A Randomized Trial to Minimize Non-Response to Aerobic Training in Operable Breast Cancer

一项旨在最大程度地减少可手术乳腺癌患者对有氧训练无反应的随机试验

基本信息

批准号：
10599876
负责人：
Jessica Scott
金额：
$ 68.71万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-16 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10599876
关键词：
Address Adjuvant Therapy Adverse event Aerobic Exercise Age Biological Blood Vessels Breast Cancer Patient Breast Cancer survivor Breast Cancer therapy Cancer Survivor Cardiac Output Cardiopulmonary Cardiovascular Diseases Cessation of life Classification Clinical Common Terminology Criteria for Adverse Events Data Diagnosis Dose Evaluation Event Exercise Therapy Frequencies Heart Home Interruption Intervention Investigation Length Life Style Lung Malignant Neoplasms Masks Measurement Measures Modification Monitor Morbidity - disease rate Muscle Oncology Outcome Oxygen Oxygen Consumption Participant Patient Outcomes Assessments Patient Self-Report Peripheral Phase Phase II/III Trial Physiological Policies Population Quality of life Random Allocation Randomized, Controlled Trials Regimen Reporting Safety Sampling Studies Skeletal Muscle Stretching Survivors System Testing Time Venous Woman Work arm attentional control cardiorespiratory fitness cardiovascular disorder risk clinical care clinically relevant cohort cytotoxic effective therapy efficacy testing evidence based guidelines exercise physiologist exercise program follow-up functional improvement improved instrument inter-individual variation malignant breast neoplasm mortality novel prevent primary endpoint programs radiation-induced injury randomized trial response standard of care tele-exercise therapy adherence treadmill treatment response treatment strategy trial design virtual

项目摘要

PROJECT SUMMARY Cardiovascular disease (CVD) is the primary cause of late mortality (death ≥5 yrs from diagnosis) in early breast cancer (EBC). Effective treatment strategies that improve function across multiple systems are a major clinical need to reduce CVD in EBC. Aerobic exercise therapy (AT) is a pleiotropic intervention demonstrated in randomized controlled trials (RCTs) to improve cardiorespiratory fitness (CRF), a strong, independent predictor of CVD and all-cause mortality in BC and other malignancies. However, virtually all AT RCTs in oncology report the mean CRF change for the overall cohort; presentation of the mean result masks variability in responses. To directly address this gap, our group explored response variability in our recently completed RCT among 174 EBC patients (2.8 yrs. post-adjuvant therapy) who were allocated to 150 min/wk of: (1) linear AT (70% CRF); (2) nonlinear AT (55% to 100% CRF); or (3) stretching (attention control) for 16 consecutive wks. Despite high AT adherence, we found that: (1) CRF change ranged from -10% to +24%, and (2) ~60% were classified as CRF non-responders based on the CRF technical error (TE; a robust measure of biological variability and measurement error). These findings indicate that AT following the conventional volume (~150 min/wk) and / or length (~16 wks) is insufficient for improving CRF in a substantial proportion of EBC survivors. AT-induced improvement in CRF is associated with corresponding reductions in CVD risk; thus, there is a critical need to test the efficacy of alternative AT approaches that can optimize CRF response rate. Preliminary findings from our group, and others, indicate that in order to augment CRF, increased AT volume and / or length is required to allow for multisystem adaptation (i.e., across all components of the cardiopulmonary- vascular-muscular axis). There have been no RCTs directly assessing AT length and volume on CRF response rate in any cancer population. The objective of this study is therefore to evaluate the effects of AT program length and volume on CRF response rate and other pertinent outcomes in EBC. AIM 1: Compare the effects of nonlinear AT program length and volume on CRF response rates. AIM 2: Evaluate the effects on physiological determinants of CRF. AIM 3: Ascertain the difference in patient-reported outcomes, feasibility, and safety. Using a 4-arm RCT design, we will randomly allocate 152 (n=38/group) EBC survivors following completion of adjuvant therapy to: Arm A: volume only (300 min/wk for 16 weeks), Arm B: length only (150 min/wk for 32 weeks), Arm C: length and volume (300 min/wk for 32 weeks), or Arm D: control (150 min/wk for 16 weeks). IMPACT: Results from this investigation will identify the AT regimen that maximizes CRF response rate and other clinically relevant endpoints in EBC. Ultimately, these findings will inform policy, evidence-based guidelines, and standard clinical care.

项目概要心血管疾病 (CVD) 是早期晚期死亡（诊断后死亡≥5 年）的主要原因改善多个系统功能的有效治疗策略是乳腺癌 (EBC) 的主要治疗策略。临床需要减少 EBC 中的 CVD 有氧运动疗法 (AT) 是一种多效性干预措施。改善心肺健康 (CRF) 的随机对照试验 (RCT)，这是一个强大的独立预测因子然而，几乎所有的 AT 随机对照试验都针对肿瘤学。报告整个队列的平均 CRF 变化；平均结果的呈现掩盖了为了解决这一差距，我们的小组在最近完成的随机对照试验中直接探索了反应的变异性。 174 名 EBC 患者（辅助治疗后 2.8 年）被分配至每周 150 分钟：(1) 线性 AT (70% CRF)；(2) 非线性 AT（55% 至 100% CRF）；或 (3) 连续 16 周的拉伸（注意力控制）。尽管 AT 依从性很高，但我们发现：(1) CRF 变化范围为 -10% 至 +24%，(2) ~60% 根据 CRF 技术错误（TE；一种稳健的生物测量方法）将患者分类为 CRF 无反应者这些发现表明 AT 遵循常规体积（~150）。分钟/周）和/或长度（~16 周）不足以改善大部分 EBC 幸存者的 CRF。 AT 引起的 CRF 改善与 CVD 风险的相应降低相关；迫切需要测试可优化 CRF 初步反应率的替代 AT 方法的功效。我们小组和其他小组的研究结果表明，为了增强 CRF，需要增加 AT 体积和/或需要长度以允许多系统适应（即跨越心肺的所有组成部分）血管-肌肉轴）尚无直接评估 CRF 上 AT 长度和体积的随机对照试验。因此，本研究的目的是评估 AT 的效果。项目长度和数量对 CRF 响应率和 EBC 中其他相关结果的影响：比较非线性 AT 程序长度和容量对 CRF 响应率的影响目标 2：评估对 CRF 响应率的影响。 CRF 的生理决定因素 3：确定患者报告的结果、可行性、使用 4 臂 RCT 设计，我们将随机分配 152 名（n=38/组）EBC 幸存者。辅助治疗完成后： A 组：仅训练量（每周 300 分钟，持续 16 周），B 组：仅长度（150 分钟/周）分钟/周，持续 32 周），C 组：长度和训练量（300 分钟/周，持续 32 周），或 D 组：对照（150 分钟/周，持续 32 周）影响：本次调查的结果将确定能够最大限度提高 CRF 反应的 AT 方案最终，这些发现将为基于证据的政策提供信息。指南和标准临床护理。