2 Clinical Need and Practice

2 Clinical Need and Practice

2.1 Although brain tumours account for only 1.5% of all primary cancers and 2% of cancer deaths, they result in 7% of life‑years lost before the age of 70. About 55% of primary brain cancers occur in males. Approximately 29% of adult patients survive one year after diagnosis and 13% survive 5 years.

2.2 Malignant glioma is the most common form of primary brain tumour. The incidence in England and Wales is 4 per 100,000 population. There are about 3,500 new cases in the UK each year. They represent 50% to 60% of all primary brain tumours, and about 0.8% of all malignant neoplasms in adults in England and Wales.

2.3 Anaplastic, or grade III, astrocytomas (AA) comprise some 30–35% of malignant gliomas, glioblastoma multiforme (GBM), also known as grade IV astrocytomas, 40–45% and anaplastic, or grade III, oligodendrogliomas (AO) 5–15%. The average age of people with GBM is 10 years greater than that of people with AA. Median survival time from diagnosis for GBM is of the order of 5 to 12 months, but for AA is longer at 11 to 36 months. The WHO grading system for gliomas ranges from I (benign) to IV (malignant and aggressive) and is detailed in appendix E.

2.4 People with malignant glioma can suffer from a range of symptoms and impairments. Some symptoms may be general and others may be specific to the area of brain where the tumour is located. General symptoms include headache, anorexia, nausea, vomiting, seizures, drowsiness, personality changes, and cognitive slowing. More focal (specific) symptoms could include difficulties with hearing, speech, ambulation, dexterity, visual difficulties, and mood disturbances. These symptoms can have a profound effect on the quality of life of the patient as well as their ability to work and to care for themselves. A significant physical and emotional burden is often placed on carers, particularly as the disease progresses.

2.5 Treatment of malignant glioma varies from country to country. In the UK, about 30% of patients receive only supportive care with steroids, with or without anticonvulsants.

2.6 More intensive treatment is offered to patients with less severe disability, measured on the Karnofsky scale (Karnofsky performance status > 60): see appendix D for details. The tumour is removed as far as possible, but can usually not be fully excised because of the infiltrative nature of these tumours. The remaining tumour tissue undergoes radical radiotherapy. The whole procedure adds some 4 to 5 months to median survival. In the USA, chemotherapy is routinely given 6 weeks after radiation (adjuvant chemotherapy), but this is not the practice in the UK or Europe.

2.7 The great majority (at least 70%) of malignant gliomas recur locally after initial treatment, usually with very disabling neurological deficit and poor and rapidly deteriorating quality of life. Options for further treatment at this stage are limited and palliative. In the UK and Europe, clinical or imaging evidence of tumour progression after radiation therapy is employed as indication for first line chemotherapy.

2.8 For a patient whose tumour recurs or progresses following surgery/radiotherapy, the chemotherapy treatment options are limited because the currently available agents have only a small chance of being effective. Although high dose oral procarbazine is used as a single agent in the USA, it is not usual in the UK except in combination with lomustine and vincristine (PCV) regimen. This currently constitutes standard first line chemotherapy. Lomustine alone is sometimes used as first line therapy. The likelihood of response depends on age, tumour type and Karnofsky performance status (see appendix D). In general anaplastic astrocytoma (AA) is more responsive to chemotherapy than glioblastoma multiforme (GBM).

2.9 Current UK practice is to give first line chemotherapy to less than one third of patients whose tumour recurs after initial treatment, or about 15% of all diagnosed cases of brain tumour. This represents about 500 to 600 new cases per year.

2.10 Chemotherapy is given in cycles. PCV is given for 28 consecutive days in 56‑day cycles, or for 21 consecutive days in 42‑day cycles, usually for a maximum of 6 cycles. Therapy is usually stopped after 2 cycles in those who do not respond (based on both clinical and radiological monitoring) and in those who experience significant toxicity. Usual outcome measures include clinical response, imaging parameters, side effect profile, progression free survival, overall survival and quality of life.

2.11 A meta‑analysis of 10 randomised controlled trials (RCTs) of chemotherapy for glioma shows that mean survival time increases by 2 months (Confidence Interval 1 to 3 months) and that there are a number of other similarly small but significant improvements on other outcomes after chemotherapy.