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Longitudinal and time-to-event modeling for the survival of advanced pancreatic ductal adenocarcinoma patients

Acta Pharmacologica Sinica volume 46, pages 751–758 (2025)Cite this article

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers especially at advanced stage. In order to analyze the dynamics of potential prognostic biomarkers and further quantify their relationships with the overall survival (OS) of advanced PDAC patients, we herein developed a parametric time-to-event (TTE) model integrated with longitudinal submodels. Data from 104 patients receiving standard chemotherapies were retrospectively collected for model development, and other 54 patients were enrolled as external validation. The longitudinal submodels were developed with the time-course data of sum of longest diameters (SLD) of tumors, serum albumin (ALB) and body weight (BW) using nonlinear mixed effect models. The model-derived metrics including model parameters and individual predictions at different time points were further analyzed in the TTE model, together with other baseline information of patients. A linear growth-exponential shrinkage model was employed to describe the dynamics of SLD, while logistic models were used to fit the relationship of time prior to death with ALB and BW. The TTE model estimated the ALB and BW changes at the 9th week after chemotherapies as well as the baseline CA19-9 level that showed most significant impact on the OS, and the model-based simulations could provide individual survival rate predictions for patients with different prognostic factors. This study quantitatively demonstrates the importance of physical status and baseline disease for the OS of advanced PDAC patients, and highlights that timely nutrition support would be helpful to improve the prognosis.

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Fig. 1: Time courses of the observations.
Fig. 2: VPC of the longitudinal submodels.
Fig. 3: VPCs for the TTE models of OS.
Fig. 4: Simulated 1-year survival rate based on 30,000 virtual individuals.

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Acknowledgements

This study was supported by the National Key Research and Development Program of China (2022YFF1203003) and Peking University Medicine Seed Fund for Interdisciplinary Research supported by the Fundamental Research Funds for the Central Universities (BMU2021MX003).

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Author notes

  1. These authors contributed equally: Qing-yu Yao, Ping-yao Luo

Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China

    Qing-yu Yao, Ping-yao Luo, Rong Chen, Jun-sheng Xue, Ling Yong & Tian-yan Zhou

  2. Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Medicine Innovation Center for Fundamental Research on Major Immunology-related Diseases, Peking University, Beijing, 100191, China

    Qing-yu Yao

  3. Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China

    Ling-xiao Xu, Lin Shen & Jun Zhou

  4. Ningbo Institute of Marine Medicine, Peking University, Ningbo, 315010, China

    Tian-yan Zhou

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Contributions

TYZ, LS and QYY designed research; LXX, JSX and LY performed research; QYY, PYL, RC and JZ analyzed the data; QYY, PYL, TYZ and JZ wrote and revised the manuscript.

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Correspondence to Jun Zhou or Tian-yan Zhou.

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Yao, Qy., Luo, Py., Xu, Lx. et al. Longitudinal and time-to-event modeling for the survival of advanced pancreatic ductal adenocarcinoma patients. Acta Pharmacol Sin 46, 751–758 (2025). https://doi.org/10.1038/s41401-024-01403-8

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