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

Cancer Cell
Alan MacKayChris Jones

Abstract

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.

Citations

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Datasets Mentioned

BETA
E-MTAB-5552
EGAS00001002328

Methods Mentioned

BETA
biopsy
PCR
exome-sequencing
RNA-seq
methylation profiling
exome sequencing
RNAseq

Clinical Trials Mentioned

NCT01390948
NCT02992964
NCT02684058

Software Mentioned

minfi
Ensembl
R
GSEA
CopyNumber450kData
ExAc
Genome Analysis Tool Kit
GSEA java application
Mutation Surveyor
GraphPad Prism

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