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Gliomas are now diagnosed by molecular class, and three classes got their first targeted drugs in 2024-25 (vorasidenib for IDH-mutant glioma, tovorafenib for BRAF-altered paediatric glioma, dordaviprone for H3 K27M). Glioblastoma is the hardest to treat: surgery, radiotherapy with temozolomide and tumour treating fields are its backbone, with CAR-T into the brain and focused ultrasound in trials.
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). No systemic drug tested since has beaten it in phase 3: bevacizumab improved progression-free but not overall survival, and rindopepimut (ACT IV), nivolumab (CheckMate 143, 498, 548) and depatuxizumab mafodotin (INTELLANCE-1) were negative. At recurrence the options are re-resection or LITT where feasible, lomustine, re-irradiation, bevacizumab for oedema, and a clinical trial, which NCCN-aligned practice prefers; median survival after recurrence is under a year in the trial series, and half of the people in those series lived longer. 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 least.
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. In the Stupp trial (EORTC 26981-NCIC, 2005) median survival with surgery, radiotherapy and temozolomide was 14.6 months against 12.1 with radiotherapy alone, and two-year survival rose from 10 to 27 percent; half of that trial's patients lived longer than the median, and a median describes a trial population rather than one person.
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.
No conventional lymphatics: gliomas spread along white matter tracts and, rarely, through cerebrospinal fluid; medulloblastoma can seed the spine.
Same organ: Lactotroph pituitary neuroendocrine tumour (prolactinoma), Somatotroph pituitary neuroendocrine tumour (acromegaly), Corticotroph pituitary neuroendocrine tumour (Cushing disease and silent corticotroph tumour), Gonadotroph pituitary neuroendocrine tumour (non-functioning adenoma), Thyrotroph pituitary neuroendocrine tumour (TSH-secreting), Pineocytoma and pineal parenchymal tumour of intermediate differentiation, Pineoblastoma, Papillary tumour of the pineal region, Choroid plexus carcinoma, 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, Paediatric high-grade glioma (excluding diffuse midline glioma), 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), WNT-activated medulloblastoma, SHH-activated medulloblastoma, Group 3 and group 4 medulloblastoma (non-WNT/non-SHH)
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.
Background: Blood-brain barrier (BBB), EGFRvIII, H3 K27M (diffuse midline glioma), MGMT promoter methylation, The blood-brain barrier & brain metastasis. Also on OnCo: Atlas of advanced disease · How cancer spreads: the metastasis stages.
Infiltrates along white matter; recurrence is usually within 2 cm of the original site.
Extracranial metastasis is exceptional; lymph node spread does not occur because the brain has no conventional lymphatics.
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Resection → RT + temozolomide → TTFields; lomustine/bevacizumab at relapse.
Resection → vorasidenib or observation; RT/PCV for high-risk.
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.
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.
Re-resection or LITT if feasible; lomustine; bevacizumab for oedema/steroid sparing; re-irradiation; clinical trial (CAR-T, FUS-BBB, vaccines) strongly preferred.
Maximal resection; vorasidenib for residual/recurrent disease (INDIGO); radiotherapy plus PCV or temozolomide for high-risk or progressive disease.
Radiotherapy plus PCV (RTOG 9402, EORTC 26951) or temozolomide (CATNON).
Radiotherapy; dordaviprone at progression (2025); GD2 CAR-T and ONC201 first-line trials.
Resection where safe; chemotherapy (carboplatin/vincristine) or tovorafenib / dabrafenib-trametinib for BRAF-altered relapsed disease; avoid radiation in young children.
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.
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.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
Fever, cough or breathlessness, rapid weight gain or swelling, bone pain, low blood pressure or reduced urine; the labels say to start steroids and monitor at the first suspicion, and the syndrome has been fatal.
Take on an empty stomach or at bedtime to reduce nausea; PJP prophylaxis during concurrent chemoradiation.
See all on the product pages:Bevacizumab (glioblastoma use)Lomustine (CCNU)TemozolomideVorasidenib·Printable cards in the navigator
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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.
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