Efficacy and Safety of Limited-Margin Conformal Radiation Therapy for Pediatric Rhabdomyosarcoma: Long-Term Results of a Phase 2 Study

Purpose: Our purpose was to assess disease outcomes and late toxicities in pediatric patients with rhabdomyosarcoma treated with conformal photon radiation therapy (RT). Methods and Materials: Sixty-eight patients (median age, 6.9 years) were treated with conformal photon RT to the primary site on a prospective clinical trial. Target volumes included a 1-cm expansion encompassing microscopic disease. Prescribed doses were 36 Gy to this target volume and 50.4 Gy to gross residual disease. Chemotherapy consisted of vincristine/dactinomycin (n = 6), vincristine/dactinomycin/cyclophosphamide (n = 37), or vincristine/dactinomycin/cyclophosphamide-based combinations (n = 25). Patients were evaluated with primary-site magnetic resonance imaging, whole-body [¹⁸F]fluorodeoxyglucose positron emission tomography, and chest computed tomography for 5 years after treatment. Results: Five-year disease-free survival was 88% for low-risk (n = 8), 76% for intermediate-risk (n = 37), and 36% for high-risk (n = 23) patients (P ≤ .01 for low risk/intermediate risk vs high risk). The cumulative incidence of local failure (LF) at 5 years for the entire cohort was 10.4%. Tumor size at diagnosis was a significant predictor of LF (P < .01). Patients with head and neck primary tumors (n = 31) had a 35% cumulative incidence of cataracts; the risk correlated with lens dose (P = .0025). Jaw dysfunction was more severe when the pterygoid and masseter muscles received a mean dose of >20 Gy (P = .013). Orbital hypoplasia developed more frequently after a mean bony orbit dose of >30 Gy (P = .041). Late toxicity in patients with genitourinary tumors included microscopic hematuria (9 of 14), bladder-wall thickening (10 of 14), and vaginal stenosis (2 of 5). Conclusions: Long-term LF rates were low, and higher rates correlated with larger tumors. Treatment-related toxicities resulting in measurable functional deficits were not infrequent, despite the conformal RT approach.