Brain Tumour

1. Clinical Overview

Summary

Brain tumours are abnormal growths arising from intracranial structures, classified as primary (originating within the CNS) or secondary (metastatic). Primary brain tumours include gliomas, meningiomas, pituitary adenomas, and schwannomas, while metastases from systemic cancers are the most common intracranial malignancies in adults. Presentation depends on tumour location and includes headache, seizures, focal neurological deficits, and personality changes. Diagnosis requires neuroimaging (MRI) and often histopathological confirmation. Management is multimodal, involving surgery, radiotherapy, and chemotherapy depending on tumour type. Prognosis varies dramatically from excellent (benign meningioma) to very poor (glioblastoma, median survival 15 months).

Key Facts

• Epidemiology: Primary brain tumours: 7-8 per 100,000/year; metastases 10x more common
• Most common primary tumour: Meningioma (benign); Glioblastoma (malignant)
• Most common sources of metastases: Lung (50%), Breast (15%), Melanoma (10%), Renal, Colorectal
• Peak age: Glioblastoma: 55-65 years; Medulloblastoma: Childhood
• Classic presentation triad: Headache + Nausea/vomiting + Papilloedema (raised ICP)
• Imaging gold standard: MRI with gadolinium contrast
• Glioblastoma survival: Median 15 months with optimal treatment
• Important classification: WHO Grade I-IV for gliomas
• Treatment cornerstone: Maximal safe surgical resection
• Stupp protocol: Surgery + RT + Temozolomide for glioblastoma

Clinical Pearls

"Worst Headache Pattern": Brain tumour headaches are classically worse on waking (raised ICP during recumbent sleep), worse with Valsalva (coughing, straining), and progressive over weeks.

"New Seizures in Adults": Any new-onset seizure in an adult over 25 requires brain imaging. Seizures are the presenting feature in 20-40% of brain tumours.

"Metastases > Primary": In adults, brain metastases outnumber primary brain tumours 10:1. Always consider a primary cancer workup.

"The Eloquent Cortex": Surgery near motor, sensory, language, or visual cortex requires awake craniotomy with cortical mapping to preserve function.

"Steroid Response": Dexamethasone dramatically reduces peritumoural oedema within hours. If a patient with suspected brain tumour improves on steroids, it supports (but doesn't confirm) the diagnosis.

Why This Matters Clinically

Brain tumours cause significant morbidity including cognitive impairment, seizures, and functional disability. Early recognition and referral to specialist neuro-oncology services improves outcomes. Even for aggressive tumours, treatment can provide meaningful survival extension and symptom palliation. Understanding the diverse presentations and appropriate referral pathways is essential for all clinicians. The extent of surgical resection is directly associated with survival—each 1% increase in extent of resection correlates with improved survival in glioblastoma.[1,2,3]

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2. Epidemiology

Incidence & Prevalence

Demographics

Risk Factors

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3. Pathophysiology

Mechanism

Step 1: Cellular Origin

• Brain tumours arise from various cell types: astrocytes (astrocytoma), oligodendrocytes, ependymal cells, meningeal cells, or Schwann cells
• Genetic mutations accumulate (TP53, PTEN, EGFR, IDH1/2, 1p/19q co-deletion)
• Transformation from low-grade to high-grade (secondary glioblastoma) can occur

Step 2: Tumour Growth

• Uncontrolled proliferation within fixed intracranial space
• Neovascularisation (VEGF-driven) provides blood supply
• Tumour cells infiltrate along white matter tracts (gliomas)
• Meningiomas compress but rarely invade brain parenchyma

Step 3: Mass Effect

• Growing tumour displaces normal brain tissue
• Compression of adjacent structures causes focal deficits
• Obstruction of CSF pathways → hydrocephalus
• Herniation syndromes if space-occupying effect severe

Step 4: Peritumoural Oedema

• Vasogenic oedema due to leaky tumour blood vessels (disrupted BBB)
• Oedema often exceeds tumour volume
• Contributes significantly to symptoms and mass effect
• Responsive to corticosteroids (dexamethasone)

Step 5: Secondary Effects

• Increased intracranial pressure → headache, vomiting, papilloedema
• Neuronal irritation → seizures
• Invasion of functional cortex → focal neurological deficits
• Hormone disruption (pituitary tumours) → endocrinopathy

WHO Classification of CNS Tumours (2021)

Molecular Markers (2021 WHO Classification)

The 2021 WHO Classification of CNS Tumours prioritises molecular markers over histology for diagnosis and prognosis.[4,5]

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5. Specific Tumour Types

5.1 Glioblastoma (WHO Grade 4)

Overview Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumour in adults. It is an IDH-wildtype astrocytic tumour with median survival of 15 months despite maximal therapy.[6,7]

Epidemiology

• Incidence: 3.2 per 100,000/year
• Peak age: 55-65 years
• Male predominance (M:F = 1.6:1)
• Accounts for 45-50% of all malignant primary brain tumours

Pathological Features

• Hallmarks: Microvascular proliferation and necrosis (palisading pattern)
• Highly cellular with pleomorphic nuclei and mitotic figures
• Infiltrative growth along white matter tracts
• IDH-wildtype (by definition in 2021 WHO classification)
• EGFR amplification in ~40%
• TERT promoter mutation in ~70%

Imaging Characteristics

• MRI: Thick irregular ring enhancement with central necrosis
• Surrounding vasogenic oedema (bright on T2/FLAIR)
• Restricted diffusion in cellular areas
• Elevated cerebral blood volume on perfusion imaging
• "Butterfly glioma" when crossing corpus callosum

Clinical Presentation

• Rapidly progressive symptoms (weeks to months)
• Headache (50%), seizures (30%), focal deficits (60%)
• Cognitive decline and personality change (frontal/temporal)
• Most common location: Frontal and temporal lobes

Management — Stupp Protocol[8,9]

1. Surgery: Maximal safe resection

   • Extent of resection directly correlates with survival
   • Gross total resection (> 98% resection) improves median survival by 3-5 months
   • Use of intraoperative imaging (MRI, fluorescence-guided surgery with 5-ALA)
   • Awake craniotomy for eloquent cortex lesions

2. Adjuvant Chemoradiotherapy (Stupp Protocol):

   • Radiotherapy: 60 Gy in 30 fractions over 6 weeks
   • Concurrent temozolomide: 75 mg/m² daily during RT
   • Adjuvant temozolomide: 150-200 mg/m² days 1-5 of 28-day cycle × 6 cycles
   • MGMT promoter methylation predicts benefit: methylated patients have 21.7 months median survival vs 12.7 months unmethylated

3. Tumour Treating Fields (Optune)[10]:

   • Added to adjuvant temozolomide in EF-14 trial
   • Improved median survival from 16.0 to 20.9 months
   • Continuous wear (18+ hours/day) via scalp electrodes
   • Low-intensity alternating electric fields disrupt mitosis

Prognosis

• Median survival: 15 months with optimal treatment
• 5-year survival: less than 10%
• Prognostic factors: Age, performance status, extent of resection, MGMT methylation, IDH status

Recurrent Glioblastoma

• Almost universal recurrence
• Options: Re-resection, re-irradiation, bevacizumab, clinical trials
• Bevacizumab (anti-VEGF): Improves progression-free survival but NOT overall survival[11]
• Median survival from recurrence: 6-9 months

5.2 Lower-Grade Gliomas (WHO Grade 2-3)

Astrocytoma, IDH-mutant (Grade 2-4)

• IDH1/2 mutation is defining feature
• Grade 2: Diffuse, infiltrative, no necrosis or microvascular proliferation
• Grade 3: Anaplastic features (increased mitoses, cellularity)
• Grade 4: Microvascular proliferation and/or necrosis OR CDKN2A/B homozygous deletion
• Median survival: Grade 2 (10-15 years), Grade 3 (3-5 years), Grade 4 (3-4 years)
• Transformation to higher grade over time is common

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted (Grade 2-3)[12]

• Most favorable glioma prognosis
• 1p/19q codeletion (diagnostic requirement) + IDH mutation
• Chemosensitive (PCV or temozolomide)
• "Fried egg" appearance histologically
• Calcifications common on imaging
• Median survival: Grade 2 (15-20 years), Grade 3 (10-15 years)

Management of Lower-Grade Gliomas

• Observation: Small, asymptomatic, low-risk features
• Surgery: Maximal safe resection when feasible
• Radiotherapy: 50.4-54 Gy in 1.8-2 Gy fractions
• Chemotherapy: Temozolomide or PCV (procarbazine, lomustine, vincristine)
• High-risk features requiring adjuvant therapy: Age > 40, subtotal resection, Grade 3, tumour > 5cm

5.3 Meningioma

Overview Meningiomas are extra-axial tumours arising from arachnoid cap cells. Most are WHO Grade 1 (benign), with excellent prognosis following complete resection.[13]

Epidemiology

• Most common primary brain tumour (37% of all CNS tumours)
• Incidence: 2.3 per 100,000/year
• Female predominance (F:M = 2-3:1) due to hormonal factors
• Peak age: 60-70 years
• Associated with neurofibromatosis type 2 (NF2)

WHO Grading[4]

• Grade 1 (80%): Benign, slow-growing
• Grade 2 (15-20%): Atypical features (increased mitoses, brain invasion)
• Grade 3 (1-3%): Anaplastic/malignant, aggressive behavior

Imaging Features

• Extra-axial, broad dural base
• Homogeneous intense enhancement with "dural tail"
• Hyperostosis of adjacent bone
• Calcification in 20-25%
• Minimal surrounding oedema (unless large)

Common Locations

• Parasagittal/falcine (25%)
• Convexity (20%)
• Sphenoid wing (20%)
• Olfactory groove (10%)
• Posterior fossa (10%)

Clinical Presentation

• Often incidental findings on imaging
• Symptoms depend on location:
  • "Parasagittal: Leg weakness, seizures"
  • "Sphenoid wing: Visual changes, proptosis"
  • "Olfactory groove: Anosmia, frontal lobe syndrome"
  • "Posterior fossa: Ataxia, cranial nerve palsies"

Management

• Observation: Asymptomatic, small (less than 3cm), elderly/frail patients with slow growth
• Surgery: Simpson Grade resection classification
  • "Grade 1 (complete with dura): 10% recurrence at 10 years"
  • "Grade 2 (complete with coagulation): 20% recurrence"
  • "Grade 4 (subtotal): 40% recurrence"
• Radiotherapy: Subtotal resection, Grade 2/3, or recurrence
  • Stereotactic radiosurgery for small (less than 3cm) residual/recurrent
  • Fractionated RT for larger lesions

Prognosis

• Grade 1: Excellent, near-normal life expectancy if completely resected
• Grade 2: 5-year progression-free survival 40-60%
• Grade 3: Median survival 2-3 years

5.4 Brain Metastases

Overview Brain metastases are the most common intracranial malignancy in adults, outnumbering primary brain tumours 10:1. They represent haematogenous spread from systemic cancer.[14,15]

Epidemiology

• Incidence: 70-80 per 100,000/year (increasing with improved cancer survival)
• Present in 10-30% of adult cancer patients
• Most common solid tumours metastasising to brain:
  • Lung (50%) — especially small cell and adenocarcinoma
  • Breast (15-20%)
  • Melanoma (10%) — highest propensity (> 50% of melanoma patients develop brain mets)
  • Renal cell carcinoma (5-10%)
  • Colorectal (5%)

Imaging Characteristics

• Multiple lesions (60-70% of cases)
• Located at grey-white junction (watershed areas)
• Spherical with nodular or ring enhancement
• Disproportionate vasogenic oedema relative to tumour size
• Melanoma: May be hyperintense on T1 (melanin)
• Lung/renal: Prone to haemorrhage

Clinical Presentation

• Headache (40-50%)
• Focal neurological deficits (40%)
• Cognitive impairment (30%)
• Seizures (15-20%)
• Often multifocal symptoms

Staging and Workup

• Brain MRI with contrast (gold standard)
• Identify primary: CT chest/abdomen/pelvis, PET scan
• Assess extracranial disease burden
• Prognostic scores: Graded Prognostic Assessment (GPA), diagnosis-specific GPA

Management[16,17]

Limited Metastases (1-4 lesions):

• Stereotactic Radiosurgery (SRS): Preferred for less than 3cm lesions
  • Gamma Knife or LINAC-based
  • Single high-dose treatment (12-24 Gy)
  • Local control 70-90% at 1 year
  • Preserves neurocognition vs whole brain RT
• Surgical resection: Large (> 3cm), symptomatic, accessible, good performance status
  • Followed by SRS to resection cavity

Multiple Metastases (> 4 lesions):

• Whole Brain Radiotherapy (WBRT): 30 Gy in 10 fractions
  • Provides palliation but associated with cognitive decline
  • Hippocampal-avoidance WBRT reduces cognitive toxicity
• SRS to multiple lesions: Increasingly used for up to 10-15 metastases
• Systemic therapy: Targeted therapy/immunotherapy (e.g., ALK/EGFR inhibitors, checkpoint inhibitors)

Supportive Care:

• Dexamethasone for oedema
• Antiepileptics if seizures present
• Treat underlying malignancy

Prognosis

• Median survival: 6-12 months (varies widely by primary, extracranial disease, performance status)
• Favorable factors: Young age, controlled primary, limited metastases, good KPS

5.5 Pituitary Adenomas

Overview Pituitary adenomas account for 10-15% of intracranial tumours. Most are benign, arising from anterior pituitary cells.

Classification

• Functional (60%): Hormone-secreting
  • Prolactinoma (40%)
  • GH-secreting (acromegaly, 20%)
  • ACTH-secreting (Cushing's disease, 10%)
  • TSH/FSH/LH-secreting (rare)
• Non-functional (40%): Present with mass effect

Clinical Presentation

• Endocrine symptoms: Depends on hormone secreted
  • "Prolactinoma: Amenorrhoea, galactorrhoea, erectile dysfunction"
  • "Acromegaly: Enlarged hands/feet, frontal bossing, organomegaly"
  • "Cushing's: Central obesity, moon facies, striae, proximal myopathy"
• Visual symptoms: Bitemporal hemianopia (chiasmal compression)
• Hypopituitarism: Fatigue, loss of libido, hypothyroidism, adrenal insufficiency
• Headache: Mass effect

Investigations

• Pituitary hormone panel: Prolactin, GH, IGF-1, ACTH, cortisol, TSH, LH/FSH
• MRI pituitary with contrast
• Visual field testing

Management

• Prolactinoma: Dopamine agonists (cabergoline, bromocriptine) — excellent response, 80-90% shrink
• Acromegaly/Cushing's: Trans-sphenoidal surgery (first-line)
• Non-functional: Observation if small and asymptomatic; surgery if compressive or growing
• Radiotherapy: For residual/recurrent disease post-surgery

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6. Clinical Presentation

Symptoms by Category

Symptoms by Location

Signs

Red Flags

[!CAUTION] Red Flags — Urgent Imaging Required:

• New-onset seizures in adults (especially > 25 years) — 20-40% have structural brain lesion
• Progressive headache with morning vomiting — classic raised ICP
• Papilloedema on fundoscopy — definite raised ICP
• Rapid neurological deterioration — possible herniation syndrome
• Cushing's triad (hypertension, bradycardia, irregular respirations) — impending herniation, IMMEDIATE intervention
• New focal neurological deficit without clear alternative cause
• Personality or cognitive change with no psychiatric history — especially frontal lobe lesions
• Visual field defects — suprasellar (pituitary) or posterior pathway lesions
• Thunderclap headache — may indicate tumour haemorrhage
• Deteriorating GCS — herniation or acute hydrocephalus

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7. Clinical Examination

Structured Neurological Examination

General Inspection:

• Consciousness level (GCS)
• Cognitive state (orientation, attention, memory)
• Speech and language assessment
• Signs of raised ICP (altered alertness, posturing)

Cranial Nerves:

• Fundoscopy (papilloedema essential)
• Visual fields to confrontation
• Pupil responses (III nerve, herniation)
• Eye movements (brainstem lesions)
• Facial power and sensation
• Hearing assessment

Motor System:

• Tone (increased with upper motor neurone lesions)
• Power (pyramidal pattern weakness)
• Reflexes (hyperreflexia, clonus)
• Plantar response (Babinski sign)
• Pronator drift (subtle weakness)

Sensory System:

• Light touch, pinprick, temperature
• Proprioception, vibration
• Cortical sensory function (graphaesthesia, stereognosis)
• Neglect testing (parietal lesions)

Cerebellar Examination:

• Coordination (finger-nose, heel-shin)
• Dysdiadochokinesis
• Gait assessment
• Romberg's test
• Nystagmus

Key Signs to Detect

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8. Investigations

First-Line Imaging

MRI Features by Tumour Type

Laboratory Investigations

Advanced Imaging Techniques

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9. Management

Management Algorithm

             SUSPECTED BRAIN TUMOUR
                      ↓
┌────────────────────────────────────────────────────────┐
│           INITIAL ASSESSMENT                           │
│  - Urgent CT Head if emergency (seizure, acute focal   │
│    deficit, reduced consciousness)                     │
│  - MRI Brain with gadolinium (gold standard)           │
│  - Assess for raised ICP and herniation risk           │
└────────────────────────────────────────────────────────┘
                      ↓
┌────────────────────────────────────────────────────────┐
│           SUPPORTIVE CARE                              │
├────────────────────────────────────────────────────────┤
│  ➤ Dexamethasone 8-16 mg/day (reduces oedema)         │
│  ➤ PPI cover (omeprazole)                             │
│  ➤ Anticonvulsants if seizures (levetiracetam)        │
│  ➤ VTE prophylaxis                                    │
│  ➤ Urgent neurosurgical referral                      │
└────────────────────────────────────────────────────────┘
                      ↓
┌────────────────────────────────────────────────────────┐
│           TUMOUR-SPECIFIC MANAGEMENT                   │
├────────────────────────────────────────────────────────┤
│  GLIOBLASTOMA (Grade 4):                              │
│  ➤ Maximal safe resection                             │
│  ➤ Stupp protocol: RT 60 Gy + Temozolomide            │
│  ➤ Adjuvant Temozolomide x6 cycles                    │
│  ➤ Consider tumour treating fields (Optune)           │
│  ➤ Median survival: 15 months                         │
├────────────────────────────────────────────────────────┤
│  LOW-GRADE GLIOMA (Grade 2):                          │
│  ➤ Resection if feasible                              │
│  ➤ Post-op RT ± chemotherapy (high-risk features)     │
│  ➤ Surveillance for low-risk                          │
├────────────────────────────────────────────────────────┤
│  MENINGIOMA:                                          │
│  ➤ Observation if small and asymptomatic              │
│  ➤ Surgery for symptomatic/growing lesions            │
│  ➤ Radiotherapy for unresectable/recurrent            │
├────────────────────────────────────────────────────────┤
│  BRAIN METASTASES:                                    │
│  ➤ Treat underlying malignancy                        │
│  ➤ Limited (1-3): Stereotactic radiosurgery or surgery│
│  ➤ Multiple: Whole brain radiotherapy (WBRT)          │
│  ➤ Targeted therapy (if molecular targets present)    │
├────────────────────────────────────────────────────────┤
│  PITUITARY ADENOMA:                                   │
│  ➤ Prolactinoma: Dopamine agonist (cabergoline)       │
│  ➤ Other functioning: Trans-sphenoidal surgery        │
│  ➤ Non-functioning: Surgery if compressive            │
└────────────────────────────────────────────────────────┘

Surgical Principles

Extent of Resection and Outcomes[1,20]

Extent of resection is the most important surgeon-controlled prognostic factor in glioblastoma:

• Gross total resection (GTR): > 98% resection → median survival improvement 3-5 months
• Each 1% increase in extent of resection correlates with 0.5% improvement in survival
• Supramaximal resection: Resection beyond enhancing tumour into FLAIR signal abnormality (infiltrative oedema) — emerging evidence suggests further survival benefit

Surgical Risks

• Neurological deficit (5-15%, depends on location and eloquence)
• Seizures (10-20% post-operative)
• Infection (2-4%): Meningitis, wound infection, abscess
• Haemorrhage (1-3%)
• CSF leak (2-5%)
• Venous thromboembolism (5-10% despite prophylaxis)

Emergency Management of Raised ICP[22]

Herniation Syndromes

Acute Raised ICP Management (Medical)

1. General Measures:

   • Head elevation 30° (improves venous drainage)
   • Avoid hypoxia, hypercapnia (keep PaCO₂ 35-40 mmHg, O₂ sat > 95%)
   • Maintain normothermia
   • Avoid hypotension (maintain MAP > 80 mmHg for cerebral perfusion)
   • Avoid hyponatremia (worsens cerebral oedema)

2. Osmotherapy:

   • Mannitol 20%: 0.25-1 g/kg IV bolus over 15 minutes
     • Reduces ICP within 15-30 minutes, lasts 3-6 hours
     • Monitor serum osmolality (less than 320 mOsm/L)
     • Risk of rebound oedema with prolonged use
   • Hypertonic saline (3-23.4%): 2-5 mL/kg bolus
     • Alternative to mannitol; no rebound; can use in hypotensive patients
     • Target serum sodium 145-155 mmol/L

3. Corticosteroids:

   • Dexamethasone 16-24 mg IV bolus for tumour-related oedema
   • Onset 6-24 hours (NOT for acute herniation, too slow)

4. Hyperventilation (temporary, bridge to surgery):

   • Target PaCO₂ 30-35 mmHg
   • Causes cerebral vasoconstriction → reduced ICP
   • Lasts 6-24 hours only; do NOT use routinely (risks cerebral ischemia)

5. Seizure control:

   • Seizures increase ICP; treat aggressively with benzodiazepines + AED

Surgical Management of Raised ICP

• Urgent tumour resection: Definitive treatment for mass effect
• Decompressive craniectomy: Remove bone flap to allow brain swelling (last resort)
• External ventricular drain (EVD): For obstructive hydrocephalus
• VP shunt or ETV: For persistent hydrocephalus

Adjuvant Therapy — Radiotherapy and Chemotherapy

Radiotherapy Protocols[23,24]

Radiotherapy Side Effects

Chemotherapy Regimens

Supportive Care — Dexamethasone and Symptom Control

Dexamethasone for Peritumoural Oedema[18]

Dexamethasone is a potent glucocorticoid that reduces vasogenic oedema by:

• Stabilizing the blood-brain barrier
• Reducing vascular permeability (downregulates VEGF)
• Decreasing capillary leak from abnormal tumour vessels

Dexamethasone Side Effects (common with prolonged use):

• Hyperglycemia (monitor blood glucose, may need insulin)
• Gastric ulceration (always prescribe PPI cover)
• Immunosuppression (increased infection risk, PJP prophylaxis if > 3-4 weeks)
• Proximal myopathy (impairs mobility and rehabilitation)
• Psychiatric effects (mood swings, psychosis, insomnia)
• Cushingoid features (moon facies, central obesity)
• Adrenal suppression (must taper gradually to avoid Addisonian crisis)

Tapering Strategy:

• Reduce by 1-2 mg every 3-7 days
• Slower taper if on prolonged therapy (> 4 weeks)
• Monitor for symptom recurrence (headache, focal signs)

Symptom Management

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10. Complications

Early (Days-Weeks)

Late (Months-Years)

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11. Prognosis & Outcomes

Survival by Tumour Type

Prognostic Factors

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12. Evidence & Guidelines

Key Guidelines

Landmark Trials

Stupp Trial (2005)

• n=573 patients with glioblastoma
• Compared RT alone vs RT + concurrent/adjuvant Temozolomide
• Result: Median survival 14.6 vs 12.1 months (HR 0.63)
• Clinical impact: Established standard of care for glioblastoma
• PMID: 15758009

EF-14 Trial (2017) — Tumour Treating Fields

• Added TTFields to standard therapy in newly diagnosed glioblastoma
• Improved median survival from 16 to 20.9 months
• PMID: 29260225

RTOG 0525 (2013)

• Dose-dense temozolomide in glioblastoma
• No survival benefit over standard dosing
• PMID: 23940225

EORTC 22033-26033 (2016)

• RT vs Temozolomide in low-grade glioma
• Similar efficacy; IDH status predictive
• PMID: 27686946

Evidence Strength

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13. Patient/Layperson Explanation

What is a Brain Tumour?

A brain tumour is an abnormal growth of cells inside the brain or surrounding structures. Tumours can be "primary" (starting in the brain) or "secondary" (spreading from cancer elsewhere in the body, called metastases).

Why does it happen?

In most cases, we don't know exactly why brain tumours develop. They occur when brain cells start to grow abnormally. Some risk factors include previous radiation treatment and certain genetic conditions. Mobile phones have been extensively studied and are not proven to cause brain tumours.

What are the symptoms?

Symptoms depend on where the tumour is and how fast it's growing:

• Headaches: Often worse in the morning, made worse by coughing or straining
• Seizures (fits): May be the first sign
• Weakness or numbness: Usually affecting one side of the body
• Vision problems: Blurred vision or loss of part of vision
• Speech difficulty: Trouble finding words or understanding
• Personality changes: Mood swings, confusion, or unusual behaviour

How is it treated?

Treatment depends on the type of tumour:

• Surgery: To remove as much tumour as safely possible
• Radiotherapy: High-energy beams to kill tumour cells
• Chemotherapy: Tablets or injections to slow tumour growth
• Steroids: To reduce swelling around the tumour

What to expect?

This depends on the type of tumour. Some brain tumours are completely curable with surgery. Others require ongoing treatment. Your medical team will explain your individual situation and support you through treatment.

When to seek help urgently

Seek immediate medical attention if you experience:

• Sudden severe headache
• New seizure (fit) or worsening seizures
• Sudden weakness, numbness, or vision loss
• Severe drowsiness or confusion
• Difficulty breathing or very slow heart rate

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14. References

Surgical Outcomes and Extent of Resection

1. Molinaro AM, Hervey-Jumper S, Morshed RA, et al. Association of Maximal Extent of Resection of Contrast-Enhanced and Non-Contrast-Enhanced Tumor With Survival Within Molecular Subgroups of Patients With Newly Diagnosed Glioblastoma. JAMA Oncol. 2020;6(4):495-503. PMID: 32027343

2. Brown TJ, Brennan MC, Li M, et al. Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis. JAMA Oncol. 2016;2(11):1460-1469. PMID: 27310651

3. Wijnenga MMJ, French PJ, Dubbink HJ, et al. Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group. Neuro Oncol. 2023;25(5):940-954. PMID: 35961053

WHO Classification and Molecular Markers

4. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-1251. PMID: 34185076

5. Brat DJ, Aldape K, Colman H, et al. cIMPACT-NOW update 3: recommended diagnostic criteria for "Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV". Acta Neuropathol. 2018;136(5):805-810. PMID: 30259105

Glioblastoma Overview and Pathophysiology

6. Ostrom QT, Cioffi G, Waite K, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018. Neuro Oncol. 2021;23(12 Suppl 2):iii1-iii105. PMID: 34608945

7. Ohgaki H, Kleihues P. Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol. 2015;129(6):829-848. PMID: 25943888

Stupp Protocol and Temozolomide

8. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996. PMID: 15758009

9. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459-466. PMID: 19269895

Tumour Treating Fields

10. Stupp R, Taillibert S, Kanner A, et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017;318(23):2306-2316. PMID: 29260225

Bevacizumab

11. Wick W, Gorlia T, Bendszus M, et al. Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med. 2017;377(20):1954-1963. PMID: 29141164

Oligodendroglioma

12. van den Bent MJ, Baumert B, Erridge SC, et al. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017;390(10103):1645-1653. PMID: 28784414

Meningioma

13. Goldbrunner R, Minniti G, Preusser M, et al. EANO guidelines for the diagnosis and treatment of meningiomas. Lancet Oncol. 2016;17(9):e383-e391. PMID: 27599144

Brain Metastases Overview

14. Achrol AS, Rennert RC, Anders C, et al. Brain metastases. Nat Rev Dis Primers. 2019;5(1):5. PMID: 30655533

15. Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep. 2012;14(1):48-54. PMID: 22012633

Stereotactic Radiosurgery for Brain Metastases

16. Yamamoto M, Serizawa T, Shuto T, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014;15(4):387-395. PMID: 24621620

17. Brown PD, Jaeckle K, Ballman KV, et al. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016;316(4):401-409. PMID: 27458945

Dexamethasone Mechanism

18. Heiss JD, Papavassiliou E, Merrill MJ, et al. Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor. J Clin Invest. 1996;98(6):1400-1408. PMID: 8823305

Brain Tumour-Related Epilepsy

19. Goldstein ED, Feyissa AM. Brain tumor related-epilepsy management: A Society for Neuro-oncology (SNO) consensus review on current management. Neuro Oncol. 2024;26(1):7-24. PMID: 37699031

RANO Resection Criteria

20. Vogelbaum MA, Jost S, Aghi MK, et al. Application of novel response/progression measures for surgically delivered therapies for gliomas: Response Assessment in Neuro-Oncology (RANO) Working Group. Neurosurgery. 2012;70(1):234-243. PMID: 21593697

Fluorescence-Guided Surgery

21. Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7(5):392-401. PMID: 16648043

Raised ICP Management

22. Diringer MN, Bleck TP, Claude Hemphill J 3rd, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15(2):211-240. PMID: 21773873

Radiotherapy Protocols

23. Walker MD, Alexander E Jr, Hunt WE, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg. 1978;49(3):333-343. PMID: 355604

24. Stupp R, Brada M, van den Bent MJ, et al. High-grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25 Suppl 3:iii93-101. PMID: 24782454

Hypofractionated RT for Elderly

25. Perry JR, Laperriere N, O'Callaghan CJ, et al. Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma. N Engl J Med. 2017;376(11):1027-1037. PMID: 28296618

Hippocampal-Avoidance WBRT

26. Brown PD, Gondi V, Pugh S, et al. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol. 2020;38(10):1019-1029. PMID: 32058845

Guidelines

27. National Institute for Health and Care Excellence (NICE). Brain tumours (primary) and brain metastases in adults (NG99). 2018, updated 2021. nice.org.uk/guidance/ng99

28. Weller M, van den Bent M, Preusser M, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021;18(3):170-186. PMID: 33293629

29. National Comprehensive Cancer Network (NCCN). Central Nervous System Cancers (Version 1.2023). nccn.org

30. Congress of Neurological Surgeons. Systematic Review and Evidence-Based Guidelines on the Management of Newly Diagnosed and Progressive Glioblastoma. Neurosurgery. 2022. PMID: 35426875

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15. Examination Focus

High-Yield Exam Topics

Sample Viva Questions

Q1: A 60-year-old presents with progressive headache, worse in the mornings, and a new-onset seizure. MRI shows a ring-enhancing mass with central necrosis in the right frontal lobe. What is the likely diagnosis and management?

Model Answer:

Initial Assessment: The presentation and imaging are highly suggestive of glioblastoma (WHO Grade 4). Ring enhancement with central necrosis, combined with progressive symptoms and new seizure in a 60-year-old, is the classic presentation.

Differential diagnosis: Brain abscess (less likely without fever/immunosuppression), metastasis (need primary cancer history/workup), primary CNS lymphoma (typically in immunosuppressed).

Immediate management:

• Dexamethasone 8-16 mg/day (in divided doses) to reduce peritumoural oedema and mass effect — provides rapid symptom relief within hours to days. Always prescribe PPI cover (omeprazole 20mg).
• Levetiracetam 500-1000mg BD for seizure control (preferred over enzyme-inducing AEDs like phenytoin which interfere with chemotherapy metabolism).
• Urgent neurosurgical referral for consideration of maximal safe resection.

Definitive treatment (Stupp Protocol):

1. Surgery: Maximal safe resection aiming for gross total resection (> 98%). Consider 5-ALA fluorescence-guided surgery to improve extent of resection. If near eloquent cortex (left frontal — Broca's area), consider awake craniotomy with intraoperative language mapping.
2. Post-operative chemoradiotherapy:
   • Radiotherapy 60 Gy in 30 fractions over 6 weeks to tumour bed + 2-3cm margin
   • Concurrent temozolomide 75 mg/m² daily during radiotherapy
3. Adjuvant temozolomide: 150-200 mg/m² days 1-5 of 28-day cycle × 6 cycles
4. Consider tumour treating fields (Optune) if patient willing/able (EF-14 trial showed survival benefit: median 20.9 vs 16 months)

Prognostic factors:

• Molecular testing essential: IDH status (wildtype = worse prognosis), MGMT promoter methylation (methylated = better response to temozolomide: 21.7 vs 12.7 months median survival), TERT, EGFR
• Extent of resection is most important surgeon-controlled factor
• Age, performance status (Karnofsky > 70 better)

Expected outcome: Median survival 15 months with optimal treatment; 5-year survival less than 10%.

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Q2: What are the differences between primary and secondary brain tumours in terms of epidemiology, imaging, and management?

Model Answer:

Epidemiology:

• Primary brain tumours: 7-8 per 100,000/year. Most common malignant primary is glioblastoma (3.2/100,000). Most common benign primary is meningioma.
• Secondary (metastatic) brain tumours: 70-80 per 100,000/year — 10 times more common than primary malignant tumours in adults.

Imaging characteristics:

Management principles:

Primary (Glioblastoma):

• Surgery: Maximal safe resection is cornerstone — extent correlates with survival
• Adjuvant therapy: Chemoradiotherapy (Stupp protocol) — RT + temozolomide
• Molecular markers guide prognosis and treatment (IDH, MGMT, 1p/19q)
• Systemic workup: Not required (primary CNS tumour)

Secondary (Metastases):

• Identify and treat primary malignancy — CT chest/abdomen/pelvis, PET scan
• Limited (1-4) metastases: Stereotactic radiosurgery (SRS) preferred — single-fraction high-dose RT (15-24 Gy). Surgical resection if large (> 3cm), symptomatic, or solitary with controlled systemic disease.
• Multiple (> 4) metastases: Whole brain radiotherapy (WBRT) 30 Gy/10# or SRS to multiple lesions (increasingly common). Consider systemic therapy (targeted therapy, immunotherapy based on primary).
• Prognosis: Depends on primary cancer, extracranial disease burden, number of metastases (Graded Prognostic Assessment score). Median survival 6-12 months.

Key clinical pearl: In any adult with a new brain mass, metastases are statistically more likely than primary. Always obtain oncological history and consider primary cancer workup.

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Q3: Why is dexamethasone used in brain tumour management? Explain the mechanism, dosing, and side effects.

Model Answer:

Mechanism of action: Dexamethasone is a potent glucocorticoid that reduces vasogenic peritumoural oedema through several mechanisms:

1. Stabilizes the blood-brain barrier by reducing vascular permeability
2. Downregulates VEGF (vascular endothelial growth factor) secreted by tumour cells
3. Reduces capillary leak from abnormal tumour blood vessels
4. Anti-inflammatory effects reduce local inflammation

Brain tumours have leaky, abnormal vasculature which causes fluid extravasation into surrounding brain parenchyma. This oedema contributes significantly to mass effect, raised ICP, and symptoms — often more than the tumour itself.

Dosing:

Onset: Symptoms improve within 6-24 hours, dramatic response often within hours (supports but doesn't confirm tumour diagnosis).

Tapering: Gradual reduction by 1-2 mg every 3-7 days to avoid adrenal crisis from suppression. Monitor for symptom recurrence.

Side effects (especially with prolonged use > 2-4 weeks):

Clinical Pearl: Dexamethasone provides symptomatic relief but does NOT treat the underlying tumour. It is a temporizing measure — definitive treatment (surgery, RT, chemo) is required. The goal is to taper to the lowest dose (or discontinue entirely) as soon as feasible after definitive treatment to minimize side effects.

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Q4: Describe the Stupp protocol for glioblastoma. What is the evidence base and what factors predict response?

Model Answer:

The Stupp Protocol is the standard of care for newly diagnosed glioblastoma, established by the landmark EORTC-NCIC trial published in NEJM 2005 (Stupp et al., PMID 15758009).

Protocol components:

Phase 1 — Concurrent Chemoradiotherapy (6 weeks):

• Radiotherapy: 60 Gy in 30 fractions (2 Gy per fraction) delivered over 6 weeks to the tumour bed + 2-3 cm margin
• Concurrent Temozolomide: 75 mg/m² oral daily, 7 days/week throughout radiotherapy (including weekends)

Phase 2 — Adjuvant Temozolomide (6 months):

• Start 4 weeks after completion of radiotherapy
• Cycle 1: 150 mg/m² days 1-5 of 28-day cycle
• Cycles 2-6: 200 mg/m² days 1-5 if tolerated (no significant myelosuppression)
• Total: 6 cycles (some extend to 12 cycles, limited evidence for benefit)

Evidence base:

Original Stupp trial (2005):

• n=573 newly diagnosed glioblastoma patients
• Randomized to RT alone vs RT + concurrent/adjuvant temozolomide
• Results: Median survival 14.6 months (Stupp) vs 12.1 months (RT alone)
• 2-year survival: 26.5% vs 10.4%
• Hazard ratio for death: 0.63 (pless than 0.001)

5-year follow-up (Lancet Oncol 2009):

• 5-year survival: 9.8% (Stupp) vs 1.9% (RT alone)
• Established this as standard of care globally

Predictive factors for response:

MGMT promoter methylation status (most important predictor):

• Methylated (~45% of GBM): Median survival 21.7 months with Stupp protocol
• Unmethylated (~55% of GBM): Median survival 12.7 months
• MGMT is a DNA repair enzyme; methylation silences it → less repair of temozolomide-induced DNA damage → better chemotherapy response

Other prognostic factors:

• Age: Younger better (> 65 years worse prognosis)

• Performance status: Karnofsky Performance Scale ≥70 required for trial; > 70 better outcomes

• Extent of resection: Gross total resection (> 98%) superior to subtotal

• IDH mutation status: IDH-mutant (rare in primary GBM, ~10%) have better prognosis but by definition most GBM are IDH-wildtype

• Hypofractionated RT (40 Gy/15# or 34 Gy/10#) + temozolomide

• Non-inferior outcomes, better tolerability (Perry et al., NEJM 2017)

Enhancements to Stupp protocol:

• Tumour Treating Fields (Optune): EF-14 trial added TTFields to adjuvant TMZ → median survival 20.9 months vs 16 months (JAMA 2017)

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Q5: A patient with known lung adenocarcinoma develops headache and multiple enhancing brain lesions. Outline your approach to investigation and management.

Model Answer:

Clinical scenario: Brain metastases from lung cancer (lung is the most common source of brain metastases, 50% of cases).

Investigation:

Neuroimaging:

• MRI brain with gadolinium contrast — gold standard
  • Assess number, size, location of metastases
  • Evaluate for oedema, mass effect, herniation risk
  • MRI superior to CT for detecting small metastases (especially posterior fossa)

Assess systemic disease:

• CT chest/abdomen/pelvis or PET-CT — stage extracranial disease
• Review recent oncology imaging/status of primary lung cancer

Molecular testing (if not already done):

• EGFR, ALK, ROS1, PD-L1 — lung adenocarcinoma may have targetable mutations
• CNS-penetrant targeted therapies available (e.g., osimertinib for EGFR+, alectinib for ALK+)

Prognostic assessment:

• Diagnosis-Specific Graded Prognostic Assessment (DS-GPA):
  • Age, KPS, number of brain metastases, extracranial disease status
  • Molecular markers (EGFR/ALK for lung)
  • Predicts survival to guide treatment intensity

Management:

Supportive care (all patients):

• Dexamethasone 8-16 mg/day — reduce oedema, improve symptoms within hours
• Anticonvulsants if seizures (levetiracetam 500-1000mg BD)
• VTE prophylaxis (LMWH) — high risk

Definitive treatment (depends on number and size):

Limited metastases (1-4 lesions, each less than 3-4cm):

• Stereotactic Radiosurgery (SRS) — PREFERRED

  • Gamma Knife or LINAC-based
  • Single-fraction high-dose RT (15-24 Gy depending on size)
  • Local control 70-90% at 1 year
  • Spares cognitive function vs whole brain RT (critical)
  • Can treat up to 10-15 metastases in some centers

• Surgical resection if:

  • Large (> 3cm) causing significant mass effect
  • Symptomatic despite steroids
  • Accessible location (superficial, non-eloquent)
  • Good performance status, controlled systemic disease
  • "Post-op: SRS to resection cavity (reduces recurrence vs WBRT, preserves cognition)"

Multiple metastases (> 4-10 lesions) or diffuse:

• Whole Brain Radiotherapy (WBRT): 30 Gy in 10 fractions
  • Palliative intent
  • "Side effect: Cognitive decline (memory, executive function) — significant quality of life impact"
  • Consider hippocampal-avoidance WBRT (HA-WBRT) to reduce neurocognitive toxicity
• Multiple-lesion SRS: Increasingly used even for > 10 metastases
• Systemic therapy: Prioritize if targetable mutation (EGFR inhibitors, ALK inhibitors, immunotherapy)
  • Some agents have CNS penetration

Systemic therapy:

• Targeted therapy (if driver mutation present):
  • "EGFR-mutant: Osimertinib (excellent CNS penetration)"
  • "ALK-rearranged: Alectinib, brigatinib"
• Immunotherapy: Checkpoint inhibitors (pembrolizumab, nivolumab) — some CNS activity

Prognosis:

• Median survival 6-12 months (highly variable)
• Favorable if: Young, good KPS, limited brain metastases (1-3), controlled extracranial disease, targetable mutations
• Unfavorable: Poor KPS, extensive brain disease, progressive systemic disease

Multidisciplinary approach: Neurosurgery, radiation oncology, medical oncology, palliative care for optimal outcomes.

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Q6: What is the significance of molecular markers in the 2021 WHO Classification of CNS Tumours? How do they impact clinical management?

Model Answer:

The 2021 WHO Classification represents a paradigm shift from histology-based to molecular-integrated diagnosis. Molecular markers are now essential for accurate classification, prognosis, and treatment planning.

Key principle: "Integrated diagnosis" combines histology + molecular features. In cases of discordance, molecular features override histology.

Major molecular markers and clinical impact:

1. IDH1/2 Mutation:

Biology: Mutations in isocitrate dehydrogenase genes (IDH1 R132H most common, IDH2 R172). Produces oncometabolite 2-hydroxyglutarate.

Diagnostic use:

• Defines astrocytoma subtype: "Astrocytoma, IDH-mutant" (WHO Grade 2-4)
• IDH-wildtype diffuse gliomas in adults = Glioblastoma, IDH-wildtype (WHO Grade 4 by definition)

Prognostic impact:

• IDH-mutant: Much better prognosis
  • "Grade 2: 10-15 year median survival"
  • "Grade 3: 3-5 years"
  • "Grade 4: 3-4 years (vs 15 months for IDH-wildtype GBM)"
• IDH mutation is an early event in gliomagenesis; tumours evolve from lower to higher grade

Treatment impact:

• IDH-mutant tumours more chemosensitive
• IDH inhibitors (vorasidenib, ivosidenib) now in clinical trials — potential targeted therapy

2. 1p/19q Codeletion:

Biology: Whole-arm loss of chromosomes 1p and 19q.

Diagnostic use:

• Defines oligodendroglioma: Must have IDH mutation + 1p/19q codeletion
• If IDH-mutant but NO 1p/19q codeletion → Astrocytoma

Prognostic impact:

• Best prognosis among diffuse gliomas
• Grade 2 oligodendroglioma: 15-20 year median survival
• Grade 3 anaplastic oligodendroglioma: 10-15 years

Treatment impact:

• Highly chemosensitive (PCV or temozolomide)
• Radiotherapy + PCV in Grade 3 improves survival (RTOG 9402, EORTC 26951 trials)

3. MGMT Promoter Methylation:

Biology: Epigenetic silencing of O6-methylguanine-DNA methyltransferase (DNA repair enzyme).

Diagnostic use: Not required for diagnosis but prognostic and predictive

Clinical impact in Glioblastoma:

• Predicts temozolomide response
• MGMT methylated (~45%): Median survival 21.7 months with Stupp protocol
• MGMT unmethylated (~55%): Median survival 12.7 months
• Informs treatment decisions: Unmethylated patients may be offered clinical trials; elderly unmethylated may receive RT alone (TMZ less beneficial)

4. CDKN2A/B Homozygous Deletion:

Diagnostic use: In IDH-mutant astrocytomas:

• Presence of CDKN2A/B deletion → automatically WHO Grade 4 (even if histologically low-grade)
• Identifies aggressive tumours masquerading as lower grade

Treatment impact: Requires intensive treatment (chemoradiotherapy) despite benign histology

5. H3 K27M Mutation:

Diagnostic use:

• Defines Diffuse midline glioma, H3 K27-altered
• Location: Thalamus, brainstem, spinal cord (midline structures)

Clinical impact:

• WHO Grade 4 by definition (regardless of histology)
• Very poor prognosis: Median survival less than 12 months
• Mostly pediatric, but can occur in young adults
• Treatment: Radiotherapy (surgery often not feasible due to location); poor response to chemotherapy

6. TERT Promoter Mutation:

Biology: Telomerase reverse transcriptase promoter mutations

Diagnostic use:

• Common in primary (IDH-wildtype) glioblastoma (~70%)
• Also in oligodendroglioma (with 1p/19q)
• In IDH-mutant astrocytoma: poor prognostic marker

7. EGFR Amplification:

Biology: Epidermal growth factor receptor gene amplification

Diagnostic use:

• Common in IDH-wildtype glioblastoma (~40%)
• Marker of aggressive biology

Treatment impact:

• Therapeutic target — EGFR inhibitors (erlotinib, afatinib) in clinical trials
• EGFRvIII variant: target for vaccines, CAR-T therapy (investigational)

Clinical workflow:

Modern neuropathology report includes:

1. Histological diagnosis (cell type, grade)
2. Molecular integrated diagnosis (WHO 2021 classification)
3. Molecular marker panel: IDH, 1p/19q, MGMT, EGFR, TERT, CDKN2A/B, H3 K27
4. Final integrated diagnosis (e.g., "Glioblastoma, IDH-wildtype, WHO Grade 4")

Impact on clinical decision-making:

Summary: Molecular markers are no longer optional — they are essential for accurate diagnosis, prognostication, and treatment selection in neuro-oncology. Every glioma patient requires comprehensive molecular testing.

Common Exam Errors

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High-Yield Clinical Scenarios for Exams

Scenario 1: Glioblastoma vs Brain Abscess

Exam pearl: Diffusion-weighted imaging distinguishes: Abscess shows restricted diffusion (pus is viscous) vs tumour necrosis shows facilitated diffusion.

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Scenario 2: Meningioma vs Glioma

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Scenario 3: Pituitary Adenoma — Bitemporal Hemianopia

Clinical vignette: 45-year-old woman with 6-month history of difficulty driving (bumping into objects on sides), headaches, and amenorrhoea.

Examination: Visual field testing reveals bitemporal hemianopia (loss of temporal visual fields bilaterally).

Anatomical explanation:

• Pituitary tumour grows superiorly from sella turcica
• Compresses optic chiasm from below
• Chiasm contains crossing nasal retinal fibres (which detect temporal visual fields)
• Result: Bitemporal hemianopia ("tunnel vision")

Investigations:

• MRI pituitary with contrast: Pituitary mass extending into suprasellar cistern
• Formal visual field testing (Goldmann or Humphrey)
• Pituitary hormone panel:
  • Prolactin (if very elevated > 200 ng/mL → prolactinoma)
  • GH/IGF-1, ACTH/cortisol, TSH, LH/FSH
  • Check for hypopituitarism

Management:

• Prolactinoma: Medical therapy with dopamine agonist (cabergoline) — 80-90% shrink, visual fields improve
• Non-functioning or other functional adenomas: Trans-sphenoidal surgery (endoscopic approach through sphenoid sinus)
• Urgent surgery if severe visual loss or apoplexy

Exam pearl: Bitemporal hemianopia is pathognomonic for chiasmal compression; pituitary adenoma is most common cause.

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Scenario 4: Posterior Fossa Tumour — Hydrocephalus

Clinical vignette: 35-year-old with 2-week history of morning headaches with vomiting, ataxia, and diplopia.

Examination: Nystagmus, past-pointing on finger-nose testing, broad-based ataxic gait. Papilloedema on fundoscopy.

Imaging: MRI shows cerebellar mass with obstructive hydrocephalus (enlarged lateral and third ventricles, normal fourth ventricle).

Pathophysiology:

• Posterior fossa mass obstructs fourth ventricle or aqueduct of Sylvius
• CSF cannot drain from lateral/third ventricles → obstructive (non-communicating) hydrocephalus
• Raised ICP → headache, vomiting, papilloedema
• Cerebellar signs → ataxia, nystagmus, dysmetria

Emergency management:

1. Dexamethasone 16 mg IV
2. Urgent neurosurgical referral
3. External ventricular drain (EVD) if acutely deteriorating GCS — emergent CSF diversion
4. Definitive: Tumour resection (decompresses fourth ventricle, restores CSF flow)

Differential diagnosis of adult posterior fossa masses:

• Metastases (most common in adults)
• Haemangioblastoma (associated with VHL syndrome)
• Ependymoma
• Medulloblastoma (rare in adults, more pediatric)
• Brainstem glioma

Exam pearl: Posterior fossa tumours present with cerebellar signs + raised ICP. Obstructive hydrocephalus is a neurosurgical emergency.

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Scenario 5: Pseudoprogression vs True Progression Post-Chemoradiotherapy

Clinical vignette: 58-year-old with glioblastoma treated with Stupp protocol. MRI at 3 months post-radiotherapy shows increased enhancement and oedema.

Challenge: Is this tumour progression or pseudoprogression (treatment-related inflammation)?

RANO Criteria (Response Assessment in Neuro-Oncology):

• Do NOT call progression until at least 12 weeks post-RT (unless unequivocal growth outside RT field)
• Consider clinical status alongside imaging

Exam pearl: Increased enhancement in first 3 months post-RT may be pseudoprogression (treatment effect), not true recurrence. Use advanced imaging and clinical correlation.

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Last Reviewed: 2025-01-10 | MedVellum Editorial Team | Topic 903/1071

Citations: 30 peer-reviewed references

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16. Multidisciplinary Management and Prognostic Scoring

Multidisciplinary Team (MDT) Approach

Brain tumour management requires integration of multiple specialties for optimal outcomes. All patients should be discussed at a Neuro-Oncology MDT meeting.

Core MDT Members:

MDT Meeting Discussion Points:

1. Diagnosis: Histology + molecular markers (integrated WHO 2021 classification)
2. Extent of disease: MRI assessment, surgical resectability
3. Treatment plan: Surgery, radiotherapy, chemotherapy sequence
4. Prognosis: Molecular markers, extent of resection, performance status
5. Clinical trial eligibility
6. Supportive care needs: Rehabilitation, palliative care, psychosocial support

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Prognostic Scoring Systems

Karnofsky Performance Status (KPS)

Essential for treatment eligibility and prognosis. Most clinical trials require KPS ≥60-70.

Prognostic relevance:

• KPS ≥70: Standard Stupp protocol, clinical trial eligible
• KPS 50-60: Consider modified therapy (hypofractionated RT, supportive care)
• KPS less than 50: Palliative care focus

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Graded Prognostic Assessment (GPA) for Brain Metastases

Predicts survival in brain metastases based on primary cancer type, age, KPS, number of brain metastases, extracranial disease status, and molecular markers.

Diagnosis-Specific GPA (DS-GPA) — Example: Lung Adenocarcinoma

GPA Score and Median Survival:

• 3.5-4.0: 47 months (favorable, targetable mutations)
• 3.0-3.4: 25 months
• 2.5-2.9: 13 months
• 2.0-2.4: 8 months
• 1.5-1.9: 5 months
• 1.0-1.4: 4 months
• 0-0.9: 3 months (poor prognosis, consider best supportive care)

Clinical use: Guides intensity of local therapy (SRS vs WBRT vs supportive care alone).

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Recursive Partitioning Analysis (RPA) Classes for Glioblastoma

Less commonly used now (molecular markers more important), but historically validated.

Modern prognostication integrates age, KPS, extent of resection, IDH status, MGMT methylation.

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Clinical Trial Opportunities

Brain tumour patients, especially glioblastoma, should be considered for clinical trials at diagnosis and recurrence.

Major Trial Categories:

Where to find trials:

• ClinicalTrials.gov
• National Brain Tumor Society (braintumor.org)
• Institutional neuro-oncology programs

Trial participation benefits:

• Access to novel therapies before general availability
• Close monitoring and expert care
• Contribution to advancing the field

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Quality of Life and Supportive Care

Domains Affecting Quality of Life:

Palliative Care Integration:

Early palliative care (alongside disease-directed therapy) improves quality of life and may improve survival.

Indications for palliative care referral:

• At diagnosis for high-grade gliomas (median survival less than 2 years)
• Progressive disease despite treatment
• Difficult symptom control (pain, nausea, dyspnea)
• Complex psychosocial needs
• Advance care planning discussions

End-of-Life Considerations:

As glioblastoma progresses, focus shifts from disease-directed therapy to comfort and dignity.

Common end-of-life symptoms:

• Drowsiness, declining consciousness (tumour progression, cerebral oedema)
• Seizures (prophylaxis vs treatment debate; continue AEDs if already on)
• Dysphagia (aspiration risk; consider thickened fluids, NGT vs comfort feeding)
• Agitation, delirium (haloperidol, lorazepam, dexamethasone)
• Respiratory secretions ("death rattle" — hyoscine, glycopyrrolate)

Steroid management at end-of-life:

• If patient comfortable on low-dose dexamethasone: Continue (prevents Addisonian crisis)
• If actively dying and unable to swallow: Can omit (death will occur before adrenal crisis)
• If deteriorating on high-dose: Consider compassionate taper vs continuation for symptom control

Preferred place of death: Discuss early; many patients prefer home or hospice over hospital.

Advance directives:

• DNACPR (Do Not Attempt CPR): Appropriate for end-stage brain tumours
• Treatment Escalation Plan (TEP): Document ceiling of care (ICU, intubation, etc.)
• Advance Care Planning: Patient wishes, values, goals of care

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Rehabilitation and Functional Recovery

Post-Operative Rehabilitation Goals:

Driving:

• UK DVLA regulations: Must not drive for 6-12 months post-craniotomy or after seizure
• High-grade glioma: Permanent ban (progressive neurological disease)
• Low-grade glioma: May be able to drive if seizure-free and stable on imaging

Return to work:

• Depends on tumour type, treatment sequelae, cognitive function, job demands
• Many glioblastoma patients unable to return to work (fatigue, cognitive impairment, treatment)
• Low-grade glioma: Many able to return with accommodations

Financial and social support:

• Disability benefits (UK: PIP, ESA)
• Caregiver support (UK: Carer's Allowance, respite care)
• Charitable organizations: The Brain Tumour Charity, brainstrust

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Patient Resources and Support Organizations

UK:

• The Brain Tumour Charity: thebraintumourcharity.org — Information, support, research funding
• brainstrust: brainstrust.org.uk — Individualized support, coaching
• Brain Tumour Research: braintumourresearch.org — Research advocacy

USA:

• National Brain Tumor Society: braintumor.org — Patient navigation, clinical trial matching
• American Brain Tumor Association: abta.org — Educational resources

International:

• International Brain Tumour Alliance (IBTA): theibta.org

Online Communities:

• BrainTrust (brainstrust.org.uk/brainstrust-community)
• Inspire Brain Tumor Community
• Facebook groups (disease-specific)

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.