gms | German Medical Science

Objective: The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes mutate frequently in gliomas, and it has become increasingly apparent that IDH mutation status accounts for much of the prognostic information previously rendered by histological grading. In this retrospective study, we sought to determine the influence of extent of resection (EOR) on survival of patients with IDH-mutant gliomas all grades.

Method: Clinical parameters including volumetric assessment of preoperative and postoperative MRI were analyzed retrospectively on 100 IDH-mutant glioma patients: 68 patients with WHO grade II glioma, 23 patients with WHO grade III glioma and nine patients with secondary glioblastoma. All patients underwent tumor resection. IDH and TERT promoter status were assessed by sequencing. Region-of-interest analysis was performed to measure tumor volumes based on fluid-attenuated inversion-recovery (FLAIR) imaging.

Results: During a median follow-up time of 7.5 years there were 31 deaths (31%). The median age at the initial diagnosis was 36.8 years (range 36.5 - 41.1 years). The median overall survival (OS) was 12.7 years (13.9 in the IDH-mutant, TERT-mutant and 11.3 in the IDH-mutant, TERT-wildtype group, p=0.067). The estimated median progression-free survival was 3.4 years; 5.2yeary in the IDH- and TERT mutant group versus 2.5 years in the IDH-mutant, TERT-wildtype, p=0.011). Complete resection of enhancing disease (if present) as well as the predominance of the FLAIR hyperintensity with no nodular residual FLAIR hyperintense was associated with a median survival of 14.5 years versus 10.9 years for incomplete resection (p=0.047). A complete resection was also associated with a significantly prolonged progression-free survival of 5.9 years versus 2.7 years for patients with residual tumors (p=0.013). Recurrences and malignant progression were identified in 57 (57%) and 46 (46%) cases, respectively. In the multivariate analysis, the OS was predicted by EOR (hazard ratio [HR] = 2.521; 95% CI, 1.354 to 4.694; p=0.004) and TERT-promoter mutation (HR = 0.434; 95% CI, 0.254 to 0.744; p=0.002), whereas the remaining parameters including age, tumor location, histologic subtype and tumor grade were not associated with patients’ survival.

Conclusions: IDH mutations identify gliomas with a distinct molecular evolutionary origin and might influence our treatment decisions. The survival benefit among patients with IDH-mutant gliomas of all grades is predicted by greater EOR and a mutant TERT-promoter.