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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.
Affiliation
  • Mackay A; Division of Molecular Pathology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey SM2 5NG, UK; Division of Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey SM2 5NG, UK.
  • Burford A; Division of Molecular Pathology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey SM2 5NG, UK; Division of Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey SM2 5NG, UK.
  • Molinari V; Division of Molecular Pathology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey SM2 5NG, UK; Division of Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey SM2 5NG, UK.
  • Jones DTW; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Paediatric Neuro-oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Izquierdo E; Division of Molecular Pathology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey SM2 5NG, UK; Division of Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey SM2 5NG, UK.
  • Brouwer-Visser J; Roche Innovation Center, New York, NY, USA.
  • Giangaspero F; Department of Radiology, Oncology and Anatomic-Pathology Sciences, Sapienza University, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy.
  • Haberler C; Institute of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
  • Pietsch T; DGNN Brain Tumor Reference Center, Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
  • Jacques TS; UCL Great Ormond Street Institute of Child Health, London, UK; Department of Histopathology, Great Ormond Street Hospital for Children, London, UK.
  • Figarella-Branger D; Department of Pathology and Neuropathology, La Timone Hospital, Aix Marseille University, Marseille, France.
  • Rodriguez D; Nottingham University Hospitals, Nottingham, UK.
  • Morgan PS; Nottingham University Hospitals, Nottingham, UK.
  • Raman P; The Center for Data Driven Discovery in Biomedicine (D(3)b), Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Waanders AJ; The Center for Data Driven Discovery in Biomedicine (D(3)b), Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Resnick AC; The Center for Data Driven Discovery in Biomedicine (D(3)b), Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Massimino M; Pediatric Oncology Unit, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy.
  • Garrè ML; Centro di Neuro-Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
  • Smith H; F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Capper D; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Institute of Neuropathology, Berlin, Germany; Department of Neuropathology, University Hospital Heidelberg and Clinical Cooperation Unit Ne
  • Pfister SM; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Paediatric Neuro-oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelb
  • Würdinger T; Department of Neurosurgery, Brain Tumor Center Amsterdam, VU Medical Center, Amsterdam, the Netherlands.
  • Tam R; Genentech, South San Francisco, CA, USA.
  • Garcia J; F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Thakur MD; Genentech, South San Francisco, CA, USA.
  • Vassal G; Pediatric and Adolescent Oncology and Unite Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Gustave Roussy, Paris-Saclay University, Villejuif, France.
  • Grill J; Pediatric and Adolescent Oncology and Unite Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Gustave Roussy, Paris-Saclay University, Villejuif, France.
  • Jaspan T; Nottingham University Hospitals, Nottingham, UK.
  • Varlet P; Sainte-Anne Hospital, Paris-Descartes University, Paris, France.
  • Jones C; Division of Molecular Pathology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey SM2 5NG, UK; Division of Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey SM2 5NG, UK. Electronic address: chris.jones@icr.ac.uk.
Cancer Cell ; 33(5): 829-842.e5, 2018 05 14.
Article in En | MEDLINE | ID: mdl-29763623
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chemoradiotherapy / Bevacizumab / Temozolomide / Glioma / Mutation Type of study: Clinical_trials Limits: Adolescent / Child / Child, preschool / Female / Humans / Male Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2018 Document type: Article Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chemoradiotherapy / Bevacizumab / Temozolomide / Glioma / Mutation Type of study: Clinical_trials Limits: Adolescent / Child / Child, preschool / Female / Humans / Male Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2018 Document type: Article Country of publication: United States