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

描述(由申请人提供)：高复发率是促进结肠癌(CC)幸存者健康和长寿的关键障碍。减少这一障碍的一种方法是开发干预措施，将CC幸存者可以自主完成的复发降至最低，例如生活方式和行为改变。流行病学证据表明，确诊后体力活动水平的增加与无病生存率提高42%，复发率降低40%，CC特异性死亡率降低45%-71%相关。然而，这种联系的潜在分子机制仍然不清楚。鉴定促进现有肿瘤生长和循环肿瘤细胞(CTCs)扩散的生物标志物可能会促进对CC复发和进展的了解。细胞黏附分子在CC复发的发生发展中起着关键作用。细胞黏附分子，如可溶性细胞间黏附分子-1(sICAM-1)和可溶性血管黏附分子-1(sVCAM-1)，通过使CTC侵袭细胞外基质、渗透和扩散到远处器官，促进现有微转移瘤的生长和进展，并促进更多转移灶的形成。这项先导性研究将39名CC幸存者随机分为三组：小剂量(150min�wk-1)中强度有氧运动、大剂量(300min�wk-1)中等强度有氧运动或对照组，为期26周。参与者将获得居家跑步机，以支持这些运动目标的实现。我们的研究团队已经成功地开出了这些量的有氧运动处方。这项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黏附生物标志物(sICAM-1和sVCAM-1)的生物有效性的初步证据。然后我们将探索细胞黏附分子和CTCs之间的关系。这条研究路线与国家癌症研究所PAR-12-229和挑衅性问题PQA-5的当前使命一致，后者旨在阐明最佳运动处方，以改善假设的分子途径，以支持体力活动和癌症预后之间的联系。

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.