In:
Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 1 ( 2023-01-3), p. e94-e106
Abstract:
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 T 1 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.
Type of Medium:
Online Resource
ISSN:
0028-3878
,
1526-632X
DOI:
10.1212/WNL.0000000000201137
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2023
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