Importance of Exercise Training Therapy Timing With Regard to Cardiotoxicity and Patient Preference in Early Breast Cancer and Lymphoma Patients Undergoing Adjuvant Chemotherapy
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 57
- 试验地点
- 8
- 主要终点
- Changes from baseline in left ventricular (LV) global longitudinal strain (GLS)
研究概览
简要总结
Breast cancer is the most common cancer among women worldwide. Similarly, Hodgkin and non- Hodgkin lymphomas make up two of the most prevalent cancers in men and women. Even though remarkable improvements in cancer-free survival have been achieved in the last decades, the development of cardiac toxicity, associated with anthracycline-based chemotherapy (Anth-bC) counteracts the improvements in survival in these patient groups. One of the first clinical manifestation of Anth-bC cardiotoxicity is diastolic dysfunction, with further symptoms being left ventricular dysfunction and heart failure as well as a decline in exercise tolerance. Besides the direct cardiotoxic effects of anticancer treatment, many drugs also have adverse effects on the vascular endothelium.
The concept of 'Exercise is Medicine' has become well established in exercise-oncology research. Exercise therapy is now considered a safe and well-tolerated adjunct therapy inducing beneficial effects on body composition, aerobic fitness and muscular strength, pain and fatigue, quality of life (QoL), depressive symptoms, and all cause survival. However, there is insufficient data on the superiority of performing exercise training therapy before and during chemotherapy with regard to cardiotoxic and cardiovascular side effects. Further, there is no data on patient preference for and barriers toward different timings of exercise training therapy.
Therefore, the aim of the study is to compare left ventricular (LV) function measured by LV global longitudinal strain (GLS) in breast cancer and lymphoma patients undergoing Anth-bC randomised to completing an exercise-based rehabilitation programme during chemotherapy to those randomised to complete the programme after chemotherapy. Further, blood samples will be drawn to analyse biomarkers of myocardial injury (brain natriuretic peptide and high-sensitive cardiac troponin).
Additional measurements include aortic distensibility as part of the echocardiographic examination and exercise capacity through cardiopulmonary exercise testing. QoL and fatigue will be assessed in a questionnaire, compliance with exercise training through monitoring and patient preference at 3 and 6 months will be evaluated through an interview. Cardiovascular risk factors will be assessed through body composition, 24h ambulatory blood pressure monitoring, 24h electrocardiogram and the analysis of established blood markers.
Women and men aged 18 years and older with histologically confirmed breast cancer or lymphoma (ECOG grade 0-2) who are Anth-bC naïve and with reasonable life expectancy will be included in the study.
The exercise programme is part of onco-rehabilitation programmes at the Inselspital Bern, the Spital AG Thun and the Bürgerspital Solothurn. Programmes last for 12 weeks and offer two supervised sessions per week (@ 60-90 min). They usually contain an endurance component (e.g. 40 min of cycling) and a strength, agility or relaxation component. Patients are encouraged to complete a third exercise session per week at home or elsewhere. Home-based training and general physical activity will be assessed by a questionnaire and an activity monitor.
A total of 120 patients will be recruited. Measurements will be performed at baseline, after 3 months (week 13) and after 6 months (week 26).
详细描述
Study Design: A single-center, two-arm, parallel group with standard of care controlled trial with a balanced 1:1 randomization will be conducted at University Hospital Inselspital, Berne, Switzerland. A total of 120 women (60 participants per study arm) who are scheduled for first- line Anthracycline based chemotherapy (Anth-bc) presenting either at the Inselspital or Lindenhofspital Berne, the Spital AG Thun or the Bürgerspital Solothurn will be enrolled. After baseline assessments, eligible participants will be randomized to one of two arms including the exercise rehabilitation programme during chemotherapy or the control group (exercise training intervention after conclusion of chemotherapy).
Patient Population: Women and men aged 18 years and older with histologically confirmed breast cancer or lymphoma who are Anth-bC naïve and are scheduled for first-line Anth-bC, Eastern Cooperative Oncology Group (ECOG) grade 0-2, curative or palliative approach with reasonable life expectancy and a willingness to attend exercise sessions twice per week for 12 weeks (24 sessions in total).
Procedures: The following measurements will be collected at the beginning (T0), following the 12 week intervention (T1) and after another 12 weeks (T2). Participants will also be expected to attend two weekly supervised exercise sessions integrated in a multidisciplinary oncology rehabilitation programme at the Inselspital Bern, Spital AG Thun, and Bürgerspital Solothurn, and will be expected to complete one additional exercise training session at home or in the community each week.
T0: All participants will undergo baseline assessments at the University Hospital Inselspital, Berne. This includes cardiac assessment by a skilled clinical cardiac sonographer to obtain left ventricular (LV) global longitudinal strain (GLS) and aortic distensibility. Further, cardiopulmonary exercise testing (CPET) will be completed on a cycle ergometer to obtain VO2peak and to calculate corresponding training zones. Standard measures conducted during the intake process including height, weight, body composition (assessed by bio-impedance- measurement) and waist circumference will also be collected. Blood samples will be obtained from each participant and analyzed for biomarkers of myocardial injury as well as lipid profile and HbA1C. Following each visit, twenty-four-hour ambulatory blood pressure monitoring and 24h Holter ECG will be performed. The questionnaires for physical activity patterns (GPAQ) and fatigue (FACIT-F), a health history questionnaire and the activity tracking devices will also be administered by the research coordinator upon their initial visit.
T1: All measurements from T0 will be repeated. Additionally, patients from the ExEarly (experimental) group will be interviewed by the study coordinator to assess barriers for missed exercise sessions. Simultaneously, patients from the ExStandard group will be asked to anticipate barriers which may impede their participation in regular exercise training during the next 12 weeks. It will further be assessed whether it would have been feasible for them to complete the exercise programme concurrently to chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
Assessors of outcome data and analysis will be blinded to the intervention arm.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Women and men aged 18 years and older
- •Histologically confirmed breast cancer or lymphoma
- •Anth-bC naïve
- •Scheduled for first-line Anth-bC
- •Eastern Cooperative Oncology Group (ECOG) grade 0-2
- •Curative or palliative approach with reasonable life expectancy
- •Willingness to attend exercise sessions twice per week for 12 weeks (24 sessions in total)
- •Informed Consent as documented by signature (Appendix Informed Consent Form)
排除标准
- •Inability to participate in a 3-month training program
- •Contraindication to maximal CPET
- •Cancer-specific contraindications including safety blood parameters
- •Previous radiotherapy of the mediastinum and/or the the left breast
- •Structural heart disease with reduced left ventricular ejection fraction (EF<50%)
- •Valvular heart disease with more than mild regurgitation or stenosis
- •Heart rhythms other than sinus rhythm
- •Pacemaker with permanent ventricular stimulation
- •Antihypertensive medication (e.g. ACE inhibitors/ATII blockers, Ca channel blocker, beta blockers)
- •Known or suspected non-compliance, drug or alcohol abuse
- •Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
- •Previous enrolment into the current study
- •Enrolment of the investigator, his/her family members, employees and other dependent persons
结局指标
主要结局
Changes from baseline in left ventricular (LV) global longitudinal strain (GLS)
时间窗: week 13
GLS assessed by speckle tracking echocardiography is an established marker for LV systolic function with a good reproducibility, which has also been found in the investigators' laboratory. In breast cancer and lymphoma patients LV global longitudinal strain is an established measure to assess cardiotoxicity of Anth-bC.
次要结局
- Change in Blood biomarkers(week 0, 13, and 26)
- Compliance with exercise training(week 0, 13 and 26)
- Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)(week 0, 13, and 26)
- Cardiorespiratory fitness(week 0, 13, and 26)
- Vascular function(week 0, 13, and 26)
- Identification of barriers towards exercise training(week 13 and 26)
- Cardiovascular risk profile(week 0, 13, and 26)
- Changes in LV global longitudinal strain(Week 0 and 26)