Low-grade gliomas in adults

Making treatment decisions for patients with infiltrating low-grade gliomas (LGGs) is challenging. Patients frequently present with seizures and usually have little or no neurologic deficit. In this younger and relatively well patient population, despite the potential for significant morbidity, we believe that surgical resection, radiation therapy, and chemotherapy each play an important role in the optimal management of these tumors. Randomized clinical trials have begun to address some of the many questions about prognosis, natural history, and treatment, but most questions have yet to be answered. We believe that, when possible, a maximal surgical resection consistent with preservation of neurologic function should be performed, even though it is likely that no randomized clinical trial will ever be done to demonstrate a survival advantage for this approach. External beam radiation therapy is most often given to a total dose of 50.4 or 54 Gy in 1.8-Gy fractions. The role of chemotherapy is less certain, but a growing body of evidence suggests that temozolomide, a generally well-tolerated drug, is active in the treatment of LGGs. In recent years, loss of heterozygosity of chromosome 1p and 19q, as well as silencing of the MGMT gene, have been identified as promising predictors of response to adjuvant therapy in gliomas. Although randomized trials have not yet shown a survival benefit for early radiation therapy or chemotherapy, one study by the European Organisation for Research and Treatment of Cancer did show an improvement in time to tumor progression with the earlier use of radiation therapy. In addition, a trial by the Radiation Therapy Oncology Group (soon to be analyzed and reported) is comparing radiation alone with radiation followed by a year (six cycles) of standard-dose PCV chemo therapy (procarbazine, CCNU, and vincristine); this trial may shed light on the use of chemotherapy in conjunction with radiation therapy for the initial treatment of LGGs. Because patients remain at risk for tumor progression for the remainder of their lives, we recommend lifelong follow-up with MRI scans, even for patients without documented tumor regrowth over long intervals. To give clinicians a more solid basis for guiding therapy recommendations, we encourage participation in large cooperative group clinical trials.