PATH-16. MOLECULAR ALTERATIONS IN IDH-MUTANT ASTROCYTOMA: A MULTI-INSTITUTIONAL RETROSPECTIVE STUDY

Abstract BACKGROUND Many molecular alterations are being identified for diagnosis and prognosis in patients with isocitrate dehydrogenase (IDH)-mutant astrocytoma. However, contemporary survival data for these tumors with respect to their molecular alterations are lacking. Moreover, the prognostic value of histologic grading in IDH-mutant astrocytomas remains controversial. METHODS This was a retrospective study of adult IDH-mutant diffuse astrocytoma patients in whom clinical and molecular alteration data were collected. Overall survival (OS) was estimated using the Kaplan-Meier method. Group differences in OS were assessed by the log-rank test and associations between OS and measures of interest were evaluated using Cox proportional hazards regression models. RESULTS We identified 241 eligible patients with median age of 33 years (range, 16-73 years). The most frequent mutations were in IDH1 (98%), TP53 (91%), ATRX (70%), ARID1A (8%), BRCA2 (6%), TSC2 (6%), CDKN2A (6%), and CREBBP (6%). IDH2 mutations were identified in 2% of cases. By univariate analysis, age >40 years (hazard ratio [HR], 2.02; 95% CI, 1.19-3.43; P =.009) was associated with worse OS. BRCA2 wild-type status compared with mutated BRCA2 (HR, 0.42; 95% CI, 0.20-0.90; P =.024) and histology-based grade 2 compared with grade 3 astrocytoma (HR, 0.41; 95% CI, 0.23-0.74; P =.003) were associated with improved OS. In multivariable analysis, age>40 years (HR, 2.14; 95% CI, 1.22-3.75; P =.008) was associated with worse OS. Patients with WHO grade 2 astrocytoma remained associated with improved OS compared to those with grade 3 disease (HR, 0.45; 95% CI, 0.24-0.84; P =.013). CONCLUSIONS Age and histological grade remain essentials for risk stratification among IDH-mutant astrocytoma patients. Further studies are warranted to determine the role of BRCA2 mutation in prognosis.