Identification of Macrotrabecular-Massive Hepatocellular Carcinoma and Prediction of Response to Transarterial Chemoembolization Plus Antiangiogenic Therapy Using Ct Radiomics

Objective: Macrotrabecular-massive (MTM) subtype represents an aggressive form of hepatocellular carcinoma (HCC) that is associated with angiogenesis activation. We aimed to develop and validate a radiomics approach for identification of MTM subtype and explore its role in predicting response to transarterial chemoembolization (TACE) plus antiangiogenic therapy.Methods: This retrospective multicohort study consisted of five independent cohorts. XY3A cohort, XY3B cohort, and YY&HC cohort including 365 surgically resected patients with preoperative liver contrast-enhanced CT imaging data were used to train and internally and externally validate a noninvasive radiomics signature (RS). The association of the RS with angiogenesis activation gene expression was analyzed in a TCGA-LIHC cohort including 41 patients. A dataset including 58 advanced patients receiving TACE plus antiangiogenic therapy, was used to evaluate the predictive value of the RS in terms of clinical outcomes.Results: We developed the RS that included 11 radiomics features, showing good performance for identifying MTM subtype, with the AUCs of 0.837, 0.795, and 0.735 in the XY3A cohort, XY3B cohort, and YY&HC cohort, respectively. A clinical-radiomics model (CRM) that integrated the RS and high serum α-fetoprotein level showed good discrimination and calibration in the three cohorts (AUCs of 0.876, 0.817, and 0.767, respectively), though without significant improvement compared with the RS (all P > 0.05). The RS score was significantly correlated with VEGFA gene expression level (rho = -0.342, P = 0.029). In the treatment cohort, a lower baseline RS score was found in those who achieved an objective response (P = 0.008) or disease control (P = 0.033), and was independently associated with improved progression-free survival (HR, 0.478; 95% CI: 0.237, 0.963, P = 0.039).Conclusions: The preoperative CT-derived RS allows for accurate characterization of MTM subtype and helps to infer clinical outcomes in advanced patients receiving TACE plus antiangiogenic therapy.Funding: Wisdom Accumulation and Talent Cultivation Project of The Third Xiangya Hospital of Central South University.Declaration of Interest: None to declare, Ethical Approval: This retrospective study was compliant with Health Insurance Portability andAccountability Act (HIPAA) and approved by the Institutional Review Board (IRB) ofThe Third Xiangya Hospital, Central South University.