Brain Tumours

Background/Epidemiology

  • Varying group of neoplasms (some highly malignant and others benign)
  • Account for 1.6% of all tumours in the UK (incidence ~7/100,000; slightly more common in men)
  • Remember that the most common brain tumour will be metastatic disease.  The most common primary brain tumour is astrocytoma and most common benign tumour is a meningioma.
    • Brain tumours rarely metastasise but many are highly aggressive

Grading Astrocytomas

  • It is crucial to grade these tumours as the prognosis and treatment options (if any) will depend on this.
    • Grade I Pilocytic astrocytoma- 95% survival at 5 years
    • Grade II Diffuse Astrocytoma- median survival from diagnosis 7-8 years
    • Grade III Anaplastic Astrocytoma- median survival from diagnosis 2-3 years
    • Grade IV Glioblastoma- median survival from diagnosis 10 months

Pathophysiology

  • Primary glioblastoma; grade IV tumour that’s usually de-novo.  Rapidly progressive disease and patients generally have symptoms before presenting for ❤ months, have a diagnosis in 5 months and die in under a year.  They are usually found in older patients (>65).
    • EGFR overexpressed in 60% (gene amplification)
  • Secondary glioblastoma is a progressive tumour that begins as a lower grade tumour and has a much longer progression (Grade II – IV takes around 5 years; grade III – IV around 2 years).  Usually found in younger patients (<50) and has a better prognosis only if caught early (Grade IV secondary GBM still only has a survival of 7-8 months).
  • Genetics
    • EGFR gene (endothelial growth factor receptor)
      • almost always gene amplification due to a microdeletion resulting in a constituently active EGF receptor (variant III EGFR mutation).
    • PTEN gene (phosphatase and tensin homolog)
      • Located on 10q23, PTEN codes for a lipid and protein phosphatase.  If this is mutated, it can be associated with a number of human cancers (including 10-40% of all GBM).
    • p53
      • Associated with many cancers, a p53 mutation is commonly associated with secondary GBM, including its precursors (occasionally primary also).
    • Others
      • Other common gene mutations include
        • INK4a deletion on p16
      • reduced expression of RB1 protein (also associated with retinoblastoma)
      • MDM2 mutations (role of stabilising p53)
      • loss of p14 expression (p14 auxin response factor inhibits MDM2 and thus promotes p53)
      • TSC1/2 (tuberous sclerosis- condition causing tumours of the skin and nervous system)

Presentation

  • High grade disease usually presents with a short history (4-6 weeks) of symptoms due to raised intracranial pressure/mass effect
    • headache worse on lying/straining; nausea/vomiting
  • Low-grade/slower growing tumour can present with focal neurological defects
  • Seizures (generalised or focal) are common
  • NB An isolated, stable headache without any focal neurology is unlikely to be caused by a brain tumour

Investigations

  • Imaging
    • CT/MRI
      • Enhancing tumours are usually more aggressive
      • Often difficult to differentiate between tumour types
  • Biopsy and pathology

Management

  • Management is heavily dependent on age (important predictor of survival)
    • The decision for palliative care is often more appropriate
  • Surgery is the predominant treatment for the majority of patients
    • Resection if possibly, debulking if not
  • Chemotherapy and Radiotherapy also are commonly used in combination with surgery
  • Dexamethasone is often used to reduce cerebral oedema

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