cancersCancer

Paediatric high-grade glioma (excluding diffuse midline glioma)

aka pHGG, Childhood high-grade glioma, Paediatric glioblastoma, Diffuse hemispheric glioma, H3 G34-mutant, Infant-type hemispheric glioma

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.

Part ofGlioma & glioblastoma

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.

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.

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Fainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Alectinib Dabrafenib Dabrafenib + trametinib Entrectinib Lorlatinib Trametinib source
Emergency services now
Hypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Nivolumab Pembrolizumab source
Emergency services now
Bleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Temozolomide source
Check before combining
Food and drink: Alectinib
Take with food; exposure roughly triples with a high-fat meal, and the trials dosed with food.
Alectinib source
Check before combining
Food and drink: Dabrafenib + trametinib
Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
Dabrafenib + trametinib source
Check before combining
Food and drink: Entrectinib
Avoid grapefruit.
Entrectinib source

See all on the product pages:Alectinib Dabrafenib Dabrafenib + trametinib Entrectinib Lorlatinib Nivolumab Pembrolizumab Temozolomide Trametinib·Printable cards in the navigator

Anatomy and lymph node drainage

Brain: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

Gliomas infiltrate along white matter and can cross the corpus callosum, medulloblastoma sits in the cerebellum, and CNS lymphoma favours deep periventricular tissue; none spread through lymph nodes.

Subsites

Frontal lobe (glioblastoma commonest)Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (grade 4; PDGFRA, MYCN or EGFR subgroups)
Temporal lobe
Corpus callosum (butterfly glioma)
Lower-grade IDH-mutant gliomaBRAF V600E-mutant high-grade glioma (including transformed pleomorphic xanthoastrocytoma)
Cerebellum (medulloblastoma)
Brainstem and spinal cord (diffuse midline glioma, cord tumours)
Ventricles and ependymal lining (ependymoma)
Sella and pituitary (pituitary tumours, craniopharyngioma)
Deep periventricular tissue (CNS lymphoma)
Meninges and convexity (meningioma)
Grey-white junction (brain metastases)
Cerebellopontine angle and eighth nerve (vestibular schwannoma)
Pineal and suprasellar midline (germ cell tumours)

Regional lymph nodes

No conventional lymphatics: gliomas spread along white matter tracts and, rarely, through cerebrospinal fluid; medulloblastoma can seed the spine.

Same organ: Glioma & glioblastoma, Primary CNS lymphoma, Medulloblastoma, Paediatric low-grade glioma, Diffuse midline glioma, H3 K27-altered (including DIPG), Atypical teratoid/rhabdoid tumour (ATRT), Ependymoma, Craniopharyngioma, Pituitary tumours (pituitary neuroendocrine tumours) and pituitary carcinoma, Brain and spinal cord tumours (all types), Astrocytoma, IDH-mutant (grades 2 to 4), Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, Meningioma, Brain metastases (secondary brain tumours), Vestibular schwannoma (acoustic neuroma), Central nervous system germ cell tumours (germinoma and non-germinomatous), Spinal cord tumours (intramedullary and intradural)

Who gets it and what has changed

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.

Group

paediatric

What is being done about this

Finding cancer earlier

and how the field plans to fix it →

Available now

DNA methylation profilingEstablished

In trials

Nothing recorded yet.

Ideas and roadmaps

Nothing recorded yet.

Also on OnCo: Symptoms and red flags · Early detection roadmap.

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Lines of therapy by subgroup →Staging and risk scores →

Decisions you may face

4 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

Newly diagnosed, child over about three years4 Infant-type hemispheric glioma with a fusion4 BRAF V600E-mutant3 Constitutional mismatch repair deficiency3 Recurrence

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.

NCI PDQ: childhood astrocytomas, other gliomas and glioneuronal tumours

IMRT / IGRT (modern external beam)Proton therapyTemozolomideDNA 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.

NCI PDQ: childhood astrocytomas, other gliomas and glioneuronal tumours

LarotrectinibEntrectinibAlectinibLorlatinib

BRAF V600E-mutant

Dabrafenib plus trametinib (paediatric high-grade glioma cohort 2023; tumour-agnostic approval for BRAF V600E solid tumours from age six).

FDA label 2022 to 2023; NCI PDQ

Dabrafenib + trametinibDabrafenibTrametinib

Constitutional mismatch repair deficiency

PD-1 blockade (nivolumab or pembrolizumab) for hypermutant tumours; germline counselling for the family.

NivolumabPembrolizumabGermline (hereditary) testing

Recurrence

No standard; re-resection, re-irradiation, clinical trials including CAR-T and oncolytic virus studies.

Re-irradiation CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)

Subtypes & biomarkers

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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 clinicians test

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

How often this target appears

History

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1989CCG-943: chemotherapy adds to radiotherapy in childhood high-grade glioma
Sposto and colleagues, the first randomised evidence for adjuvant chemotherapy in children.
2012Histone H3 mutations discovered in paediatric glioma
Schwartzentruber and colleagues (Nature) and Wu and colleagues (Nature Genetics) find H3.3 K27M and G34 mutations.
2018HERBY: bevacizumab adds nothing to radiotherapy and temozolomide
Grill and colleagues (JCO).
Bevacizumab (glioblastoma use)Temozolomide
2021WHO 2021 defines four paediatric-type diffuse high-grade gliomas
2022Tumour-agnostic approval of dabrafenib plus trametinib for BRAF V600E solid tumours, including high-grade glioma
Dabrafenib + trametinib
2023Dabrafenib plus trametinib in BRAF V600E paediatric high-grade glioma
Hargrave and colleagues (JCO) report durable responses in the paediatric cohort.
Dabrafenib + trametinibDabrafenibTrametinib

What changed

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Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.

All 8 changes by month →

FollowWatch this cancer and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for Paediatric high-grade glioma (excluding diffuse midline glioma), drawn from the whole corpus: 2 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.

Technologies being tested · 2

CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)Focused-ultrasound blood-brain barrier opening

Open problems and what is being done

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.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Paediatric high-grade glioma (excluding diffuse midline glioma)

condition: Paediatric high-grade glioma

Open on ClinicalTrials.gov →

within

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Expert centres

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Where the expertise is

Expert centres

156 centres in 46 countries · 0 with a trial for this cancer on record · second-opinion finder →

Choose a region from the globe in the header to mark centres near you.

156 centres


MD Anderson Cancer Center Houston · cancer center	United States	NCI comprehensive	6,724	95,007	CAR-NK & CAR-macrophage Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +2	#2
Samsung Medical Center Seoul · hospital	South Korea	none recorded	1,312	17,172	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#3
Mayo Clinic Rochester, MN · hospital	United States	NCI comprehensive	4,511	44,748	Carbon-ion therapy Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#5
Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center Baltimore · cancer center	United States	NCI comprehensive	2,955	41,449	Multi-cancer early detection (MCED)Liquid biopsy (ctDNA)Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems +2	#10
Charité Universitätsmedizin Berlin Berlin · university	Germany	none recorded	1,563	17,749	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems CyberKnife robotic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#12
Massachusetts General Hospital Cancer Center Boston · hospital	United States	NCI comprehensive	3,582	54,857	Proton therapy Small-molecule kinase inhibitors Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#16
Heidelberg University Hospital / NCT / DKFZ Heidelberg · cancer center	Germany	none recorded	3,456	45,745	FAPI PET Targeted alpha therapy Carbon-ion therapy DNA methylation profiling +5	#18
Cleveland Clinic Taussig Cancer Institute Cleveland · hospital	United States	NCI comprehensive	2,264	29,412	Off-the-shelf cancer vaccines Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#20
Institut Curie Paris · cancer center	France	none recorded	1,065	15,111	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems	#21
The Christie NHS Foundation Trust Manchester · cancer center	United Kingdom	none recorded	104	2,145	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems MR-guided adaptive radiotherapy TomoTherapy and Radixact (helical radiotherapy)	#23
Stanford Health Care / Stanford Cancer Institute Stanford · university	United States	NCI comprehensive	3,000	50,162	CAR-T cell therapy SBRT / SABR (stereotactic radiotherapy)CyberKnife robotic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)+1	#30
Fudan University Shanghai Cancer Center Shanghai · cancer center	China	none recorded	1,678	18,354	TROP2 PET Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Carbon-ion therapy +1	#55
Abramson Cancer Center, University of Pennsylvania Philadelphia · cancer center	United States	NCI comprehensive	3,148	54,267	CAR-T cell therapy In vivo CAR-T PARP PET Personalised neoantigen (mRNA) vaccines +2	-
University of Michigan Rogel Cancer Center Ann Arbor, MI · cancer center	United States	NCI comprehensive	2,991	29,686	PROTACs & molecular glues (targeted protein degradation)Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems	-
University College London Hospitals / UCL Cancer Institute London · hospital	United Kingdom	none recorded	2,376	28,940	Proton therapy CAR-T cell therapy Liquid biopsy (ctDNA)Whole-exome & whole-genome sequencing +5	-

(showing the first 15)

These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Paediatric high-grade glioma but is thinly recorded here will look small.

Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost. The second-opinion finder explains how referral works in your country.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Paediatric high-grade glioma

Generated from this cancer's standard of care, biomarkers, and pipeline · 18 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example H3 G34 mutationand, to exclude diffuse midline glioma, H3 K27 status, IDH1/IDH2, NTRK, ALK, ROS1 and MET fusions in infants, BRAF V600E with CDKN2A deletion, PDGFRA, MYCN and EGFR amplification), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include Diffuse hemispheric glioma, H3 G34-mutant, Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, Infant-type hemispheric glioma.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

Newly diagnosed, child over about three years

For my situation (newly diagnosed, child over about three years), which of the standard options do you recommend and why?
Why: Guideline options include: Maximal safe resection, focal radiotherapy and temozolomide during and after radiotherapy by extrapolation from adult practice; molecular profiling of every tumour.
Am I a candidate for Temozolomide, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Infant-type hemispheric glioma with a fusion

For my situation (infant-type hemispheric glioma with a fusion), which of the standard options do you recommend and why?
Why: Guideline options include: Surgery and fusion-directed therapy: larotrectinib or entrectinib for NTRK fusions, alectinib or lorlatinib for ALK or ROS1 fusions; chemotherapy to defer radiotherapy.
Am I a candidate for Larotrectinib, Entrectinib, Alectinib or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

BRAF V600E-mutant

For my situation (braf v600e-mutant), which of the standard options do you recommend and why?
Why: Guideline options include: Dabrafenib plus trametinib (paediatric high-grade glioma cohort 2023; tumour-agnostic approval for BRAF V600E solid tumours from age six).
Am I a candidate for Dabrafenib + trametinib, Dabrafenib, Trametinib, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Constitutional mismatch repair deficiency

For my situation (constitutional mismatch repair deficiency), which of the standard options do you recommend and why?
Why: Guideline options include: PD-1 blockade (nivolumab or pembrolizumab) for hypermutant tumours; germline counselling for the family.
Am I a candidate for Nivolumab, Pembrolizumab, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Recurrence

For my situation (recurrence), which of the standard options do you recommend and why?
Why: Guideline options include: No standard; re-resection, re-irradiation, clinical trials including CAR-T and oncolytic virus studies.

Any stage

Are there clinical trials I could join, for example of Dabrafenib + trametinib, Larotrectinib, Entrectinib, CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)?
Why: Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?
Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
Why: Supportive care improves quality of life and helps patients complete treatment.
I read that “No systemic therapy has improved survival in H3 G34-mutant or H3- and IDH-wildtype tumours”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “How long to continue fusion or BRAF inhibitors in children who respond, and what happens on stopping”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.