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Pediatric high-grade glioma: a review of biology, prognosis, and treatment

  • Review
  • Published:
Journal of Radiation Oncology

Abstract

The incidence of high-grade gliomas (HGGs) in children is significantly lower than in adults, with less than 400 children diagnosed every year in the USA. While the histopathology of HGGs in children is very similar to those in adults, their biology is very different. Recent studies have led to an exponential increase in our understanding of the biology of these tumors, with the identification of distinct epigenetic subtypes, each with characteristic clinical and molecular profiles. The 2016 WHO classification of central nervous system tumors has recognized the most common subtype, with the poorest prognosis—“diffuse midline glioma H3 K27M-mutant”—marking a shift towards the integration of molecular features with the traditional histopathological diagnosis. Like adults, children with HGGs have a very poor prognosis overall, with treatment consisting of maximal safe surgical resection followed by radiation therapy. However, the role of temozolomide, which is a well-established adjuvant therapy for MGMT-methylated HGGs in adults, is less clear in children. In this review, we outline the epidemiology, recent advances in our understanding of biology, past landmark clinical trials, and promising therapeutic strategies for pediatric HGG.

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Abbreviations

HGG:

high-grade glioma

WHO:

World Health Organization

CNS:

central nervous system

LGG:

low-grade glioma

RT:

radiation therapy

MAPK:

mitogen-activated protein kinase

CCSS:

Childhood Cancer Survivor Study

AA:

anaplastic astrocytoma

GBM:

glioblastoma multiforme

DIPG:

diffuse intrinsic pontine glioma

PFS:

progression-free survival

OS:

overall survival

PXA:

pleomorphic xanthoastrocytoma

GTR:

gross total resection

EFS:

event-free survival

HSCT:

hematopoietic stem cell transplant

bMMRD:

biallelic mismatch repair deficiency

HDAC:

histone deacetylase

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Authors and Affiliations

  1. Jimmy Everest Center for Cancer and Blood Disorders, University of Oklahoma Health Sciences Center, 1200 Children’s Ave., Suite 14500, Oklahoma City, OK, 73104, USA

    Abhishek Bavle

  2. Section of Pediatric Hematology/Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Abhishek Bavle

  3. Section of Pediatric Hematology/Oncology, Baylor College of Medicine, Houston, TX, USA

    Murali Chintagumpala

  4. Texas Children’s Hospital, Houston, TX, USA

    Murali Chintagumpala

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Bavle, A., Chintagumpala, M. Pediatric high-grade glioma: a review of biology, prognosis, and treatment. J Radiat Oncol 7, 7–15 (2018). https://doi.org/10.1007/s13566-018-0344-9

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