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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| Format: | Article |
| Language: | English |
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Elsevier
2018
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| Online Access: | https://eprints.nottingham.ac.uk/51975/ |
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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 |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-14T20:22:37Z |
| format | Article |
| id | nottingham-51975 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:22:37Z |
| publishDate | 2018 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-519752018-05-24T00:10:57Z https://eprints.nottingham.ac.uk/51975/ 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 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. Elsevier 2018-05-14 Article PeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/51975/1/mmc7.pdf 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 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 Immune; CD8; MAPK; Hypermutator; H3F3A; Pediatric high-grade glioma https://www.sciencedirect.com/science/article/pii/S1535610818301752?via%3Dihub doi:10.1016/j.ccell.2018.04.004 doi:10.1016/j.ccell.2018.04.004 |
| spellingShingle | Immune; CD8; MAPK; Hypermutator; H3F3A; Pediatric high-grade glioma 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 | Immune; CD8; MAPK; Hypermutator; H3F3A; Pediatric high-grade glioma |
| url | https://eprints.nottingham.ac.uk/51975/ https://eprints.nottingham.ac.uk/51975/ https://eprints.nottingham.ac.uk/51975/ |