Different diagnostic values of imaging parameters to predict pseudoprogression in glioblastoma subgroups stratified by MGMT promoter methylation

Eur Radiol. 2017 Jan;27(1):255-266. doi: 10.1007/s00330-016-4346-y. Epub 2016 Apr 5.

Abstract

Objectives: The aim of this study was to determine whether diffusion and perfusion imaging parameters demonstrate different diagnostic values for predicting pseudoprogression between glioblastoma subgroups stratified by O6-mythylguanine-DNA methyltransferase (MGMT) promoter methylation status.

Methods: We enrolled seventy-five glioblastoma patients that had presented with enlarged contrast-enhanced lesions on magnetic resonance imaging (MRI) one month after completing concurrent chemoradiotherapy and undergoing MGMT promoter methylation testing. The imaging parameters included 10 or 90 % histogram cutoffs of apparent diffusion coefficient (ADC10), normalized cerebral blood volume (nCBV90), and initial area under the time signal-intensity curve (IAUC90). The results of the areas under the receiver operating characteristic curve (AUCs) with cross-validation were compared between MGMT methylation and unmethylation groups.

Results: MR imaging parameters demonstrated a trend toward higher accuracy in the MGMT promoter methylation group than in the unmethylation group (cross-validated AUCs = 0.70-0.95 and 0.56-0.87, respectively). The combination of MGMT methylation status with imaging parameters improved the AUCs from 0.70 to 0.75-0.90 for both readers in comparison with MGMT methylation status alone. The probability of pseudoprogression was highest (95.7 %) when nCBV90 was below 4.02 in the MGMT promoter methylation group.

Conclusions: MR imaging parameters could be stronger predictors of pseudoprogression in glioblastoma patients with the methylated MGMT promoter than in patients with the unmethylated MGMT promoter.

Key points: • The glioblastoma subgroup was stratified according to MGMT promoter methylation status. • Diagnostic values of diffusion and perfusion parameters for predicting pseudoprogression were compared. • Imaging parameters showed higher diagnostic accuracy in the MGMT promoter methylation group. • Imaging parameters were independent to MGMT promoter methylation status for predicting pseudoprogression. • Imaging biomarkers might demonstrate different diagnostic values according to MGMT promoter methylation.

Keywords: Diffusion-weighted imaging; Glioblastoma; MGMT promoter methylation; Perfusion MR; Pseudoprogression.

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Chemoradiotherapy
  • DNA Methylation
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics
  • Diffusion Magnetic Resonance Imaging / methods
  • Disease Progression
  • Female
  • Glioblastoma / diagnostic imaging*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics
  • ROC Curve
  • Retrospective Studies
  • Tumor Suppressor Proteins / genetics

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • DNA Repair Enzymes