Glioblastoma

Glioblastoma, previously known as glioblastoma multiforme (GBM), is an aggressive and common type of brain cancer with a very poor prognosis. It typically arises in the brain's astrocytes and represents 15% of all brain tumours.

Despite maximum treatment efforts, the median survival rate is approximately 15 months, with a five-year survival rate of less than 10%.

Signs and Symptoms

Initial signs and symptoms of glioblastoma are nonspecific and may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Common symptoms include seizures, headaches, nausea and vomiting, memory loss, changes to personality, mood or concentration, and localised neurological problems. The symptoms depend more on the tumour location than its pathological properties, and the tumour can sometimes remain asymptomatic until it reaches a significant size.

Risk Factors

The cause of most glioblastoma cases is unclear. Known risk factors include exposure to ionising radiation and certain genetic disorders such as neurofibromatosis and Li–Fraumeni syndrome. Environmental factors like exposure to smoking, pesticides, and working in petroleum refining or rubber manufacturing have also been associated. Viruses such as SV40, HHV-6, and cytomegalovirus may play a role in the development of glioblastoma.

Pathogenesis

Glioblastomas usually form in the cerebral white matter, grow quickly, and can become very large before producing symptoms. They may extend into the meninges or ventricular wall, and malignant cells carried in the cerebrospinal fluid (CSF) could rarely spread to the spinal cord. About 50% of glioblastomas occupy more than one lobe of a hemisphere or are bilateral.

Diagnosis

Diagnosis typically involves a combination of CT and MRI scans, followed by a tissue biopsy. Glioblastomas often appear as ring-enhancing lesions on MRI, but this is not specific. Definitive diagnosis requires a stereotactic biopsy or craniotomy with tumour resection and pathologic confirmation.

Histopathology helps distinguish glioblastoma from high-grade astrocytomas, often relying on molecular markers like IDH1 and IDH2 mutations, as these are not present in glioblastomas.

Treatment

Treatment of glioblastoma is challenging due to the tumour's resistance to conventional therapies and the brain's susceptibility to damage. Standard treatment involves surgery, radiation, and chemotherapy.

Surgery

Surgery is the first line of treatment aimed at pathological diagnosis, symptom alleviation, and tumour removal. Complete resection is rarely possible due to the infiltrative nature of glioblastoma.

Radiotherapy

Radiotherapy is a mainstay post-surgery, typically administered with temozolomide. Standard doses range between 60-65 Gy, aimed at maximising tumour control while minimising damage to healthy tissue.

Chemotherapy

Temozolomide is the most common chemotherapeutic agent used, often combined with radiation to improve survival. Treatment efficacy is higher in tumours with MGMT promoter methylation.

Other Treatments

Alternating electric field therapy has shown some promise, with initial trials indicating improved survival. However, its efficacy remains debated. Immunotherapy and oncolytic virotherapy are under investigation but have not yet shown significant success in clinical trials.

Prognosis

Prognosis remains poor, with a median survival of 10-13 months post-diagnosis. Factors such as age, Karnofsky performance score (KPS), and MGMT methylation status influence survival outcomes.

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Self-assessment MCQs (single best answer)

What percentage of all brain tumours does glioblastoma represent?

Which of the following is NOT a common symptom of glioblastoma?

Which genetic disorder is known to be a risk factor for glioblastoma?

What is the median survival rate for glioblastoma patients following maximum treatment efforts?

In which part of the brain do glioblastomas typically form?

What imaging technique is commonly used to diagnose glioblastoma?

Which chemotherapeutic agent is most commonly used in the treatment of glioblastoma?

What is the primary goal of surgery in glioblastoma treatment?

What is the typical dose range for radiotherapy in glioblastoma treatment?

Which factor does NOT influence the survival outcome for glioblastoma patients?