Long-term side effects of radiotherapy for pediatric localized neuroblastoma : results from clinical trials NB90 and NB94

Strahlenther Onkol. 2015 Jul;191(7):604-12. doi: 10.1007/s00066-015-0837-z. Epub 2015 Apr 21.

Abstract

Introduction: Neuroblastoma (NB) is the most frequent indication for extracranial pediatric radiotherapy. As long-term survival of high-risk localized NB has greatly improved, we reviewed treatment-related late toxicities in pediatric patients who received postoperative radiotherapy (RT) for localized NB within two French prospective clinical trials: NB90 and NB94.

Patients and methods: From 1990-2000, 610 children were enrolled. Among these, 35 were treated with induction chemotherapy, surgery, and RT. The recommended RT dose was 24 Gy at ≤ 2 years, 34 Gy at > 2 years, ± a 5 Gy boost in both age groups.

Results: The 22 patients still alive after 5 years were analyzed. The median follow-up time was 14 years (range 5-21 years). Late effects after therapy occurred in 73 % of patients (16/22), within the RT field for 50 % (11/22). The most frequent in-field effects were musculoskeletal abnormalities (n = 7) that occurred only with doses > 31 Gy/1.5 Gy fraction (p = 0.037). Other effects were endocrine in 3 patients and second malignancies in 2 patients. Four patients presented with multiple in-field late effects only with doses > 31 Gy.

Conclusion: After a median follow-up of 14 years, late effects with multimodality treatment were frequent. The most frequent effects were musculoskeletal abnormalities and the threshold for their occurrence was 31 Gy.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Dose Fractionation, Radiation
  • Female
  • France
  • Gene Amplification
  • Humans
  • Infant
  • Male
  • N-Myc Proto-Oncogene Protein
  • Neoplasm, Residual / mortality
  • Neoplasm, Residual / radiotherapy
  • Neoplasms, Radiation-Induced / etiology
  • Neuroblastoma / genetics
  • Neuroblastoma / mortality
  • Neuroblastoma / radiotherapy*
  • Nuclear Proteins / genetics
  • Oncogene Proteins / genetics
  • Prospective Studies
  • Radiation Injuries / etiology*
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant*
  • Survival Analysis

Substances

  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins