Carmustine implants and temozolomide for the treatment of newly diagnosed high-grade glioma

Gliomas are the most common type of brain tumour. They develop from the glial cells that support the nerve cells of the brain and spinal cord. There are 4 main types: astrocytoma, ependymoma, oligodendroglioma and mixed tumours. Gliomas are graded according to their likely rate of growth, from grade 1 (slowest growing) to grade 4 (fastest growing). Grade 3 and 4 gliomas are considered high-grade gliomas. Grade 3 gliomas include anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma. Grade 4 gliomas are usually GBM.

Brain tumours account for fewer than 2% of all primary cancers. Approximately 1,860 new cases of malignant glioma are diagnosed in England and Wales each year. High-grade gliomas are more common in men than women, and the incidence increases with age. People diagnosed with GBM are on average older than people diagnosed with grade 3 gliomas.

Symptoms of high-grade glioma depend on the size, location and degree of infiltration of the tumour. They include headache, nausea, vomiting, seizures, visual disturbance, speech and language problems, and changes in cognitive and/or functional ability. Functional ability of patients can be categorised using scales of performance status, such as the WHO performance status classification (see appendix A for details).

Approximately 30% of adults with high-grade gliomas survive for at least 1 year, and 13% survive for 5 years. The median survival of patients with anaplastic astrocytoma is around 2 to 3 years, and that of patients with GBM is approximately 1 year. Age, performance status and tumour histology are indicators of pretreatment prognosis. Patients with high-grade gliomas have a better prognosis if they are younger, have a better performance status, or have a grade 3 tumour.

Diagnosis of high-grade glioma is provisionally made through a CT scan or MRI. The diagnosis is then confirmed and the tumour classified histologically, either at the time of surgical resection or by a single-event biopsy if surgery is not possible. There is a growing understanding of the molecular genetics of gliomas, which is allowing a more accurate classification of glioma and may give an indication of prognosis and likely response to treatment.

In the UK, treatment usually consists of surgical resection where possible, followed by radiotherapy. Surgery may achieve either complete resection or partial resection of the tumour. Radiotherapy has been demonstrated to prolong survival and is usually recommended after surgery. Adjuvant chemotherapy is not considered part of standard therapy in the UK, but is used more routinely in the USA. The most frequently used regimens are a combination of procarbazine, lomustine and vincristine (PCV therapy), or single-agent treatment with carmustine or lomustine.