Development of MR-based preoperative nomograms predicting DNA copy number subtype in lower grade gliomas with prognostic implication.

Objectives: We aimed to determine the value of MR-based preoperative nomograms in predicting DNA copy number (CN) subtype in lower grade glioma (LGG) patients.

Methods: The overall survival (OS) data were analyzed. MRI data of 170 subjects were retrospectively analyzed. The correlation was explored by univariate and multivariate regression analysis.

Results: CN2 subtype was associated with shortest median OS (CN2 subtype vs. others: 46.8 vs. 221.7 months, p < 0.05). The time-dependent receiver operating characteristic for the CN2 subtype was 0.80 (95% CI: 0.74-0.85) for survival at 1 year, 0.80 (95% CI: 0.75-0.85) for survival at 2 years, and 0.77 (95% CI: 0.73-0.83) for survival at 3 years. On multivariate analysis, hemorrhage (OR: 0.118; p < 0.001; 95% CI: 0.037-0.376), poorly defined margin (OR: 4.592; p < 0.001; 95% CI: 1.965-10.730), extranodular growth (OR: 0.247; p = 0.006; 95% CI: 0.091-0.671), and volume ≥ 60 cm (OR: 4.734.256; p < 0.001; 95% CI: 2.051-10.924) were associated with CN1 subtype (AUC: 0.781). Proportion CE tumor (OR: 5.905; p = 0.007; 95% CI: 1.622-21.493), extranodular growth (OR: 9.047; p = 0.001; 95% CI: 2.349-34.846), width ≥ median (OR: 0.231; p = 0.049; 95% CI: 0.054-0.998), and depth ≥ median (OR: 0.192; p = 0.023; 95% CI: 0.046-0.799) were associated with CN2 subtype (AUC: 0.854). Necrosis/cystic (OR: 6.128; p = 0.007; 95% CI: 1.635-22.968), hemorrhage (OR: 5.752; p = 0.002; 95% CI: 1.953-16.942), poorly defined margin (OR: 0.164; p < 0.001; 95% CI: 0.063-0.427), and volume ≥ median (OR: 4.422; p < 0.001; 95% CI: 1.925-10.160) were associated with CN3 subtype (AUC: 0.808). All three nomograms showed good discrimination and calibration. Decision curve analysis supported that all nomograms were clinically useful. The average accuracy of the tenfold cross-validation was 0.680 (CN1), 0.794 (CN2), and 0.894 (CN3), respectively.

Conclusions: The shortest OS was observed in patients with CN2 subtype. This preliminary radiogenomics analysis revealed that the MR-based preoperative nomograms provide individualized prediction of DNA copy number subtype in LGG patients.

Key Points: • This preliminary radiogenomics analysis of LGG revealed that the MR-based preoperative nomograms provide individualized prediction of DNA copy number subtype in LGG patients. • The AUC for the ROC curve was 0.781 for CN1 subtype, 0.854 for CN2 subtype, and 0.808 for CN3 subtype. Decision curve analysis supported that all nomograms were clinically useful. • The sensitivity was 0.779 (CN1), 0.731 (CN2), and 0.851 (CN3), respectively. The specificity was 0.664 (CN1), 0.872 (CN2), and 0.625 (CN3), respectively. And the accuracy was 0.717 (CN1), 0.849 (CN2), and 0.692 (CN3), respectively.