Correlation Between the Residual Tumor Volume, Extent of Tumor Resection, and O6-Methylguanine DNA Methyltransferase Status in Patients with Glioblastoma

World Neurosurg. 2018 Aug:116:e147-e161. doi: 10.1016/j.wneu.2018.04.134. Epub 2018 Apr 27.

Abstract

Background: There is limited information on O6-methylguanine DNA methyltransferase (MGMT) status, extent of surgical resection, and its impact on overall outcomes in patients with glioblastoma (GBM).

Methods: After institutional review board approval, 233 newly diagnosed patients with GBM with known MGMT status (2009-2015) were included in our analysis. Clinical, imaging, and follow-up data were collected from the database. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary end points, respectively.

Results: Of patients, 51.9% were younger than 65 years and 44.2% were noted to have promoter methylation of MGMT. Median residual tumor volume was 1.1 cm3 and extent of complete resection of enhancing tumor on imaging was 96%. Estimated median OS and PFS were 10.9 months and 5.4 months, respectively. MGMT status was an independent predictor of PFS (hazard ratio [HR], 0.52; P = 0.005) but only marginally associated with OS (P = 0.059). In MGMT methylated patients, extent of resection (≥86%) and good performance status (Karnofsky Performance Status ≥70) were independently associated with PFS and OS, respectively (PFS: HR, 0.21; P = 0.015; OS: HR, 0.05; P = 0.002). In MGMT promoter unmethylated patients, extent of resection (≥86%) was independently associated with OS (P = 0.039). Concurrent chemoradiotherapy was associated with OS/PFS irrespective of age and MGMT status.

Conclusions: Greater extent of resection of enhancing tumor was associated with improved PFS in MGMT promoter methylated patients, OS regardless of MGMT status. Elderly patients with methylated MGMT promoter were found to have improved PFS whereas younger patients had improved OS with MGMT promoter methylated status.

Keywords: Correlation; Glioblastoma; MGMT; Outcome; Resection.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / surgery
  • DNA Modification Methylases / drug effects
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / drug effects
  • DNA Repair Enzymes / metabolism
  • Disease-Free Survival
  • Female
  • Glioblastoma / genetics
  • Glioblastoma / pathology*
  • Glioblastoma / surgery
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • Humans
  • Male
  • Methyltransferases / metabolism*
  • Middle Aged
  • Neoplasm, Residual / pathology*

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • Guanine
  • O-(6)-methylguanine
  • DNA Modification Methylases
  • Methyltransferases
  • DNA Repair Enzymes