Investigating Molecular-Genetic Correlates of Fatigue

虽然疲劳的潜在机制已经在几种疾病条件下进行了研究，但数据并不是决定性的，目前这种症状仍然处理不善。有关前列腺癌患者治疗相关性疲劳的纵向研究已经进行，但探索放射治疗前后生理机制变化的研究有限，这些研究可以确定哪些人在治疗过程中和治疗后存在持续疲劳的风险。疲劳是一种多维症状，包括时间、感觉、认知/心理、情感/情绪、行为和生理等多个维度。这项前瞻性的观察性研究是第一项探索前列腺癌患者接受体外放射治疗(EBRT)后疲劳和一系列症状(尿路、性、胃肠道、精神症状)的分子遗传学机制的研究。 这项研究的主要目的是描述接受和不接受前列腺手术的患者在EBRT完成之前、期间和之后所经历的自我报告的疲劳、尿路、性和胃肠道症状、抑郁、疲劳灾变和健康相关生活质量(HRQOL)的变化。这项研究的次要目标是调查EBRT相关疲劳的促炎细胞因子(肿瘤坏死因子、胰岛素样生长因子-I、IL-6、IL-8、转化生长因子和转化生长因子)，并确定在EBRT完成之前、期间和之后使用Buffy外套收集的白细胞基因表达的变化，以及这些生物标志物水平的变化与自我报告的疲劳、尿路症状、性症状和胃肠道症状、抑郁、疲劳灾变和HRQOL评分的关系。这项研究还旨在测量患者在EBRT之前、期间和完成时的骨骼肌力量、活动水平和能量消耗，并将这些发现与自我报告的疲劳、身体症状(如尿路、胃肠道和性功能)、抑郁和HRQOL评分相关联。

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.