Dose-response of aerobic training during total neoadjuvant therapy for locally advanced rectal cancer

项目摘要/摘要 随机试验证实有氧训练(AT)可减轻治疗所致的生理损伤 以及广泛数量的癌症患者群体的心理社会结果。然而，无论AT是否明确 影响癌症治疗的耐受性在很大程度上是未知的。要解决这一基本的知识鸿沟， 运动-肿瘤学研究，本研究的目的是评估AT治疗的剂量反应 局部进展期直肠癌患者的耐受性和相关结局 新辅助治疗(TNT)。LARC是进行AT治疗最终试验的理想模型 耐受性有几个原因：(1)美国每年LARC诊断率高(&gt；40,000)，(2)糟糕 TNT的耐受性(60%的患者完成了推荐的方案)，以及(3)强大的生物学基础 (TNT引起的血液功能损害是耐受性差的主要原因，AT是 在临床前和临床研究中证明可以增强血液功能)。因此，在这个阶段2 随机试验，总共225名不活跃(60分钟中等强度运动/周)的LARC患者 计划启动TNT的将按性别(男性与女性)和年龄(55岁与55岁)和 随机分配(1：1：1比例)接受治疗前每周90分钟、150分钟或300分钟 至术前(~32周)。所有的AT剂量方案将根据标准的AT原则和 使用我们的数字AT平台实施，允许在患者家中使用远程 实时监控。我们将解决三个具体目标：目标1：确定AT在TNT治疗中的剂量反应 耐受性。目的2：评价AT对血液学功能的量效关系。目标3：探索AT的剂量-反应 肿瘤的临床结局。拟议的研究通过测试直接解决了未得到满足的临床需求，这是第一次 在接受LARC治疗的患者中，AT对多种治疗相关结果的时间、剂量-反应效应 TNT。这项拟议的研究将改进癌症治疗患者的行为干预方案 通过使用我们的数字锻炼方法，为不在附近居住的患者扩大进入AT的途径 一家研究网站。接受癌症治疗不是运动疗法的合格条件，因此， 目前，锻炼并不被认为是癌症治疗的标准方面。因此，如果成功，调查结果 这项研究还将改变关于癌症运动疗法的临床范式，增加一个 越来越多的证据支持将AT整合到标准的临床癌症治疗中。

PROJECT SUMMARY/ABSTRACT Randomized trials demonstrate aerobic training (AT) attenuates treatment-induced impairments in physiological and psychosocial outcomes in a broad number of cancer patient populations. However, whether AT specifically impacts the tolerability of cancer treatment is largely unknown. To address this fundamental knowledge gap in exercise-oncology research, the objective of this study is to evaluate the dose-response of AT on treatment tolerability and related outcomes in patients with locally advanced rectal cancer (LARC) initiating total neoadjuvant therapy (TNT). LARC is an ideal model in which to conduct a definitive trial of AT on treatment tolerability for several reasons: (1) high rate of LARC diagnoses annually in the U.S. (>40,000), (2) poor tolerability of TNT (<60% of patients complete the recommended regimen), and (3) strong biological rationale (TNT-induced impairment in hematological function is the major cause of poor tolerability, and AT is demonstrated to enhance hematological function in preclinical and clinical studies). Therefore, in this phase 2 randomized trial, a total of 225 inactive (<60 mins of moderate-intensity exercise/wk) patients with LARC scheduled to initiate TNT will be stratified by sex (male vs. females) and age (<55 years vs. >55 years) and randomly allocated (1:1:1 ratio) to receive: 90 mins/week, 150 mins/week, or 300 mins/week from pre-treatment to pre-surgery (~32 weeks). All AT dose regimens will be prescribed according to standard AT principles and implemented using our digital AT platform permitting all sessions to be performed in patients’ homes with remote real-time monitoring. We will address 3 specific aims: AIM 1: Determine dose-response of AT on TNT treatment tolerability. AIM 2: Evaluate AT dose-response on hematological function. AIM 3: Explore AT dose-response on tumor clinical outcomes. The proposed study directly addresses an unmet clinical need by testing, for the first time, the dose-response effects of AT on multiple treatment-related outcomes in patients with LARC receiving TNT. The proposed study will improve behavioral intervention protocols for patients undergoing cancer treatment by using our digital exercise approach that expands access to AT for patients not residing within close proximity of a research site. Receiving cancer treatment is not a qualifying condition for exercise therapy and, as such, exercise is not currently considered a standard aspect of cancer management. Therefore, if successful, findings from this investigation will also shift clinical paradigms regarding exercise therapy in cancer by adding to a growing body of evidence supporting integration of AT into standard clinical cancer care.