Malignant gliomas

Gliomas are a heterogeneous group of neoplasms that comprise the majority of tumors originating in the central nervous system (CNS). In adults, the most frequently encountered of these are high-grade or malignant neoplasms of astrocytic and oligodendrocytic lineage, ie, anaplastic astrocytoma (AA), glioblastoma multiforme (GBM), and anaplastic oligodendroglioma (AO), respectively. Tumors of mixed lineage are also seen, the most common of which is designated anaplastic oligoastrocytoma (AOA). Standard treatment for these tumors is typically surgery, followed by radiation then chemotherapy. Surgery is required for a definitive histopathologic diagnosis, which in turn will dictate subsequent therapy options. Moreover, aggressive tumor resection improves survival outcomes, and in many cases, the patient's neurologic function. We generally advocate the safest, maximal resection attainable for patients with these tumors as a way to improve prognosis. In almost all cases, surgery is followed by radiation therapy. Postsurgical irradiation is the most effective treatment currently available for improving survival. There is also mounting evidence to suggest that additional radiation, given in the form of brachytherapy or radiosurgery, at initial diagnosis as a "boost" to standard radiation or at tumor recurrence, may provide added improvement in survival outcome. Radiosurgery and brachytherapy are therapies often used to treat eligible patients at this institution. Adjuvant chemotherapy, conventionally given after radiation, may offer a modest survival benefit in some patients with GBM. Bischloroethylnitrosourea (BCNU) is the typical first-line agent used, but chemotherapy seems to be most beneficial in young patients, with little if any impact on survival for patients over 60 years old. At this institution, we often defer treatment with adjuvant chemotherapy for elderly patients with GBM due to lack of efficacy and the attendant risk with chemotherapy. For anaplastic astrocytomas, oligodendrogliomas, and oligoastrocytomas, a commonly accepted standard is adjuvant chemotherapy following irradiation with the three-drug regimen--procarbazine, CCNU, and vincristine (PCV). This is due to an earlier clinical trial that showed a survival advantage in patients treated with adjuvant PCV compared with patients that received BCNU. However, recent data suggest that treatment with either PCV or BCNU may be appropriate. Both regimens now appear to have equal efficacy for anaplastic gliomas in light of a more recent analysis done with larger numbers of patients. AOs are a unique case with respect to tumor chemosensitivity and patient survival. Molecular studies have identified a subpopulation of patients with AO whose tumors have lost chromosomes 1p and 19q. Patients with this molecular pattern have an exceptional responsiveness to PCV chemotherapy and have prolonged survival. Currently, trials are being conducted to confirm this finding and to determine the best treatment regimen for these patients, with particular regard to the timing of radiation and chemotherapy.