See related separate articles Brain Tumours in Children and Brain Tumours in Adults.

Gliomas are tumours arising from glial cells and may occur in the spinal cord or the brain, the latter being more common. Gliomas are the most common type of brain tumour and can be either supratentorial or infratentorial. There are four main types of glioma:

• Ependymomas (ependymal cells).
• Astrocytomas (astrocytes), of which glioblastoma multiforme is the most common.
• Oligodendrogliomas (oligodendrocytes).
• Mixed gliomas, e.g. oligoastrocytomas.

Gliomas are graded according to their likely rate of growth (grade 1 is the slowest growing and grade 4 is the fastest growing). Grades 1 and 2 are considered low-grade, are well-differentiated and usually associated with a better outcome. Grade 3 and 4 gliomas are considered high-grade gliomas, are undifferentiated or anaplastic and have a worse prognosis.

Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumour. It involves glial cells and has small areas of necrotising tissue surrounded by anaplastic cells. There are also hyperplastic blood vessels.

Astrocytomas have been graded in several different ways, but the most commonly accepted method is now the World Health Organization (WHO) classification system:

• Grade 1 - typically low-grade, e.g. pilocytic astrocytoma.
• Grade 2 - diffusely infiltrating, but low-grade.
• Grade 3 - includes anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma.
• Grade 4 - usually GBM which has endothelial cell proliferation and/or tumour necrosis.

Epidemiology¹

• Neuroglial tumours account for 80% of primary brain tumours.
• Glioblastoma multiforme (GBM) is the most common glioma to occur in adults, being diagnosed at an average age of 55 years.
• Low-grade astrocytomas tend to be seen in younger adults aged 20-30 and anaplastic astrocytomas and oligodendrogliomas typically present in the mid-forties.

Presentation

Brain tumours present as a space-occupying lesion. Symptoms of high-grade glioma depend on the size, location and degree of infiltration of the tumour. The following are some features that might be seen:

• Headache - typically worse on waking.
• Nausea and vomiting.
• Seizures - especially low-grade astrocytomas.
• Visual disturbance.
• Speech and language problems.
• Changes in cognitive and/or functional ability.
• Acute intracranial haemorrhage, which may rarely occur in association with glioblastoma multiforme.

Investigations

• Involves brain imaging, e.g. CT scan and/or MRI scan with or without contrast. Glioblastoma multiforme (GBM) typically has ring enhancement.
• Tissue specimens for pathology are usually required (if they are possible to obtain), as there is a large variety of tumours that may occur.²
• Tissue may also be examined for chromosomal analysis.

Management

• Treatment usually consists of surgical resection where possible, followed by radiotherapy. Radiotherapy has been shown to prolong survival.³
• Radiotherapy may be external or internal beam radiation. External beam is the most common and may be delivered as standard external beam or stereotactic.
• Adjuvant chemotherapy may be used but is not considered part of standard therapy in the UK.
• The most frequently used regimens are a combination of procarbazine, lomustine (CCNU®) and vincristine (PCV therapy), or single-agent treatment with carmustine or lomustine.³
• Photodynamic therapy involves targeting lesions with a laser after rendering them light-sensitive. It is currently being evaluated by the National Institute for Health and Clinical Excellence (NICE) but evidence of efficacy and safety is currently limited.^4,5

Treatment of specific tumours

Grades 1 and 2 tumours:

• This includes pilocytic astrocytomas, pleomorphic xanthoastrocytomas and subependymomas.
• They can be cured by complete resection.
• Incompletely resected tumours may not cause any problems or can be treated further with radiotherapy.
• If these measures fail then, rarely, chemotherapy may help.

• Maximum possible surgical debulking.
• Radiotherapy is used as standard treatment.
• Adjuvant chemotherapy has been used in trials but its role needs to be clearly established, e.g. bevacizumab and irinotecan.⁶
• However, recurrence after radiotherapy should be treated with chemotherapy. NICE recommends that patients with recurrent malignant glioma who have failed first-line chemotherapy treatment with other agents may be considered for treatment with temozolomide.⁷
• NICE advises carmustine implants in patients with newly diagnosed high-grade glioma if 90% or more of the tumour has been removed.³

• Surgery is the mainstay of therapy, but the tumour is usually infiltrative and therefore complete resection is difficult.
• Radiotherapy improves survival rates.
• Temozolomide is recommended by NICE as an option for the treatment of newly diagnosed GBM.³
• Concomitant and adjuvant chemotherapy with temozolomide given during and after radiotherapy improves survival.⁸
• Recurrence can be treated with a second resection if possible and/or further chemotherapy with temozolomide.

• Surgical resection and radiotherapy are the mainstays of treatment.⁹
• Chromosomal analysis has revealed that oligodendrogliomas with loss of 1p19q respond well to chemotherapy and radiotherapy.¹

Prognosis

• Gliomas are associated with a poor prognosis, especially high-grade tumours in older patients. Survival rates of approximately 30% at one year and 14% at two years have been reported.¹⁰
• Patients with high-grade gliomas have a better prognosis if they are younger, have a better performance status, have a grade 3 tumour or if complete resection is achieved.³
• The median survival of patients with anaplastic astrocytoma is 2-3 years, and that of patients with glioblastoma multiforme (GBM) is approximately 1 year.³
• Low-grade astrocytomas can rarely recur and thus patients must be followed up for at least 15 years.

Document references

1. Chandana SR, Movva S, Arora M, et al; Primary brain tumors in adults. Am Fam Physician. 2008 May 15;77(10):1423-30. [abstract]
2. Laigle-Donadey F, Doz F, Delattre JY; Brainstem gliomas in children and adults. Curr Opin Oncol. 2008 Nov;20(6):662-7. [abstract]
3. Glioma (newly diagnosed and high grade) - carmustine implants and temozolomide, NICE Technology Appraisal (2007)
4. Photodynamic therapy for brain tumours, NICE Interventional Procedure Guideline (March 2009)
5. Nieder C, Adam M, Molls M, et al; Therapeutic options for recurrent high-grade glioma in adult patients: recent advances. Crit Rev Oncol Hematol. 2006 Dec;60(3):181-93. Epub 2006 Jul 27. [abstract]
6. Desjardins A, Reardon DA, Herndon JE 2nd, et al; Bevacizumab Plus Irinotecan in Recurrent WHO Grade 3 Malignant Gliomas. Clin Cancer Res. 2008 Nov 1;14(21):7068-73. [abstract]
7. Brain cancer - temozolomide, NICE (2001); ref TA23
8. Short SC; Survival from brain tumours in England and Wales up to 2001. Br J Cancer. 2008 Sep 23;99 Suppl 1:S102-3.
9. Hartmann C, von Deimling A; Oligodendrogliomas: impact of molecular genetics on treatment. Neurol India. 2005 Jun;53(2):140-8. [abstract]
10. Rachet B, Mitry E, Quinn MJ, et al; Survival from brain tumours in England and Wales up to 2001. Br J Cancer. 2008 Sep 23;99 Suppl 1:S98-101.

Acknowledgements