2-Hydroxyglutarate MR spectroscopy for prediction of isocitrate dehydrogenase mutant glioma: a systemic review and meta-analysis using individual patient data.

Background: Noninvasive and accurate modality to predict isocitrate dehydrogenase (IDH) mutant glioma may have great potential in routine clinical practice. We aimed to investigate the diagnostic performance of 2-hydroxyglutarate (2HG) magnetic resonance spectroscopy (MRS) for prediction of IDH mutant glioma and provide an optimal cutoff value for 2HG.
Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed to identify original articles investigating the diagnostic performance of 2HG MRS up to March 20, 2018. Pooled sensitivity and specificity were calculated using a bivariate random-effects model. Subgroup analysis and meta-regression were performed to explain heterogeneity effects. An optimal cutoff value for 2HG was calculated from studies providing individual patient data.
Results: Fourteen original articles with 460 patients were included. The pooled sensitivity and specificity for the diagnostic performance of 2HG MRS for prediction of IDH mutant glioma were 95% (95% CI, 85-98%) and 91% (95% CI, 83-96%), respectively. The Higgins I2 statistic demonstrated that heterogeneity was present in the sensitivity (I2 = 50.69%), but not in the specificity (I2 = 30.37%). In the meta-regression, echo time (TE) was associated with study heterogeneity. Among the studies using point-resolved spectroscopy (PRESS), a long TE (97 ms) resulted in higher sensitivity (92%) and specificity (97%) than a short TE (30-35 ms; sensitivity of 90%, specificity of 88%; P < 0.01). The optimal 2HG cutoff value of 2HG using individual patient data was 1.76 mM.
Conclusion: 2HG MRS demonstrated excellent specificity for prediction of IDH mutant glioma, with TE being associated with heterogeneity in the sensitivity.
Key Points: 1. HG MRS has excellent diagnostic performance in the prediction of IDH mutant glioma. 2. The pooled sensitivity was 95% and the pooled specificity was 91%. 3. Echo time was associated with study heterogeneity in the meta-regression.