Abstract

Background and ObjectivesCurrently, the prognostic performance of the staging systems proposed by the 8th edition of the American Joint Committee on Cancer (AJCC 8th) and the Liver Cancer Study Group of Japan (LCSGJ) in resectable intrahepatic cholangiocarcinoma (ICC) remains controversial. The aim of this study was to use machine learning techniques to modify existing ICC staging strategies based on clinical data and to demonstrate the accuracy and discrimination capacity in prognostic prediction.Patients and MethodsThis is a retrospective study based on 1,390 patients who underwent surgical resection for ICC at Eastern Hepatobiliary Surgery Hospital from 2007 to 2015. External validation was performed for patients from 2015 to 2017. The ensemble of three machine learning algorithms was used to select the most important prognostic factors and stepwise Cox regression was employed to derive a modified scoring system. The discriminative ability and predictive accuracy were assessed using the Concordance Index (C-index) and Brier Score (BS). The results were externally validated through a cohort of 42 patients operated on from the same institution.ResultsSix independent prognosis factors were selected and incorporated in the modified scoring system, including carcinoembryonic antigen, carbohydrate antigen 19-9, alpha-fetoprotein, prealbumin, T and N of ICC staging category in 8th edition of AJCC. The proposed scoring system showed a more favorable discriminatory ability and model performance than the AJCC 8th and LCSGJ staging systems, with a higher C-index of 0.693 (95% CI, 0.663–0.723) in the internal validation cohort and 0.671 (95% CI, 0.602–0.740) in the external validation cohort, which was then confirmed with lower BS (0.103 in internal validation cohort and 0.169 in external validation cohort). Meanwhile, machine learning techniques for variable selection together with stepwise Cox regression for survival analysis shows a better prognostic accuracy than using stepwise Cox regression method only.ConclusionsThis study put forward a modified ICC scoring system based on prognosis factors selection incorporated with machine learning, for individualized prognosis evaluation in patients with ICC.

Highlights

  • Intrahepatic cholangiocarcinoma (ICC) is a malignant neoplasm originating from the epithelial cells of bile ducts located above the secondary bile duct branch [1]

  • The proposed scoring system showed a more favorable discriminatory ability and model performance than the American Joint Committee on Cancer (AJCC) 8th and Liver Cancer Study Group of Japan (LCSGJ) staging systems, with a higher Concordance Index (C-index) of 0.693 in the internal validation cohort and 0.671 in the external validation cohort, which was confirmed with lower Brier Score (BS) (0.103 in internal validation cohort and 0.169 in external validation cohort)

  • This study put forward a modified intrahepatic cholangiocarcinoma (ICC) scoring system based on prognosis factors selection incorporated with machine learning, for individualized prognosis evaluation in patients with ICC

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Summary

Introduction

Intrahepatic cholangiocarcinoma (ICC) is a malignant neoplasm originating from the epithelial cells of bile ducts located above the secondary bile duct branch [1] It is the second most common primary malignancy of liver and its incidence has been increasing in recent years [2,3,4]. The eighth edition of American Joint Committee on Cancer (AJCC 8th) staging system and the Liver Cancer Study Group of Japan (LCSGJ) staging system are widely used in clinical practice [10,11,12,13]. The prognostic performance of the staging systems proposed by the 8th edition of the American Joint Committee on Cancer (AJCC 8th) and the Liver Cancer Study Group of Japan (LCSGJ) in resectable intrahepatic cholangiocarcinoma (ICC) remains controversial. The aim of this study was to use machine learning techniques to modify existing ICC staging strategies based on clinical data and to demonstrate the accuracy and discrimination capacity in prognostic prediction

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