Prospective Longitudinal Analysis of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy Identifies Broad Clinical Utility for the Management of Patients With IDH -Mutant Glioma

作者：Changho Choi, Jack Raisanen, Sandeep Ganji, Song Zhang, Sarah McNeil, Zhongxu An, Akshay Madan, Kimmo J. Hatanpaa, Vamsidhara Vemireddy, Christie A. Sheppard, Dwight Oliver, Keith Hulsey, Vivek Tiwari, Tomoyuki Mashimo, James Battiste, Samuel Barnett, Christopher J. Madden, Toral Patel, Edward Pan, Craig R. Malloy, Bruce Mickey, Robert Bachoo, Elizabeth A. Maher · 发表于：Journal of Clinical Oncology · 年份：2016 · DOI：10.1200/jco.2016.67.1222 · 被引用次数：199 · 研究领域：Glioma Diagnosis and Treatment、Advanced MRI Techniques and Applications、Mitochondrial Function and Pathology

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 t...