A Nomogram Modeling (11)C-MET PET/CT and Clinical Features in Glioma Helps Predict IDH Mutation

Purpose: We developed a (11)C-Methionine positron emission tomography/computed tomography ((11)C-MET PET/CT)-based nomogram model that uses easy-accessible imaging and clinical features to achieve reliable non-invasive isocitrate dehydrogenase (IDH)-mutant prediction with strong clinical translational capability. Methods: One hundred and ten patients with pathologically proven glioma who underwent pretreatment (11)C-MET PET/CT were retrospectively reviewed. IDH genotype was determined by IDH1 R132H immunohistochemistry staining. Maximum, mean and peak tumor-to-normal brain tissue (TNRmax, TNRmean, TNRpeak), metabolic tumor volume (MTV), total lesion methionine uptake (TLMU), and standard deviation of SUV (SUV(SD)) of the lesions on MET PET images were obtained via a dedicated workstation (Siemens. syngo.via). Univariate and multivariate logistic regression models were used to identify the predictive factors for IDH mutation. Nomogram and calibration plots were further performed. Results: In the entire population, TNRmean, TNRmax, TNRpeak, and SUV(SD) of IDH-mutant glioma patients were significantly lower than these values of IDH wildtype. Receiver operating characteristic (ROC) analysis suggested SUV(SD) had the best performance for IDH-mutant discrimination (AUC = 0.731, cut-off ≤ 0.29, p < 0.001). All pairs of the (11)C-MET PET metrics showed linear associations by Pearson correlation coefficients between 0.228 and 0.986. Multivariate analyses demonstrated that SUV(SD) (>0.29 vs. ≤ 0.29 OR: 0.053, p = 0.010), dichotomized brain midline structure involvement (no vs. yes OR: 26.52, p = 0.000) and age (≤ 45 vs. >45 years OR: 3.23, p = 0.023), were associated with a higher incidence of IDH mutation. The nomogram modeling showed good discrimination, with a C-statistics of 0.866 (95% CI: 0.796–0.937) and was well-calibrated. Conclusions: (11)C-Methionine PET/CT imaging features (SUV(SD) and the involvement of brain midline structure) can be conveniently used to facilitate the pre-operative prediction of IDH genotype. The nomogram model based on (11)C-Methionine PET/CT and clinical age features might be clinically useful in non-invasive IDH mutation status prediction for untreated glioma patients.