Radio-chemotherapy improves survival in IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma patients.

Abstract

Isocitrate dehydrogenase (IDH) mutations are beginning to drive decisions on therapy for glioma patients. Here we sought to determine the impact of adjuvant treatment in patients with IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma (sHGA) WHO grades III/IV. Clinical data of 109 sHGA patients grades III/IV, in addition to IDH mutation-, 1p/19q-codeletion- and MGMT-promoter methylation status-were retrospectively analyzed. Survival analysis in relation to adjuvant treatment modalities and molecular profiling were performed. Out of 109 patients, 88 patients (80.7%) harbored IDH mutations, 30 patients had a 1p/19q-codeletion (27.5%) and 69 patients (63.3%) exhibited a methylated MGMT-promoter status. At a median follow-up of 9.8years, 62 patients (57%) died. The postsurgical treatment included: radio-chemotherapy (RT-CT; 54.5%), RT alone (19.3%), and CT alone (22.7%). The median overall survival (OS) in the entire group was 3.4years (1.9-6.7years). Patients who received RT-CT had a significantly longer OS compared with those who underwent RT alone (6.5 vs. 1.2years, HR 0.35, CI 0.32-0.51, p=0.011). In the IDH-mutant 1p/19q non-codeleted sHGA subgroup the RT-CT cohort had a significantly longer OS in comparison to the RT cohort (6.4 vs. 1.2years, HR 2.7, CI 1.1-6.5, p=0.022). In the stepwise multivariable Cox model for OS of all 88 IDH-mutant sHGA patients, survival was strongly associated with only one factor, namely, adjuvant RT-CT at diagnosis of a sHGA. This retrospective long-term study demonstrates that RT and CT (mostly PCV) significantly improves progression-free and overall survival in IDH-mutant secondary high-grade astrocytoma patients, regardless of 1p/19q-codeletion status.