Predicting the recurrence of hepatocellular carcinoma (≤ 5 cm) after resection surgery with promising risk factors: habitat fraction of tumor and its peritumoral micro-environment.

PURPOSE: Characterizing the composition of hepatocellular carcinoma (HCC) and peritumoral micro-environment may provide sensitive biomarkers. We aimed to predict the recurrence-free survival (RFS) of HCC (≤ 5 cm) with habitat imaging of HCC and its peritumoral micro-environment. MATERIAL AND METHODS: A total of 264 patients with HCC were included. Taking advantage of the enhancement ratio at the arterial and hepatobiliary phase of contrast-enhanced MRI, all HCCs and their peritumoral tissue of 3 mm and 4 mm were encoded with different habitats. Besides, the quantitative fraction of each habitat of HCC and peritumoral tissue were calculated. Univariable and multivariable Cox regression analysis was performed to select the prognostic factors. The nomogram-based predictor was established. Kaplan-Meier analysis was conducted to stratify the recurrence risk. Fivefold cross-validation was performed to determine the predictive performance with the concordance index (C-Index). Decision curve analysis was used to evaluate the net benefit. RESULTS: Qualitatively, the spatial distribution of the habitats varied for different survival outcomes. Quantitatively, the fraction of habitat 3 in peritumoral tissue of 4 mm (f3-P4) was selected as independent risk factors (OR = 89.2, 95% CI = 14.5-549.2, p < 0.001) together with other two clinical variables. Integrating both clinical variables and f3-P4, a nomogram was constructed and showed high predictive efficacy (C-Index: 0.735, 95% CI 0.617-0.854) and extra net benefit according to the decision curve. Furthermore, patients with low f3-P4 or risk score given by nomogram have far longer RFS than those with high f3-P4 or risk score (stratification by f3-P4: 131.9 vs 55.0 months and stratification by risk score:131.9 vs 34.1 months). CONCLUSION: Habitat imaging of HCC and peritumoral microenvironment can be used for effectively and non-invasively estimating the RFS, which holds potential in guiding clinical management and decision making.