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


Journal

Revue neurologique
ISSN: 0035-3787
Titre abrégé: Rev Neurol (Paris)
Pays: France
ID NLM: 2984779R

Informations de publication

Date de publication:
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

534-543

Informations de copyright

Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Auteurs

A Bani-Sadr (A)

Service de neuroradiologie, groupe hospitalier Est, hospices de civils de Lyon, 59, boulevard Pinel, 69634 Lyon cedex, France.

L P Berner (LP)

Service de neuroradiologie, groupe hospitalier Est, hospices de civils de Lyon, 59, boulevard Pinel, 69634 Lyon cedex, France.

M Barritault (M)

Service d'anatomopathologie, groupe hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69394 Lyon cedex, France; Université Claude-Bernard Lyon 1, Lyon, France.

L Chamard (L)

Service de neuroradiologie, groupe hospitalier Est, hospices de civils de Lyon, 59, boulevard Pinel, 69634 Lyon cedex, France.

C M Bidet (CM)

Service de radiologie, centre hospitalier de Valence, 179, boulevard Juin, 26000 Valence, France.

O F Eker (OF)

Service de neuroradiologie, groupe hospitalier Est, hospices de civils de Lyon, 59, boulevard Pinel, 69634 Lyon cedex, France; Université Claude-Bernard Lyon 1, Lyon, France.

M Hermier (M)

Service de neuroradiologie, groupe hospitalier Est, hospices de civils de Lyon, 59, boulevard Pinel, 69634 Lyon cedex, France.

J Guyotat (J)

Service de neurochirurgie D, groupe hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69634 Lyon cedex, France; Université Claude-Bernard Lyon 1, Lyon, France.

E Jouanneau (E)

Service de neurochirurgie D, groupe hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69634 Lyon cedex, France; Service de neuro-oncologie, groupe hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69394 Lyon cedex, France.

D Meyronet (D)

Service d'anatomopathologie, groupe hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69394 Lyon cedex, France; Université Claude-Bernard Lyon 1, Lyon, France.

S Gouttard (S)

Pôle d'activité médicale imagerie, hospices civils de Lyon, 162, avenue Lacassagne, 69424 Lyon cedex, France.

A D'Hombres (A)

Service de radiothérapie, centre hospitalier Lyon Sud, 165, chemin du Grand-Revoyet, 69310 Pierre-Bénite, France.

C Iziquierdo (C)

Service de neuro-oncologie, groupe hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69394 Lyon cedex, France.

J Honnorat (J)

Service de neuro-oncologie, groupe hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69394 Lyon cedex, France; Université Claude-Bernard Lyon 1, Lyon, France.

Y Berthezène (Y)

Service de neuroradiologie, groupe hospitalier Est, hospices de civils de Lyon, 59, boulevard Pinel, 69634 Lyon cedex, France; Université Claude-Bernard Lyon 1, Lyon, France.

F Ducray (F)

Service de neuro-oncologie, groupe hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69394 Lyon cedex, France; Université Claude-Bernard Lyon 1, Lyon, France. Electronic address: francois.ducray@chu-lyon.fr.

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Classifications MeSH