Outcomes After Proton Therapy for Treatment of Pediatric High-Risk Neuroblastoma

Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):401-408. doi: 10.1016/j.ijrobp.2019.01.095. Epub 2019 Feb 7.


Purpose: Patients with high-risk neuroblastoma (HR-NBL) require radiation to the primary tumor site and sites of persistent metastatic disease. Proton radiation therapy (PRT) may promote organ sparing, but long-term outcomes have not been studied.

Methods and materials: Sequential patients with HR-NBL received PRT: 2160 cGy (relative biological effectiveness) to primary tumor bed and persistent metastatic sites, with 3600 cGy (relative biological effectiveness) to gross residual disease.

Results: From September 2010 through September 2015, 45 patients with HR-NBL received PRT after systemic therapy, primary tumor resection, and high-dose chemotherapy with stem cell rescue. Median age was 46 months at the time of PRT (range, 10 months to 12 years); 23 patients (51%) were male. Primary tumors were adrenal in 40 (89%); 11 (24%) received boost. Ten metastatic sites in 8 patients were radiated. Double scattered proton beams were used for 19 (42%) patients, in combination with x-rays for 2 (5%). The remaining 26 (58%) received pencil beam scanning, available since January 2013. We observed 97% freedom from primary site recurrence at 3, 4, and 5 years. Overall survival rates were 89%, 80%, and 80% and disease-free survival rates were 77%, 70%, and 70%, at 3, 4, and 5 years, respectively. With median follow-up of 48.7 months from diagnosis (range, 11-90 months) for all patients (57.4 months for those alive), 37 (82%) patients are alive, and 32 (71%) are without evidence of disease. One patient experienced locoregional recurrence; the remaining 12 (27%) experienced relapse at distant, nonradiated sites. Acute toxicities during treatment were mainly grade 1. No patient has experienced World Health Organization grade 3 or 4 long-term renal or hepatic toxicity. Pencil beam scanning plans required less planning time and resources than double scattered plans.

Conclusions: We observe excellent outcomes in patients treated with PRT for HR-NBL from 2010 through 2015, with 82% of patients alive and 97% free of primary site recurrence. No patient has experienced long-term renal or liver toxicity. This treatment maximizes normal tissue preservation and is appropriate for this patient population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms / radiotherapy
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Neoplasm, Residual
  • Neuroblastoma / mortality
  • Neuroblastoma / pathology
  • Neuroblastoma / radiotherapy*
  • Neuroblastoma / secondary
  • Proton Therapy / adverse effects
  • Proton Therapy / methods*
  • Relative Biological Effectiveness
  • Risk
  • Survival Rate
  • Thoracic Neoplasms / radiotherapy
  • Thoracic Neoplasms / secondary
  • Time Factors
  • Treatment Outcome