Gliomas

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Gliomas arise from the supporting cells of the brain tissue. Most are known as astrocytomas, but other types include oligodendroglioma and ependymoma.

Astrocytomas are primary brain tumours arising from cells known as astrocytes. They are classified into 4 grades:

1. Grade 1 is benign, and is also known as pilocytic astrocytoma.
2. Grade 2 (‘low-grade gliomas’), are not very aggressive, however may become aggressive with time.
3. Grade 3 astrocytomas (‘anaplastic astrocytomas’) are more aggressive than low-grade gliomas.
4. The most aggressive astrocytomas are Grade 4 (‘glioblastoma multiforme’).

Astrocytomas may be treated with surgery, radiotherapy, and/or chemotherapy.

Glioblastoma Multiforme (GBM)
Glioblastoma multiforme (also known as GBM) are the most aggressive type of astrocytomas. They grow rapidly rapidly, and often spread deep into the surrounding brain tissue. In some cases they develop from a low-grade astrocytoma or an oligodendroglioma.

GBMs are very difficult to treat effectively due to a number of factors 1) They spread extensively throughout the brain; 2) They are relatively resistant to conventional treatments such as radiotherapy and chemotherapy; 3) The limited ability of the brain to repair itself, meaning that extremely aggressive surgery may have devastating neurological consequences.

In adults, GBM occurs most often in men, and tends to affect people most commonly between the age of 50 and 70. The cerebral hemispheres are the most frequent site of involvement, especially the frontal and temporal lobes.

Symptoms vary according to the size and location of the tumour, and depending on the location of the brain tumor, but may include any of the following:

• Headaches
• Nausea and/or vomiting
• Personality and/or mood changes
• Seizures
• Memory problems
• Speech impairment
• Weakness
• Unsteadiness

Making a diagnosis requires sophisticated brain scans, including magnetic resonance imaging (MRI), and often magnetic resonance spectroscopy (MRS). Making a firm diagnosis requires a biopsy, and this can be done as an independent operation (stereotactic biopsy) or as part of the removal of the brain tumor (craniotomy).

The treatment of GBM varies according to the location of the tumor, as well as the “functional status” (or disability) of the patient. Other factors are also considered. Palliative (supportive) care, with no active intervention, may be offered to very disabled patients. Active treatment options include surgery, radiotherapy, and chemotherapy.

The primary goal of surgery is to remove as much of tumour as possible without causing damage to eloquent brain tissue (parts of the brain needed for important functions such as speech, walking, movement, and memory. Unfortunately, GBMs are surrounded by a zone tumour cells which invade surrounding brain, and make it impossible to remove every single tumor cell. Nevertheless, surgery is frequently able to reduce the amount of solid tumor tissue, leaving a less formidable amount of tumour which can be treated with radiotherapy and chemotherapy. Surgery also has the advantage of reducing intracranial pressure. Surgery frequently prolongs life, and results an improvement in the quality of life remaining.

Once the wound is healed (typically a couple of weeks after surgery), radiotherapy can commence. The aim of radiotherapy is to destroy tumor cells whilst leaving normal brain tissue relatively unharmed. Multiple sessions of standard-dose "fractions" of radiation are delivered to the tumor site as well as a margin in order to treat the zone of infiltrating tumor cells. This process is repeated for a total of 10 to 30 treatments (over 2 to 6 weeks), and provides most patients with better outcomes compared to surgery alone.

Chemotherapy with the oral drug temozolomide is the current standard of treatment for GBM in most countries. Temozolomide, an oral alkylating agent, is swallowed every day during radiotherapy, and then in 6-8 cycles for 5 days at higher doses once radiation is completed. The addition of temozolomide to radiotherapy is thought to increase median survival by around 2 months, and to more than double the number of patients whoc survive for 2 years or longer.

Stupp et al., N Engl J Med 2005; 352:987-996