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Development and validation of machine learning models for predicting prognosis and guiding individualized postoperative chemotherapy: A real-world study of distal cholangiocarcinoma

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Background Distal cholangiocarcinoma (dCCA), originating from the common bile duct, is greatly associated with a dismal prognosis. A series of different studies based on cancer classification have been developed, aimed… Click to show full abstract

Background Distal cholangiocarcinoma (dCCA), originating from the common bile duct, is greatly associated with a dismal prognosis. A series of different studies based on cancer classification have been developed, aimed to optimize therapy and predict and improve prognosis. In this study, we explored and compared several novel machine learning models that might lead to an improvement in prediction accuracy and treatment options for patients with dCCA. Methods In this study, 169 patients with dCCA were recruited and randomly divided into the training cohort (n = 118) and the validation cohort (n = 51), and their medical records were reviewed, including survival outcomes, laboratory values, treatment strategies, pathological results, and demographic information. Variables identified as independently associated with the primary outcome by least absolute shrinkage and selection operator (LASSO) regression, the random survival forest (RSF) algorithm, and univariate and multivariate Cox regression analyses were introduced to establish the following different machine learning models and canonical regression model: support vector machine (SVM), SurvivalTree, Coxboost, RSF, DeepSurv, and Cox proportional hazards (CoxPH). We measured and compared the performance of models using the receiver operating characteristic (ROC) curve, integrated Brier score (IBS), and concordance index (C-index) following cross-validation. The machine learning model with the best performance was screened out and compared with the TNM Classification using ROC, IBS, and C-index. Finally, patients were stratified based on the model with the best performance to assess whether they benefited from postoperative chemotherapy through the log-rank test. Results Among medical features, five variables, including tumor differentiation, T-stage, lymph node metastasis (LNM), albumin-to-fibrinogen ratio (AFR), and carbohydrate antigen 19-9 (CA19-9), were used to develop machine learning models. In the training cohort and the validation cohort, C-index achieved 0.763 vs. 0.686 (SVM), 0.749 vs. 0.692 (SurvivalTree), 0.747 vs. 0.690 (Coxboost), 0.745 vs. 0.690 (RSF), 0.746 vs. 0.711 (DeepSurv), and 0.724 vs. 0.701 (CoxPH), respectively. The DeepSurv model (0.823 vs. 0.754) had the highest mean area under the ROC curve (AUC) than other models, including SVM (0.819 vs. 0.736), SurvivalTree (0.814 vs. 0.737), Coxboost (0.816 vs. 0.734), RSF (0.813 vs. 0.730), and CoxPH (0.788 vs. 0.753). The IBS of the DeepSurv model (0.132 vs. 0.147) was lower than that of SurvivalTree (0.135 vs. 0.236), Coxboost (0.141 vs. 0.207), RSF (0.140 vs. 0.225), and CoxPH (0.145 vs. 0.196). Results of the calibration chart and decision curve analysis (DCA) also demonstrated that DeepSurv had a satisfactory predictive performance. In addition, the performance of the DeepSurv model was better than that of the TNM Classification in C-index, mean AUC, and IBS (0.746 vs. 0.598, 0.823 vs. 0.613, and 0.132 vs. 0.186, respectively) in the training cohort. Patients were stratified and divided into high- and low-risk groups based on the DeepSurv model. In the training cohort, patients in the high-risk group would not benefit from postoperative chemotherapy (p = 0.519). In the low-risk group, patients receiving postoperative chemotherapy might have a better prognosis (p = 0.035). Conclusions In this study, the DeepSurv model was good at predicting prognosis and risk stratification to guide treatment options. AFR level might be a potential prognostic factor for dCCA. For the low-risk group in the DeepSurv model, patients might benefit from postoperative chemotherapy.

Keywords: postoperative chemotherapy; prognosis; machine; machine learning; model

Journal Title: Frontiers in Oncology
Year Published: 2023

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