(P 68) METASTASIS-DIRECTED RADIOTHERAPY FOR EWING SARCOMA PATIENTS ENROLLED ON AEWS1221: A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP (COG)

Objective: Local control outcomes at metastatic sites in Ewing sarcoma (ES) are largely unknown. AEWS1221 was the first COG study to prospectively evaluate stereotactic body radiation therapy (SBRT) for the treatment of bone metastases in addition to conventionally fractionated radiotherapy (CFRT). Data collection and review for all metastases-directed local therapy is ongoing. We report the available data and analysis to date regarding the approach to definitive local radiation therapy for the treatment of metastases in ES patients enrolled on AEWS1221.

Methods: AEWS1221 was a prospective, randomized trial designed to evaluate IGF-1R inhibition in newly diagnosed metastatic ES patients, with similar outcomes in both randomized arms. Definitive local therapy, defined as surgery, SBRT, or CFRT, was recommended at the end of consolidation chemotherapy for all metastatic sites documented at time of diagnosis regardless of arm assignment. SBRT was recommended for unresected bone metastases < 5 cm in size at diagnosis. CFRT was recommended for unresected metastases >5 cm at diagnosis. Whole lung irradiation (WLI) with anterior-posterior, posterior-anterior opposed fields was recommended for lung metastases. Prescription doses were: SBRT, 40 Gy in 5 fractions; CFRT, 55.8 Gy in 31 fractions; WLI, 15 Gy in 10 fractions for patients >6 years and 12 Gy in 8 fractions for patients ≤6 years.

Results: Of 298 eligible enrolled patients, 169 patients (56.7%) completed consolidation chemotherapy without relapse and had discrete metastasis at enrollment beyond bone marrow disease. Eighty-five patients (50.3%) had bone metastases at enrollment. As of May 1, 2023, 165 patients had metastases directed local therapy records submitted for central review. Eighty-one patients received WLI only (49%), 36 patients received bone metastases radiotherapy only (22%), and 20 received WLI and bone metastases radiotherapy (12%). The remaining 28 patients (17%) received radiation therapy for non-bone and lung metastases, including soft tissue metastases and distant lymph node disease. Seventy-four patients (43.5%) had bone metastases eligible for SBRT; of these, 28 (38%) received SBRT. The three-year cumulative incidence of failure at bone sites treated with SBRT was 8.4% (95% CI, 3.6-19.0%) and 20.1% (95% CI, 11.9-32.6%) at bone sites not treated with SBRT.

Conclusion: Radiation to metastatic sites in ES appears feasible as most patients enrolled on AEWS1221 received at least some form of definitive local radiation therapy to metastatic sites at end of planned chemotherapy. Preliminary review of radiation approaches demonstrate a modest percentage of eligible patients (38%) treated with SBRT, and a nominally lower cumulative incidence of failure at bone sites treated with SBRT (8.4%) compared to bone sites not treated with SBRT (20.1%). Future analyses will evaluate local failure rates at metastatic sites by treatment modality, survival outcomes, protocol deviations, and toxicities with these approaches.