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

Ethan B. Ludmir, David R. Grosshans, Mary Frances McAleer, Susan L. McGovern, Douglas J. Harrison, M. Fatih Okcu, Murali Chintagumpala, Anita Mahajan, Arnold C. Paulino

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)143-150
Number of pages8
JournalRadiotherapy and Oncology
StatePublished - May 1 2019


  • Cyclophosphamide
  • Intracranial extension
  • Parameningeal
  • Proton beam therapy
  • Radiotherapy
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging


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