Abstract
The oncometabolite 2-hydroxyglutarate (2HG) is produced by mutated isocitrate dehydrogenase (IDH). Magnetic resonance spectroscopy (MRS) detects 2HG noninvasively and has been reported to accurately identify IDH mutated tumors. 2HG-MRS may be able to help monitor disease activity over time, adding significantly to the diagnostic utility of conventional MRI. To evaluate implementation of 2HG spectroscopy and relationship to disease state, we performed 2HG-MRS on 21 patients with known glioma or MRI abnormalities suspicious for glioma (without prior biopsy) at our institution. When pathology was available, cases were assessed for diagnosis and tumor grade, IDH and 1p19q status as well as treatment history and clinical course. Analysis of 2HG-MRS results were done blinded to known IDH status. In 12 tumors with known IDH status, 9 cases were IDH-mutated, and 3 IDH-wildtype, and 5 were 1p19q-codeleted (and thus necessarily IDH-mutated). Out of all 21 patients, 8 were positive for 2HG by MRS and 13 were negative. In tumors with known IDH mutation, there was concordance with positive 2HG-MRS in 4 of 9. Due to this unexpected rate of apparent false negative 2HG-MRS, the 5 discordant cases were further reviewed. Three were clinically and radiographically stable by conventional MRI post treatment, so it is possible that absence of detectable 2HG reflected lack of active disease. However, 2 cases were negative for 2HG-MRS despite apparent progressive radiographic disease by conventional MRI. In contrast, all 4 concordant cases showed evidence of active or progressive tumor by conventional MRI. 2HG-MRS can aid conventional MRI in identification of IDH mutated gliomas non-invasively and may provide a more definitive assessment of treatment response for IDH mutated gliomas. However, it remains possible that some of our discordant cases represent insufficient sensitivity of 2HG-MRS, and further investigation is needed to optimize the sensitivity and specificity of 2HG-MRS for this purpose.
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