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Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate

Author(s)
Andronesi, O. C.; Loebel, F.; Bogner, W.; Marjanska, M.; Iafrate, A. J.; Dietrich, J.; Batchelor, T. T.; Gerstner, E. R.; Kaelin, W. G.; Chi, A. S.; Rosen, B. R.; Cahill, D. P.; Vander Heiden, Matthew G.; ... Show more Show less
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Abstract
Purpose: Measurements of objective response rates are critical to evaluate new glioma therapies. The hallmark metabolic alteration in gliomas with mutant isocitrate dehydrogenase (IDH) is the overproduction of oncometabolite 2-hydroxyglutarate (2HG), which plays a key role in malignant transformation. 2HG represents an ideal biomarker to probe treatment response in IDH-mutant glioma patients, and we hypothesized a decrease in 2HG levels would be measureable by in vivo magnetic resonance spectroscopy (MRS) as a result of antitumor therapy. Experimental Design: We report a prospective longitudinal imaging study performed in 25 IDH-mutant glioma patients receiving adjuvant radiation and chemotherapy. A newly developed 3D MRS imaging was used to noninvasively image 2HG. Paired Student t test was used to compare pre- and posttreatment tumor 2HG values. Test-retest measurements were performed to determine the threshold for 2HG functional spectroscopic maps (fSM). Univariate and multivariate regression were performed to correlate 2HG changes with Karnofsky performance score (KPS). Results: We found that mean 2HG (2HG/Cre) levels decreased significantly (median=48.1%; 95% confidence interval=27.3%-56.5%; P=0.007) in the posttreatment scan. The volume of decreased 2HG correlates (R2=0.88, P=0.002) with clinical status evaluated by KPS. Conclusions: We demonstrate that dynamic measurements of 2HG are feasible by 3D fSM, and the decrease of 2HG levels can monitor treatment response in patients with IDH-mutant gliomas. Our results indicate that quantitative in vivo 2HG imaging maybe used for precision medicine and early response assessment in clinical trials of therapies targeting IDH-mutant gliomas.
Date issued
2016-04
URI
http://hdl.handle.net/1721.1/116921
Department
Koch Institute for Integrative Cancer Research at MIT
Journal
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Citation
Andronesi, O. C. et al. “Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate.” Clinical Cancer Research 22, 7 (November 2015): 1632–1641 © 2015 American Association for Cancer Research
Version: Author's final manuscript
ISSN
1078-0432
1557-3265

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