Diffuse Gliomas (WHO Grade 2–3)

Abstract Grade 2 and grade 3 diffuse gliomas are challenging tumors to treat. They are uncommon, with an incidence rate of 1.35 per 100,000 per year, making them difficult to study. They have a younger median age of onset: 30–40 and 40–60 years old for grade 2 and 3, respectively, making long-term treatment toxicity significant in decision-making. The overwhelming majority of gliomas are sporadic. IDH mutation and 1p/19q co-deletion carry the most weight in prognostication; both are prognostic and predictive. Tumors that are “molecularly equivalent to GBM” and harbor TERT promoter gene mutation, EGFR amplification, or loss of chromosome 7p with gain of chromosome 10q have poor prognosis. The most common presentation for all glial tumors is seizures and is most frequent in grade 2 gliomas. Higher grade gliomas have a higher incidence of presenting with fixed neurologic deficits. Gadolinium-enhanced brain magnetic resonance imaging is the standard for assessing suspected brain tumors. As of 2016, pathologic diagnosis is based on molecular markers including IDH mutation and 1p/19q co-deletion. Surgery is required for tissue diagnosis, and a maximal safe resection has been shown to improve overall survival. Radiation doses of 50–54 Gy and 60 Gy for grade 2 and 3 tumors, respectively, is standard. Chemotherapy for oligodendrogliomas is well established, and both procarbazine, lomustine, and vincristine (PCV) and temozolomide (TMZ) are used. For grade 3 astrocytic tumors, TMZ is generally used but is supported by evidence in the adjuvant setting only. Recent preliminary data support concomitant TMZ use in IDH-mutated astrocytomas only. Results from CATNON and CODEL studies should answer these questions.