Article
The Impact of extent of resection and MGMT-promotor methylation in newly diagnosed IDH1R non mutated glioblastoma
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Published: | June 9, 2017 |
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Purpose: The purpose of this prospective single-center analysis was the incorporation of molecular diagnostics in the assessment of extent of resection (EOR) as a progrostic factor for patients with glioblastoma (GBM).
Patients and Methods: Histology, MGMT promoter methylation status, isocitrate dehydrogenase 1 (IDH-1)R132H-mutation status, EOR and clinical data were prospectively added to a glioma patient database. We analyzed patients with newly diagnosed WHO grade IV glioblastomas and excluded those with IDH-1 R132H mutations. Survival analyses were performed using the Kaplan-Meier method. Prognostic factors were calculated by proportional hazard models.
Results: 176 patients were included in the analysis. 104 patients (59.4%) had gross total resection (GTR), 71 patients (40.6 %) had subtotal or partial resection. 80 patients (45.7%) displayed MGMT-promoter methylation, 95 patients (54.3%) showed no MGMT-promoter methylation. In Cox regression analysis, both MGMT-promoter methylation (HR 1.55; 95% CI, 1.01-2.19; p=0.0133) and GTR (HR 1.48; 95% CI, 1.06-2.07; p=0.0206) were significantly associated with favorable progression free survival (PFS). Furthermore, both MGMT-promoter methylation (HR 2.13; 95% CI, 1.45-3.12; p=0.0001) and GTR (HR 1.81; 95% CI, 1.24-2.63; p=0.0020) were even associated with favorable overall survival (OS). Of other risk factors analyzed, only age ( > 60 vs. <=60 years) was significantly associated with PFS (HR 1.60; 95% CI, 1.14-2.24; p=0.006) and OS (HR 2.19; 95% CI, 1.51-3.19; p<0.0001). No significant difference was observed between GTR, MGMT-non-methylated and non-GTR, MGMT-methylated GBM patients (PFS p=0.726; OS p=0.477).
Conclusion: GTR and MGMT-promoter methylation are independent prognostic factors for improved OS and PFS in a homogeneous cohort of non-IDH-1 mutant, newly diagnosed glioblastomas. If achieved, GTR compensates the biological disadvantage of lacking methylation of the MGMT-promoter region in primary GBM.