2-hydroxyglutarate MR Spectroscopy for Prediction of Isocitrate Dehydrogenase Mutant Glioma: A Systemic Review and Meta-analysis using Individual Patient Data

Abstract

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 cut-off 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 was performed to explain heterogeneity effects. An optimal cut-off 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 cut-off 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.