Academic Journal
Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate
| العنوان: | Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate |
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| المؤلفون: | 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. |
| المساهمون: | Koch Institute for Integrative Cancer Research at MIT, Vander Heiden, Matthew G. |
| المصدر: | PMC |
| بيانات النشر: | American Association for Cancer Research (AACR) |
| سنة النشر: | 2018 |
| المجموعة: | DSpace@MIT (Massachusetts Institute of Technology) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| تدمد: | 1078-0432 1557-3265 |
| Relation: | http://dx.doi.org/10.1158/1078-0432.CCR-15-0656; Clinical Cancer Research; http://hdl.handle.net/1721.1/116921; 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; orcid:0000-0002-6702-4192 |
| الاتاحة: | http://hdl.handle.net/1721.1/116921 |
| Rights: | Creative Commons Attribution-Noncommercial-Share Alike ; http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| رقم الانضمام: | edsbas.20018278 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 10780432 15573265 |
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