Key Facts

Brain tumours are a heterogeneous group with prognosis varying widely by type and grade. Early diagnosis with MRI and appropriate MDT management are essential. The WHO 2021 classification integrates molecular markers for diagnosis.

Epidemiology

Primary: ~12,000/year in UK. All ages (peak 50-70 for GBM; meningioma increases with age). M > F for gliomas; F > M for meningiomas. Brain metastases: ~30,000/year; most common overall intracranial tumour.

Aetiology

• Most primary brain tumours have no known cause
• Risk factors: prior cranial radiotherapy (meningioma, glioma), genetic syndromes (NF1 — optic glioma; NF2 — bilateral vestibular schwannoma, meningioma; tuberous sclerosis; Li-Fraumeni; VHL)
• Metastases: lung (most common source), breast, melanoma, renal, colorectal

Pathophysiology

Tumours cause symptoms through: mass effect (raised ICP), infiltration/destruction of brain parenchyma, perilesional oedema (vasogenic — responds to dexamethasone), seizures (cortical irritation), hydrocephalus (obstruction of CSF flow), haemorrhage (GBM, metastases — melanoma, renal, choriocarcinoma). WHO 2021 classification: integrated histological and molecular diagnosis (IDH mutation status, 1p/19q codeletion, MGMT promoter methylation).

General Presentation

• Headache (raised ICP pattern): worse on waking, progressive, worse with coughing/straining/bending; ~50%
• Seizures: new-onset seizures in adult — brain tumour until proven otherwise; commonest presenting feature of low-grade gliomas
• Focal neurological deficit: depends on location (see below)
• Cognitive/personality change: frontal lobe tumours; insidious
• Nausea/vomiting: raised ICP (especially posterior fossa)
• Papilloedema: bilateral disc swelling

Location-Specific Symptoms

• Frontal: personality change, disinhibition, executive dysfunction, contralateral hemiparesis, expressive dysphasia (dominant), anosmia (olfactory groove)
• Temporal: seizures (complex partial with aura), receptive dysphasia (dominant), memory impairment, contralateral upper quadrantanopia
• Parietal: contralateral sensory loss, astereognosis, agraphaesthesia, spatial neglect (non-dominant), dysphasia (dominant)
• Occipital: contralateral homonymous hemianopia, visual hallucinations
• Posterior fossa: ataxia, nystagmus, cranial nerve palsies, hydrocephalus
• Pituitary: visual field defect (bitemporal hemianopia), hormonal dysfunction

Red Flags (2WW Criteria — NICE NG12)

• New progressive headache + any of: papilloedema, seizures, focal neurological deficit
• New-onset seizures in adult
• Progressive focal neurological deficit

Imaging

• MRI brain with gadolinium: gold standard; characterises tumour (location, size, enhancement, oedema, mass effect, relationship to eloquent areas)
• CT head: often first-line in acute presentation; may show mass, oedema, haemorrhage, calcification
• MR spectroscopy: distinguishes tumour from non-neoplastic lesions (raised choline, reduced NAA)
• MR perfusion: elevated cerebral blood volume in high-grade tumours
• CT CAP: staging for metastatic workup if brain metastasis identified

Histology

• Stereotactic biopsy or surgical resection: definitive diagnosis; WHO grading and molecular markers (IDH, 1p/19q, MGMT, ATRX)

Bloods

• FBC, U&Es, LFTs, coagulation: pre-surgical baseline
• Pituitary function tests: if pituitary tumour suspected (prolactin, IGF-1, cortisol, TFTs, gonadotrophins)

Other

• Visual fields: formal perimetry for pituitary/optic pathway tumours
• EEG: if seizures

Acute Management

• Dexamethasone 8-16mg/day (usually 4mg QDS): reduces vasogenic oedema; rapid symptom improvement; add PPI (lansoprazole 30mg OD)
• Anticonvulsants: for seizures — levetiracetam 250-1500mg BD (preferred — fewer drug interactions); do NOT use prophylactically (NICE)
• Raised ICP management: dexamethasone, head elevation, consider osmotic agents or neurosurgery if severe

Definitive Treatment (MDT — Neuro-Oncology)

Glioblastoma (GBM):

• Maximal safe surgical resection
• Stupp protocol: concurrent radiotherapy (60 Gy in 30 fractions) + temozolomide → adjuvant temozolomide × 6 cycles
• MGMT promoter methylation predicts better response to temozolomide
• Tumour treating fields (TTfields — Optune): emerging adjunct therapy

Low-grade glioma (WHO grade 2):

• Surgery ± radiotherapy ± chemotherapy (PCV regimen) depending on risk factors

Meningioma:

• Observation (small, asymptomatic) or surgical resection; radiotherapy for recurrence/incomplete resection

Brain metastases:

• Single metastasis: surgical resection + whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS)
• Multiple: WBRT, SRS to dominant lesions, systemic therapy
• Treat primary cancer

Supportive/Palliative

• Early palliative care involvement for high-grade tumours
• MDT: neurosurgery, oncology, palliative care, specialist nursing, psychology, physiotherapy, occupational therapy, SALT
• Driving: must notify DVLA; restrictions depend on tumour type and treatment

Referral Criteria

• 2WW referral per NICE NG12 criteria
• Neuro-oncology MDT: all confirmed brain tumours

GBM: median survival ~15 months with treatment (Stupp protocol); 5-year survival ~5%. MGMT methylated GBM: better prognosis (~21 months median). Low-grade glioma: 5-10 year median survival (IDH-mutant better prognosis). Meningioma (WHO grade 1): excellent prognosis after resection; recurrence ~10% at 10 years. Brain metastases: depends on primary; without treatment ~1-2 months; with treatment 3-12 months. Vestibular schwannoma: benign; excellent prognosis with surgery or radiosurgery.

WHO CNS Tumour Classification (2021 — Key Integrated Diagnoses)

Brain Tumour Location by Type