Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: A matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group

Eur J Cancer. 2017 Mar:73:38-47. doi: 10.1016/j.ejca.2016.12.007. Epub 2017 Feb 3.

Abstract

Background: Overall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. The purpose of this study is to analyse benefit and toxicity of re-irradiation at first progression.

Methods: At first progression, 31 children with DIPG, aged 2-16 years, underwent re-irradiation (dose 19.8-30.0 Gy) alone (n = 16) or combined with systemic therapy (n = 15). At initial presentation, all patients had typical symptoms and characteristic MRI features of DIPG, or biopsy-proven high-grade glioma. An interval of ≥3 months after upfront radiotherapy was required before re-irradiation. Thirty-nine patients fulfilling the same criteria receiving radiotherapy at diagnosis, followed by best supportive care (n = 20) or systemic therapy (n = 19) at progression but no re-irradiation, were eligible for a matched-cohort analysis.

Results: Median OS for patients undergoing re-irradiation was 13.7 months. For a similar median progression-free survival after upfront radiotherapy (8.2 versus 7.7 months; P = .58), a significant benefit in median OS (13.7 versus 10.3 months; P = .04) was observed in favour of patients undergoing re-irradiation. Survival benefit of re-irradiation increased with a longer interval between end-of-radiotherapy and first progression (3-6 months: 4.0 versus 2.7; P < .01; 6-12 months: 6.4 versus 3.3; P = .04). Clinical improvement with re-irradiation was observed in 24/31 (77%) patients. No grade 4-5 toxicity was recorded. On multivariable analysis, interval to progression (corrected hazard ratio = .27-.54; P < .01) and re-irradiation (corrected hazard ratio = .18-.22; P < .01) remained prognostic for survival. A risk score (RS), comprising 5 categories, was developed to predict survival from first progression (ROC: .79). Median survival ranges from 1.0 month (RS-1) to 6.7 months (RS-5).

Conclusions: The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability.

Keywords: Diffuse intrinsic pontine glioma (DIPG); Matched-cohort analysis; Radiotherapy; Re-irradiation; Survival prediction model.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Brain Stem Neoplasms / mortality
  • Brain Stem Neoplasms / radiotherapy*
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Glioma / mortality
  • Glioma / radiotherapy*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Multivariate Analysis
  • Prognosis
  • Re-Irradiation / statistics & numerical data*
  • Retrospective Studies
  • Survival Analysis