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. 2019 Jan 1;84(1):190-197.
doi: 10.1093/neuros/nyy049.

Surgery for Glioblastoma in Light of Molecular Markers: Impact of Resection and MGMT Promoter Methylation in Newly Diagnosed IDH-1 Wild-Type Glioblastomas

Florian Gessler  1 , Joshua D Bernstock  2 , Anne Braczynski  3 , Stephanie Lescher  4 , Peter Baumgarten  1   3 , Patrick N Harter  3 , Michel Mittelbronn  3 , Tianxia Wu  5 , Volker Seifert  1 , Christian Senft  1
Affiliations

Surgery for Glioblastoma in Light of Molecular Markers: Impact of Resection and MGMT Promoter Methylation in Newly Diagnosed IDH-1 Wild-Type Glioblastomas

Florian Gessler et al. Neurosurgery. .

Abstract

Background: Previous studies addressing the influence of surgery on the outcome of patients with glioblastomas (GBM) have not addressed molecular markers. The value of surgery versus the tumor's major biological markers remains unclear.

Objective: We investigate the extent of resection as a prognosticator for patients with newly diagnosed primary GBM with the incorporation of molecular diagnostics as per the updated WHO 2016 diagnostic criteria for GBM.

Methods: Patients with newly diagnosed GBM who underwent resection were prospectively included within a database. We analyzed patients with newly diagnosed GBM and excluded patients who presented with IDH1 R132H mutations. Gross total resection (GTR) was defined as complete removal of enhancing disease.

Results: One hundred seventy-five patients were included within the analysis. One hundred four patients (59.4%) had GTR, 71 patients (40.6%) had subtotal or partial resection. Eighty patients (45.7%) displayed O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, 95 patients (54.3%) showed no MGMT promoter methylation. In Cox regression analysis, MGMT promoter methylation (hazard ratio [HR] 1.55; 95% confidence interval [CI], 1.01-2.19; P = .0133) and GTR (HR 1.48; 95% CI, 1.06-2.07; P = .0206) were significantly associated with favorable progression-free survival. MGMT promoter methylation (HR 2.13; 95% CI, 1.45-3.12; P = .0001) and GTR (HR 1.81; 95% CI, 1.24-2.63; P = .002) were associated with favorable overall survival (OS). Of other risk factors analyzed, age (>60 vs ≤ 60 yr) was significantly associated with progression-free survival (HR 1.60; 95% CI, 1.14-2.24; P = .006) and OS (HR 2.19; 95% CI, 1.51-3.19; P < .0001).

Conclusion: GTR and MGMT promoter methylation are independent prognosticators for improved overall and progression-free survival in a homogeneous cohort of newly diagnosed patients with IDH wild-type glioblastoma.

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Figures

FIGURE.
FIGURE.
Kaplan–Meier curves for survival. A, Kaplan–Meier curves illustrating progression-free survival stratified between MGMT promoter methylation status and EOR. B, Kaplan–Meier curves illustrating overall survival stratified between MGMT promoter methylation status and EOR. EOR = Extent of resection; MGMT = O6-methylguanine-DNA methyltransferase.
See this image and copyright information in PMC

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