Oligodendroglioma

Abstract

Surgery, radiotherapy, and chemotherapy are the standard treatment modalities for all primary brain tumors. Oligodendroglial tumors are uncommon primary brain tumors that typically are classified as low-grade or anaplastic based on their histologic appearance. A great deal of controversy has surrounded the diagnosis of an oligodendroglioma because no unique immunohistochemical marker exists to diagnose this tumor, forcing pathologists to render a diagnosis based on subjective microscopic features. Although once considered relatively rare, oligodendroglial tumors have been increasing in incidence because pathologists have become less rigorous about this diagnosis. However, recent advances in our understanding of the molecular genetic changes associated with brain tumors have identified loss of heterozygosity of chromosomes 1p and 19q as a unique genetic signature of most oligodendroglial tumors, an advance that has paved the way for pathologists to use molecular diagnostics to identify these tumors with improved reliability. These genetic derangements have significant clinical and therapeutic implications because they have been associated with a predictable and durable response to treatment, particularly chemotherapy, and an improved prognosis. The unique chemosensitivity of oligodendroglial tumors has been recognized by neurooncologists for at least 15 years, and various chemotherapeutic agents have been used to manage these diseases. However, the appropriate timing of chemotherapy, and the drugs of choice remain controversial. Increasingly, neurooncologists are reluctant to use radiotherapy as initial management for these diseases because of concerns surrounding the late neurocognitive sequelae of cranial irradiation. These toxicities are particularly important for patients with low-grade oligodendrogliomas in whom the prognosis often exceeds 10 years. Consequently, with the accumulating evidence supporting the chemosensitivity of low-grade and anaplastic oligodendrogliomas and the recent ability to use molecular diagnostics to identify a chemosensitive subset of oligodendrogliomas, neurooncologists are increasingly administering chemotherapy as the initial intervention for all oligodendroglial tumors that harbor favorable genetic derangements. Additionally, although immediate postoperative treatment is uniformly administered to patients with anaplastic oligodendrogliomas, there has been an increasing tendency to defer definitive therapy for those with low-grade oligodendrogliomas until evidence of progression. The development of temozolomide, an oral and well-tolerated alkylating agent that has activity against oligodendroglial tumors, has accelerated this trend to the extent that currently many patients with newly diagnosed low-grade and anaplastic oligodendrogliomas are offered this drug as initial treatment. This paper reviews the current management of oligodendrogliomas, with an emphasis on the expanding role of chemotherapy for these neoplasms.