Cover image: Sen. John McCain, seen here in early December, underwent brain surgery in July, after which a biopsy showed he had glioblastoma. He recently was hospitalized due to side effects from chemotherapy and radiation treatments. | Justin Gilliland/New York Times

Introduction

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive cancer that begins within the brain

• M/C glial tumour

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Classification

4 molecular subtypes:

• Classical subtype:
  • Epidermal growth factor receptor (EGFR) gene
    • Extra copies of the gene (97%)
    • Higher expression
  • TP53 (p53)
    • Rarely mutated in this subtype, but often mutated in glioblastoma
  • Loss of heterozygosity (LOH) in chromosome 10 is also frequently seen in the classical subtype alongside chromosome 7 amplification
• Proneural subtype:
  • High rates of alterations in:
    • TP53 (p53)
    • PDGFRA
      • Gene encoding a-type platelet-derived growth factor receptor
    • IDH1
      • Gene encoding isocitrate dehydrogenase-1
• Mesenchymal subtype:
  • High rates of mutations or other alterations inNF1, the gene encoding Neurofibromin 1
  • EGFR
    • Fewer alterations in the gene and less expression than other types
• Neural subtype:
  • Expression of neuron markers:
    • NEFL, GABRA1, SYT1 and SLC12A5

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Aetiology

• Genetic disorders:
  • Neurofibromatosis
  • Li–Fraumeni syndrome
• Previous radiation therapy

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Clinical features

Depends more on the location of the tumor than on its pathological properties

• Initially non-specific:
  • Headaches
  • Personality changes
  • Nausea
• Symptoms similar to stroke

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Diagnosis

Imaging

Histopathology

Management

Symptomatic therapy

 

• Anticonvulsants:
  • Phenytoin concurrent with radiation
• Corticosteroids:
  • Dexamethasone (4-8 mg 4-6 hourly)
    • Reduces peritumoral edema (through rearrangement of the blood–brain barrier)
    • Diminishes mass effect
    • Lowers intracranial pressure, with a decrease in headache or drowsiness.

Palliative therapy

Surgery

• First stage of treatment of glioblastoma
• Advantages:
  • Resection for a pathological diagnosis
  • Alleviation of symptoms related to mass effect
  • Potentially removing disease before secondary resistance to radiotherapy and chemotherapy occurs
• Near-complete initial removal
  • Guided by 5-aminolevulinic acid (fluorescent dye)
• High recurrence rate
  • Controlled by other modalities

Chemoradiotherapy

• Radiation + Temozolomide (TMZ)
  • Subsequent to surgery, radiotherapy becomes the mainstay of treatment for people with glioblastoma

Other drugs:

• Oxygen diffusion-enhancing compound:
  • Trans-sodium crocetinate (TSC) as radiosensitizers
• Boron neutron capture therapy
  • Alternative treatment for glioblastoma multiforme but is not in common use
• Antiangiogenic therapy:
  • Bevacizumab
    • Control symptoms but do not affect overall survival

Other modalities:

• Alternating electric field therapy + temozolomide 
  • For newly diagnosed and recurrent glioblastoma