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Internal Medicine

Glioblastoma

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

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

Aetiology

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

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

Diagnosis

Imaging

Histopathology

OLYMPUS DIGITAL CAMERA
Histopathological image of cerebral glioblastoma. H&E stain. | CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=516831

Management

Symptomatic therapy

 

  • Anticonvulsants:
  • 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

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