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 (GBM) is the most common.
- Oligodendrogliomas (oligodendrocytes).
- Mixed gliomas - eg, 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.
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 - eg, 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.
- The annual incidence of malignant glioma is 3-5/100,000.
- Exposure to ionising irradiation has been associated with increased risk of development of glioma.
- Certain hereditary syndromes carry an increased risk for glioma, including neurofibromatosis type 1.
- 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.
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 GBM.
- Involves brain imaging - eg, CT scan and/or MRI scan with or without contrast. 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.
- Tissue may also be examined for chromosomal analysis.
- Primary treatment involves surgery to achieve tumour debulking, followed by a multimodal regimen of radiotherapy and chemotherapy.[4, 5]
- Intraoperative MRI can be used to increase the extent of resection of low-grade gliomas.
- Chemotherapy can be added to radiotherapy for patients with unfavorable low-grade glioma to improve progression free survival.
- The most frequently used chemotherapy regimens are a combination of procarbazine, lomustine (CCNU®) and vincristine (PCV therapy), or single-agent treatment with carmustine or lomustine.
- 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 Care Excellence (NICE) but evidence of efficacy and safety is currently limited.[9, 10]
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.
Grade 3 tumours
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, eg, bevacizumab and irinotecan.
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.
NICE also recommends carmustine implants as an option for the treatment of newly diagnosed high-grade (Grade 3 or 4) glioma; however, only for patients in whom at least 90% of the tumour has been resected.
Glioblastoma multiforme (GBM)
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.
- Concomitant and adjuvant chemotherapy with temozolomide given during and after radiotherapy improves survival.
- 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.
- Chromosomal analysis has revealed that oligodendrogliomas with loss of 1p19q respond well to chemotherapy and radiotherapy.
- Cerebral oedema and raised intracranial pressure.
- Thromboembolic events (tumour-induced hypercoagulable state as well as a consequence of neurological deficits, immobilisation and steroid treatment).
- 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.
- 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.
- The median survival of patients with anaplastic astrocytoma is two to three years, and that of patients with GBM approximately one year.
- Low-grade astrocytomas can rarely recur and therefore long-term follow-up is required.
Further reading and references
High-grade gliomas: ESMO Clinical Practice Guidelines for diagnosis treatment and follow up; European Society of Medical Oncology (2014)
Chandana SR, Movva S, Arora M, et al; Primary brain tumors in adults. Am Fam Physician. 2008 May 1577(10):1423-30.
Laigle-Donadey F, Doz F, Delattre JY; Brainstem gliomas in children and adults. Curr Opin Oncol. 2008 Nov20(6):662-7.
Eyupoglu IY, Buchfelder M, Savaskan NE; Surgical resection of malignant gliomas-role in optimizing patient outcome. Nat Rev Neurol. 2013 Mar9(3):141-51. doi: 10.1038/nrneurol.2012.279. Epub 2013 Jan 29.
Ryken TC, Parney I, Buatti J, et al; The role of radiotherapy in the management of patients with diffuse low grade glioma : A systematic review and evidence-based clinical practice guideline. J Neurooncol. 2015 Dec125(3):551-83. doi: 10.1007/s11060-015-1948-1. Epub 2015 Nov 3.
Aghi MK, Nahed BV, Sloan AE, et al; The role of surgery in the management of patients with diffuse low grade glioma : A systematic review and evidence-based clinical practice guideline. J Neurooncol. 2015 Dec125(3):503-30. doi: 10.1007/s11060-015-1867-1. Epub 2015 Nov 3.
Ziu M, Kalkanis SN, Gilbert M, et al; The role of initial chemotherapy for the treatment of adults with diffuse low grade glioma : A systematic review and evidence-based clinical practice guideline. J Neurooncol. 2015 Dec125(3):585-607. doi: 10.1007/s11060-015-1931-x. Epub 2015 Nov 3.
Glioma (newly diagnosed and high grade) - carmustine implants and temozolomide; NICE Technology Appraisal Guidance, June 2007
Photodynamic therapy for brain tumours; NICE Interventional Procedure Guidance, March 2009
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 Dec60(3):181-93. Epub 2006 Jul 27.
Desjardins A, Reardon DA, Herndon JE 2nd, et al; Bevacizumab Plus Irinotecan in Recurrent WHO Grade 3 Malignant Gliomas. Clin Cancer Res. 2008 Nov 114(21):7068-73.
Guidance on the use of temozolomide for the treatment of recurrent malignant glioma (brain cancer); NICE Technology Appraisal Guidance, April 2001
Short SC; Survival from brain tumours in England and Wales up to 2001. Br J Cancer. 2008 Sep 2399 Suppl 1:S102-3.
Hartmann C, von Deimling A; Oligodendrogliomas: impact of molecular genetics on treatment. Neurol India. 2005 Jun53(2):140-8.
Rachet B, Mitry E, Quinn MJ, et al; Survival from brain tumours in England and Wales up to 2001. Br J Cancer. 2008 Sep 2399 Suppl 1:S98-101.