| Literature DB >> 28248126 |
Changho Choi1, Jack M Raisanen1, Sandeep K Ganji1, Song Zhang1, Sarah S McNeil1, Zhongxu An1, Akshay Madan1, Kimmo J Hatanpaa1, Vamsidhara Vemireddy1, Christie A Sheppard1, Dwight Oliver1, Keith M Hulsey1, Vivek Tiwari1, Tomoyuki Mashimo1, James Battiste1, Samuel Barnett1, Christopher J Madden1, Toral R Patel1, Edward Pan1, Craig R Malloy1, Bruce E Mickey1, Robert M Bachoo1, Elizabeth A Maher1.
Abstract
Purpose Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-hydroxyglutarate (2HG), the oncometabolite produced in neoplasms harboring a mutation in the gene coding for isocitrate dehydrogenase ( IDH). We conducted a prospective longitudinal imaging study to determine whether quantitative assessment of 2HG by MRS could serve as a noninvasive clinical imaging biomarker for IDH-mutated gliomas. Patients and Methods 2HG MRS was performed in 136 patients using point-resolved spectroscopy at 3 T in parallel with standard clinical magnetic resonance imaging and assessment. Data were analyzed in patient cohorts representing the major phases of the glioma clinical course and were further subgrouped by histology and treatment type to evaluate 2HG. Histologic correlations were performed. Results Quantitative 2HG MRS was technically and biologically reproducible. 2HG concentration > 1 mM could be reliably detected with high confidence. During the period of indolent disease, 2HG concentration varied by less than ± 1 mM, and it increased sharply with tumor progression. 2HG concentration was positively correlated with tumor cellularity and significantly differed between high- and lower-grade gliomas. In response to cytotoxic therapy, 2HG concentration decreased rapidly in 1p/19q codeleted oligodendrogliomas and with a slower time course in astrocytomas and mixed gliomas. The magnitude and time course of the decrease in 2HG concentration and magnitude of the decrease in tumor volume did not differ between oligodendrogliomas treated with temozolomide or carmustine. Criteria for 2HG MRS were established to make a presumptive molecular diagnosis of an IDH mutation in gliomas technically unable to undergo a surgical procedure. Conclusion 2HG concentration as measured by MRS was reproducible and reliably reflected the disease state. These data provide a basis for incorporating 2HG MRS into clinical management of IDH-mutated gliomas.Entities:
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Year: 2016 PMID： 28248126 PMCID： PMC5477829 DOI： 10.1200/JCO.2016.67.1222
Source DB: PubMed Journal: J Clin Oncol ISSN： 0732-183X Impact factor: 44.544