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

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 Garrè, Helen Smith, David CapperStefan M Pfister, Thomas Würdinger, Rachel Tam, Josep Garcia, Meghna Das Thakur, Gilles Vassal, Jacques Grill, Tim Jaspan, Pascale Varlet, Chris Jones

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)829-842.e5
JournalCancer Cell
Volume33
Issue number5
DOIs
Publication statusPublished - May 14 2018

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    Mackay, A., Burford, A., Molinari, V., Jones, D. T. W., 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