Article
Monitoring of treatment response in IDH-mutant gliomas by assessment of 2-hydroxyglutarate with in-vivo magnetic resonance spectroscopy
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Authors
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Franziska Loebel
- Department of Neurosurgery, Massachusetts General Hospital / Harvard Medical School, Boston, MA, USA; Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Boston, MA, USA
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Wolfgang Bogner
- Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Boston, MA, USA
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Elizabeth R. Gerstner
- Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital / Harvard Medical School, Boston, MA, USA
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Bruce R. Rosen
- Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Boston, MA, USA
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Andrew S. Chi
- Department of Neurology, Massachusetts General Hospital / Harvard Medical School, Boston, MA, USA
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Daniel P. Cahill
- Department of Neurosurgery, Massachusetts General Hospital / Harvard Medical School, Boston, MA, USA
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Ovidiu C. Andronesi
- Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Boston, MA, USA
| Published: | May 13, 2014 |
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Outline
Text
Objective: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), found in a distinct subset of human gliomas characterized by younger age and improved prognosis, cause marked elevation of the metabolite 2-hydroxyglutarate (2HG). Previous results of our group show that 2HG can be specifically detected using in-vivo Magnetic Resonance Spectroscopy (MRS). As elevated levels of 2HG are specific for IDH-mutant gliomas and present in nearly all tumor cells, this metabolite has been suggested to be an ideal biomarker for assessment of treatment response in IDH-mutant glioma patients. The aim of the present study was to show that changes in 2HG-levels after radiation treatment can be detected and monitored with in-vivo MRS in IDH-mutant glioma patients.
Method: IDH-mutant glioma patients (N=10) with residual tumor after surgery were subjected to in-vivo MRS scans using a 3 Tesla clinical scanner, before and after undergoing adjuvant radiotherapy. An additional group of patients (N=5) with residual disease who did not receive adjuvant treatment served as positive control. Levels of 2HG were assessed quantitatively with a newly developed 3-dimensional (3D) multi-voxel spectral editing (MEGA-LASER) sequence, and evaluated using LC Model software.
Results: We were able to show detectable levels of 2HG in all pre-treatment scans of patients that did not have gross total resection of their tumor (9 out of 10), confirming the sensitivity of our method. 3D metabolic maps were obtained for 2HG and several important metabolites for brain tumor assessment. The first three post-treatment spectra demonstrated detectable 2HG signals, which were found to vary when compared to their corresponding baseline scans. Our initial findings will be confirmed and statistically validated in our larger cohort.
Conclusions: Our results show for the first time that treatment response can be detected and monitored in IDH-mutant glioma patients by measuring changes of 2HG levels with in-vivo MRS. This non-invasive, objective method has the potential to prevent multiple invasive procedures (i.e. biopsies) for treatment monitoring. Moreover, the clinical application of our method could improve management of IDH-mutant glioma patients by differentiating treatment response from pseudo-response, tumor recurrence and progression.
