Combined analysis of MGMT methylation and dynamic-susceptibility-contrast MRI for the distinction between early and pseudo-progression in glioblastoma patients

Rev Neurol (Paris). 2019 Oct;175(9):534-543. doi: 10.1016/j.neurol.2019.01.400. Epub 2019 Jun 14.

Abstract

Introduction: Currently, no single diagnostic modality allows the distinction between early progression (EP) and pseudo-progression (Psp) in glioblastoma patients. Herein we aimed to identify the characteristics associated with EP and Psp, and to analyze their diagnostic value alone and in combination.

Material and methods: We reviewed the clinical, conventional magnetic resonance imaging (MRI), and molecular characteristics (MGMT promoter methylation, IDH mutation, and EGFR amplification) of glioblastoma patients who presented an EP (n=59) or a Psp (n=24) within six months after temozolomide radiochemotherapy. We analyzed relative cerebral blood volume (rCBV) and relative vessel permeability on K2 maps (rK2) in a subset of 33 patients using dynamic-susceptibility-contrast MRI.

Results: In univariate analysis, EP was associated with neurological deterioration, higher doses of dexamethasone, appearance of a new enhanced lesion, subependymal enhancement, higher rCBV and rK2 values. Psp occurred earlier after radiotherapy completion and was associated with IDH1 R132H mutation, and MGMT methylation. In multivariate analysis, rCBV, rK2, and MGMT methylation status were independently associated with EP and Psp. All patients with a methylated MGMT promoter and a low rCBV (<1.75) were classified as Psp while all patients with an unmethylated MGMT promoter and a high rCBV (≥1.75) were classified as EP. Among patients with discordant MGMT methylation and rCBV characteristics, higher rK2 values tended to be associated with EP.

Conclusion: Combined analysis of MGMT methylation, rCBV and vessel permeability on K2 maps seems helpful to distinguish EP from Psp. A prospective study is warranted to confirm these results.

Keywords: Chemoradiotherapy; Disease progression; Glioblastoma; Perfusion magnetic resonance imaging; Radiation injuries.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Chemoradiotherapy / adverse effects
  • Contrast Media
  • DNA Methylation*
  • DNA Modification Methylases / analysis
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / analysis
  • DNA Repair Enzymes / genetics*
  • Diagnosis, Differential
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glioblastoma / diagnosis*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Radiation Injuries / diagnosis
  • Radiation Injuries / genetics
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • Contrast Media
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes