Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial.
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Date
2018-05-14Author
Mackay, A
Burford, A
Molinari, V
Jones, DTW
Izquierdo, E
Brouwer-Visser, J
Giangaspero, F
Haberler, C
Pietsch, T
Jacques, TS
Figarella-Branger, D
Rodriguez, D
Morgan, PS
Raman, P
Waanders, AJ
Resnick, AC
Massimino, M
Garrè, ML
Smith, H
Capper, D
Pfister, SM
Würdinger, T
Tam, R
Garcia, J
Thakur, MD
Vassal, G
Grill, J
Jaspan, T
Varlet, P
Jones, C
Type
Journal Article
Metadata
Show full item recordAbstract
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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Subject
CD8-Positive T-Lymphocytes
Humans
Glioma
DNA Polymerase III
Proto-Oncogene Proteins B-raf
Neurofibromin 1
Survival Analysis
Mutation
Adolescent
Child
Child, Preschool
Female
Male
Neoplasm Grading
Chemoradiotherapy
Bevacizumab
Temozolomide
Research team
Glioma Team
Language
eng
Date accepted
2018-04-10
License start date
2018-05
Citation
Cancer cell, 2018, 33 (5), pp. 829 - 842.e5
Publisher
CELL PRESS