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

• 批准号: 10377998
• 负责人: Jessica Scott
• 金额: $ 70.11万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 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/10377998
• 关键词: Address; Adjuvant Therapy; Adverse event; Aerobic; 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; 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; Randomized Controlled Trials; Regimen; Reporting; Safety; Sampling Studies; Skeletal Muscle; Stretching; Survivors; System; Testing; Time; Training; Venous; Woman; Work; arm; attentional control; base; cardiorespiratory fitness; cardiovascular disorder risk; clinical care; clinically relevant; cohort; cytotoxic radiation; effective therapy; efficacy testing; evidence based guidelines; exercise physiologist; exercise program; follow-up; improved; improved functioning; 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

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.

项目摘要 心血管疾病（CVD）是早期死亡率晚期死亡率（死亡≥5岁）的主要原因 乳腺癌（EBC）。改善多个系统功能的有效治疗策略是主要的 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 随机对照试验（RCT）以改善心肺适应性（CRF），这是一个强，独立的预测指标 卑诗省和其他恶性肿瘤中的CVD和全因死亡率。但是，几乎全部在肿瘤学的RCT中 报告整个队列的平均CRF变化；表示平均结果的呈现掩盖可变性 回答。为了直接解决这一差距，我们的小组探索了我们最近完成的RCT的响应变异性 在174名EBC患者（2.8岁的辅助疗法）中，分配给150分钟/wk的患者：（1）线性 （70％CRF）； （2）在（55％至100％CRF）处的非线性；或（3）连续16个WKS的拉伸（注意控制）。 尽管依从性很高，但我们发现：（1）CRF变更范围从-10％到 +24％，（2）〜60％为 根据CRF技术错误归类为CRF非反应器（TE；生物学的强大测量 可变性和测量误差）。这些发现表明，按照传统体积（〜150） 最小 / wk）和 /或长度（〜16 wks）不足以在相当一部分EBC存活中改善CRF。 CRF的AT引起的改善与CVD风险的相应降低有关；因此，有一个 在可以优化CRF响应率的方法上测试替代方案效率的临界需求。初步的 我们小组和其他人的发现表明，为了增加CRF，数量和 /或增加 需要长度以允许多系统适应（即，在心肺的所有组件中 血管肌肉轴）。尚无RCT直接评估CRF的长度和音量 任何癌症人群的缓解率。因此，这项研究的目的是评估AT的影响 EBC中CRF响应率和其他相关结果的程序长度和数量。目标1：比较 非线性在程序长度和体积上对CRF响应率的影响。目标2：评估对 CRF的生理决定者。目标3：确定患者报告的结果，可行性，可行性的差异， 和安全。使用4臂RCT设计，我们将随机分配152（n = 38/组）EBC生存 完成调整疗法对：ARM A：仅体积（300分钟/周16周），ARM B：仅长度（150） 最小/周32周），ARM C：长度和体积（300分钟/周32周）或ARM D：对照（150分钟/wk 16周）。影响：这项投资的结果将确定最大化CRF响应的AT方案 EBC中的比率和其他临床相关终点。最终，这些发现将为政策，基于证据的信息提供信息 指南和标准临床护理。