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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2018 May 16

PMID 29763623

Citations 107

Authors

Alan Mackay

Anna Burford

Valeria Molinari

David T W Jones

Elisa Izquierdo

Jurriaan Brouwer-Visser

Felice Giangaspero

Christine Haberler

Torsten Pietsch

Thomas S Jacques

Dominique Figarella-Branger

Daniel Rodriguez

Paul S Morgan

Pichai Raman

Angela J Waanders

Adam C Resnick

Maura Massimino

Maria Luisa Garre

Helen Smith

David Capper

Stefan M Pfister

Thomas Wurdinger

Rachel Tam

Josep Garcia

Meghna Das Thakur

Gilles Vassal

Jacques Grill

Tim Jaspan

Pascale Varlet

Chris Jones

Affiliations

Soon will be listed here.

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.

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