Molecular, pathological, radiological, and immune profiling of non-brainstem pediatric high-grade glioma from the HERBY phase II randomized trial

Mackay, Alan and Burford, Anna and Molinari, Valeria and Jones, David T.W. and Izquierdo, Elisa and Brouwer-Visser, Jurriaan and Giangaspero, Felice and Haberler, Christine and Pietsch, Torsten and Jacques, Thomas S. and Figarella-Branger, Dominique and Rodriguez, Daniel and Morgan, Paul S. and Raman, Pichai and Waanders, Angela J. and Resnick, Adam C. and Massimino, Maura and Garrè, Maria Luisa and Smith, Helen and Capper, David and Pfister, Stefan M. and Würdinger, Thomas and Tam, Rachel and Garcia, Josep and Thakur, Meghna Das and Vassal, Gilles and Grill, Jacques and Jaspan, Tim and Varlet, Pascale and Jones, Chris (2018) Molecular, pathological, radiological, and immune profiling of non-brainstem pediatric high-grade glioma from the HERBY phase II randomized trial. Cancer Cell, 33 (5). 829-842.e5. ISSN 1878-3686

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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.

Item Type: Article
Keywords: Immune; CD8; MAPK; Hypermutator; H3F3A; Pediatric high-grade glioma
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine
Identification Number: https://doi.org/10.1016/j.ccell.2018.04.004
Depositing User: Eprints, Support
Date Deposited: 23 May 2018 09:10
Last Modified: 24 May 2018 00:10
URI: http://eprints.nottingham.ac.uk/id/eprint/51975

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