# Paediatric high-grade glioma (excluding diffuse midline glioma)

Source: https://onco.cc/cancers/paediatric-high-grade-glioma/  
OnCo record `paediatric-high-grade-glioma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

High-grade gliomas in children look like adult glioblastoma under the microscope but are driven by different genes, so they are now classified separately. Surgery and radiotherapy remain the mainstay and chemotherapy adds little; the real gains are in small subsets with a targetable gene change, such as BRAF V600E tumours and the fusion-driven tumours of infants.

## Summary

WHO 2021 separates paediatric-type diffuse high-grade gliomas from adult glioblastoma into four types: diffuse midline glioma, H3 K27-altered (covered on its own page); diffuse hemispheric glioma, H3 G34-mutant, of adolescents and young adults with TP53 and ATRX mutations; diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, with PDGFRA amplification, MYCN amplification or EGFR alteration defining methylation subgroups; and infant-type hemispheric glioma, defined by NTRK, ALK, ROS1 or MET fusions in children under about three. Hypermutant tumours arising in constitutional mismatch repair deficiency and radiation-induced gliomas after treatment of another childhood cancer are distinct further groups. Methylation profiling is essential because morphology cannot separate these entities and some low-grade-appearing tumours prove high grade molecularly.

Treatment is maximal safe resection followed by focal radiotherapy, with temozolomide during and after radiotherapy adopted from adult practice although the ACNS0126 study did not show it clearly improved on historical outcomes; the HERBY trial (2018) showed adding bevacizumab did not help. Radiotherapy is deferred or avoided in infants, whose tumours are chemosensitive and in whom fusion-directed drugs work: larotrectinib and entrectinib for NTRK fusions, alectinib or lorlatinib for ALK and ROS1 fusions, with responses that can allow less surgery. In BRAF V600E-mutant high-grade glioma dabrafenib plus trametinib produced durable responses in the paediatric cohort reported in 2023, and the combination has a tumour-agnostic approval for BRAF V600E solid tumours from the age of six. Constitutional mismatch repair deficiency tumours respond to PD-1 blockade.

The outlook for H3 G34-mutant and H3- and IDH-wildtype tumours has changed little; the pipeline includes CDK4/6 inhibition with temozolomide after radiotherapy, IDH inhibitors for the rare IDH-mutant adolescent tumours, CAR-T cells directed at GD2 and B7-H3 delivered into the ventricles, oncolytic viruses and focused-ultrasound opening of the blood-brain barrier. Late effects of radiotherapy on the developing brain weigh on every decision.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: pHGG; Childhood high-grade glioma; Paediatric glioblastoma; Diffuse hemispheric glioma, H3 G34-mutant; Infant-type hemispheric glioma
- Tags: subtype-page; cns; paediatric
- Group: paediatric
- Burden: A minority of childhood brain tumours but a leading cause of death among them; most children with hemispheric high-grade glioma die within a few years of diagnosis, while infants with fusion-driven tumours can do far better.
- Subtypes: Diffuse hemispheric glioma, H3 G34-mutant (adolescents; TP53 and ATRX); Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (grade 4; PDGFRA, MYCN or EGFR subgroups); Infant-type hemispheric glioma (NTRK, ALK, ROS1 or MET fusion); BRAF V600E-mutant high-grade glioma (including transformed pleomorphic xanthoastrocytoma); Hypermutant glioma in constitutional mismatch repair deficiency; Radiation-induced glioma after treatment of an earlier childhood cancer
- Biomarkers: H3 G34 mutation (H3F3A) and, to exclude diffuse midline glioma, H3 K27 status; IDH1/IDH2 (wildtype in most; mutant in some adolescents); NTRK, ALK, ROS1 and MET fusions in infants; BRAF V600E with CDKN2A deletion; PDGFRA, MYCN and EGFR amplification; Mismatch repair protein loss and tumour mutation burden (constitutional mismatch repair deficiency); DNA methylation class

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/paediatric-high-grade-glioma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/paediatric-high-grade-glioma/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/paediatric-high-grade-glioma/#what-it-is [6 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/paediatric-high-grade-glioma/#finding-it [7 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/paediatric-high-grade-glioma/#treating-it [5 settings, 4 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/paediatric-high-grade-glioma/#evidence [2 trials, 3 key papers, 6 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/paediatric-high-grade-glioma/#science [9 targets, 2 pathways]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/paediatric-high-grade-glioma/where-you-are/ [1 centre]
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/paediatric-high-grade-glioma/#living-with-it [18 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/paediatric-high-grade-glioma/coming/ [11 medicines, 2 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/paediatric-high-grade-glioma/data/ [59 connected records]

## Standard of care

- Newly diagnosed, child over about three years: Maximal safe resection, focal radiotherapy and temozolomide during and after radiotherapy by extrapolation from adult practice; molecular profiling of every tumour. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/))
- Infant-type hemispheric glioma with a fusion: Surgery and fusion-directed therapy: larotrectinib or entrectinib for NTRK fusions, alectinib or lorlatinib for ALK or ROS1 fusions; chemotherapy to defer radiotherapy. ([Larotrectinib](https://onco.cc/drugs/larotrectinib/), [Entrectinib](https://onco.cc/drugs/entrectinib/), [Alectinib](https://onco.cc/drugs/alectinib/), [Lorlatinib](https://onco.cc/drugs/lorlatinib/))
- BRAF V600E-mutant: Dabrafenib plus trametinib (paediatric high-grade glioma cohort 2023; tumour-agnostic approval for BRAF V600E solid tumours from age six). ([Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Dabrafenib](https://onco.cc/drugs/dabrafenib/), [Trametinib](https://onco.cc/drugs/trametinib/))
- Constitutional mismatch repair deficiency: PD-1 blockade (nivolumab or pembrolizumab) for hypermutant tumours; germline counselling for the family. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/))
- Recurrence: No standard; re-resection, re-irradiation, clinical trials including CAR-T and oncolytic virus studies. ([Re-irradiation](https://onco.cc/terms/re-irradiation/), [CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)](https://onco.cc/technologies/glioma-car-t/))

## State of the art

- Molecular classification has split paediatric high-grade glioma into biologically distinct types, each with a different outlook and, for two of them, a targeted drug.
- Fusion-driven infant gliomas are now among the most treatable high-grade brain tumours.
- For the common H3- and IDH-wildtype and H3 G34-mutant tumours, surgery and radiotherapy remain the only treatments with proven benefit.

## Open problems

- No systemic therapy has improved survival in H3 G34-mutant or H3- and IDH-wildtype tumours.
- How long to continue fusion or BRAF inhibitors in children who respond, and what happens on stopping.
- Radiotherapy to the developing brain costs cognition and growth; avoiding it in infants depends on drugs that reach the brain.
- Small numbers make randomised trials slow; international platform trials are the answer being tried.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Glioma
- Wikipedia: https://en.wikipedia.org/wiki/Glioma
- NCI PDQ: childhood astrocytomas, other gliomas and glioneuronal tumours: https://www.cancer.gov/types/brain/hp/child-astrocytoma-treament-pdq

## Connected records

- cancers: [Astrocytoma, IDH-mutant (grades 2 to 4)](https://onco.cc/cancers/idh-mutant-astrocytoma/), [Brain and spinal cord tumours (all types)](https://onco.cc/cancers/brain-tumours/), [Childhood cancers (all types)](https://onco.cc/cancers/childhood-cancers/), [Diffuse midline glioma, H3 K27-altered (including DIPG)](https://onco.cc/cancers/dipg-dmg/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [Oligodendroglioma, IDH-mutant and 1p/19q-codeleted](https://onco.cc/cancers/oligodendroglioma/), [Paediatric low-grade glioma](https://onco.cc/cancers/paediatric-low-grade-glioma/)
- technologies: [CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)](https://onco.cc/technologies/glioma-car-t/), [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/), [Focused-ultrasound blood-brain barrier opening](https://onco.cc/technologies/bbb-focused-ultrasound/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Growth and final height after treatment in childhood, and growth hormone](https://onco.cc/technologies/rejuv-paed-growth-and-height/), [How long it takes to diagnose cancer in a young person, and what the evidence actually says](https://onco.cc/technologies/rejuv-ayac-diagnostic-delay/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Memory, attention and learning after treatment of a childhood cancer](https://onco.cc/technologies/rejuv-paed-neurocognitive/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [The pituitary, puberty and the hypothalamic axis after cranial radiotherapy in childhood](https://onco.cc/technologies/rejuv-paed-pituitary-and-puberty/)
- targets: [ALK](https://onco.cc/targets/alk/), [BRAF](https://onco.cc/targets/braf/), [Histone H3.3 (H3-3A)](https://onco.cc/targets/h3-3a/), [MEK1/2](https://onco.cc/targets/mek/), [NTRK](https://onco.cc/targets/ntrk/), [ROS1](https://onco.cc/targets/ros1/), [TP53](https://onco.cc/targets/tp53/)
- drugs: [Alectinib](https://onco.cc/drugs/alectinib/), [Bevacizumab (glioblastoma use)](https://onco.cc/drugs/bevacizumab-glioma/), [Dabrafenib](https://onco.cc/drugs/dabrafenib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Entrectinib](https://onco.cc/drugs/entrectinib/), [Larotrectinib](https://onco.cc/drugs/larotrectinib/), [Lorlatinib](https://onco.cc/drugs/lorlatinib/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [Trametinib](https://onco.cc/drugs/trametinib/)
- companies: [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/)
- institutions: [SIOP Europe (European Society for Paediatric Oncology)](https://onco.cc/institutions/siop-europe/)
- pathways: [Glioma (KEGG map)](https://onco.cc/pathways/glioma-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [CDKN2A/B homozygous deletion](https://onco.cc/terms/cdkn2a-homozygous-deletion/), [H3 K27M (diffuse midline glioma)](https://onco.cc/terms/h3k27m/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/), [Re-irradiation](https://onco.cc/terms/re-irradiation/)
- trials: [A Study Comparing Abemaciclib Plus Temozolomide to Temozolomide Monotherapy in Children and Young Adults With High-grade Glioma Following Radiotherapy](https://onco.cc/trials/nct06413706/), [HERBY](https://onco.cc/trials/herby/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/)
- key papers: [Dabrafenib plus trametinib in relapsed or refractory BRAF V600-mutant paediatric high-grade glioma](https://onco.cc/key-papers/paper-hargrave-dabrafenib-trametinib-paediatric-hgg-jco-2023/), [Integrated molecular meta-analysis of 1,000 paediatric high-grade and diffuse intrinsic pontine gliomas](https://onco.cc/key-papers/paper-mackay-paediatric-hgg-cancer-cell-2017/), [The 2021 WHO classification of tumours of the central nervous system: a summary](https://onco.cc/key-papers/paper-who-2021-cns-louis-neuro-oncology-2021/)
- people: [Darren R. Hargrave](https://onco.cc/people/darren-hargrave/), [Jacques Grill](https://onco.cc/people/jacques-grill/)
- biomarkers: [H3 K27M mutation](https://onco.cc/biomarkers/h3-k27m/)

---
JSON: https://onco.cc/api/v1/entities/paediatric-high-grade-glioma.json