Isocitrate Dehydrogenase Mutations in Low-Grade Gliomas Correlate With Prolonged Overall Survival in Older Patients

Abstract BACKGROUND Older age has been associated with worse outcomes in low-grade gliomas (LGGs). Given their rarity in the older population, determining optimal treatment plans and patient outcomes remains difficult. OBJECTIVE To retrospectively study LGG survival outcomes in an older population stratified by molecular genetic profiles. METHODS We included patients age ≥40 yr with pathologically confirmed World Health Organization grade II gliomas treated at a single institution between 1995 and 2015. We collected tumor genomic information when available. RESULTS Median overall survival for the entire group (n = 111, median age 51 yr, range 40-77 yr) was 15.75 yr with 5- and 10-yr survival rates of 84.3% and 67.7%, respectively. On univariate analysis, patients with isocitrate dehydrogenase (IDH) mutation had significantly increased survival compared to IDH wildtype (hazard ratio [HR] 0.17 [0.07-0.45], P < .001). Older age, seizure at presentation, larger tumor size, IDH wildtype, biopsy only, chemotherapy, and radiation were significantly associated with shorter survival based on univariate analyses. In patients with known IDH status (n = 73), bivariate analysis of IDH mutation status and age showed only IDH status significantly influenced overall survival (HR 0.22 [0.07-0.68], P = .008). Greater surgical resection was predictive of survival, although extent of resection significantly correlated with IDH mutation status (odds ratio 7.5; P < .001). CONCLUSION We show that genomic alterations in LGG patients ≥40 occur at high rates like the younger population and predict a similar survival advantage. Maximizing surgical resection may have survival benefit, although feasibility of resection is often linked to IDH status. Given the importance of molecular genetics, a redefinition of prognostic factors associated with these tumors is likely to emerge.