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20Brain / CNS Tumours

Snapshot. First split METASTASES vs PRIMARY: brain metastases are the commonest brain tumour in adults (lung/breast/melanoma/renal/GI) — multiple lesions favour mets; a solitary lesion favours a primary. Adult primaries: glioblastoma (GBM) = commonest malignant primary; meningioma = commonest overall (benign, extra-axial); primary CNS lymphoma (PCNSL); lower-grade gliomas (younger). WHO 2021 classifies glioma MOLECULARLY — the adult triad: ① ASTROCYTOMA, IDH-mutant (grades 2–4) · ② OLIGODENDROGLIOMA, IDH-mutant + 1p/19q co-deleted · ③ GLIOBLASTOMA, IDH-wildtype (always grade 4). "Astrocytoma" without an IDH mutation is no longer low-grade-anything — an IDH-wildtype diffuse glioma with the molecular features behaves as GBM whatever the histology looks like. Performance status + age GATE treatment — frail/elderly/poor-PS often → palliative.
Workup
MRI brain with contrast + DWI (diffusion-weighted) + perfusion ± MRS (spectroscopy) — count lesions (single vs multiple) and characterise: DWI restricts in abscess/lymphoma; perfusion high in GBM, low in PCNSL · multiple lesions → hunt a systemic primary (CT chest/abdo/pelvis + mammogram ± PET) · tissue via stereotactic biopsy/resection (⚠ hold steroids if PCNSL possible — "melts" the tumour, non-diagnostic) · molecular profile for glioma: IDH, 1p/19q, MGMT methylation · ECOG/Karnofsky — gates the whole plan · exclude mimics: abscess, subacute infarct, haemorrhage, tumefactive demyelination.
Treatment by setting
SettingTreatment
Symptomatic oedema / seizure
any diagnosis
Dexamethasone for rapid relief ⚠ hold pre-biopsy if PCNSL is possible
Seizure → antiepileptic no routine seizure prophylaxis without a seizure history
BRAIN METASTASES
SRS (1–4 lesions) / WBRT (many) / surgery (solitary, accessible, symptomatic) + treat the primary stereotactic radiosurgery · whole-brain RT
⚠ Poor performance status → best supportive care instead (QUARTZ) WBRT adds little over steroids + supportive care in poor-PS patients
CNS-penetrant systemic options by driver vital when unfit for RT / surgery — EGFR-mutant lung → osimertinib · ALK → alectinib / lorlatinib · HER2+ breast → tucatinib combination or T-DXd · BRAF melanoma → dabrafenib + trametinib ± IO
⚠ HR+ breast tamoxifen and AIs do cross the BBB usefully; abemaciclib has the best CNS penetration (phase II activity in HR+ brain mets) but is not a substitute for local therapy in bulky / symptomatic disease
GLIOBLASTOMA — fit
IDH-wildtype
Stupp protocol — maximal safe resection → RT (~60 Gy) + concurrent temozolomide → 6 cycles adjuvant temozolomide ± tumour-treating fields
MGMT-methylation predicts temozolomide benefit
Bevacizumab at recurrence symptom / oedema control only
GLIOBLASTOMA — elderly / frail
Short-course (hypofractionated) RT ± temozolomide
MGMT-methylated → temozolomide alone is reasonable
Poor PS → best supportive care
PILOCYTIC ASTROCYTOMA
WHO grade 1 · children / young adults · cerebellum, optic pathway, brainstem
CIRCUMSCRIBED, not a diffuse glioma — gross-total resection is usually CURATIVE the best-prognosis brain tumour in the section; do not counsel it like a glioma
Residual / unresectable / progressing → BRAF-directed therapy, and the LESION TYPE picks the drug KIAA1549-BRAF FUSION (the commonest) → MEK inhibitor alone (selumetinib / trametinib) — ⚠ a BRAF inhibitor can PARADOXICALLY ACTIVATE a fusion · BRAF V600E → dabrafenib + trametinib
Alternatives where targeted therapy is unavailable: carboplatin-based chemo (esp. optic-pathway, young) · radiotherapy AVOIDED in the young if possible decades of survivorship ahead — late RT effects matter more here than anywhere
Dabrafenib + trametinib watch → PYREXIA (hold BOTH for fever) · LFTs · LVEF (echo) · eyes · skin
ASTROCYTOMA — IDH-mutant
grades 2–4 · younger adults, seizures common
Maximal safe resection FIRST — every grade extent of resection is prognostic; then the grade + risk decide what follows
Grade 2, LOW-risk (<40 + gross-total resection) → observe, MRI surveillance the one glioma you may watch after surgery
Grade 2, HIGH-risk (≥40, or residual disease) → RT + adjuvant chemo (PCV or temozolomide) (RTOG 9802) adding PCV to RT roughly doubled overall survival in high-risk low-grade glioma
Grade 2, residual/recurrent, wanting to defer chemo/RT → VORASIDENIB (INDIGO) an IDH1/2 inhibitor — PFS HR 0.39; the first targeted therapy here; delays chemo/RT · ⚠ hepatotoxicity — monitor LFTs
Grade 3 → RT + adjuvant temozolomide (CATNON) adjuvant TMZ after RT improves survival in non-co-deleted grade 3
Grade 4 IDH-mutant (or CDKN2A/B homozygous deletion → auto-grade 4) → treat along the GBM pathway RT + temozolomide — the mutation still carries a better prognosis than true GBM
OLIGODENDROGLIOMA
IDH-mutant + 1p/19q co-deleted
Resection → high-risk → RT + PCV the best-prognosis diffuse glioma and the most chemo-sensitive — long-term survival with RT + PCV; the 1p/19q co-deletion is both the diagnosis and the chemo-sensitivity marker
MENINGIOMA
Observe if small / asymptomatic
Surgery ± RT if symptomatic / growing
PRIMARY CNS LYMPHOMA (PCNSL)
High-dose methotrexate-based chemo ± rituximab — NOT primarily surgery
Recognising it periventricular; homogeneous enhancement, DWI-restricted, low perfusion; immunosuppressed / elderly
Check HIV, slit-lamp eye exam, CSF
Frail / elderly / poor PS (ECOG 3–4)
Best supportive / palliative care dexamethasone + comfort — fitness, not just the tumour, drives the plan
RADIOTHERAPY — dose & technique
modality detail across the settings above
SRS — single-fraction, size-dependent dose, 1–4 metastases
WBRT — fractionated for multiple lesions hippocampal-avoidance reduces neurocognitive decline
GBM (Stupp) — ~60 Gy/30 fx concurrent with temozolomide
Watch
Dexamethasone → hyperglycaemia, proximal myopathy, insomnia, immunosuppression; ⚠ do NOT give before biopsy if PCNSL is possible (melts the tumour → non-diagnostic). Temozolomide → myelosuppression (esp. thrombocytopenia). RT → fatigue + radiation necrosis (mimics recurrence on MRI). Vorasidenib → hepatotoxicity (LFT monitoring). Rising intracranial pressure → herniation (neurosurgical emergency). ECOG 3–4 → best supportive care.
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