Targeting metastatic sites with radiation and outcomes in high-risk pediatric rhabdomyosarcoma.

Abstract

10002 Background: Outcomes for pediatric patients with metastatic rhabdomyosarcoma (RMS) remain poor despite therapy intensification and novel agents. RMS13 (NCT01871766) was a phase II prospective multicenter trial evaluating a response-based approach to metastatic site radiotherapy (RT). We report outcomes related to metastatic disease management in this high-risk (HR) population. Methods: Event-free survival (EFS) and metastatic site control were analyzed for HR patients treated with interval compressed chemotherapy, risk-adapted RT to primary and metastatic site, and maintenance therapy. EFS was defined from therapy start to relapse, progression, death or last follow-up. Metastatic RT was delivered between interval-compressed and maintenance therapy for non–bone marrow metastatic sites without complete response (CR). RT omission criteria included PET negativity, lesion size <1 cm, or complete surgical resection with negative margins. Metastatic RT used protons: 25 Gy in 5 or 50.4 Gy in 28 fractions, by lesion size. Primary tumor control consisted primarily of proton RT, with limited use of surgery plus adjuvant RT. Results: From 2015 to 2020, 39 HR patients were enrolled (median age 9.5 years). Most patients were FOXO1 fusion–positive (64%), had nodal involvement (74%), and an Oberlin score >1 (67%). Median follow-up was 23.1 months overall (78.5 months for non-progressors). Five-year EFS was 31.6% (95% CI, 19.7-50.6%), differing by Oberlin score >1 – 16.2% (95% CI, 6.6–39.8%), ≤1 - 61.5% (95% CI, 40-94.6%). Twenty-six patients relapsed: 22 had distant failure (DF), 6 had local failure (LF), and 2 had both DF and LF. The 5-year cumulative incidence of LF was 14.4% (95% CI, 5–28), and 54% for DF (95% CI, 36–69), establishing DF as the predominant pattern of failure. Twenty-six patients reached the protocol window for metastatic-site RT (weeks 47–54): 11 soft-tissue metastases, 6 bone, 8 both, and 1 bone marrow only, with a 5-year EFS of 42.3% (95% CI 23.3-61.3%). Among 21 patients achieving CR at metastatic sites without RT, 5-year EFS was 38.1% (95% CI 17.3–58.9%), and cumulative incidence of any DF was 57.1% (95% CI 35.9–78.3%). Seven patients (33%) recurred at initially involved metastatic sites, primarily soft tissue. In-site recurrence occurred in 7/17 (41%) non-irradiated soft-tissue sites versus 1/12 (8%) bony sites. Only one recurrence occurred among irradiated soft-tissue sites. Conclusions: Soft-tissue metastatic sites in CR that were not irradiated had high recurrence rates, while bony sites achieved durable control without RT. Future trials should consider consolidative RT for soft-tissue metastases regardless of response in HR RMS. Clinical trial information: NCT01871766 . Recurrence by metastatic site. CR, no RT (N) Recurrence, non-RT, N(%) PR, RT (N) Recurrence, No RT, N (%) Bone metastases (n=14) 12 1 (8) 2 0 Soft-tissue metastases (n=19) 17 7 (41) 2 1 (5.9) CR, complete response; PR, partial response; RT, radiotherapy.