Multiphase enhanced computed tomography features captured by delta radiomics reveal prognosis and tumor heterogeneity in patients with hepatocellular carcinoma treated with transarterial chemoembolization.

BACKGROUNDAlthough transarterial chemoembolization (TACE) is a widely used locoregional therapy for intermediate-stage hepatocellular carcinoma (HCC), there is substantial inter-patient heterogeneity in treatment response. This study aimed to develop a delta radiomic model based on pre-treatment enhanced computed tomography (CT) to predict the prognosis of HCC patients undergoing TACE and to reveal tumor heterogeneity.

METHODSA total of 269 patients treated with TACE between January 2016 and June 2020 were enrolled from two medical centers and divided into three cohorts: a training cohort (n = 126), an internal validation cohort (n = 84), an external test cohort (n = 59). Radiological features of the tumor area were extracted on multiple phases of CT before treatment, and progression-free survival (PFS) was predicted through the least absolute shrinkage and selection operator Cox (LASSO-Cox) regression algorithm. Overall survival (OS) was evaluated using the Kaplan-Meier curve. Genetic and tumor microenvironment differences related to the prognosis of TACE were analyzed in 23 patients with CT from The Cancer Genome Atlas (TCGA). Single-cell data from the comprehensive Gene Expression Omnibus (GEO) public database were used to explore the expression of different genes in cells.

RESULTSThe area under the receiver operating characteristic curves of the delta radiomic model for predicting 2-year PFS in TACE-treated patients were 0.812, 0.720, and 0.807 in the training, internal validation, and external test cohorts, respectively. The Rad-score was calculated based on radiomic features selected through LASSO. The Rad-score stratified patients into high- and low-risk groups, with significant differences in OS across all cohorts. The high-risk group had a higher immune score. It is worth noting that in the immune infiltration analysis, there were significant differences in B cells, resting CD4 memory T cells, active natural killer cells, and mast cells among different risk groups.

CONCLUSIONSThe delta radiomics model based on multiphase enhanced CT accurately predicts prognosis and reflects tumor heterogeneity in HCC patients treated with TACE, and contributes to treatment planning.