Alvares Danilo, Barrett Jessica K, Mercier François, Roumpanis Spyros, Yiu Sean, Castro Felipe, Schulze Jochen, Zhu Yajing
MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
Hoffmann-La Roche Ltd, Basel, Switzerland.
Stat Med. 2025 Feb 10;44(3-4):e10322. doi: 10.1002/sim.10322.
Predicting cancer-associated clinical events is challenging in oncology. In Multiple Myeloma (MM), a cancer of plasma cells, disease progression is determined by changes in biomarkers, such as serum concentration of the paraprotein secreted by plasma cells (M-protein). Therefore, the time-dependent behavior of M-protein and the transition across lines of therapy (LoT), which may be a consequence of disease progression, should be accounted for in statistical models to predict relevant clinical outcomes. Furthermore, it is important to understand the contribution of the patterns of longitudinal biomarkers, upon each LoT initiation, to time-to-death or time-to-next-LoT. Motivated by these challenges, we propose a Bayesian joint model for trajectories of multiple longitudinal biomarkers, such as M-protein, and the competing risks of death and transition to the next LoT. Additionally, we explore two estimation approaches for our joint model: simultaneous estimation of all parameters (joint estimation) and sequential estimation of parameters using a corrected two-stage strategy aiming to reduce computational time. Our proposed model and estimation methods are applied to a retrospective cohort study from a real-world database of patients diagnosed with MM in the US from January 2015 to February 2022. We split the data into training and test sets in order to validate the joint model using both estimation approaches and make dynamic predictions of times until clinical events of interest, informed by longitudinally measured biomarkers and baseline variables available up to the time of prediction.
在肿瘤学中,预测癌症相关的临床事件具有挑战性。在多发性骨髓瘤(MM)中,一种浆细胞癌,疾病进展由生物标志物的变化决定,例如浆细胞分泌的副蛋白(M蛋白)的血清浓度。因此,在预测相关临床结果的统计模型中,应考虑M蛋白的时间依赖性行为以及治疗线(LoT)之间的转换,这可能是疾病进展的结果。此外,了解每次LoT开始时纵向生物标志物模式对死亡时间或下次LoT时间的贡献也很重要。受这些挑战的推动,我们提出了一种贝叶斯联合模型,用于多个纵向生物标志物(如M蛋白)的轨迹以及死亡和转换到下一个LoT的竞争风险。此外,我们探索了两种联合模型的估计方法:同时估计所有参数(联合估计)和使用校正的两阶段策略顺序估计参数,旨在减少计算时间。我们提出的模型和估计方法应用于一项回顾性队列研究,该研究来自2015年1月至2022年2月在美国诊断为MM的患者的真实世界数据库。我们将数据分为训练集和测试集,以便使用两种估计方法验证联合模型,并根据纵向测量的生物标志物和预测时可用的基线变量,对感兴趣的临床事件发生时间进行动态预测。
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