11 - Stereotactic Body Radiation Therapy (SBRT) and Comprehensive Metastasis-Directed Therapy for Ewing Sarcoma Patients Enrolled on AEWS1221: A Report from the Children's Oncology Group (COG)

02:10pm - 02:20pm ET

Grand Ballroom

Presenter(s)

Nadia Laack, MD, MS - Mayo Clinic, Rochester, MN

N. N. Laack II¹, D. J. Indelicato², N. DelRocco³, C. E. Hill-Kayser⁴, B. R. Eaton⁵, S. A. Terezakis⁶, I. Tfirn⁷, A. Buxton³, J. Glade-Bender⁸, D. Reed⁸, R. G. Gorlick⁹, K. A. Janeway¹⁰, S. G. Dubois¹¹, and S. K. Ahmed¹²; ¹Department of Radiation Oncology, Mayo Clinic, Rochester, MN, ²Department of Radiation Oncology, University of Florida, Jacksonville, FL, ³Children's Oncology Group, Monrovia, CA, ⁴University of Pennsylvania, Philedelphia, PA, ⁵Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, ⁶University of Minnesota: Department of Radiation Oncology, Minneapolis, MN, ⁷childrensoncologygroup, Monrovia, CA, ⁸Memorial Sloan Kettering Cancer Center, New York City, NY, ⁹MD Anderson Cancer Center, Houston, TX, ¹⁰Dana Farber Cancer Institute, Boston, MA, ¹¹Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, ¹²Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ

Purpose/Objective(s): Local control at metastatic sites in Ewing sarcoma (ES) is poorly described. AEWS1221 was the first COG study to prospectively evaluate stereotactic body radiotherapy (SBRT) for unresected bone metastases <5 cm. We hypothesized SBRT is feasible and that comprehensive metastasis-directed therapy (CMDT) reduces local recurrence and improves survival in patients event-free after consolidation.

Materials/Methods: AEWS1221 was a prospective randomized COG trial for newly diagnosed metastatic ES. After consolidation, definitive local therapy (surgery, SBRT, or conventionally fractionated RT [CFRT]) was recommended to all metastatic sites present at diagnosis. SBRT dose was 40 Gy/5 fractions (35 Gy/5 if overlapping whole-lung fields); other sites received conventional fractionated radiotherapy (CFRT). Central review of baseline and response imaging and RT plans was performed. SBRT success was defined as acceptable/minor deviation. Endpoints included cumulative incidence of local recurrence in bone metastases (CILR) after local therapy for SBRT, CFRT-only, and no local therapy, and patient-level post–local therapy EFS/OS by CMDT status.

Results: Of 298 eligible patients, 169 (57%) were event-free through consolidation with discrete metastases beyond marrow; 167 had local therapy records for review. Eighty-five had bone metastases, 74 were SBRT-eligible, and SBRT was confirmed in 44/74 (60%) (33 also received CFRT). SBRT was successfully delivered in 32/44 (73%) patients. Minor and major SBRT deviations occurred in 12 (9%) and 22 (16%) treated bone lesions. Three-year CILR was 2% (95% CI 0.2–10) with any SBRT, 9.5% (2–27) with CFRT-only, and 33% (9–60) with no local therapy. Suspected treatment-related toxicities were similar with SBRT, CFRT, or no RT (50%, 48%, 33%; p=0.6). Three-year post–local therapy EFS/OS were 59%/67.9% with CMDT versus 26%/27.8% without CMDT (p<0.001 and p=0.002).

Conclusion: Among metastatic ES patients event-free after consolidation, SBRT for small bone metastases was feasible with low incidence of local failure. Patients treated with CMDT had improved EFS and OS, supporting comprehensive local therapy to all baseline metastatic sites as a standard approach. Future analyses will expand on these univariate findings.

Acknowledgements: NCTN Operations Center Grant U10CA180886, NCTN Statistics & Data Center Grant U10CA180899, & St. Baldrick’s Foundation