Tumor control with palliative external beam radiation therapy (EBRT) in advanced and unresectable osteosarcoma (OS) progressing after standard treatment

e22508 Background: Advanced OS still represents an unmet medical need. Chemotherapy and targeted therapies have only limited activity in this disease. Moreover, OS is considered a radioresistant tumor at doses conventionally achieved by EBRT. We retrospectively evaluated the impact of palliative EBRT in patients (pts) with advanced OS. Methods: Main inclusion criteria: confirmed histological diagnosis of OS; EBRT for advanced/metastatic disease deemed unresectable after multidisciplinary tumor board discussion; ECOG performance status ≤3, age ≥18 years at RT start; progressive disease at site of irradiation with symptoms (e.g., pain or neurological deficit) or involving critical structures (e.g., superior vena cava compression). Endpoints: progression-free survival (PFS), PFS for RT-treated lesions (RT-PFS), best response with RT, overall survival. All survival endpoints were computed from RT start. We calculated the equivalent total dose in 2 Gy fractions (EQD2). Results: 23 pts, 15 males, median age at diagnosis 33 (17-82), median age at RT start 36 (20-83) were included. All pts had grade 3-4 OS (12 osteoblastic; 6 chondroblastic; 5 other), 7 were metastatic at diagnosis. At time of RT, median metastatic sites were 2 (1-5), 15 pts were symptomatic (11 pain, 4 neurological deficit) and were mainly heavily pretreated [median previous chemotherapies 2 (1-5), median previous surgery 1 (0-2)]. Overall, 45 lesions underwent EBRT. Median EBRT dose per lesion was 33 Gy (IQR 25 - 46.5) with a median dose per fraction of 3 Gy (IQR 3-7.5). Calculated median EQD2 was 50 Gy (IQR 36 - 88). Median PFS, RT-PFS, and overall survival were 5 (95%CI 2-9), 11 (5-15), and 12 months (8-16), respectively. Compared to systemic progression, median progression delay of irradiated lesions was 6 months (95%CI 2 - 12). In 40 lesions evaluable for dimensional response, we observed tumor shrinkage > 30% in 7 lesions, stability in 24, and progression in 9. Conclusions: EBRT might have a role in the treatment of advanced OS. In consideration of the limited activity of medical treatments, EBRT might help in disease control in the advanced setting, delaying progression especially at critical sites.