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基于效用的晚期乳腺癌贝叶斯个性化治疗选择

Utility-based Bayesian personalized treatment selection for advanced breast cancer.

作者信息

Lee Juhee, Thall Peter F, Lim Bora, Msaouel Pavlos

机构信息

Department of Statistics, University of California Santa Cruz, Santa Cruz, CA.

Department of Biostatistics, UT M.D. Anderson Cancer Center, Houston, TX.

出版信息

J R Stat Soc Ser C Appl Stat. 2022 Nov;71(5):1605-1622. doi: 10.1111/rssc.12582. Epub 2022 Sep 9.

Abstract

A Bayesian method is proposed for personalized treatment selection in settings where data are available from a randomized clinical trial with two or more outcomes. The motivating application is a randomized trial that compared letrozole plus bevacizimab to letrozole alone as first-line therapy for hormone receptor positive advanced breast cancer. The combination treatment arm had larger median progression-free survival time, but also a higher rate of severe toxicities. This suggests that the risk-benefit trade-off between these two outcomes should play a central role in selecting each patient's treatment, particularly since older patients are less likely to tolerate severe toxicities. To quantify the desirability of each possible outcome combination for an individual patient, we elicited from breast cancer oncologists a utility function that varied with age. The utility was used as an explicit criterion for quantifying risk-benefit trade-offs when making personalized treatment selections. A Bayesian nonparametric multivariate regression model with a dependent Dirichlet process prior was fit to the trial data. Under the fitted model, a new patient's treatment can be selected based on the posterior predictive utility distribution. For the breast cancer trial dataset, the optimal treatment depends on the patient's age, with the combination preferable for patients 70 years or younger and the single agent preferable for patients older than 70.

摘要

本文提出了一种贝叶斯方法,用于在具有两个或更多结果的随机临床试验数据可用的情况下进行个性化治疗选择。其激励性应用是一项随机试验,该试验比较了来曲唑联合贝伐单抗与单纯来曲唑作为激素受体阳性晚期乳腺癌的一线治疗方法。联合治疗组的无进展生存期中位数更长,但严重毒性发生率也更高。这表明,这两种结果之间的风险效益权衡应在选择每位患者的治疗方案中发挥核心作用,特别是因为老年患者更难以耐受严重毒性。为了量化个体患者每种可能结果组合的可取性,我们向乳腺癌肿瘤学家询问了一个随年龄变化的效用函数。在进行个性化治疗选择时,该效用被用作量化风险效益权衡的明确标准。采用具有相依狄利克雷过程先验的贝叶斯非参数多元回归模型对试验数据进行拟合。在拟合模型下,可以根据后验预测效用分布为新患者选择治疗方案。对于乳腺癌试验数据集,最佳治疗方案取决于患者的年龄,70岁及以下患者更适合联合治疗,70岁以上患者更适合单药治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec05/9880964/4e114bcd7f16/nihms-1809751-f0001.jpg

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