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Glioblastoma multiforme (GBM WHO grade IV) is the most commonly occurring and most malignant brain tumour, characterised by extensive infiltration of the brain. Although there is no clear explanation as to what causes a GBM, certain genetic predispositions do appear to play a role, and prior exposure of the brain to ionising radiation has been associated with significantly higher rates of occurrence of gliomas. The prognosis of GBM is unfortunately uniformly poor, and treatment is therefore centred primarily on maintenance of quality of life. First diagnosis is not unusually made when the tumour has already reached significant proportions, as it is often the case that patients become symptomatic only then. Without treatment, survival is typically up to three months from the time of diagnosis. With optimal multi-modal treatment the median survival time for the vast majority is about one year. Younger age, gross debulking and better general condition appear to be favourable factors for a longer survival time. A GBM may be primary, when it is arising directly as a Grade IV glioma, or secondary, arising from a Grade II or III glioma. Primary GBM develops more commonly in older patients, while secondary GBM develops more commonly in younger patients. Although the majority of GBM cases are registered from the fourth decade of life onwards, brainstem GBM is a paediatric malignancy, occurring most often in the very young. The time taken for progression from a lower grade glioma to a GBM is variable, ranging from several months to more than a decade, with a mean interval of about 5 years. The current treatment strategy consists of maximum possible reduction of tumour bulk without causing fresh neurological deficit, followed by combined radio-chemotherapy with TMZ over a six weeks period followed by six months of adjuvant chemotherapy with TMZ on a four weekly cycle. Surgical removal of the tumour is never “complete” per se, as even “gross total resection” implies removal of only what can be identified in neuroradiological films and under the microscope, while real tumour borders typically extend beyond visibility — besides, the extent of tumour removal depends on the location and the presence and topographical relevance of “eloquent” areas. Basing on the growth`s speed of GBM treatment should start within 2 to 4 weeks after surgery. Unfortunately the tumor cells still present may re-start growing after some time, and this will require starting another treatment. Careful surveillance with serial MRI or CT scans is a crucial part of medical care, because tumour regrowth requires alteration of current treatment or, for patients in the observation phase, restarting treatment. A regime for combined radio-chemotherapy following surgery is as follows: Radiation:
Chemotherapy:
Recurrences may either be local at the site of first occurrence, or in other areas of the brain. The treatment of recurrences needs to be tailored to the individual case, keeping the patient’s general condition in perspective, because of the possible risk of iatrogenic neurotoxicity. Besides best supportive care if the performance status (PS) is poor, repeated surgery in the case of local GBM or for symptomatic large lesions can be an option as well as systemic chemotherapy with Bevacizumab (this drug has been approved by the FDA in USA but is not registered in UK) +/- chemotherapy (CPT-11,BCNU, TMZ); PCV, TMZ, Nitrosourea, platinum based regimens and Cyclophosphamide. It is also possible to consider re-irradiation in selected cases with:
last changed 27/05/2011. |
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