乳腺癌患者睡眠行为干预改善头痛
虽然癌症患者的生存率不断提高，但是仍有大约一半癌症患者长期饱受头痛或失眠等慢性症状的折磨。不过，对于癌症患者，采用日常药物治疗慢性头痛或失眠可能存在困难，因为此类药物与化疗或其他癌症治疗可能相互干扰，而且患者通常不愿在其用药清单再增加更多药物。由于头痛与失眠可能互为因果，故对睡眠行为进行非药物干预可能改善头痛症状。
2021年8月6日，美国癌症学会《癌症》在线发表斯坦福大学医学院、加利福尼亚公共卫生研究所、德克萨斯大学奥斯汀医学院的随机对照研究二次分析报告，探讨了乳腺癌患者化疗期间睡眠行为简单干预对头痛症状的影响。
NCT02165839: Brief Behavioral Intervention for Insomnia During Chemotherapy
该多中心非盲随机对照研究于2015年1月～2019年6月从斯坦福女性癌症中心和斯坦福癌症中心入组女性乳腺癌化疗期间失眠患者139例，按1∶1随机分为两组：
干预组（73例）简单行为治疗，包括时空康复教育及技巧（例如睡眠、昼夜节律紊乱与癌症的关系）、光照和刺激控制（白天增加光照、夜间减少光照，关于褪黑激素是昼夜节律激素的教育，关于床、睡眠、性生活的教育）、鼓励睡眠活动和午睡习惯、睡眠压缩（若睡眠质量低，则晚睡15分钟）
对照组（66例）健康饮食教育
两组均由经过培训的工作人员提供至少6周干预。入组0周、6周、6个月、12个月时测量头痛评分和心率变化。根据治疗意向，利用混合效应模型分析各组头痛评分变化。通过主要成分分析和聚合分层聚类对患者的16种表现型进行分析，包括年龄、头痛、疼痛、恶心呕吐、情绪功能、认知功能、身体功能、整体健康状况、失眠严重程度指数、匹兹堡睡眠质量指数、疲劳简明量表、心率变化五项指标。
结果，随着时间的推移，简单行为治疗患者与健康饮食教育患者相比，头痛症状显著减少（P=0.02，均数比较效应量：0.43）。
主要成分分析表明，头痛、睡眠、疲劳、恶心呕吐可加重症状，认知功能、身体功能、情绪功能可减轻症状。
聚合分层聚类表明，I类患者（58例）头痛、失眠、恶心呕吐症状最重，II类患者（50例）心率变化最小、头痛和失眠症状较轻，III类患者（31例）心率变化与头痛失眠症状成反比，提示自主神经功能障碍。
因此，该研究结果表明，癌症相关失眠简单行为治疗可有效减轻乳腺癌患者的头痛症状。此外，患者表现型分析表明，大多数头痛患者的头痛表现型与偏头痛相似，以睡眠障碍、恶心呕吐和身体功能低下为特征，自主神经系统对于此类头痛发作的病理生理学机制具有潜在作用，可通过规律睡眠、规律运动、规律进水、健康营养进行调整，建议放化疗前后保持这些规律健康的行为，可能有助于预防癌症患者发生慢性头痛。
Cancer. 2021 Aug 6. Online ahead of print.
Headache outcomes of a sleep behavioral intervention in breast cancer survivors: Secondary analysis of a randomized clinical trial.
Woldeamanuel YW, Blayney DW, Jo B, Fisher SE, Benedict C, Oakley-Girvan I, Kesler SR, Palesh O.
Stanford University School of Medicine, Palo Alto, California; Canary Center at Stanford for Cancer Early Detection, Palo Alto, California; Public Health Institute, Oakland, California; Medable Inc., Palo Alto, California; University of Texas at Austin, Austin, Texas.
Breast cancer survivors often have persisting headache and insomnia burden. This study shows that a sleep behavioral therapy reduces headache burden in breast cancer survivors.
BACKGROUND: Breast cancer survivors often have persisting headache. In a secondary analysis of the Brief Behavioral Therapy for Cancer-Related Insomnia (BBT-CI) clinical trial (ClinicalTrials.gov identifier NCT02165839), the authors examined the effects of BBT-CI on headache outcomes in patients with breast cancer.
METHODS: Patients with breast cancer who were receiving chemotherapy were randomly assigned to receive either the BBT-CI intervention or the Healthy EAting Education Learning for healthy sleep (HEAL) control intervention, and both were delivered over 6 weeks by trained staff. Headache outcomes and heart rate variability (HRV) were measured at baseline, 6 weeks, 6 months, and 12 months. Mixed-effects models were used to examine longitudinal headache outcomes in the groups according to the intention to treat. Principal component analysis and agglomerative hierarchical clustering were conducted to reduce 16 variables for data-driven phenotyping.
RESULTS: Patients in the BBT-CI arm (n = 73) exhibited a significant reduction in headache burden over time (P = .02; effect size [Cohen d] = 0.43), whereas the reduction was not significant among those in the HEAL arm (n = 66). The first principal component was positively loaded by headache, sleep, fatigue, and nausea/vomiting and was negatively loaded by cognitive, physical, and emotional functioning. Agglomerative hierarchical clustering revealed 3 natural clusters. Cluster I (n = 58) featured the highest burden of headache, insomnia, and nausea/vomiting; cluster II (n = 50) featured the lowest HRV despite a low burden of headache and insomnia; and cluster III (n = 31) showed an inverse relation between HRV and headache-insomnia, signifying autonomic dysfunction.
CONCLUSIONS: BBT-CI is efficacious in reducing headache burden in breast cancer survivors. Patient phenotyping demonstrates a headache type featuring sleep disturbance, nausea/vomiting, and low physical functioning-revealing similarities to migraine.
LAY SUMMARY: Breast cancer survivors often have persisting headache symptoms. In patients with cancer, treatment of chronic headache disorders using daily medications may be challenging because of drug interactions with chemotherapy and other cancer therapies as well as patients' reluctance to add more drugs to their medicine list. Headache and sleep disorders are closely related to each other. This study demonstrates that a sleep behavioral therapy reduced headache burden in breast cancer survivors. In addition, the majority of headache sufferers had a headache type with similarities to migraine-featuring sleep disturbance, nausea/vomiting, and low physical functioning.
KEYWORDS: behavior therapy; breast neoplasms; clinical trial; headache; sleep initiation and maintenance disorders
PMID: 34357593
DOI: 10.1002/cncr.33844