Molecular alterations in IDH-mutant astrocytoma: A multi-institutional retrospective study

Several molecular alterations have been identified to provide prognosis for patients with isocitrate dehydrogenase (IDH)-mutant astrocytoma. However, contemporary baseline survival data with respect to their molecular alterations are lacking. The prognostic value of histologic grading remains controversial.

This was a retrospective multi-site study of adult IDH-mutant diffuse astrocytoma patients. Overall survival (OS) was estimated using the Kaplan-Meier method. Associations between OS and measures of interest were evaluated using Cox proportional hazards regression models.

We identified 241 eligible patients. The most frequent mutations were IDH1 (98%), TP53 (91%), ATRX (70%), ARID1A (8%), BRCA2 (6%), TSC2 (6%), CDKN2A (6%), and CREBBP (6%). IDH2 mutations were identified in 2%. By univariate analysis, age > 40 (hazard ratio [HR], 2.03; 95% CI, 1.20-3.45; p = .009) was associated with worse OS. Wildtype BRCA2 compared with mutated BRCA2 (HR, 0.42; 95% CI, 0.20-0.90; p = .024) and Central Nervous System World Health Organization (CNS WHO) grade 2 astrocytoma compared with grade 3 disease (HR, 0.40; 95% CI, 0.21-0.78; p = .007) were associated with better OS. In multivariable analysis, age > 40 (HR, 2.06; 95% CI, 1.18-3.59; p = .011) was associated with worse OS and CNS WHO grade 2 (HR, 0.42; 95% CI, 0.21-0.83; p = .012) remained associated with improved OS. We identified an association between increased tumor mutation burden (TMB) and worse OS.

Age and CNS WHO grade remain essentials for risk stratification among IDH-mutant astrocytoma patients. Further studies are warranted to determine the prognostic implications of BRCA2 mutations and TMB.