BI-15 * RADIO- CHEMOTHERAPY IMPROVES SURVIVAL FOR IDH MUTANT, 1p19q-NON-CODELETED SECONDARY HIGH-GRADE-ASTROCYTOMA

Abstract

OBJECTIVES: The RTOG 9402 trial reported an improved Outcome in IDH mutant and 1p19q-codeleted anaplastic oligodendroglial tumors after chemotherapy (CT) with radiotherapy (RT). We evaluated the efficacy of CT and RT in patients with IDH mutant, 1p19q-noncodeleted secondary high-grade astrocytoma (sHGA) WHO grades III and IV. PATIENTS AND METHODS: Treatment data from 109 patients with sHGA grades III and IV, developed from histologically confirmed low-grade astrocytoma grade II were retrospectively analyzed. IDH mutation-, 1p19q/codeletion- and MGMT-promoter methylation status were evaluable in all patients. Progression-free survival and overall survival (OS) in relation to adjuvant treatment modalities and molecular profiling were performed using the Kaplan-Meier method. RESULTS: Out of 109 patients, 88 patients (80.7%) harbored an IDH1 or 2 mutations, 30 patients a 1p19q-codeletion (27.5%), and 63 patients (57.8%) exhibited a methylated MGMT-promoter status. During the follow-up time 57 patients (52.2%) died. The postsurgical treatment for the 88 IDH mutant sHGA included: RT alone in 17 patients (19.3%), a combined RT and CT (RCT) in 48 patients (54.5%) and CT alone in 20 patients (22.7%). 3 patients did not receive any adjuvant treatment due to bad neurological conditions. At a median follow-up of 9.8 years, the median OS of all IDH mutant sHGA was 5.67 years (1.9-17.4 years). The OS in patients who received RCT was 6.4 years, which is significantly longer compared with those who underwent RT alone (1.2 years, hazard ratio 0.35, 95% CI 0.32-0.51. p = 0.011). After including only IDH mutant sHGA patients without a 1p19q-codeletion, the Kaplan-Meier curves estimates a significantly improved OS in the RCT cohort (33 patients) in comparison to patients who received RT alone (10 patients) (6.4 vs 1.2 years, hazard ratio 0.4, 95% CI 0.34-0.6, p = 0.022). CONCLUSIONS: Addition of alkylating-agent chemotherapy to radiation significantly improved overall survival in patients with IDH mutant and 1p19q-noncodeleted sHGA.