Children with DIPG and high-grade glioma treated with temozolomide, irinotecan, and bevacizumab: the Seattle Children's Hospital experience

J Neurooncol. 2020 Jul;148(3):607-617. doi: 10.1007/s11060-020-03558-w. Epub 2020 Jun 16.


Introduction: Beyond focal radiation, there is no consensus standard therapy for pediatric high-grade glioma (pHGG) and outcomes remain dismal. We describe the largest molecularly-characterized cohort of children with pHGG treated with a 3-drug maintenance regimen of temozolomide, irinotecan, and bevacizumab (TIB) following radiation.

Methods: We retrospectively reviewed 36 pediatric patients treated with TIB at Seattle Children's Hospital from 2009 to 2018 and analyzed survival using the Kaplan-Meier method. Molecular profiling was performed by targeted DNA sequencing and toxicities, steroid use, and palliative care utilization were evaluated.

Results: Median age at diagnosis was 10.9 years (18 months-18 years). Genetic alterations were detected in 26 genes and aligned with recognized molecular subgroups including H3 K27M-mutant (12), H3F3A G34-mutant (2), IDH-mutant (4), and hypermutator profiles (4). Fifteen patients (42%) completed 12 planned cycles of maintenance. Side effects associated with chemotherapy delays or modifications included thrombocytopenia (28%) and nausea/vomiting (19%), with temozolomide dosing most frequently modified. Median event-free survival (EFS) and overall survival (OS) was 16.2 and 20.1 months, with shorter survival seen in DIPG (9.3 and 13.3 months, respectively). Survival at 1, 2, and 5 years was 80%, 10% and 0% for DIPG and 85%, 38%, and 16% for other pHGG.

Conclusion: Our single-center experience demonstrates tolerability of this 3-drug regimen, with prolonged survival in DIPG compared to historical single-agent temozolomide. pHGG survival was comparable to analogous 3-drug regimens and superior to historical agents; however, cure was rare. Children with pHGG remain excellent candidates for the study of novel therapeutics combined with standard therapy.

Keywords: Bevacizumab; Diffuse intrinsic pontine glioma; Irinotecan; Pediatric high-grade glioma; Temozolomide.

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Brain Stem Neoplasms / drug therapy*
  • Brain Stem Neoplasms / pathology
  • Child
  • Child, Preschool
  • Diffuse Intrinsic Pontine Glioma / drug therapy*
  • Diffuse Intrinsic Pontine Glioma / pathology
  • Female
  • Follow-Up Studies
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Infant
  • Irinotecan / administration & dosage
  • Male
  • Neoplasm Grading
  • Retrospective Studies
  • Survival Rate
  • Temozolomide / administration & dosage


  • Bevacizumab
  • Irinotecan
  • Temozolomide