Investigating Molecular-Genetic Correlates of Fatigue

尽管在几种疾病条件下研究了疲劳的潜在机制，但数据并不具有结论性，并且目前对这种症状的管理仍然很差。有关前列腺癌患者治疗相关性疲劳的纵向研究已经开展，但探索放疗前后生理机制变化的研究有限，无法识别治疗期间和治疗后有持续疲劳风险的个体。疲劳被定义为一种多维度的症状，包括时间、感觉、认知/精神、情感/情感、行为和生理维度。这项前瞻性观察性研究是首个探讨前列腺癌患者接受外束放射治疗（EBRT）时疲劳和一系列症状（泌尿、性、胃肠道、精神）的分子遗传学机制的研究。

Although the underlying mechanisms of fatigue have been studied in several disease conditions, the data are not conclusive, and this symptom remains poorly managed at present. Longitudinal studies related to treatment-related fatigue in prostate cancer patients have been conducted, but there are limited studies exploring the changes in physiologic mechanisms before and after radiotherapy which can identify individuals who are at risk for enduring fatigue during and after therapy. Fatigue is conceptualized as a multidimensional symptom which incorporates temporal, sensory, cognitive/mental, affective/emotional, behavioral, and physiological dimensions. This prospective, observational study is the first study to explore the molecular-genetic mechanisms underlying fatigue and the cluster of symptoms (urinary, sexual, gastrointestinal, psychiatric) experienced by prostate cancer patients undergoing External Beam Radiation Therapy (EBRT). The primary objective of the study is to describe the changes in the self-reported fatigue; urinary, sexual, and gastrointestinal symptoms; depression; fatigue catastrophizing; and health-related quality of life (HRQOL) experienced by patients with and without prostate surgery before, during, and after EBRT completion. The secondary objectives of this study are to investigate the pro-inflammatory cytokine profile of EBRT-related fatigue (TNF, IGF-I, IL-6, IL-8, TGF and ) and to determine changes in white blood cell gene expression using buffy coat collection before, during, and after EBRT completion and to relate these changes in the levels of these biological markers to self-reported fatigue; urinary, sexual, and gastrointestinal symptoms; depression; fatigue catastrophizing; and HRQOL scores. This study also aims to measure the skeletal muscle strength, activity levels and energy expenditure of patients before, during, and at completion of EBRT and relate these findings with self-reported fatigue, physical symptoms (e.g. urinary, gastrointestinal, and sexual functioning), depression, and HRQOL scores.