Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial

Cancer Cell. 2018 May 14;33(5):829-842.e5. doi: 10.1016/j.ccell.2018.04.004.


The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8+ tumor-infiltrating lymphocytes, and longer survival with the addition of BEV. Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Future clinical trials will need to take into account the diversity represented by the term "HGG" in the pediatric population.

Trial registration: NCT01390948.

Keywords: CD8; H3F3A; MAPK; hypermutator; immune; pediatric high-grade glioma.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bevacizumab / therapeutic use*
  • CD8-Positive T-Lymphocytes
  • Chemoradiotherapy / methods*
  • Child
  • Child, Preschool
  • DNA Polymerase III / genetics
  • Female
  • Glioma / genetics
  • Glioma / immunology
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • Male
  • Mutation*
  • Neoplasm Grading
  • Neurofibromin 1 / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Survival Analysis
  • Temozolomide / therapeutic use*


  • Neurofibromin 1
  • Bevacizumab
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • DNA Polymerase III
  • Temozolomide

Associated data