RMS13 (NCT01871766) Response-Adapted Metastasis RT Shows Soft-Tissue “CR” Still Relapses in HR RMS

RMS13 is a Phase II prospective multicenter pediatric high-risk metastatic rhabdomyosarcoma study testing interval-compressed multiagent chemotherapy plus risk-adapted proton radiotherapy (RT) to primary tumor and selected metastatic sites, followed by maintenance therapy (n=39; median age 9.5 years; 64% FOXO1 fusion–positive; 67% Oberlin score >1). With median follow-up 23.1 months (78.5 months for non-progressors), 5-year EFS was 31.6% overall, splitting sharply by Oberlin score (>1: 16.2% vs ≤1: 61.5%); failures were predominantly distant (5-year cumulative incidence 54% vs local failure 14.4%). Among metastatic-site complete responders who omitted RT (n=21), 7/21 (33%) recurred at initially involved metastatic sites—driven by soft tissue (in-site recurrence 7/17 [41%] non-irradiated soft-tissue sites vs 1/12 [8%] bony sites), while only 1 recurrence occurred among irradiated soft-tissue sites; these outcomes sit in the disappointing historical range for upfront metastatic RMS (3-year EFS ~27% overall; 5-year EFS ~23% for Oberlin 2 and ~6% for Oberlin 3 in COG datasets), underscoring that systemic control remains the main limiter even when local control is intensified.