Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial - Prédicteurs moléculaires et nouvelles cibles en oncologie Accéder directement au contenu
Article Dans Une Revue Cancer Cell Année : 2018

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

1 The institute of cancer research [London]
2 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
3 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
4 NEUROMED I.R.C.C.S. - Istituto Neurologico Mediterraneo
5 Medizinische Universität Wien = Medical University of Vienna
6 University of Bonn Medical Center [Bonn, Germany]
7 UCL Great Ormond Street Institute of Child Health [London, UK]
8 ACPNP - Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM]
9 AMU - Aix Marseille Université
10 NUH - Nottingham University Hospitals NHS Trust
11 CHOP - Children’s Hospital of Philadelphia
12 IRCCS Istituto Nazionale dei Tumori [Milano]
13 Istituto Giannina Gaslini, Genova
14 F. Hoffmann-La Roche [Basel]
15 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
16 BIH - Berlin Institute of Health
17 Freie Universität Berlin
18 HU Berlin - Humboldt-Universität zu Berlin = Humboldt University of Berlin = Université Humboldt de Berlin
19 Heidelberg University Hospital [Heidelberg]
20 KITZ - Hopp Children's Cancer Center Heidelberg [Heidelber, Germany]
21 VU University Medical Center [Amsterdam]
22 Genentech, Inc. [San Francisco]
23 PMNCO - Prédicteurs moléculaires et nouvelles cibles en oncologie
24 Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy]
25 IGR - Institut Gustave Roussy
26 UMR 8203 - Vectorologie et thérapeutiques anti-cancéreuses [Villejuif]
27 TIMONE - Hôpital de la Timone [CHU - APHM]
28 Hôpital Sainte-Anne [Paris]
29 UPD5 - Université Paris Descartes - Paris 5
Jurriaan Brouwer-Visser
  • Fonction : Auteur

Résumé

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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hal-04515955 , version 1 (18-06-2024)

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Alan Mackay, Anna Burford, Valeria Molinari, David T.W. Jones, Elisa Izquierdo, et al.. Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial. Cancer Cell, 2018, 33 (5), pp.829 - 842.e5. ⟨10.1016/j.ccell.2018.04.004⟩. ⟨hal-04515955⟩
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