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WHO grade has no prognostic value in the pediatric high-grade glioma included in the HERBY trial

Varlet, P; Le Teuff, G; Le Deley, M-C; Giangaspero, F; Haberler, C; Jacques, TS; Figarella-Branger, D; ... Grill, J; + view all (2020) WHO grade has no prognostic value in the pediatric high-grade glioma included in the HERBY trial. Neuro-Oncology , 22 (1) pp. 116-127. 10.1093/neuonc/noz142. Green open access

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Abstract

BACKGROUND: The World Health Organization (WHO) adult glioma grading system is questionable in paediatric high-grade gliomas (HGGs), which are biologically distinct from adult HGGs. We took advantage of the neuropathological review data obtained during one of the largest prospective randomized pediatric HGG trials, namely HERBY (NCT01390948), to address this issue in children with newly diagnosed non-brainstem HGG. // METHODS: HGG diagnosis was confirmed by pre-randomization, real-time central pathology review using WHO 2007 criteria, followed by a consensus review blinded to clinical factors and outcomes. We evaluated association between WHO 2007 grade and other clinical/ radiological/biological characteristics; and the prognostic value of WHO 2007 grade, midline location and selected biomarkers (Ki-67 index/Olig2/CD34/EGFR/p53/ H3F3A K27M mutation) on overall survival (OS). // RESULTS: Real-time central neuropathological review was feasible in a multicenter study, with a mean time 2.4 days, and led to the rejection of high-grade glioma diagnosis in 20/163 cases (12.3%). The different grading criteria and resulting WHO grade were not significantly associated with overall survival in the entire population (n=118), nor in midline and non-midline subgroups. H3F3A K27M-mutation was significantly associated with poor outcome. No significant prognostic value was observed for grade, even after regrading H3F3A K27M-mutated midline glioma as grade IV (WHO 2016). Midline location and a high Ki-67 index (≥20%) were associated with poor outcome (p=0.004 and p=0.04, respectively). A 10% increase in Ki-67 index was associated with a HR of 1.53 (95% CI 1.27-1.83; p<0.0001). // CONCLUSION: Our findings suggest WHO grade III vs. IV has no prognostic value in paediatric HGG.

Type: Article
Title: WHO grade has no prognostic value in the pediatric high-grade glioma included in the HERBY trial
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/neuonc/noz142
Publisher version: https://doi.org/10.1093/neuonc/noz142
Language: English
Additional information: © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
Keywords: Ki-67, grading criteria, high-grade glioma, paediatric
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10080014
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