The COURAGE Trial: Colon Recurrence and Aerobic Exercise: A Feasibility Study

描述（由申请人提供）：疾病复发率高是促进结肠癌（CC）幸存者健康和长寿的关键障碍。减少这种障碍的一种方法是制定干预措施，以尽量减少CC幸存者可以自主完成的复发，如生活方式和行为改变。流行病学证据表明，增加诊断后体力活动水平与无病生存率提高42%，复发率降低40%和CC特异性死亡率降低45-71%相关。然而，这种关联的潜在分子机制仍未确定。表征促进现有肿瘤生长和循环肿瘤细胞（CTC）扩散的生物标志物可以推进CC复发和进展的知识。细胞粘附分子在CC复发的发生和发展中起关键作用。细胞粘附分子，如可溶性细胞间粘附分子-I（sICAM-1）和可溶性血管粘附分子-I（sVCAM-1），促进现有微转移瘤的生长和进展，并通过使CTC能够侵入细胞外基质、渗透和散布在整个血流中以及外渗到远端器官中来促进额外转移灶的形成。这项初步研究将39名CC幸存者随机分为三个相等大小的组：低剂量（150分钟·周-1）中等强度有氧运动，高剂量（300分钟·周-1）中等强度有氧运动，或对照组，为期26周。将为参与者提供家用跑步机，以支持实现这些锻炼目标。我们的研究团队已经证明了在规定这些有氧运动量方面的成功。本试验的主要目的是量化和描述需要减少剂量或停止运动的医疗保健事件的可行性和发生率，并收集关于两种不同剂量的有氧运动对与CC复发和转移相关的两种细胞粘附生物标志物（sICAM-1和sVCAM-1）的生物学疗效的初步证据。然后，我们将探讨细胞粘附分子和CTC之间的关系。这一调查路线与美国国家癌症研究所PAR-12-229的当前使命和挑衅性问题PQA-5一致，其目的是阐明最佳运动处方，以改善假设为身体活动和癌症预后之间关联基础的分子途径。

DESCRIPTION (provided by applicant): The high rate of recurrent disease is a critical barrier to promote the health and longevity of colon cancer (CC) survivors. An approach to reduce this barrier is to develop interventions to minimize recurrence that CC survivors can accomplish autonomously, such as lifestyle and behavioral modification. Epidemiologic evidence suggests that increasing levels of post-diagnosis physical activity is associated with a 42% improvement in disease-free survival, 40% reduction in recurrence, and 45-71% reduction in CC-specific mortality. However, the underlying molecular mechanisms of this association remain unidentified. Characterizing biomarkers that promote existing tumor growth and dissemination of circulating tumor cells (CTCs) may advance knowledge of CC recurrence and progression. Cell-adhesion molecules play a pivotal role in the development and progression of CC recurrence. Cell-adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular adhesion molecule-1 (sVCAM-1), promote the growth and progression of existing micro-metastases, and promote the formation of additional metastatic foci by enabling CTC invasion of the extracellular matrix, infiltration and dissemination throughout the blood stream, and extravasation into distant organs. This pilot study will randomize 39 CC survivors to three equal-sized groups: low dose (150 min�wk-1) moderate-intensity aerobic exercise, high-dose (300 min�wk-1) moderate-intensity aerobic exercise, or a control group, for 26-weeks. Participants will be provided with in-home treadmills to support the achievement of these exercise goals. Our research team has demonstrated success in prescribing these volumes of aerobic exercise. The primary aims of this trial are to quantify and describe the feasibility, incidence of healthcare events requiring dose-reduction or cessation of exercise and to gather preliminary evidence regarding the biologic efficacy of two distinct doses of aerobic exercise on two cell-adhesion biomarkers associated with CC recurrence and metastasis (sICAM-1 and sVCAM-1). We will then explore the relationship between cell-adhesion molecules and CTCs. This line of investigation aligns with the current mission of the National Cancer Institute PAR-12-229, and provocative question PQA-5, which aim to elucidate the optimal exercise prescription to improve molecular pathways hypothesized to underlie the association between physical activity and cancer prognosis.