Abstract
BACKGROUND: Current guidelines recommend surgical resection as the first-line option for patients with solitary hepatocellular carcinoma (HCC); unfortunately, postoperative recurrence rate remains high and there is no reliable prediction tool. We explored the potential of radiomics coupled with machine-learning algorithms to improve the predictive accuracy for HCC recurrence. METHODS: A total of 470 patients who underwent contrast-enhanced CT and curative resection for solitary HCC were recruited from 3 independent institutions. In the training phase of 210 patients from Institution 1, a radiomics-derived signature was generated based on 3384 engineered features extracted from primary tumor and its periphery using aggregated machine-learning framework. We employed Cox modeling to build predictive models. The models were then validated using an internal dataset of 107 patients and an external dataset of 153 patients from Institution 2 and 3. FINDINGS: Using the machine-learning framework, we identified a three-feature signature that demonstrated favorable prediction of HCC recurrence across all datasets, with C-index of 0.633-0.699. Serum alpha-fetoprotein, albumin-bilirubin grade, liver cirrhosis, tumor margin, and radiomics signature were selected for preoperative model; postoperative model incorporated satellite nodules into above-mentioned predictors. The two models showed superior prognostic performance, with C-index of 0.733-0.801 and integrated Brier score of 0.147-0.165, compared with rival models without radiomics and widely used staging systems (all P < 0.05); they also gave three risk strata for recurrence with distinct recurrence patterns. INTERPRETATION: When integrated with clinical data sources, our three-feature radiomics signature promises to accurately predict individual recurrence risk that may facilitate personalized HCC management.