Table 4.

Summary Box: Key Points

Key points
Classification	• Astrocytoma, IDH-mutant: associated with ATRX and TP53 mutation, WHO grade 2-4 depending on histologic features and CDKN2A homozygous deletion status • Oligodendroglioma, IDH-mutant: characterized by 1p/19q codeletion and TERT promoter mutation, WHO grade 2-3 based on histologic features and CDKN2A homozygous deletion status
Mechanisms of gliomagenesis	• Mutant IDH enzyme activity promotes D-2-hydroxyglutarate (D-2HG) formation, leading to altered epigenetic state and metabolic reprogramming • D-2HG suppresses T-cell function, damping down tumor-directed immune response
Imaging features	• Frontal, hyperintense lesions on T2/FLAIR imaging; contrast enhancement more frequent in grade 3 and grade 4 tumors • T2—FLAIR mismatch sign has high specificity for astrocytic IDH-mutant gliomas
Treatment guidelines	• Maximal safe resection is associated with improved outcomes • Observation after surgery can be considered for low-risk patients with grade 2 IDH-mutant gliomas following a gross total resection • Radiation followed by chemotherapy is the standard of care for patients with high risk, grade 2 IDH-mutant gliomas and all patients with grade 3 and grade 4 IDH-mutant gliomas
Therapies in development	• Direct IDH inhibitors are under investigation for treatment of grade 2, non-enhancing, IDH-mutant glioma • Canonical IDH1 R132H mutation is a clonal neoantigen being targeted by vaccine-based therapy in clinical trials