A machine learning predictive model for recurrence of resected distal cholangiocarcinoma: Development and validation of predictive model using artificial intelligence

Marc Perez, Carsten Palnaes Hansen, Fernando Burdio, Patricia Sanchez-Velázquez, Antonio Giuliani, Francesco Lancellotti, Nicola de Liguori-Carino, Giuseppe Malleo, Giovanni Marchegiani, Mauro Podda, Adolfo Pisanu, Giuseppe Massimiliano De Luca, Alessandro Anselmo, Leandro Siragusa, Stefan Kobbelgaard Burgdorf, Christoph Tschuor, Andrea Benedetti Cacciaguerra, Ye Xin Koh, Yoshio Masuda, Mark Yeo Hao XuanNico Seeger, Stefan Breitenstein, Filip Lukasz Grochola, Marcello Di Martino, Luis Secanella, Juli Busquets, Dimitri Dorcaratto, Isabel Mora-Oliver, Sara Ingallinella, Roberto Salvia, Mohammad Abu Hilal, Luca Aldrighetti, Benedetto Ielpo*

*Corresponding author for this work

Abstract

INTRODUCTION: Distal Cholangiocarcinoma (dCCA) represents a challenge in hepatobiliary oncology, that requires nuanced post-resection prognostic modeling. Conventional staging criteria may oversimplify dCCA complexities, prompting the exploration of novel prognostic factors and methodologies, including machine learning algorithms. This study aims to develop a machine learning predictive model for recurrence after resected dCCA.

MATERIAL AND METHODS: This retrospective multicentric observational study included patients with dCCA from 13 international centers who underwent curative pancreaticoduodenectomy (PD). A LASSO-regularized Cox regression model was used to feature selection, examine the path of the coefficient and create a model to predict recurrence. Internal and external validation and model performance were assessed using the C-index score. Additionally, a web application was developed to enhance the clinical use of the algorithm.

RESULTS: Among 654 patients, LNR (Lymph Node Ratio) 15, neural invasion, N stage, surgical radicality, and differentiation grade emerged as significant predictors of disease-free survival (DFS). The model showed the best discrimination capacity with a C-index value of 0.8 (CI 95 %, 0.77%-0.86 %) and highlighted LNR15 as the most influential factor. Internal and external validations showed the model's robustness and discriminative ability with an Area Under the Curve of 92.4 % (95 % CI, 88.2%-94.4 %) and 91.5 % (95 % CI, 88.4%-93.5 %), respectively. The predictive model is available at https://imim.shinyapps.io/LassoCholangioca/.

CONCLUSIONS: This study pioneers the integration of machine learning into prognostic modeling for dCCA, yielding a robust predictive model for DFS following PD. The tool can provide information to both patients and healthcare providers, enhancing tailored treatments and follow-up.

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