Development and validation of an MRI-based nomogram for the preoperative prediction of tumor mutational burden in lower-grade gliomas

Abstract

Background: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors. In this study, we aimed to determine the value of magnetic resonance (MR)-based preoperative nomogram in predicting TMB status in lower-grade glioma (LGG) patients. Methods: Overall survival (OS) data were derived from The Cancer Genome Atlas (TCGA) and then analyzed by using the Kaplan-Meier method and time-dependent receiver operating characteristic (tdROC) analysis. The magnetic resonance imaging (MRI) data of 168 subjects obtained from The Cancer Imaging Archive (TCIA) were retrospectively analyzed. The correlation was explored by univariate and multivariate regression analyses. Finally, we performed tenfold cross validation. TMB values were retrieved from the supplementary information of a previously published article. Results: The high TMB subtype was associated with the shortest median OS (high vs. low: 50.9 vs. 95.6 months, P<0.05). The tdROC for the high-TMB tumors was 74% (95% CI: 61-86%) for survival at 12 months, and 71% (95% CI: 60-82%) for survival at 24 months. Multivariate logistic regression analysis confirmed that three risk factors [extranodular growth: Odds ratio (OR): 8.367, 95% CI: 3.153-22.199, P<0.01; length-width ratio ≥ median: OR: 1.947, 95% CI: 1.025-3.697, P<0.05; frontal lobe: OR: 0.455, 95% CI: 0.229-0.903, P<0.05] were significant independent predictors of high-TMB tumors. The nomogram showed good calibration and discrimination. This model had an area under the curve (AUC) of 0.736 (95% CI: 0.655-0.817). Decision curve analysis (DCA) demonstrated that the nomogram was clinically useful. The average accuracy of the tenfold cross validation was 71.6% for high-TMB tumors. Conclusions: Our results indicated that a distinct OS disadvantage was associated with the high TMB group. In addition, extranodular growth, nonfrontal lobe tumors and length-width ratio ≥ median can be conveniently used to facilitate the prediction of high-TMB tumors.