Patterns of failure following proton beam therapy for head and neck rhabdomyosarcoma

Purpose: Pediatric patients with rhabdomyosarcoma (RMS) of the head and neck (H&N) are treated with multimodal therapy, often with radiotherapy (RT) as definitive local therapy. We report on the patterns of failure following proton beam therapy (PBT) for H&N RMS. Methods: Forty-six H&N RMS patients were enrolled on a prospective registry protocol between 2006 and 2015. All were treated with a combination of chemotherapy (ChT) and PBT. Most patients (25 patients, 54%) had parameningeal tumors, of which 11 (24%) had intracranial extension (ICE). Thirteen patients (28%) had primary tumors greater than 5 cm. Median total cyclophosphamide (CPM) equivalent dose was 13.2 g/m(2) (range 0-16.8 g/m(2)). Median RT dose was 50.4 Gy(RBE) (range 36 Gy[RBE]-50.8 Gy[RBE]). Results: With median follow-up of 3.9 years, five-year overall survival was 76%, and five-year progression-free survival was 57%. Seventeen patients (37%) experienced relapse, including 7 with local failure (LF). Five-year local control (LC) was 84%. Tumor size greater than 5 cm predicted increased risk of LF (hazard ratio [HR] 6.49, p = 0.03), as did the presence of ICE at diagnosis (HR 5.21, p = 0.03). Six relapses occurred in patients with ICE; all included a component of central nervous system relapse, with leptomeningeal disease and/or LF with an intracranial component. Delayed RT delivery after week 4 of ChT predicted increased risk of relapse for ICE patients (HR 10.49, p = 0.006). Conclusions: PBT confers excellent LC, and a favorable late toxicity profile as compared with prior photon RT data. Our observations support ongoing trial efforts to dose-escalate RT for patients with larger tumors. However, these data raise concerns regarding excess failures among patients with ICE. (C) 2019 Elsevier B.V. All rights reserved.