Molecular, Pathological, Radiological, and Immune Profiling of Non-Brainstem Pediatric High-Grade Glioma
abstract
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Access this abstract now Full Text Available for ClinicalKey SubscribersThe 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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Molecular, Pathological, Radiological, and Immune Profiling of Non-Brainstem Pediatric High-Grade Glioma From the HERBY Phase II Randomized Trial
Cancer Cell 2018 May 14;33(5)829-842.e5, A Mackay, A Burford, V Molinari, DTW Jones, E Izquierdo, J Brouwer-Visser, F Giangaspero, C Haberler, T Pietsch, TS Jacques, D Figarella-Branger, D Rodriguez, PS Morgan, P Raman, AJ Waanders, AC Resnick, M Massimino, ML Garrè, H Smith, D Capper, SM Pfister, T Würdinger, R Tam, J Garcia, MD Thakur, G Vassal, J Grill, T Jaspan, P Varlet, C JonesFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Recently, the results of the HERBY trial, a phase II, open-label, randomized, multicenter trial evaluating bevacizumab in addition to temozolomide/ radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma between the ages of 3 and 18 years was published.1 This trial showed that the addition of bevacizumab did not improve survival in this patient population.
As part of this study, the investigators also carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post hoc subgroup analysis, they found that hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytomas, driven by BRAF V600E or NF1 mutation, had significantly more CD8+ tumor-infiltrating lymphocytes and were associated with longer survival with the addition of bevacizumab. In contrast, histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. These results show the molecular and immunologic diversity in pediatric high-grade gliomas, which will have to be taken into account in future studies.
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