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.

项目摘要/摘要 随机试验表明有氧训练（AT）减弱了治疗诱导的生理障碍 和大量癌症患者人群中的社会心理结局。但是，是否专门 影响癌症治疗的耐受性在很大程度上未知。解决这个基本知识差距 运动肿瘤研究，本研究的目的是评估AT治疗的剂量反应 局部晚期直肠癌患者（LARC）的耐受性和相关结局启动了 新辅助治疗（TNT）。 LARC是一个理想的模型，在其中进行AT治疗的明确试验 由于多种原因的耐受性：（1）美国每年的LARC诊断率高（> 40,000），（2）差 TNT的耐受性（<60％的患者完成建议方案），（3）强大的生物学原理 （TNT诱导的血液学功能损伤是耐受性差的主要原因，并且AT 证明可以在临床前和临床研究中增强血液学功能）。因此，在这个阶段2 随机试验，共有225例非活动性（现代强度运动/周）患者LARC患者 计划启动TNT将按性别（男性与女性）和年龄（<55岁vs.> 55岁）进行分层 随机分配（1：1：1）要接收：90分钟/周，每周150分钟或距预处理300分钟/周 进行手术前（〜32周）。剂量方案的所有方案将根据标准规定原则和 使用我们的数字在平台上实施，允许在患者的家中进行所有课程 实时监控。我们将解决3个具体目标：目标1：确定AT TNT治疗的剂量反应 耐受性。 AIM 2：对血液学功能的剂量反应进行评估。目标3：探索剂量反应 肿瘤临床结果。拟议的研究直接通过测试来解决未满足的临床需求，第一次 时间，AT对LARC患者的多种治疗相关结局的剂量反应效应 TNT。拟议的研究将改善接受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，该方法扩大了无法居住在附近的患者的访问权限 研究地点。接受癌症治疗不是运动疗法的合格条件，因此， 锻炼目前不被认为是癌症管理的标准方面。因此，如果成功的话， 通过这项调查，还将通过添加到 越来越多的证据体支持AT整合到标准临床癌症护理中。