Prognostic impact of obesity in newly-diagnosed glioblastoma: a secondary analysis of CeTeG/NOA-09 and GLARIUS

J Neurooncol. 2022 Aug;159(1):95-101. doi: 10.1007/s11060-022-04046-z. Epub 2022 Jun 15.

Abstract

Purpose: The role of obesity in glioblastoma remains unclear, as previous analyses have reported contradicting results. Here, we evaluate the prognostic impact of obesity in two trial populations; CeTeG/NOA-09 (n = 129) for MGMT methylated glioblastoma patients comparing temozolomide (TMZ) to lomustine/TMZ, and GLARIUS (n = 170) for MGMT unmethylated glioblastoma patients comparing TMZ to bevacizumab/irinotecan, both in addition to surgery and radiotherapy.

Methods: The impact of obesity (BMI ≥ 30 kg/m2) on overall survival (OS) and progression-free survival (PFS) was investigated with Kaplan-Meier analysis and log-rank tests. A multivariable Cox regression analysis was performed including known prognostic factors as covariables.

Results: Overall, 22.6% of patients (67 of 297) were obese. Obesity was associated with shorter survival in patients with MGMT methylated glioblastoma (median OS 22.9 (95% CI 17.7-30.8) vs. 43.2 (32.5-54.4) months for obese and non-obese patients respectively, p = 0.001), but not in MGMT unmethylated glioblastoma (median OS 17.1 (15.8-18.9) vs 17.6 (14.7-20.8) months, p = 0.26). The prognostic impact of obesity in MGMT methylated glioblastoma was confirmed in a multivariable Cox regression (adjusted odds ratio: 2.57 (95% CI 1.53-4.31), p < 0.001) adjusted for age, sex, extent of resection, baseline steroids, Karnofsky performance score, and treatment arm.

Conclusion: Obesity was associated with shorter survival in MGMT methylated, but not in MGMT unmethylated glioblastoma patients.

Keywords: Glioblastoma; MGMT; Obesity; Temozolomide.

Publication types

  • Clinical Trial

MeSH terms

  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain Neoplasms* / complications
  • Brain Neoplasms* / diagnosis
  • Brain Neoplasms* / therapy
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism
  • Glioblastoma* / complications
  • Glioblastoma* / diagnosis
  • Glioblastoma* / therapy
  • Humans
  • Obesity / complications
  • Prognosis
  • Temozolomide / therapeutic use

Substances

  • Antineoplastic Agents, Alkylating
  • DNA Modification Methylases
  • DNA Repair Enzymes
  • Temozolomide