Introduction: Mutation in isocitrate dehydrogenase 1 (IDH1) or isocistrate dehydrogenase 2 (IDH2) is present in a large percentage of gliomas and is associated with improved patient survival. Retinoic acid treatment with isotretinoin may delay tumor recurrence in malignant gliomas; however, its survival benefit remains controversial. This study aims to evaluate the effects of isotretinoin in patient with diffuse gliomas.
Methods: We retrospectively identified glioma patients treated at UCLA and collaborating institutions. Molecular biomarkers including MGMT, IDH1 and IDH2 were evaluated by methylation specific PCR and sequencing, respectively. Overall Survival (OS) was evaluated by Kaplan-Meier analysis and Cox proportional hazard model.
Results: A total of 830 patients were evaluated, including: 128 grade II, 153 grade III, and 549 grade IV patients. Patients with IDH1/IDH2 mutation showed improved OS; Grade II: 135.7 months vs. 69.5 months (mutant vs. wildtype, n=115 and n=13, p=.002); Grade III: 114 months vs. 31 months (n=112 and n=41, p=.002); and Grade IV: 36.1 months vs. 17.9 months (n=69 and n=480, p<.001). Treatment with isotretinoin upfront (21 days on, 7 days off, 1-28 cycles) is associated with an increased median OS in grade IV IDH1 wildtype patients from 17 months to 20.3 months (n=302, non-isotretinoin vs. n=117, isotretinoin, p<.001, Cox models HR=1.47, p= .006). Similar associations were observed when patients were further stratified with respect to treatment protocols. In patients who received concurrent radiation/temozolomide upfront and bevacizumab at recurrence, median OS was 21.5 months (n=116, non-isotretinoin) vs. 30.0 months (n=25, isotretinoin), p=.006; Cox models HR=2.13, p=.006.
Conclusions: IDH1/IDH2 mutation is associated with longer OS in gliomas. Treatment with isotretinoin upfront is associated with longer survival in patients with grade IV IDH1 wildtype tumors. The etiology of this association is unclear. Additional studies are needed to determine if isotretinoin treatment improves OS in other glioma patients.
Patient Care: Supports IDH1 as a prognostic biomarker for gliomas. Retinoic acid therapy may help improve patient survival.
Learning Objectives: The proposed abstract demonstrates that mutations in the isocitrate dehydrogenase genes (IDH1/IDH2) are associated with significantly improved overall survival in grade II-IV glioma patients. Treatments with isotretinoin appeared to have an impact on overall survival but this association was only observed in patients with grade IV IDH1 wild-type tumors.