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

Varlet, Pascale; Mackay, Alan; Burford, Anna; Molinari, Valeria; Jones, David T.W.; Izquierdo, Elisa; Brouwer-Visser, Jurriaan; Giangaspero, Felice; Haberler, Christine; Pietsch, Torsten; Jacques, Thomas S.; Figarella-Branger, Dominique; Rodriguez, Daniel; Morgan, Paul S.; Raman, Pichai; Waanders, Angela J.; Resnick, Adam C.; Massimino, Maura; Garrè, Maria Luisa; Smith, Helen; Capper, David; Pfister, Stefan M.; Würdinger, Thomas; Tam, Rachel; Garcia, Josep; Thakur, Meghna Das; Vassal, Gilles; Grill, Jacques; Jaspan, Tim; Varlet, Pascle; Jones, Chris

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.

Citation

Varlet, P., Mackay, A., Burford, A., Molinari, V., Jones, D. T., Izquierdo, E., Brouwer-Visser, J., Giangaspero, F., Haberler, C., Pietsch, T., Jacques, T. S., Figarella-Branger, D., Rodriguez, D., Morgan, P. S., Raman, P., Waanders, A. J., Resnick, A. C., Massimino, M., Garrè, M. L., Smith, H., …Jones, C. (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. https://doi.org/10.1016/j.ccell.2018.04.004

• Journal Article Type: Article
• Acceptance Date: Feb 27, 2018
• Publication Date: 2018-05
• Deposit Date: May 23, 2018
• Publicly Available Date: May 31, 2018
• Journal: Cancer Cell
• Print ISSN: 1535-6108
• Electronic ISSN: 1878-3686
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 33
• Issue: 5
• Article Number: 829-842.e5
• Pages: 829-842.e5
• DOI: https://doi.org/10.1016/j.ccell.2018.04.004
• Keywords: Immune; CD8; MAPK; Hypermutator; H3F3A; Pediatric high-grade glioma
• Public URL: https://nottingham-repository.worktribe.com/output/932167
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1535610818301752?via%3Dihub
• Contract Date: May 23, 2018