Glioblastoma / Brain Tumours
GBM · Glioblastoma Multiforme · High-Grade Glioma · Astrocytoma · Brain Cancer
~300,000 new brain tumour cases/year worldwide — GBM is the most common malignant primary brain tumour
Glioblastoma (GBM, WHO Grade 4) is the most aggressive primary brain tumour with a median survival of 14–16 months with standard therapy. The 2021 WHO CNS classification introduced molecular markers — IDH, MGMT, TERT, EGFR, 1p/19q — as defining features of brain tumour diagnosis, not just histology. MGMT promoter methylation is the most actionable biomarker — predicts benefit from temozolomide chemotherapy and certain clinical trials.
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Subtypes
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Diagnostic Tests
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Treatment Options
For Informational Purposes Only
Content on this page is for educational purposes only and does not constitute medical advice.
🗺 What Do I Do Next? — Your Roadmap
Just diagnosed with Glioblastoma / Brain Tumours? Here are your essential next steps.
Get the Full Diagnostic Workup
Before any treatment begins, you need 10 key tests — imaging, blood markers, biopsy, and molecular profiling. See the Diagnostic Workup section below. Do NOT start treatment without molecular testing — it determines which therapies work for your specific subtype.
Know Your Molecular Subtype
Glioblastoma / Brain Tumours is not one disease — it has 4 distinct subtypes defined by biomarkers (IDH1, IDH2, MGMT methylation, EGFR amplification, and more). Your subtype determines which treatments apply to you. See Subtypes & Mutations below.
Assemble Your Care Team
You need a multidisciplinary team: oncologist (medical, surgical, radiation), pathologist, radiologist, and ideally a molecular tumour board review. Seek a second opinion at a major cancer centre for any Stage III-IV diagnosis.
Review All Treatment Options
Treatment for Glioblastoma / Brain Tumours spans Surgery, Chemotherapy, Radiation, Targeted Therapy, Other. See the full Treatment Options section below. Ask your oncologist which options apply to your specific subtype and stage.
Ask About Clinical Trials
Many of the most effective treatments started as clinical trials. Ask your oncologist about eligibility. Search clinicaltrials.gov with your cancer type + molecular profile. Academic centres have the most trials.
Key Biomarkers & Mutations
Subtypes & Molecular Profiles
The classic, most aggressive form. Median OS ~14–16 months with standard Stupp protocol (surgery + chemoradiation + temozolomide maintenance). Bevacizumab improves PFS but not OS. Tumour treating fields (TTFields, Optune device) combined with temozolomide extends OS modestly. No approved targeted therapies despite EGFR amplification being common — EGFR TKIs have failed in GBM.
KEY THERAPIES FOR THIS SUBTYPE
Diagnostic Workup
10 testsIMAGING
MRI Brain with Gadolinium (multiparametric)
At diagnosis, within 48h post-surgery, then every 2–3 monthsRing-enhancing lesion pattern in GBM. Assess oedema, mass effect, eloquent cortex involvement. Pre-surgical planning. Includes DWI, perfusion, spectroscopy.
MRI Spine (if posterior fossa or high-grade)
Suspected leptomeningeal diseaseLeptomeningeal spread — rare in GBM but must be excluded in high-grade tumours involving cerebellum or brainstem.
PET-CT (FDG or Amino Acid tracers)
When MRI equivocal — progression vs pseudoprogressionDistinguish tumour progression from radiation necrosis (pseudoprogression). Amino acid PET (MET, FET, FDOPA) superior to FDG for gliomas.
ENDOSCOPY & PROCEDURE
Surgical Resection / Stereotactic Biopsy
At diagnosisTissue for diagnosis and full molecular characterisation. Maximal safe resection improves OS. Biopsy when resection not safe.
Neuropsychological Assessment
Pre-surgery and after treatmentBaseline cognitive function — guide intraoperative cortical mapping, assess treatment impact on cognition, rehabilitation planning.
GENETIC & MOLECULAR
IDH1/2 Mutation Testing (IHC + sequencing)
On surgical specimen — all gliomasIDH1 R132H IHC covers ~90% of IDH mutations; sequencing for remainder. Defines GBM (IDH-WT) vs astrocytoma/oligodendroglioma (IDH-mutant). Critical WHO 2021 classification.
MGMT Promoter Methylation (pyrosequencing / methylation array)
On surgical specimen — all GBMPredicts temozolomide benefit. Methylated = significantly better outcome. Guides treatment in elderly GBM (TMZ alone vs RT).
1p/19q FISH
On surgical specimen — IDH-mutant gliomas1p/19q co-deletion defines oligodendroglioma — required for diagnosis. Must be combined with IDH mutation.
EGFR Amplification / EGFRvIII
On surgical specimen — GBMEGFR amp in ~50% of GBM, EGFRvIII in ~25%. No approved targeted therapy but clinical trial eligibility (EGFRvIII-directed CAR-T, vaccines).
H3K27M Mutation
On surgical specimen — midline location gliomasDefines diffuse midline glioma (WHO Grade 4) — brainstem, thalamus, spinal cord. Extremely poor prognosis. ONC201 (dopamine receptor antagonist) FDA-approved for H3K27M mutant diffuse glioma.
Treatment Options
11 optionsSURGERY
Maximal Safe Resection (Craniotomy)
Extent of resection strongly correlates with OS in GBM. Awake craniotomy for eloquent cortex tumours (speech, motor areas). Intraoperative MRI + fluorescence (5-ALA) maximises resection.
CHEMOTHERAPY
TMZ Monotherapy (Elderly MGMT-Methylated)
Elderly GBM with MGMT methylation — RT + TMZ may be replaced by TMZ alone if RT not tolerable (NOA-08, Nordic trials).
CCNU (Lomustine) + Temozolomide
MGMT-methylated GBM — CeTeG trial: CCNU/TMZ improved median OS vs standard TMZ (48.1 vs 31.4 months). Option for methylated GBM.
PCV Chemotherapy
Oligodendroglioma (1p/19q co-deleted) — RTOG 9802 and EORTC 26951: PCV + RT superior to RT alone. Standard with or after RT.
RADIATION
Stupp Protocol (RT + Temozolomide)
Standard first-line GBM treatment for fit patients. Stupp 2005 trial: RT + TMZ vs RT alone — significant OS benefit (14.6 vs 12.1 months, 5-year OS 9.8 vs 1.9%).
Hypofractionated RT + TMZ (Elderly GBM)
Elderly (>65–70) or poor performance status GBM — equivalent outcomes to standard Stupp with less treatment burden.
Re-irradiation (FSRT / SRS)
Recurrent GBM — focal re-irradiation at relapse for small volume, good performance status. Bevacizumab concurrent to reduce radionecrosis.
TARGETED THERAPY
Bevacizumab (Avastin)
Recurrent GBM — improves PFS but not OS. Reduces steroid requirements, controls tumour oedema, improves quality of life. Second-line standard in many centres.
Vorasidenib (Voranigo)
IDH1/2 mutant Grade 2 glioma after surgery — INDIGO trial 2024: significantly delays progression vs placebo. First approved targeted therapy for low-grade glioma.
ONC201 (Dordaviprone)
H3K27M-mutant diffuse midline glioma — FDA-approved 2024. Dopamine receptor D2/3 antagonist with activity in this rare, deadly subtype.
OTHER
Tumour Treating Fields (TTFields — Optune)
Alternating electric fields applied via transducer arrays to scalp — approved for newly diagnosed GBM (+ TMZ maintenance) and recurrent GBM. OS benefit ~2.5 months (EF-14 trial).