Combined analysis of MGMT methylation and dynamic-susceptibility-contrast MRI for the distinction between early and pseudo-progression in glioblastoma patients.
Adult
Aged
Biomarkers, Tumor
/ analysis
Brain Neoplasms
/ diagnosis
Chemoradiotherapy
/ adverse effects
Contrast Media
DNA Methylation
DNA Modification Methylases
/ analysis
DNA Repair Enzymes
/ analysis
Diagnosis, Differential
Disease Progression
Female
Follow-Up Studies
Glioblastoma
/ diagnosis
Humans
Magnetic Resonance Imaging
/ methods
Male
Middle Aged
Predictive Value of Tests
Prognosis
Radiation Injuries
/ diagnosis
Retrospective Studies
Time Factors
Treatment Outcome
Tumor Suppressor Proteins
/ analysis
Chemoradiotherapy
Disease progression
Glioblastoma
Perfusion magnetic resonance imaging
Radiation injuries
Journal
Revue neurologique
ISSN: 0035-3787
Titre abrégé: Rev Neurol (Paris)
Pays: France
ID NLM: 2984779R
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
05
07
2018
revised:
05
12
2018
accepted:
21
01
2019
pubmed:
19
6
2019
medline:
1
5
2020
entrez:
19
6
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 31208813
pii: S0035-3787(18)30736-7
doi: 10.1016/j.neurol.2019.01.400
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Contrast Media
0
Tumor Suppressor Proteins
0
DNA Modification Methylases
EC 2.1.1.-
MGMT protein, human
EC 2.1.1.63
DNA Repair Enzymes
EC 6.5.1.-
Types de publication
Evaluation Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
534-543Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.