Association Between Tumor Compartment Volumes, the Incidence of Pretreatment Seizures, and Statin-Mediated Protective Effects in Glioblastoma

Neurosurgery. 2019 Oct 1;85(4):E722-E729. doi: 10.1093/neuros/nyz079.

Abstract

Background: Seizures are a common initial symptom of malignant brain tumors such as glioblastoma (GBM). However, why some of these tumors are epileptogenic and others never trigger seizures remains controversial.

Objective: To identify potential clinical and radiological features of epileptogenic tumors and the effect of initial seizures on survival.

Methods: The analyzed patient cohort was retrospectively compiled (bicentric), only isocitrate dehydrogenase wild-type GBMs were included. Volumetric assessment was performed on pretreatment magnetic resonance imaging with the aid of a semi-automated 3D measurement (tumor, necrosis, and edema volume). Two ratios were calculated, reflecting the proportion of peritumoral edema and necrosis (NTR) toward the tumor volume. For overall survival analyses, only patients after a surgical resection (residual tumor volume <2 cm3) followed by standard radiation and chemotherapy were included.

Results: Pretreatment seizures occurred in 33% of cases (n = 224), younger patients (≤60 yr) were predominantly affected (P = .022). All measured volumes were inversely correlated with the onset of seizures (P = .001). In multivariate analyses, the total tumor volume and the NTR were considerably smaller within epileptogenic GBMs (P = .050, P = .019, respectively). A positive statin intake was associated with significantly lesser seizure (P = .007, odds ratio 4.94). Neither the occurrence of seizures nor the intake of statins had an impact on OS (P = .357, P = .507, respectively).

Conclusion: The size and amount of necrosis was significantly smaller in epileptogenic GBMs, maybe owed to the fact that these tumors were clinically detected at an earlier stage of their growth. Furthermore, the intake of statins was associated with a decreased occurrence of pretreatment seizures.

Keywords: Glioblastoma; Necrosis; Neuroimaging; Oncology; Prognostic markers; Seizures.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / epidemiology
  • Cohort Studies
  • Female
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / drug therapy*
  • Glioblastoma / epidemiology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Incidence
  • Male
  • Middle Aged
  • Neuroprotective Agents / administration & dosage*
  • Retrospective Studies
  • Seizures / diagnostic imaging
  • Seizures / drug therapy*
  • Seizures / epidemiology
  • Tumor Burden / drug effects*
  • Tumor Burden / physiology

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Neuroprotective Agents