Impact of the H3K27M mutation on survival in pediatric high-grade glioma: A systematic review and meta-analysis

Victor M. Lu, Mohammed A. Alvi, Kerrie L. McDonald, David J. Daniels

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

OBJECTIVE Pediatric high-grade gliomas (pHGGs), including diffuse intrinsic pontine glioma, present a prognostic challenge given their lethality and rarity. A substitution mutation of lysine for methionine at position 27 in histone H3 (H3K27M) has been shown to be highly specific to these tumors. Data are accumulating regarding the poor outcomes of patients with these tumors; however, the quantification of pooled outcomes has yet to be done, which could assist in prioritizing management. The aim of this study was to quantitatively pool data in the current literature on the H3K27M mutation as an independent prognostic factor in pHGG. METHODS Searches of seven electronic databases from their inception to March 2018 were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted and pooled using a meta-analysis of proportions. Meta-regression was used to identify potential sources of heterogeneity. RESULTS Six observational studies satisfied the selection criteria for inclusion. They reported the survival outcomes of a pooled cohort of 474 pHGG patients, with 258 (54%) and 216 (46%) patients positive and negative, respectively, for the H3K27M mutation. Overall, the presence of the mutation was independently and significantly associated with a worse prognosis (HR 3.630, p < 0.001). Overall survival was significantly shorter (by 2.300 years; p = 0.008) when the H3K27M mutation was present in pHGG. Meta-regression did not identify any study covariates of heterogeneous concern. CONCLUSIONS According to the current literature, pHGG patients positive for the H3K27M mutation are more than 3 times more susceptible to succumbing to this disease by more than 2 years, compared to patients negative for the mutation. More robust outcome data are required to improve our quantitative understanding of this pathological entity in order to assist in prioritizing clinical management. Future larger prospective studies are required to overcome inherent biases in the current literature to validate the quantitative findings of this study.

Original languageEnglish (US)
Pages (from-to)308-316
Number of pages9
JournalJournal of Neurosurgery: Pediatrics
Volume23
Issue number3
DOIs
StatePublished - Mar 2019

Keywords

  • Diffuse intrinsic pontine glioma
  • Glioblastoma
  • H3K27M
  • High-grade glioma
  • Histone 3
  • Midline glioma
  • Oncology
  • Pediatric
  • Prognosis

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

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