Cardiovascular (CV) events related to the receipt of potentially cardiotoxic anthracycline-based chemotherapy (Anth-bC), are emerging as leading causes of morbidity and mortality for survivors of lymphoma (the 5th most common cancer in North America). The objective of our proposal is to reduce this cancer treatment related CV morbidity by developing, enabling, and testing a physical activity intervention that commences and continues throughout receipt of Anth-bC for the purpose of attenuating physical inactivity, preserving exercise capacity, CV & cognitive function, strength, and health-related quality of life (HRQOL) for those with lymphoma. The need for and the design of this program is based in part on feedback from lymphoma survivor focus groups treated in our NIH funded Comprehensive Cancer Center - preliminary pilot data (Section 3.C.1). Several novel features of this proposal include: 1) Performance of physical activity during receipt of cancer treatment where exercise intolerance originates. 2) Creation of patient communities that enable cancer patients to support one another during treatment. 3) Administration of aerobic & strength activities suited to one's individual lifestyle in the home guided by instruction provided from 4 close to home cardiac rehabilitation facilities experienced in exercising immunocompromised individuals and those with other pre-existing activity limitations due to cancer. 4) Utilization of newly developed magnetic resonance cardiopulmonary exercise treadmill testing methods to measure the two components (cardiac function and peripheral factors) that contribute to peak VO2 (a measure of maximal exercise capacity). This new information will provide mechanistic insight into how physical activity helps preserve exercise capacity and reduce fatigue. 5) Assessment of the relationships between cognitive function, activity, and exercise capacity thereby helping to unravel the association between physical activity, HRQOL and cognitive function in cancer patients. In this application, we propose to refine the physical activity intervention during the R21 Phase in patients who participate in the intervention for 6 months. If suitable milestones are achieved, we will conduct a randomized clinical trial in the R33 Phase to test the utility of the integrated physical activity intervention for sustaining peak V02, 6-min walk distance, cardiac and cognitive function, strength, activity, and HRQOL. If we achieve our study goals, this proposed intervention could reduce CV mortality and heart failure related hospital admissions, translate into clinical practice via extension through cardiac rehabilitation centers (often located close to cancer centers), increase health-related quality of life, reduce fatigue to perform activities of daily living, and attenuate cognitive function decline in lymphoma survivors. The results of this study could help to change existing sedentary behavior paradigms during receipt of chemotherapy and ultimately lead to improved long term outcomes for those with lymphoma and potentially other forms of cancer.

PROJECT NARRATIVE Lymphoma survivors are increasingly experiencing morbidity and mortality due to cardiovascular events that often result from the anthracycline-based chemotherapy used to treat their cancer. Our team of experienced investigators will test the utility of a patient-centric, individually tailored physical activity intervention implemented throughout chemotherapy to attenuate physical inactivity, reduce fatigue, and preserve exercise capacity, cardiac and cognitive function, strength, and health-related quality of life: all metrics that associate with or reduce cardiovascular risk. By fostering a lifestyle that maintains or increases physical activity and exercise capacity, this project seeks to reduce overall cardiovascular morbidity and mortality of lymphoma survivors and thereby improve their overall survival and quality of life.