Abstract

Abstract INTRODUCTION The onco-metabolite, 2-hydroxyglutarate (2HG), is non-invasive biomarker detected by magnetic resonance spectroscopy (MRS), indicating isocitrate dehydrogenase (IDH) mutant glioma. Especially in patients with brainstem lesions where biopsies are at high risk of causing neurological deficit, 2HG-MRS may be useful. Here, we examined the utility of 2HG-MRS for diagnosing IDH mutant adult diffuse brainstem glioma and the ability of prognosis prediction. METHODS Three tesla -MRS (3T-MRS) was performed on patients with radiographically confirmed brainstem tumor. A single-voxel was set in the lesion with reference to the T2 / FLAIR image, and analyzed according to the 2HG-tailored MRS protocol (Philips, Achieva, PRESS, TE 35 ms). All patients underwent biopsy using an intraoperative navigation system (Brain LABTM) or stereotactic biopsy system (Komai’s CT-stereotactic frame) before initial treatment. IDH and H3K27M mutation status were confirmed by immunohistochemistry and DNA sequence. We examined the relationship between 2HG values and patient survival period. RESULTS Ten patients (7 male and 3 female, median age 33.5) underwent 2HG-MRS and biopsy. Four had H3K27M mutation and 4 had IDH mutation (1 R132H, 2 R132S, and 1 R132G). Two had neither H3K27M nor IDH mutation. H3-K27 and IDH mutations were mutually exclusive. All tumor located at pons mainly. There was no significant radiological difference between H3K27M and IDH mutant in conventional MRI sequence. Pearson's chi-square test demonstrated that 2HG concentrations > 1.5 mM were 100% in sensitivity and 83.3% in specificity for IDH mutant glioma (p = 0.0098). The median overall survival was 130.5 months in IDH mutant glioma (n=4) and 25 months in IDH wild-type glioma (n=6), respectively. CONCLUSIONS 3T-MRS was able to detect 2HG in adult brainstem glioma. A noninvasive 2HG-MRS study may be helpful in the diagnosis and predicting prognosis of adult diffuse brainstem glioma patient.

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