Patterns of failure following proton beam therapy for head and neck rhabdomyosarcoma. (May 2019)

• Record Type: Journal Article
• Authors: Ludmir, Ethan B.; Grosshans, David R.; McAleer, Mary Frances; McGovern, Susan L.; Harrison, Douglas J.; Okcu, M. Fatih; Chintagumpala, Murali M.; Mahajan, Anita; Paulino, Arnold C.
• Is Part Of: Radiotherapy and oncology. Volume 134(2019)
• Page Start: 143
• Page End: 150
• Publication Date: 2019-05
• Subjects: Rhabdomyosarcoma -- Radiotherapy -- Proton beam therapy -- Intracranial extension -- Parameningeal -- Cyclophosphamide; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2019.02.002
• Languages: English
• ISSNs: 0167-8140

Abstract

Highlights: Proton beam therapy (PBT) provides excellent local control for pediatric patients with head and neck rhabdomyosarcoma (RMS). Tumor size greater than 5 cm predicted increased risk of local failure, supporting ongoing dose escalation trial efforts. Tumors with intracranial extension (ICE) had high rates of local and leptomeningeal relapse. Delayed delivery of local therapy may drive higher rates of relapse seen among patients with ICE tumors. The late toxicity profile of patients treated with PBT compares favorably to that of prior series using IMRT. Abstract: 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.