective multi-institutional study. Data on patients with osteosarcoma treated with definitive intent PT were queried from the Proton Collaborative Group (PCG) prospective registry. A similar query was performed on an institutional database with IRB approval. Overall survival rates were calculated by Kaplan-Meier. Toxicities were scored using CTCAE v4.0. Forty osteosarcoma patients across 9 institutions received definitive intent PT between 2011-2021 and met the eligibility criteria. Median age was 32 years (Range: 6-86 years). Median PT dose was 66.6 GyRBE (Range: 50.4-80.0 GyRBE); 38 patients received proton therapy alone, whereas 2 received combined proton/photon therapy. Seventeen (42.5%) patients received doses ≥70 GyRBE. Median follow-up was 3.1 years (Range: 0.9-10.5 years). One-year and three-year overall survival rates were 83.5% and 59.1%, respectively, with 14 deaths due to disease. Excluding skin desquamation and alopecia, 22 patients (55.0%) developed any acute grade 2+ toxicity, and 5 patients (12.5%) developed any grade 3 toxicities. No acute grade 4-5 toxicities were reported. The most frequent grade 2+ non-skin toxicities were fatigue (37.5%), anorexia/weight loss (17.5%), mucositis/esophagitis (22.5%), pain (20.0%), and nausea/vomiting (10.0%). The most frequent grade 3 toxicities were anorexia/weight loss (5.0%), mucositis/esophagitis (5.0%), and neurologic symptoms (5.0%). In this multi-institutional study, 42.5% of osteosarcoma patients treated with PT received doses between 70-80 Gy, with 12.5% experiencing any grade 3 toxicity. Long-term outcomes for disease control, late toxicity, and quality-of-life are needed to more fully assess the benefits and risks of dose-escalated radiotherapy in this radioresistant tumor. The authors plan to assess the outcomes of osteosarcoma patients treated with dose-escalated radiotherapy for unresectable or gross residual disease in future studies.