Disease Control and Patterns of Failure After Proton Beam Therapy for Rhabdomyosarcoma

Int J Radiat Oncol Biol Phys. 2021 Mar 1;109(3):718-725. doi: 10.1016/j.ijrobp.2020.09.050.

Abstract

Purpose: Pediatric patients with rhabdomyosarcoma (RMS) are treated with multimodal therapy, often with radiation therapy (RT) as part of local therapy. We report on the efficacy and patterns of failure after proton beam therapy (PBT) for RMS.

Methods and materials: Between January 2006 and February 2017, patients with RMS were enrolled in a prospective institutional review board-approved registry protocol for pediatric patients undergoing PBT. Demographics, clinical characteristics, and treatment related outcomes were reviewed.

Results: Ninety-four RMS patients were treated with a combination of chemotherapy (CT) and PBT. The majority of patients had head and neck (49%) and genitourinary (30%) primaries. Median tumor size was 4.1 cm (range, 1.0-16.5 cm); 33 patients (35%) had primary tumors >5 cm. Median cyclophosphamide equivalent dose was 14.4 g/m2 (range, 0-30.8 g/m2). Median time from CT initiation to RT initiation was 13 weeks (range, 1-58 weeks). With median follow-up of 4 years, 4-year overall survival (OS) was 71%, and 4-year progression-free survival (PFS) was 63%. Thirty patients (32%) experienced relapse (13% with local failure [LF]). Four-year local control (LC) was 85% overall; 4-year LC rates were 100% for low-risk, 85% for intermediate-risk, and 55% for high-risk patients (P = .02). Tumor size predicted LC (P = .007), with 7% versus 33% LF rate by tumor size (≤5 cm vs >5 cm). Delayed RT delivery (≥13 weeks from initiation of CT) predicted worse LC (P = .01). Increased tumor size predicted both inferior PFS (P = .02) and OS (P = .01). Delayed RT delivery predicted both inferior PFS (P = .04) and OS (P = .03).

Conclusions: PBT provides LC comparable to prior studies using photon RT. Inferior LC, PFS, and OS rates were observed for patients with larger tumors and those treated with delayed RT. This finding supports ongoing prospective efforts to dose-escalate treatment of tumors >5 cm; however, these data call into question the optimal timing of local therapy, particularly for patients treated with reduced-dose cyclophosphamide.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Child
  • Child, Preschool
  • Combined Modality Therapy / methods
  • Cyclophosphamide / administration & dosage
  • Female
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Recurrence, Local
  • Outcome Assessment, Health Care
  • Progression-Free Survival
  • Prospective Studies
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy
  • Proton Therapy / methods*
  • Rhabdomyosarcoma, Alveolar / drug therapy
  • Rhabdomyosarcoma, Alveolar / mortality
  • Rhabdomyosarcoma, Alveolar / pathology
  • Rhabdomyosarcoma, Alveolar / radiotherapy*
  • Rhabdomyosarcoma, Embryonal / drug therapy
  • Rhabdomyosarcoma, Embryonal / mortality
  • Rhabdomyosarcoma, Embryonal / pathology
  • Rhabdomyosarcoma, Embryonal / radiotherapy*
  • Risk Factors
  • Treatment Failure
  • Tumor Burden
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / radiotherapy

Substances

  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide