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

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 in...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956280/
https://www.ncbi.nlm.nih.gov/pubmed/29763623
http://dx.doi.org/10.1016/j.ccell.2018.04.004
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author 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
author_facet 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
author_sort Mackay, Alan
collection PubMed
description 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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spelling pubmed-59562802018-05-17 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 Cancer Cell Article 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. Cell Press 2018-05-14 /pmc/articles/PMC5956280/ /pubmed/29763623 http://dx.doi.org/10.1016/j.ccell.2018.04.004 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
title Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial
title_full Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial
title_fullStr Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial
title_full_unstemmed Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial
title_short Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial
title_sort molecular, pathological, radiological, and immune profiling of non-brainstem pediatric high-grade glioma from the herby phase ii randomized trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956280/
https://www.ncbi.nlm.nih.gov/pubmed/29763623
http://dx.doi.org/10.1016/j.ccell.2018.04.004
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