Local control and patterns of failure after SBRT for pediatric and young adult patients with Osteosarcoma

Summary: Pediatric Osteosarcoma is an aggressive bone malignancy characterized by high rates of disease relapse. Patients with metastatic or recurrent disease typically have a poor survival and radiotherapy is often used for symptom control, although local control is challenging given the radioresistance of this histology. By using Stereotactic Body Radiation Therapy (SBRT) to deliver high biologically equivalent doses (BED), local control (LC) can be potentially improved. We evaluate the treatment outcomes and patterns of failure with the use of SBRT for pediatric and young adult patients with metastatic osteosarcoma. This study included patients with metastatic osteosarcoma < 30 years of age receiving SBRT at our institution between February 2019 and June 2024. The primary endpoint was LC, defined as time from completing SBRT to first local progression. In-field failure was defined as progression with the irradiated field. Secondary endpoints were progression-free survival (PFS, time from SBRT to first local or distant progression or death), overall survival (OS, time from SBRT to death or last follow-up) and toxicities. Kaplan-Meier method was used for survival analysis and Cox proportional hazards model for univariate analysis. The study included 7 Osteosarcoma patients (5 male, 2 female) receiving 34 courses of SBRT. The median age at diagnosis was 13.1 years (range: 8.8–17.8) and 17.1 years (range: 9.6–22.2) at first SBRT. Median SBRT dose was 30 Gy (range: 25-50) in 5 fractions, and median BED was 48 Gy (range: 37.5–100). The common sites for SBRT were extraspinal osseous metastases (56%), lung (29%), and spine (9%). 86% patients had received primary definitive surgery for their Osteosarcoma, while 18% metastatic sites underwent surgery. At a median follow-up on 5.9 months (range: 1.7-52.2), LC was achieved in 88% of lesions, with four lesions failing locally. Freedom from local failure at 1 year was 69.2%. All 4 local failures were seen in patients receiving a BED< 48 Gy. No other clinical factors significantly predicted for worse LC. Distant progression was observed for 88% lesions, with a median distant PFS of 2.9 months. Five of the seven patients had died at last follow-up, with a median OS of 19.1 months. Toxicity was low, with only 4 patients who had CTCAE grade 2 toxicites, 1 patient with grade 2 chronic pneumonitis, and 2 with grade 3 rib myositis, all of which resolved. Our study suggests that SBRT is safe and achieves effective LC in pediatric patients with metastatic osteosarcoma, though distant progression can limit survival outcomes. Higher BED was associated with improved LC, supporting dose escalation strategies for these patients. Sohil N. Reddy (he/him/his), B.S. (Presenting Author) - The Ohio State University College of Medicine; Rituraj Upadhyay, MD (Co-Author) - The Ohio State University; Brett Klamer, B.S., M.A. (Co-Author) - The Ohio State University Center for Biostatistics; Raj Singh, MD (Co-Author) - Department of Radiation Oncology, The James Cancer Hospital and Solove Research Institute at The Ohio State University Wexner Medical Center; Raju Raval (he/him/his), MD, DPhil (Co-Author) - The Ohio State University; Joshua D.. Palmer, MD (Co-Author) - Department of Radiation Oncology, The James Cancer Hospital and Solove Research Institute at The Ohio State University Wexner Medical Center; Sujith Baliga (he/him/his), M.D. (Co-Author) - The Ohio State University Wexner Medical Center