癌症患者对Dexamethasone和安慰剂引起的呼吸困难反应的预测性生物标志物

Predictive Biomarkers of Dyspnea Response to Dexamethasone and Placebo in Cancer Patients

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JOURNAL OF PAIN AND SYMPTOM MANAGEMENT

影响因子:3.5

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

DOI: 10.1016/j.jpainsymman.2024.07.003

摘要

在“缓解癌症患者呼吸困难的Dexamethasone（ABCD）”试验中，Dexamethasone未能比安慰剂更有效改善未筛选的癌症患者的呼吸困难。然而，目前尚不清楚炎症较重的患者是否更可能获得治疗反应。为此，分析血清中细胞因子对呼吸困难反应的预测能力。我们对ABCD双盲、随机临床试验的次级分析进行，比较高剂量Dexamethasone与安慰剂（NCT03367156）。主要观察指标为14天内呼吸困难强度变化。血液中TNF、IL-6、IL-8和IL-10水平在基线、7天和14天时测定。采用广义加性模型分析基线细胞因子水平与7天和14天呼吸困难变化之间的关系。128名入组患者中，45人提供血样。结果显示，Dexamethasone组的TNF、IL-6和IL-8在14天内下降（P<0.05），而安慰剂组无明显变化。基线较低的TNF在安慰剂组中与7天呼吸困难减轻相关（P=0.0013），而基线较高TNF在Dexamethasone组中与7天呼吸困难减轻相关（组间差异P=0.0019）。类似的趋势也出现在IL-6（P=0.000051）、IL-8（P=0.00063）和IL-10（P=0.01）在第7天的变化，以及所有细胞因子在第14天的变化中。Dexamethasone能降低血清细胞因子水平，而安慰剂则无此作用。较高的基线细胞因子水平可能帮助识别更可能对Dexamethasone反应、对安慰剂反应较差的患者。

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.