Anaplastic astrocytomas: biology and treatment

Abstract

Anaplastic astrocytomas (AA), WHO grade III gliomas, comprise 10–15% of all glial neoplasms. Currently, the only factors that have been shown to influence prognosis in patients with AA are age and Karnofsky performance status. Attempts have been made to identify biological prognostic factors for response to therapy and clinical outcome, as well as potential targets for new therapies. The most important predictor of response to therapy and survival in AA tumors is the presence or absence of the 1p19q co-deletion, a translocation that defines a subset of oligodendroglial tumors, and anaplastic oligodendrogliomas in particular. A further likely prognostic biomarker is the methylation status of O6-methylguanine-DNA-methyltranferase gene (the predominant DNA repair enzyme following alkylator-based chemotherapy-induced injury). Owing to a paucity of clinical trials specifically in patients with AA, most patients receive temozolomide-containing regimens, based on data acquired from patients with glioblastoma multiforme. At present, there are no cooperative group trials being conducted for the adjuvant treatment of AA, although several randomized trials have been proposed. Evidence-based management of patients with AA supports maximum safe resection followed by involved-field radiotherapy for newly diagnosed patients, and temozolomide for recurrent disease. This treatment paradigm varies considerably from actual practice.