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  • Extent of Resection and MGMT Promotor Methylation Status are Independent Risk Factors in IDH1_R132H Wild-type Primary Glioblastomas

    Final Number:

    Florian Gessler MD; Anne Braczynski MD; Stephanie Tritt MD; Peter Baumgarten MD; Patrick Harter; Joshua Bernstock MSc, MPH; Tianxia Wu PhD; Michel Mittelbronn MD; Volker Seifert MD, PhD; Christian Senft MD, PhD

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2017 Annual Meeting

    Introduction: Previous pivotal studies on the influence of extent of resection (EOR) in primary glioblastoma (GBM) have failed to incorporate molecular tumor markers, so the impact of extensive surgical approaches in the light of MGMT methylation and/or IDH mutation status is unclear.

    Methods: We retrospectively analyzed our prospectively collected database of patients undergoing surgery for newly diagnosed GBM WHO °IV and included only IDH1_R132H wild-type patients. All patients had volumetric assessment of EOR and received adjuvant treatment according to local tumor board recommendation and patient preference. We hypothesized that gross total resection was associated with better outcome. This analysis was approved by our local ethics committee.

    Results: 175 patients (median age: 60 years) were included. Median overall survival (OS) was 18.0 months. MGMT promotor methylation was present in 80 patients (45.7%). Complete removal of contrast-enhancing tissue (CRET) was achieved in 104 patients (59.4%). In Cox regression analysis, both MGMT-promoter methylation (HR 1.55; 95% CI, 1.01-2.19; p=0.013) and CRET (HR 1.48; 95% CI, 1.06-2.07; p=0.020) were significantly associated with favorable progression-free survival (PFS). Further, both MGMT promotor methylation (HR 2.13; 95% CI, 1.45-3.12; p=0.0001) and CRET (HR 1.81; 95% CI, 1.24-2.63; p=0.002) were independently associated with longer OS. No benefit was seen for resections <99%. 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 outcome differences were observed between non-MGMT methylated patients undergoing CRET, and non-CRET, MGMT methylated patients (PFS: p=0.726; OS: p=0.477).

    Conclusions: Both CRET and MGMT promotor methylation are independent prognostic factors for improved OS and PFS. Our study incorporates molecular markers and our data highlight the importance of aggressive surgical approaches. If achieved, CRET might compensate for the biological disadvantage of lacking MGMT promotor methylation.

    Patient Care: Our data establish a rationale to maximize tumor resection in IDH1 wild-type glioblastomas irrespective of MGMT promotor methylation status.

    Learning Objectives: By the conclusion of this sessions, participants should be able to 1) describe the importance of molecular markers in the diagnosis and treatment of patients with glioblastoma, and 2) discuss the importance of MGMT promotor methylation and extent of resection in primary glioblastoma


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