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

局部晚期直肠癌新辅助治疗期间有氧训练的剂量反应

• 批准号: 10451201
• 负责人: Andrea Cercek
• 金额: $ 128.43万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-06 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10451201
• 关键词: Address; Adherence; Aerobic; Age; Anemia; Antiemetics; Apoptosis; Attenuated; Behavior Therapy; Biological; Biological Assay; Blinded; Cancer Control; Cancer Patient; Case Report Form; Cell Differentiation process; Cessation of life; Clinical; Clinical Research; Common Terminology Criteria for Adverse Events; Complete Blood Count; Correlative Study; Data; Diagnosis; Disease-Free Survival; Dose; Erythrocytes; Evaluation; Event; Exercise; Exercise Therapy; F2-Isoprostanes; Fatigue; Female; Flow Cytometry; Generations; Guidelines; Hematology; Hematopoietic stem cells; Hemoglobin; Home; Impairment; In complete remission; Incidence; Investigation; Knowledge; Malignant Neoplasms; Mass Spectrum Analysis; Modeling; Modification; Neoadjuvant Therapy; Neutropenia; Oncologist; Oncology; Operative Surgical Procedures; Outcome; Pathologic; Patient Education; Patient Outcomes Assessments; Patient Schedules; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase II/III Trial; Physiological; Pilot Projects; Postoperative Complications; Protocols documentation; Qualifying; Quality of life; Reactive Oxygen Species; Recovery; Rectal Cancer; Regimen; Reporting; Research; Risk; Safety; Sample Size; Schedule; Site; Standardization; Structure; Survival Rate; Techniques; Testing; Time; Toxic effect; Training; Translating; Treatment-related toxicity; Walking; Work; adjudicate; cancer care; cancer diagnosis; cancer survival; cancer therapy; cancer type; chemoradiation; chemotherapy; clinical practice; design; digital; evidence base; exercise intensity; improved; male; malignant breast neoplasm; meetings; neutrophil; patient population; point of care; preclinical study; primary endpoint; psychosocial; randomized trial; real time monitoring; response; sex; standard of care; treadmill; treatment planning; tumor

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.

项目总结/摘要 随机试验表明，有氧训练（AT）可以减轻治疗引起的生理功能障碍， 和心理社会的结果。然而，无论具体 影响癌症治疗的耐受性在很大程度上是未知的。为了解决这一基本知识差距， 运动-肿瘤学研究，本研究的目的是评估AT对治疗的剂量反应 局部晚期直肠癌（LARC）患者的耐受性和相关结局 新辅助治疗（TNT）。LARC是进行AT治疗确定性试验的理想模型 耐受性有几个原因：（1）美国每年LARC诊断率高（> 40，000），（2）LARC诊断率低（> 40，000），（3）LARC诊断率低（> 40，000），（4）LARC诊断率低（> 40，000），（5）LARC诊断率低（> 40，000），（6）LARC诊断率低（> 40，000），（7）LARC诊断率低（> 40，000），（8）LARC诊断率低（> 40，000），（9）LARC诊断率 TNT的耐受性（<60%的患者完成了推荐的治疗方案），以及（3）强有力的生物学原理 （TNT诱导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实增强血液学功能）。因此，在第二阶段 一项随机试验，共有225名不活动（每周中等强度运动<60分钟）的LARC患者 计划启动TNT的患者将按性别（男性vs.女性）和年龄（<55 years vs. >55岁）分层， 随机分配（1：1：1比例）接受：90分钟/周、150分钟/周或300分钟/周，从治疗前开始 至术前（约32周）。所有AT给药方案将根据标准AT原则进行处方， 使用我们的数字AT平台实施，允许所有会话在患者家中进行， 实时监控。我们将讨论3个具体目标：目的1：确定AT对TNT治疗的剂量反应 耐受性目的2：评价AT对血液功能的剂量效应。目的3：探索AT剂量反应 肿瘤临床结果。拟议的研究通过测试直接解决了未满足的临床需求， 时间，AT对接受LARC治疗的患者中多种治疗相关结局的剂量-反应效应 TNT炸药这项研究将改善接受癌症治疗的患者的行为干预方案 通过使用我们的数字化运动方法，为居住在不太近的患者扩大AT的使用范围 一个研究网站。接受癌症治疗不是运动疗法的合格条件，因此， 运动目前并不被认为是癌症管理的标准方面。因此，如果成功， 这项研究也将改变癌症运动疗法的临床模式， 越来越多的证据支持将AT整合到标准临床癌症护理中。