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Objective:
To investigate the potential of radiomics features and dual-source dual-energy CT (DECT) parameters in differentiating between benign and malignant mediastinal masses and predicting patient outcomes.

Materials and Methods:
In this retrospective study, we analyzed data from 90 patients (38 females, mean age 51 ± 25 years) with confirmed mediastinal masses who underwent contrast-enhanced DECT. Attenuation, radiomics features, and DECT-derived imaging parameters were evaluated by two experienced readers. We performed analysis of variance (ANOVA) and chi-square statistic tests for data comparison. Receiver operating characteristic curve analysis and Cox regression tests were used to differentiate between mediastinal masses.

Results:
Of the 90 mediastinal masses, 49 (54%) were benign, including cases of thymic hyperplasia/thymic rebound (n = 10), mediastinitis (n = 16), and thymoma (n = 23). The remaining 41 (46%) lesions were classified as malignant, consisting of lymphoma (n=28), mediastinal tumor (n = 4), and thymic carcinoma (n = 9). Significant differences were observed between benign and malignant mediastinal masses in all DECT-derived parameters (<em>p</em> = 0.001) and 38 radiomics features (<em>p</em> = .044) obtained from contrast-enhanced DECT. The combination of these methods achieved an area under the curve of 0.98 (95% CI, 0.893–1.000; <em>p</em> < 0.001) to differentiate between benign and malignant masses, with 100% sensitivity and 91% specificity. Throughout a follow-up of 1800 days, a multiparametric model incorporating radiomics features, DECT parameters, and gender showed promising prognostic power in predicting all-cause mortality (c-index = 0.8 [95% CI, 0.702–0.890], <em>p</em> < 0.001).

Conclusion:
In conclusion, our study highlights the potential of an approach that combines radiomics features and DECT-derived imaging markers for the noninvasive differentiation of benign and malignant mediastinal masses. The observed significant differences in DECT-derived imaging markers and radiomics features provide valuable information for the characterization of these masses. Incorporating these advanced imaging techniques into clinical practice may enhance the management and treatment planning for patients with mediastinal masses, ultimately improving patient care and outcomes. Further research and validation are needed to fully establish the clinical utility of these techniques and their impact on patient management.