In Vivo 2-Hydroxyglutarate Monitoring with Edited MR Spectroscopy for the Follow-up of IDH -Mutant Diffuse Gliomas: The IDASPE Prospective Study

Anna Luisa Di Stefano, Lucia Nichelli, Giulia Berzero, Romain Valabregue, Mehdi Touat, Laurent Capelle, Clément Pontoizeau, Franck Bielle, Julie Lerond, Marine Giry, Chiara Villa, Bertrand Baussart, Caroline Dehais, Damien Galanaud, Capucine Baldini, Julien Savatovsky, Frédéric Dhermain, Dinesh K. Deelchand, Chris Ottolenghi, Stéphane LehéricyMałgorzata Marjańska, Francesca Branzoli, Marc Sanson

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background and ObjectivesD-2-hydroxyglutarate (2HG) characterizes IDH-mutant gliomas and can be detected and quantified with edited MRS (MEGA-PRESS). In this study, we investigated the clinical, radiologic, and molecular parameters affecting 2HG levels.MethodsMEGA-PRESS data were acquired in 71 patients with glioma (24 untreated, 47 treated) on a 3 T system. Eighteen patients were followed during cytotoxic (n = 12) or targeted (n = 6) therapy. 2HG was measured in tumor samples using gas chromatography coupled to mass spectrometry (GCMS).ResultsMEGA-PRESS detected 2HG with a sensitivity of 95% in untreated patients and 62% in treated patients. Sensitivity depended on tumor volume (>27 cm3; p = 0.02), voxel coverage (>75%; p = 0.002), and expansive presentation (defined by equal size of T1 and FLAIR abnormalities, p = 0.04). 2HG levels were positively correlated with IDH-mutant allelic fraction (p = 0.03) and total choline levels (p < 0.001) and were higher in IDH2-mutant compared with IDH1R132H-mutant and non-R132H IDH1-mutant patients (p = 0.002). In patients receiving IDH inhibitors, 2HG levels decreased within a few days, demonstrating the on-target effect of the drug, but 2HG level decrease did not predict tumor response. Patients receiving cytotoxic treatments showed a slower decrease in 2HG levels, consistent with tumor response and occurring before any tumor volume change on conventional MRI. At progression, 1p/19q codeleted gliomas, but not the non-codeleted, showed detectable in vivo 2HG levels, pointing out to different modes of progression characterizing these 2 entities.DiscussionMEGA-PRESS edited MRS allows in vivo monitoring of 2-hydroxyglutarate, confirming efficacy of IDH inhibition and suggests different patterns of tumor progression in astrocytomas compared with oligodendrogliomas.

Original languageEnglish (US)
Pages (from-to)E94-E106
JournalNeurology
Volume100
Issue number1
DOIs
StatePublished - Jan 3 2023

Bibliographical note

Funding Information:
The authors would like to thank Edward J. Auerbach, PhD, for implementing MRS sequences on the Siemens platform. The MRS sequences used in this study are part of the MRS package developed by Edward J. Auerbach, Ph.D., and Małgorzata Marjańska, Ph.D., and provided by the University of Minnesota under a C2P agreement. Lucia Nichelli acknowledges support from the scholarship “Bourse de Recherche Alain Rahmouni SFR-CERF 2019”. Małgorzata Marjańska acknowledges support from National Institutes of Health grants BTRC P41 EB027061 and P30 NS076408. The authors would like to thank Edward J. Auerbach, PhD, for implementing MRS sequences on the Siemens platform. The MRS sequences used in this study are part of the MRS package developed by Edward J. Auerbach, Ph.D., and Małgorzata Marjańska, Ph.D., and provided by the University of Minnesota under a C2P agreement.

Funding Information:
L. Nichelli has received support from the scholarship “Bourses de Recherche Alain Rahmouni 2019.” M. Touat reports consulting or advisory role from Agios Pharmaceutical, Integragen, and Taiho Oncology, outside the submitted work; research funding from Sanofi, outside the submitted work. S. Lehéricy reports research funding from ANR-11-INBS-0006 (France Life Imaging–FLI), and Biogen outside the submitted work M. Marjańska has received support from National Institutes of Health grants BTRC P41 EB027061 and P30 NS076408. M. Sanson reports consulting or advisory role from Genenta, Abbvie, Taiho Oncology, Orion Pharma, Mundipharma outside the submitted work and research funding from Astra-Zeneca, outside the submitted work. The other authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Funding Information:
This study (NCT02597335) was funded by the INCa- Institut National du Cancer (PHRC Cancer 2012, sponsor Assistance Publique Hôpitaux de Paris), by the grant INCa-DGOS-Inserm_12560 of the SiRIC CURAMUS, by funding from the program “investissements d'avenir” ANR-10-IAIHU-06, and by a grant from the Ligue Nationale contre le Cancer (LNCC; équipe labellisée).

Publisher Copyright:
© American Academy of Neurology.

Center for Magnetic Resonance Research (CMRR) tags

  • SMCT
  • CTR

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint

Dive into the research topics of 'In Vivo 2-Hydroxyglutarate Monitoring with Edited MR Spectroscopy for the Follow-up of IDH -Mutant Diffuse Gliomas: The IDASPE Prospective Study'. Together they form a unique fingerprint.

Cite this