呼吸困难反应对地塞米松和安慰剂的呼吸困难的预测性生物标志物
Predictive Biomarkers of Dyspnea Response to Dexamethasone and Placebo in Cancer Patients
影响因子:3.50000
分区:医学2区 / 临床神经病学2区 卫生保健与服务2区 医学：内科2区
发表日期:2024 Aug 06
作者:
David Hui, Sandra K Hanneman, Kristofer Jennings, Amy Ontai, Stanley Cron, Eduardo Bruera
摘要
在癌症患者的呼吸困难（ABCD）试验中，地塞米松在未选择的癌症患者中的呼吸困难并没有改善呼吸困难。但是，目前尚不清楚炎症较大的患者是否更有可能得出治疗反应。要检查细胞因子对呼吸困难反应的预测效用。我们对ABCD双盲，随机临床试验进行了次要分析，比较了高剂量地刺激性的临床试验（NCT03367156）。主要结果是在14天内呼吸困难。在基线，第七天和第14天，测量了血细胞因子水平（TNF，IL-6，IL-8和IL-10）。我们使用了广义添加剂模型来检查基线细胞因子水平与从基线到第七天到第七天的呼吸困难和dexamethasone和Glosbo组的基线的变化之间的关联。在地塞米松组中，TNF，IL-6和IL-8在14天内减少，但不安慰剂（p <0.05）。下基线TNF与安慰剂组第七天的呼吸困难强度更大相关（p = 0.0013）；相反，较高的基线TNF与地塞米松组的第7天到第7天之前的呼吸困难强度更大有关（组p = 0.0019之间的差异）。在第七天的IL-6（p = 0.000051），IL-8（p = 0.00063）和IL-10（p = 0.01）的IL-6（p = 0.000051），IL-6（p = 0.00063）（p = 0.0001）中，观察到类似的模式，第14天的所有细胞因子都会观察到类似的模式。在第14天，所有细胞因子都随着地塞米松而降低，而不是安慰剂。较高的基线细胞因子水平可能会发现可能对地塞米松反应的患者对安慰剂反应的可能性较小。
Abstract
In the Alleviating Breathlessness in Cancer Patients with Dexamethasone (ABCD) trial, dexamethasone did not improve dyspnea more than placebo in unselected cancer patients. However, it is unclear if patients with greater inflammation would be more likely to derive a treatment response.To examine the predictive utility of cytokines for dyspnea response.We performed a secondary analysis of the ABCD double-blind, randomized clinical trial comparing high-dose dexamethasone to placebo (NCT03367156). The primary outcome was dyspnea intensity over 14 days. Blood cytokine levels (TNF, IL-6, IL-8, and IL-10) were measured at baseline, day seven, and day 14. We used a generalized additive model to examine the association between baseline cytokine level and change in dyspnea from baseline to day seven and baseline to day 14 in dexamethasone and placebo groups.Of the 128 enrolled patients, 45 provided blood samples. TNF, IL-6, and IL-8 decreased over 14 days in the dexamethasone group but not placebo (P<0.05). Lower baseline TNF was associated with a greater reduction in dyspnea intensity by day seven in the placebo group (P=0.0013); conversely, higher baseline TNF was associated with a greater reduction in dyspnea intensity by day 7 in the dexamethasone group (difference between groups P=0.0019). Similar patterns were observed for IL-6 (P=0.000051), IL-8 (P=0.00063), and IL-10 (P=0.01) on day seven, and all cytokines on day 14.Cytokines decreased with dexamethasone, but not placebo. Higher baseline cytokine levels may identify patients likely to respond to dexamethasone and less likely to respond to placebo.