Subjective sleep and overall survival in chemotherapy-naive patients with metastatic colorectal cancer
Subjective sleep and overall survival in chemotherapy-naive patients with metastatic colorectal cancer
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DOI：
10.1016/j.sleep.2014.10.022
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发表时间：
2015-03-01
期刊：
影响因子：
4.8
通讯作者：
Palesh, Oxana
中科院分区：
文献类型：
--
作者：
Innominato, Pasquale F.;Spiegel, David;Palesh, Oxana
背景：睡眠障碍在晚期癌症患者中很普遍。他们对临床结局的影响是不好理解。方法：事后分析进行了361化疗初治转移性结直肠癌患者完成两次EORTC QLQ-C30问卷在一个随机的国际III期临床试验。该研究采用多变量考克斯比例风险模型，评估主观睡眠抱怨对总生存率（OS）的影响，作为正常或时间依赖性协变量（TDC）。对整个研究人群进行了预后分析，并分别在每个治疗组（传统FOLFOX 2，或时间调节的chronoFLO 4）。结果：202例患者（56%）在基线和188例（52%）在治疗中报告了睡眠问题。基线睡眠问题与早期死亡（HR：1.36; p = 0.011）、进展（HR：1.43; p = 0.002）和治疗反应不良（RR：0.58; p = 0.016）的风险较高独立相关。TDC分析证实了睡眠问题对OS的独立预后影响（HR：1.37; p = 0.008），而在治疗中仅使用单变量分析观察到这种影响。与FOLFOX 2相比，睡眠问题对基线OS、治疗期间OS和TDC的负面预后价值在chronoFLO 4组最大。结论：主观睡眠问题与转移性结直肠癌患者的不良临床结局相关，并影响时辰治疗的有效性。需要良好调节的昼夜节律计时系统以增加时间疗法活性。需要前瞻性研究来确定治疗方法对睡眠障碍对癌症患者生活质量和生存率的影响。(C)2014爱思唯尔有限公司版权所有。
Backround: Sleep disorders are prevalent in patients with advanced cancer. Their impact on clinical outcomes is not well understood.Methods: A post-hoc analysis was conducted in 361 chemo-naive patients with metastatic colorectal cancer completing twice the EORTC QLQ-C30 questionnaire within a randomized international phase III trial. The study assessed the effect on overall survival (OS) of subjective sleep complaint, used as a normal or a time-dependent covariate (TDC), using a multivariate Cox proportional hazard model. Prognostic analysis was conducted on the whole study population and separately in each treatment arm (conventional FOLFOX2, or chronomodulated chronoFLO4).Results: Sleep problems were reported by 202 patients (56%) at baseline and by 188 (52%) on treatment. Sleep problems at baseline were independently associated with a higher risk of earlier death (HR: 1.36; p = 0.011), progression (HR: 1.43; p = 0.002) and poor treatment response (RR: 0.58; p = 0.016). TDC analysis confirmed the independent prognostic effect of sleep problems on OS (HR: 1.37; p = 0.008), while on treatment this effect was only observed using univariate analysis. The negative prognostic value of sleep problems on OS at baseline, on treatment, and as a TDC was greatest on chronoFLO4 compared to FOLFOX2.Conclusions: Subjective sleep problems are associated with poor clinical outcomes in metastatic colorectal cancer patients and affect chronotherapy effectiveness. There is a need for a well-tuned circadian timing system in order to increase chronotherapy activity. Prospective studies are needed for determining the impact of therapeutic approaches on sleep disorders upon quality of life and survival of cancer patients. (C) 2014 Elsevier B.V. All rights reserved.