In Vivo 2-Hydroxyglutarate Monitoring With Edited MR Spectroscopy for the Follow-up of IDH-Mutant Diffuse Gliomas: The IDASPE Prospective Study. (3rd January 2023)

• Record Type: Journal Article
• Authors: Di Stefano, Anna Luisa; Nichelli, Lucia; Berzero, Giulia; Valabregue, Romain; Touat, Mehdi; Capelle, Laurent; Pontoizeau, Clément; Bielle, Franck; Lerond, Julie; Giry, Marine; Villa, Chiara; Baussart, Bertrand; Dehais, Caroline; Galanaud, Damien; Baldini, Capucine; Savatovsky, Julien; Dhermain, Frédéric; Deelchand, Dinesh K.; Ottolenghi, Chris; Lehéricy, Stéphane; Marjańska, Małgorzata; Branzoli, Francesca; Sanson, Marc
• Is Part Of: Neurology. Volume 100:Number 1(2023)
• Page Start: e94
• Page End: e106
• Publication Date: 2023-01-03
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000201137
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Background and Objectives: D-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. Methods: MEGA-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). Results: MEGA-PRESS detected 2HG with a sensitivity of 95% in untreated patients and 62% in treated patients. Sensitivity depended on tumor volume (>27 cm 3 ; 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 IDH1 R132H -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. Discussion: MEGA-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.