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

17 Citations (Scopus)

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. In a pediatric high-grade non-brainstem glioma cohort, Mackay et al. show that hypermutator tumors and those resembling pleomorphic xanthoastrocytoma are highly infiltrated by CD8+ lymphocytes and benefit from the addition of bevacizumab, whereas the histone H3 subgroups are immune cold and have a poor outcome.

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

Fingerprint

Glioma
temozolomide
Pediatrics
Histones
Tumor-Infiltrating Lymphocytes
Mutation
Radiology
Multicenter Studies
Neoplasms
Radiotherapy
Clinical Trials
Lymphocytes
Pathology
Survival
Population
Bevacizumab
Turcot syndrome

Keywords

  • CD8
  • H3F3A
  • hypermutator
  • immune
  • MAPK
  • pediatric high-grade glioma

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Mackay, A., Burford, A., Molinari, V., Jones, D. T. W., Izquierdo, E., Brouwer-Visser, J., ... 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

Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial. / 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, Pascale; Jones, Chris.

In: Cancer Cell, Vol. 33, No. 5, 14.05.2018, p. 829-842.e5.

Research output: Contribution to journalArticle

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 2018, 'Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial', Cancer Cell, vol. 33, no. 5, pp. 829-842.e5. https://doi.org/10.1016/j.ccell.2018.04.004
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, Pascale ; Jones, Chris. / Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial. In: Cancer Cell. 2018 ; Vol. 33, No. 5. pp. 829-842.e5.
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AU - Izquierdo, Elisa

AU - Brouwer-Visser, Jurriaan

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