Chapter 11 - Approach to the low-grade glioma patient

Abstract

Treatment decisions in low-grade gliomas are complex and need to be made in context of new molecular and clinical data that have changed our understanding and management of these cancers over the past decade. Low-grade gliomas are increasingly defined based on molecular markers that are included in the most recent WHO classification of 2016. Most diffuse low-grade gliomas can be separated into three molecularly, prognostically, and clinically distinct groups: Isocitrate dehydrogenase (IDH)-mutant tumors with the classic oligodendroglioma marker of co-deletion of chromosomes 1p and 19q (these highly chemotherapy-sensitive tumors have the most favorable prognosis overall), IDH-mutant non–co-deleted tumors (these are mostly astrocytomas and, compared to the co-deleted tumors, are less chemosensitive with a comparatively worse prognosis), and IDH wild-type tumors (these have the worst prognosis of the three groups and can behave similarly to glioblastoma). Assessment of risk for early progression is complex and incorporates molecular, histopathologic, and clinical features. Select patients can be initially observed, whereas patients that are considered at higher risk are often treated with postoperative therapy at the time of diagnosis. There are phase III data supporting combination treatment with radiation plus lomustine, procarbazine, and vincristine (PCV) in patients with low-grade gliomas, which is most effective in IDH-mutant, 1p/19q-co-deleted low-grade gliomas. The precise role of this regimen for patients with non–co-deleted low-grade gliomas and comparison of this regimen with radiation and temozolomide, which is the standard treatment for glioblastomas, has remained controversial. Further prospective data are needed to answer these important clinical questions.