Glioma & glioblastoma

Gliomas are classified by the WHO 2021 system on molecular grounds: IDH-wild-type glioblastoma (grade 4, ~50% of gliomas, median age 65, median survival ~15 months with maximal therapy), IDH-mutant astrocytoma (grades 2-4) and 1p/19q-codeleted oligodendroglioma (better prognosis, decades of survival possible), and paediatric-type tumours including H3 K27M-mutant diffuse midline glioma (median survival ~11 months) and BRAF-altered low-grade glioma (the commonest childhood brain tumour, rarely life-threatening but chronically disabling). The two shared barriers are the blood-brain barrier, which excludes most drugs, and diffuse infiltration, which makes complete resection impossible.

Glioblastoma treatment has been static since 2005: maximal safe resection (improved by 5-ALA fluorescence, intraoperative MRI, and awake mapping; the extent of resection is itself prognostic and is now graded by the RANO resect classes), radiotherapy with concurrent and adjuvant temozolomide (Stupp), and tumour treating fields (EF-14). MGMT promoter methylation predicts temozolomide benefit; unmethylated tumours gain less, though not nothing, and how much remains debated (in the elderly trials NOA-08 and Nordic, unmethylated tumours did better with radiotherapy than with temozolomide alone). Every major systemic trial since has failed: bevacizumab (PFS only), rindopepimut (ACT IV), nivolumab (CheckMate 143, 498, 548), depatuxizumab mafodotin (INTELLANCE-1), and many more. At recurrence, lomustine, re-resection, re-irradiation, LITT, and bevacizumab for oedema are the options, with median survival under a year. DCVax-L's externally controlled phase 3 remains contested.

Progress has come at the edges. Vorasidenib (INDIGO, approved 2024) is the first targeted therapy for grade 2 IDH-mutant glioma, delaying radiation and chemotherapy by years. Dabrafenib with trametinib (2023) was the first targeted therapy approved for BRAF V600E paediatric low-grade glioma; tovorafenib (2024) followed for relapsed or refractory BRAF-altered tumours, including BRAF fusions. Dordaviprone (August 2025) is the first drug approved for H3 K27M diffuse midline glioma. Methylation-based classification and intraoperative nanopore sequencing have transformed diagnosis. For glioblastoma itself the most promising directions are locoregional CAR-T (IL13Rα2, GD2, multi-target), focused-ultrasound and LITT-based barrier opening to deliver ADCs, radioconjugates, and chemotherapy, neoadjuvant immunotherapy with window designs, personalised neoantigen vaccines (NeoVax), and combinations built on the unmethylated-MGMT population where temozolomide adds nothing.

State of the art

Vorasidenib in low-grade glioma.
Methylation-based diagnosis.
TTFields.
Three first-in-class targeted approvals for glioma subtypes in 2024-25: vorasidenib (IDH-mutant), tovorafenib (BRAF paediatric), dordaviprone (H3 K27M).
Molecular classification (WHO 2021, methylation classifier, intraoperative nanopore) now defines diagnosis.
Locoregional CAR-T produces objective responses in recurrent glioblastoma and DIPG, though transient.
Focused ultrasound opens the blood-brain barrier in humans with 4-6x higher drug delivery; efficacy trials underway.

Anatomy and lymph node drainage

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

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)Glioblastoma, IDH-wild-type (WHO grade 4; TERT promoter, EGFR amplification, +7/−10) · Astrocytoma, IDH-mutant (grades 2-4; CDKN2A/B deletion defines grade 4)
Temporal lobe
Corpus callosum (butterfly glioma)
Lower-grade IDH-mutant gliomaAstrocytoma, IDH-mutant (grades 2-4; CDKN2A/B deletion defines grade 4) · Oligodendroglioma, IDH-mutant and 1p/19q-codeleted (grades 2-3)
Cerebellum (medulloblastoma)
Brainstem and spinal cord (diffuse midline glioma, cord tumours)Diffuse midline glioma, H3 K27M-altered (including DIPG)
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: Meningioma

Preclinical models

6 cell lines, 1 mouse models and 5 repositories are listed for this cancer.

Who gets it and what has changed

About 300,000 CNS tumours occur per year, most of them not glioblastoma; IDH-mutant and paediatric low-grade gliomas can be lived with for decades and now have targeted drugs.

Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

Median survival for glioblastoma with maximal therapy is about 15 months.

Group

central nervous system

What is being done about this

Finding cancer earlier

Available now

In trials

Fluorothymidine F-18 (FLT)Phase 2

Ideas and roadmaps

Nothing recorded yet.

Also on Nuclide: Roadmaps.

Advanced diseaseShow where advanced disease can reach, and what treats itThe sites decide which scans are done at staging and follow-up, and every site listed has a treatment approach.

Most people reading this do not have advanced disease. The map describes what can happen over the whole course of the illness, across autopsy and registry series; today's staging scans find spread earlier, and each site has treatments, from focused radiotherapy for a few spots to drugs that reach the brain.

What helpsResection, radiotherapy with temozolomide and TTFields; vorasidenib for IDH-mutant glioma; locoregional CAR-T and focused-ultrasound drug delivery in trials.

Elsewhere in the brain (white matter tracts, corpus callosum)most common
Infiltrates along white matter; recurrence is usually within 2 cm of the original site.
Spinal cord and leptomeningesless common
Outside the nervous systemrare
Extracranial metastasis is exceptional; lymph node spread does not occur because the brain has no conventional lymphatics.

Standard of care

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Glioblastoma

Resection → RT + temozolomide → TTFields; lomustine/bevacizumab at relapse.

NCCN Guidelines: Central Nervous System Cancers

IDH-mutant grade 2

Resection → vorasidenib or observation; RT/PCV for high-risk.

NCCN Guidelines: Central Nervous System Cancers

Diagnosis

MRI with contrast; maximal safe resection with 5-ALA and intraoperative mapping, with early postoperative MRI to measure the extent of resection; integrated histo-molecular diagnosis with methylation classification where available.

Glioblastoma, newly diagnosed

Radiotherapy 60 Gy in 30 fractions with concurrent and 6 cycles adjuvant temozolomide; from age 65, short-course radiotherapy (40 Gy in 15 fractions) with temozolomide (CCTG CE.6); for older patients unfit for combined treatment, temozolomide alone or hypofractionated radiotherapy alone, chosen by MGMT status (Nordic, NOA-08); TTFields with maintenance temozolomide; trials for MGMT-unmethylated patients.

Temozolomide

Glioblastoma, recurrent

Re-resection or LITT if feasible; lomustine; bevacizumab for oedema/steroid sparing; re-irradiation; clinical trial (CAR-T, FUS-BBB, vaccines) strongly preferred.

IDH-mutant grade 2 glioma

Maximal resection; vorasidenib for residual/recurrent disease (INDIGO); radiotherapy plus PCV or temozolomide for high-risk or progressive disease.

Oligodendroglioma grade 3 / astrocytoma grade 3

Radiotherapy plus PCV (RTOG 9402, EORTC 26951) or temozolomide (CATNON).

Temozolomide

H3 K27M diffuse midline glioma

Radiotherapy; dordaviprone at progression (2025); GD2 CAR-T and ONC201 first-line trials.

Paediatric low-grade glioma

Resection where safe; chemotherapy (carboplatin/vincristine) or tovorafenib / dabrafenib-trametinib for BRAF-altered relapsed disease; avoid radiation in young children.

Subtypes & biomarkers

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Subtypes

Glioblastoma, IDH-wild-type (WHO grade 4; TERT promoter, EGFR amplification, +7/−10)
Astrocytoma, IDH-mutant (grades 2-4; CDKN2A/B deletion defines grade 4)
Oligodendroglioma, IDH-mutant and 1p/19q-codeleted (grades 2-3)
Diffuse midline glioma, H3 K27M-altered (including DIPG)
Paediatric low-grade glioma (BRAF fusion or V600E, NF1)
Diffuse hemispheric glioma H3 G34-mutant; infant-type hemispheric glioma (NTRK/ALK/ROS1 fusions)

Biomarkers clinicians test

IDH1/2
1p/19q codeletion
MGMT methylation
H3K27M
EGFR amplification
Methylation class
IDH1/2 mutation (vorasidenib eligibility)
MGMT promoter methylation (temozolomide benefit)
H3 K27M (dordaviprone eligibility)
BRAF fusion / V600E (tovorafenib, dabrafenib-trametinib)
TERT promoter, EGFR amplification, +7/−10 (molecular glioblastoma)
CDKN2A/B homozygous deletion (grade 4 astrocytoma)
DNA methylation class (Heidelberg classifier)
NTRK/ALK/ROS1 fusions (infant gliomas)
TMB / mismatch repair (rare hypermutant, IO-responsive)

How often this target appears

History

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1926Bailey and Cushing classify gliomas
Histologic classification that lasted, in essence, until 2016.
1978Radiotherapy proven to extend survival (BTSG)
Whole-brain then involved-field radiation becomes standard.
1999Temozolomide approved (anaplastic astrocytoma)
Temozolomide
2005Stupp regimen: temozolomide + RT
2008IDH1 mutations discovered in glioma
Parsons/Vogelstein glioblastoma genome sequencing; reclassification follows.
2009Bevacizumab accelerated approval at recurrence
Radiographic response without survival benefit.
2014AVAglio / RTOG 0825: bevacizumab no OS benefit; 5-ALA and methylation classifier emerge
2015TTFields improves OS (EF-14)
2016WHO 2016 integrates molecular markers; ACT IV vaccine fails
2017Short-course radiotherapy plus temozolomide extends survival from age 65 (CCTG CE.6)
2020CheckMate 143: immunotherapy fails at recurrence
CheckMate 548 (2022) and CheckMate 498 (2023) follow in newly diagnosed disease; all three negative.
2021WHO 2021: IDH-wild-type glioblastoma defined molecularly
2022GD2 CAR-T responses in DIPG (Stanford)
2023INDIGO: vorasidenib in grade 2 IDH-mutant glioma; DCVax-L contested publication
2024Vorasidenib approved
2025Dordaviprone approved for H3 K27M diffuse midline glioma
6 August 2025; first systemic therapy for the disease.
2026ASCO 2026: NeoVax personalised vaccine immune responses; multi-target CAR-T; tovorafenib EU approval

What changed

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

All 23 changes by month →

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In development

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What is in development for Glioma & glioblastoma, drawn from the whole corpus: 1 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.

Drugs in phase 2 · 1

Phase 2PET tracer

Fluorothymidine F-18 (FLT)

Open problems and what is being done

Blood-brain barrier.
Immunologically cold, heterogeneous, infiltrative.
Glioblastoma: no systemic drug has beaten the 2005 standard; getting drugs across the blood-brain barrier is the crux.
Glioblastoma's standard has not changed since 2005: every phase 3 systemic agent since temozolomide has failed, so median survival has not moved in 20 years.
MGMT-unmethylated glioblastoma (~60%) gains almost nothing from chemotherapy and has no approved alternative.
Blood-brain barrier and diffuse infiltration limit delivery and resection; imaging cannot distinguish progression from pseudoprogression reliably.
Immunotherapy failure: low TMB, T-cell exclusion, dexamethasone, and treatment-induced lymphopenia; neoadjuvant approaches are the only signal.
Antigen heterogeneity and loss (EGFRvIII, IL13Rα2) undermine single-target vaccines, ADCs, and CAR-T.
Paediatric tumours (DIPG) have one approved drug with 22% response; durable control remains out of reach.
Trial design: single-arm and external-control comparisons (DCVax-L, historical vaccine data) have repeatedly misled the field.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Glioma & glioblastoma

condition: glioblastoma

Open on ClinicalTrials.gov →

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