论文标题

使用间隔经过特定原因的关节模型的个性化活检时间表

Personalized Biopsy Schedules Using an Interval-censored Cause-specific Joint Model

论文作者

Yang, Zhenwei, Rizopoulos, Dimitris, Heijnsdijk, Eveline A. M., Newcomb, Lisa F., Erler, Nicole S.

论文摘要

进行活检以检测癌症进展的主动监视(AS)已被认为是减少前列腺癌过度治疗的有效方法。大多数人群都为所有患者使用固定的活检时间表。但是,理想的测试频率仍然未知,这种侵入性测试的常规使用会使患者负担。一个新兴的想法是基于每个患者的特定进展风险生成个性化的活检时间表。为了实现这一目标,我们提出了间隔经过审核的特异性关节模型(ICJM),该模型对纵向生物标志物对癌症进展的影响进行了建模,同时考虑了早期治疗开始的竞争事件。潜在的似然函数包括癌症进展的间隔审查,竞争的治疗风险以及癌症进展是否发生以来是否发生自右最后一次活检或经历竞争事件的患者的不确定性。该模型可以产生特定于患者的风险概况,直到地平线时间为止。如果风险超过一定阈值,则进行活检。可以通过平衡活检时间表的两个指标来选择最佳阈值:活检的预期数量和癌症进展检测的预期延迟。一项仿真研究表明,与固定时间表相比,我们个性化的时间表可以大大减少每位患者活检数量的34%-54%,尽管以稍长的检测延迟为代价。

Active surveillance (AS), where biopsies are conducted to detect cancer progression, has been acknowledged as an efficient way to reduce the overtreatment of prostate cancer. Most AS cohorts use fixed biopsy schedules for all patients. However, the ideal test frequency remains unknown, and the routine use of such invasive tests burdens the patients. An emerging idea is to generate personalized biopsy schedules based on each patient's progression-specific risk. To achieve that, we propose the interval-censored cause-specific joint model (ICJM), which models the impact of longitudinal biomarkers on cancer progression while considering the competing event of early treatment initiation. The underlying likelihood function incorporates the interval-censoring of cancer progression, the competing risk of treatment, and the uncertainty about whether cancer progression occurred since the last biopsy in patients that are right-censored or experience the competing event. The model can produce patient-specific risk profiles until a horizon time. If the risk exceeds a certain threshold, a biopsy is conducted. The optimal threshold can be chosen by balancing two indicators of the biopsy schedules: the expected number of biopsies and expected delay in detection of cancer progression. A simulation study showed that our personalized schedules could considerably reduce the number of biopsies per patient by 34%-54% compared to the fixed schedules, though at the cost of a slightly longer detection delay.

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