近日，北京大学周田彦等研究人员合作完成晚期胰腺导管腺癌患者生存的纵向和时间到事件建模。2024年10月21日，国际知名学术期刊《中国药理学报》在线发表了这一成果。

研究人员表示，胰腺导管腺癌（PDAC）是最致命的癌症之一，尤其是在晚期。

为了分析潜在预后生物标志物的动态，并进一步量化其与晚期PDAC患者总生存期（OS）之间的关系，研究人员开发了一种集成纵向子模型的参数化时间到事件（TTE）模型。

研究人员回顾性收集了104名接受标准化疗的患者数据用于模型开发，另有54名患者作为外部验证。

纵向子模型使用肿瘤最长直径总和（SLD）、血清白蛋白（ALB）和体重（BW）的时间序列数据，并通过非线性混合效应模型进行开发。

模型派生的指标，包括不同时间点的模型参数和个体预测，进一步在TTE模型中分析，并结合患者的其他基线信息。线性生长-指数收缩模型被用于描述SLD的动态变化，而逻辑模型则用于拟合死亡前时间与ALB和BW之间的关系。

TTE模型估计了化疗后第9周ALB和BW的变化以及基线CA19-9水平，这些因素对OS的影响最为显著，基于模型的模拟可以为具有不同预后因素的患者提供个体生存率预测。

这项研究定量证明了身体状态和基线疾病对晚期PDAC患者OS的重要性，并强调及时的营养支持对改善预后具有帮助。

附：英文原文

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

Author: Yao, Qing-yu, Luo, Ping-yao, Xu, Ling-xiao, Chen, Rong, Xue, Jun-sheng, Yong, Ling, Shen, Lin, Zhou, Jun, Zhou, Tian-yan

Issue&Volume: 2024-10-21

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.

DOI: 10.1038/s41401-024-01403-8

Source: https://www.nature.com/articles/s41401-024-01403-8