Low-grade gliomas represent one of the most vexing management issues for neuro-oncologists. The relatively long survival compared to other gliomas makes consideration of treatment toxicity, and thus timing of potentially damaging interventions such as surgery, radiation, and chemotherapy, crucial. Moreover, the rarity of these tumors makes clinical trials to ascertain optimal care challenging.
The discovery that most low-grade gliomas harbor isocitrate dehydrogenase mutations that confer a favorable prognosis has improved diagnosis and risk stratification of these tumors. Although level 1 evidence is still lacking, increasing data support the concept of maximal safe tumor debulking as a first step in tumor management. Preliminary results from a large randomized trial suggest chemotherapy is of comparable effectiveness to radiation therapy. Most important, the final results of a phase 3 trial comparing radiation with or without procarbazine, CCNU (lomustine), and vincristine (PCV) chemotherapy indicate a large survival advantage to combined radiation and chemotherapy.
While the combination of radiation and PCV provides the best proven overall survival with low-grade gliomas, important questions remain. These include whether the better-tolerated temozolomide is as effective as PCV and whether the use of initial chemotherapy as a strategy to defer the potential delayed cognitive toxicity associated with radiation will yield equivalent survival results with a favorable toxicity profile.