Construction of a random survival forest model based on a machine learning algorithm to predict early recurrence after hepatectomy for adult hepatocellular carcinoma.

Background And Aims: Hepatocellular carcinoma (HCC) exhibits a propensity for early recurrence following liver resection, resulting in a bleak prognosis. At present, majority of the predictive models for the early postoperative recurrence of HCC rely on the linear assumption of the Cox Proportional Hazard (CPH) model. However, the predictive efficacy of this model is constrained by the intricate nature of clinical data. The present study aims to investigate the efficacy of the random survival forest (RSF) model, which is a machine learning algorithm, in predicting the early postoperative recurrence of HCC, and compare its performance with that of the traditional CPH model. This analysis seeks to elucidate the potential advantages of the RSF model over the CPH model in addressing this clinical challenge.

Methods: The present retrospective cohort study was conducted at a single center. After excluding 41 patients, a total of 541 patients were included in the final model construction and subsequent analysis. The patients were randomly divided into two groups at a 7:3 ratio: training group (n = 378) and validation group (n = 163). The least absolute shrinkage and selection operator (LASSO) regression was used to identify the risk factors in the training group. Then, the identified factors were used to develop the RSF and CPH regression models. The predictive ability of the model was assessed using the concordance index (C-index). The accuracy of the model predictions was evaluated using the receiver operating characteristic curve (ROC) and area under the receiver operating characteristic curve (AUC). The clinical practicality of the model was measured by decision curve analysis (DCA), and the overall performance of the model was evaluated using the Brier score. The RSF model was visually represented using the Shapley additive explanations (SHAP) framework. Then, the RSF, CPH regression, and albumin-bilirubin (ALBI) grade models were compared.

Results: The following variables were examined by LASSO regression: alpha fetoprotein (AFP), gamma-glutamyl transpeptidase to platelet ratio (GPR), blood transfusion (BT), microvascular invasion (MVI), large vessel invasion (LVI), Edmondson-Steiner (ES) grade, liver capsule invasion (LCI), satellite nodule (SN), and Barcelona clinic liver cancer (BCLC) grade. Then, a RSF model was developed using 500 trees, and the variable importance (VIMP) ranking was MVI, LCI, SN, BT, BCLC, ESG, AFP, GPR and LVI. After these aforementioned factors were applied, the RSF and CPH regression models were developed and compared using the ALBI grade model. The C-index for the RSF model (0.896 and 0.798, respectively) outperformed that of the CPH regression model (0.803 and 0.772, respectively) and ALBI grade model (0.517 and 0.515, respectively), in both the training and validation groups. Three time points were selected to assess the predictive capabilities of these models: 6, 12 and 18 months. For the training group, the AUC value for the RSF model at 6, 12 and 18 months was 0.971 (95% CI: 0.955-0.988), 0.919 (95% CI: 0.887-0.951) and 0.899 (95% CI: 0.867-0.932), respectively. For the validation cohort, the AUC value for the RSF model at 6, 12 and 18 months was 0.830 (95% CI: 0.728-0.932), 0.856 (95% CI: 0.787-0.924) and 0.832 (95% CI: 0.764-0.901), respectively. The AUC values were higher in the RSF model, when compared to the CPH regression model and ALBI grade model, in both groups. The DCA results revealed that the net clinical benefits associated to the RSF model were superior to those associated to the CPH regression model and ALBI grade model in both groups, suggesting a higher level of clinical utility in the RSF model. The Brier score for the RSF model at 6, 12 and 18 months was 0.062, 0.125 and 0.178, respectively, in the training group, and 0.111, 0.128 and 0.149, respectively, in the validation group. In summary, the RSF model demonstrated superior performance, when compared to the CPH regression model and ALBI grade model. Furthermore, the RSF model demonstrated superior predictive ability, accuracy, clinical practicality, and overall performance, when compared to the CPH regression model and ALBI grade model. In addition, the RSF model was able to successfully stratify patients into three distinct risk groups (low-risk, medium-risk and high-risk) in both groups (p < 0.001).

Conclusions: The RSF model demonstrates efficacy in predicting early recurrence following HCC surgery, exhibiting superior performance, when compared to the CPH regression model and ALBI grade model. For patients undergoing HCC surgery, the RSF model can serve as a valuable tool for clinicians to postoperatively stratify patients into distinct risk categories, offering guidance for subsequent follow-up care.