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: 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
• 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

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（诊断后≥5年死亡）的主要原因。 乳腺癌（EBC）。改善多系统功能的有效治疗策略是一个主要的 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， 改善心肺功能（CRF）的随机对照试验（RCT），这是一个强有力的独立预测因素 BC和其他恶性肿瘤的CVD和全因死亡率。然而，几乎所有肿瘤学的AT RCT 报告整个队列的平均CRF变化;平均结果的显示掩盖了 应答为了直接解决这一差距，我们小组在最近完成的随机对照试验中探索了反应的变异性 在174例EBC患者（辅助治疗后2.8年）中，分配至150 min/wk：（1）线性AT (70% CRF）;（2）非线性AT（55%至100%CRF）;或（3）拉伸（注意力控制）连续16周。 尽管AT依从性高，但我们发现：（1）CRF变化范围为-10%至+24%，（2）~60%为 根据CRF技术错误（TE;生物学的稳健测量）分类为CRF无应答者 可变性和测量误差）。这些结果表明，AT在常规容量（~150 min/wk）和/或长度（~16 wk）不足以改善相当大比例的EBC存活者的CRF。 AT诱导的CRF改善与相应的CVD风险降低相关;因此， 迫切需要测试替代AT方法的有效性，以优化CRF缓解率。初步 我们小组和其他人的研究结果表明，为了增加CRF，增加AT体积和/或 需要长度以允许多系统适配（即，心肺功能的所有组成部分- 血管-肌肉轴）。尚无直接评估CRF上AT长度和体积的RCT 任何癌症人群的反应率。因此，本研究的目的是评估AT的作用 项目长度和数量对CRF应答率和EBC中其他相关结局的影响。目标1：比较 非线性AT程序长度和体积对CRF应答率的影响。目标2：评估对 CRF的生理决定因素。目的3：确定患者报告结局、可行性 和安全性采用4组RCT设计，我们将随机分配152例（n=38/组）EBC幸存者， 完成辅助治疗：A组：仅容量（300分钟/周，持续16周），B组：仅长度（150分钟/周） 分钟/周，持续32周），C组：长度和体积（300分钟/周，持续32周），或D组：对照组（150分钟/周，持续32周） 16周）。影响：本研究的结果将确定最大化CRF缓解的AT方案 EBC中的发生率和其他临床相关终点。最终，这些发现将为政策提供信息， 指导方针和标准临床护理。