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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
| Setting | Approach | Guideline |
|---|---|---|
| Glioblastoma | Resection → RT + temozolomide → TTFields; lomustine/bevacizumab at relapse. | not mapped |
| IDH-mutant grade 2 | Resection → vorasidenib or observation; RT/PCV for high-risk. | not mapped |
| 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. | not mapped |
| 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. | not mapped |
| 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. | not mapped |
| IDH-mutant grade 2 glioma | Maximal resection; vorasidenib for residual/recurrent disease (INDIGO); radiotherapy plus PCV or temozolomide for high-risk or progressive disease. | not mapped |
| Oligodendroglioma grade 3 / astrocytoma grade 3 | Radiotherapy plus PCV (RTOG 9402, EORTC 26951) or temozolomide (CATNON). | not mapped |
| H3 K27M diffuse midline glioma | Radiotherapy; dordaviprone at progression (2025); GD2 CAR-T and ONC201 first-line trials. | not mapped |