Epco-62. Assessment of Age in the Clinical Risk Stratification of Patients With Idh-Mutant Gliomas

BACKGROUND Isocitrate dehydrogenase mutant (IDHm) low-grade gliomas have a slow growing phase, but eventually become aggressive tumors. To delay long-term toxic effects of chemoradiation, low-risk patients are monitored after surgery. Traditionally, patients >40 were considered high-risk, however, this remains controversial. Recent promising results with the IDHm-inhibitor vorasidenib sparking debate, challenging age-based risk stratification. We evaluated survival relative to age and molecular data. METHODS 598 IDHm astrocytoma grades 2-3 and 288 IDHm oligodendroglioma grades 2-3 were analyzed by NGS and WTS at Caris Life Sciences (Phoenix, AZ). Samples were stratified by age at diagnosis (12-26y, 27-40y, 41-60y, and >60y). Overall survival was obtained from insurance claims data and analyzed using Kaplan-Meier and Cox proportional hazards models. Comparisons in survival were made between 27-40y and 41-60y given larger sample size. Multivariate regression analysis included radiotherapy, temozolomide, and mutation status as covariates. RESULTS IDHm astrocytomas age distribution was 12-26y, n=74 (12.4%); 27-40y, n=271 (45.3%); 41-60y, n=205 (34.3%); and >60y, n=48 (8.0%). Univariate analysis showed that 27-40y patients had shorter survival (HR=1.63, 95% CI:1.07–2.50, p=0.022). However, after multivariate analysis, age was not associated with survival (HR =1.02, 95% CI:0.74-1.4, p=0.912). In contrast, TP53 (HR=4.0, 95%CI:1.43-11.24, p=0.008– mutation rate=95.4%) and TERT-promoter (HR=10.36, 95% CI:4.05-26.45, p<0.0001– mutation rate=9.0%) mutations were independently associated with poorer survival. IDHm oligodendrogliomas age distribution was 12-26y, n=18 (5.5%); 27-40y, n=76 (23.2%); 41-60y, n=137 (41.8%); and >60y, n=57 (17.4%). Univariate and multi-variate analysis did not show any association between age and survival (HR =0.94, 95% CI:0.48-1.83, p=0.912, and HR =1.33, 95% CI:0.81-2.19, p=0.248, respectively). However, KRAS mutations were independently associated with poorer survival (HR=4.36, 95% CI:1.12-16.92, p=0.033- mutation rate=3%). CONCLUSIONS While age (27-40y vs. 41-60y) was not associated with survival, genetic alterations such as KRAS (oligodendroglioma), TP53 and TERT mutations (astrocytoma) were independently associated with poorer survival.