Exercise-focused Rehabilitation for Cancer Survivors: Creating a CORE Component of Oncology Care

The publication of the AHA statement, Cardio-Oncology Rehabilitation (CORE) to Manage Cardiovascular Outcomes in Cancer Patients and Survivors, represents a breakthrough for exercise to become standard of care for cancer survivors. Incorporating exercise as part of cancer care has taken a long time. Looking at exercise and cancer articles in my paper files, I was disheartened to realize that the same recommendations to encourage cancer survivors to exercise were being made in 1999¹ to present.² In those 20 years, a multitude of research studies identified the positive impact of exercise for cancer survivors with different types of cancer, varying ages and time since diagnosis. The American College of Sports Medicine³ acknowledged the safety and efficacy of exercise, and cancer societies, including the American Cancer Society⁴, American Society for Clinical Oncology⁵, and the National Comprehensive Cancer Network⁶, recommend exercise for cancer survivors. Yet the majority of cancer survivors do not meet recommendations for physical activity.⁷

elIt takes 17 years for 14% of original research to reach clinics and benefit patients outside of a controlled study⁸, and despite research support and society recommendation, clinical programs delivering exercise opportunities to cancer survivors are lacking. As a result, the majority of the more than 16 million cancer survivors in the United States⁹ are not provided an exercise rehabilitation opportunity. I applaud the American Heart Association (AHA) for their support of cancer survivors. The publication of the AHA statement on Cardio-Oncology Rehabilitation (CORE) to Manage Cardiovascular Outcomes in Cancer Patients and Survivors lays out the evidence for the importance of cardiovascular morbidity among cancer survivors and provides a road map for diminishing the risk through clinically based exercise programs.

In oncology, we have made great strides in identifying and treating cancer resulting in a large and growing cancer survivor population. However, our therapies result in collateral damage including, as reviewed in the AHA statement, increased risk for cardiovascular disease compared to the general population. The data for improved cardiovascular outcomes for individuals with cardiac disease participating in cardiac rehabilitation are clear¹⁰ and data for improved cardiovascular outcomes is growing for cancer survivors.¹¹ However, other impacts of cancer and cancer treatment are also amenable to exercise.

Cancer survivors have greater functional limitations and impaired mobility than non-cancer patients.¹² The predisposition to strength and functional declines may lay in muscle changes brought about by inactivity and direct impact of cancer therapy. Toth et al identified change at the molecular and cellular level of muscle among cancer survivors receiving chemotherapy that scale up to whole person muscle strength and function.¹³ Similar to low cardiorespiratory fitness, lack of strength is also associated with all-cause mortality in general population¹⁴ and cancer mortality.^15,16 Additionally, research suggests exercise improves function¹⁷ and prevents mortality¹⁸ for the general population with a growing literature base supporting similar improvements for cancer survivors.¹⁹ For older cancer survivors in particular, physical function is important as disability impairs quality of life, threatens independence, and increases morbidity and mortality²⁰ and those ≥ 65 years comprise the largest proportion of survivors.²¹

Increased physical activity improves cancer outcomes. Associations between physical activity and improved cancer outcomes have been noted since 2005 when Holmes et al identified improved overall survival with increased physically activity in breast cancer survivors in the Nurses’ Health Study.²² This survival benefit has been highlighted in multiple studies for breast cancer and other cancers.^23,24,25 A tantalizing finding, randomized trials of exercise during cancer treatment may improve disease free survival²⁶ and progression free survival²⁷ and appears to be associated with decreased circulating tumor cells.²⁸ The algorithm, Figure 1 in the AHA statement, focuses on exercise to reduce cardiovascular morbidity and mortality for those at risk but acknowledges that cancer survivors without cardiovascular risk factors benefit from exercise and suggest community programs. Given the value of exercise for maintaining strength and function and for potentially improving cancer outcomes, this recommendation should not be overlooked as it represents a large number of cancer survivors who could achieve benefit.

Dr. Gilchrist and co-authors’ identification of cardiac rehabilitation programs as a model and platform on which to build CORE is practical and insightful. Cardiac rehabilitation has an exercise infrastructure and is often located near cancer centers making it an ideal opportunity for cancer patients. Multimodal interventions are needed to comprehensively address challenges of cancer survivors and are already fundamental to how cardiac rehabilitation is delivered. Staff is trained to deliver exercise interventions to populations that often have chronic health issues. Given the overlap in risk factors for cardiac disease and cancer, many of the components of cardiac rehabilitation are relevant for cancer survivors including, physical activity and nutrition counseling, psychological management, weight management and smoking cessation. Additional training to provide a basic understanding of the late and lingering side effects of cancer survivors would be needed and is nicely outlined in the AHA statement.

As an example of this partnership with cardiac rehabilitation, the University of Vermont Medical Center has an exercise-based oncology rehabilitation program partnered with our cardiac rehabilitation facility.²⁹ Since 2011, all cancer survivors no matter the time since diagnosis or stage of disease can be referred to participate. As recommended by the AHA statement, survivors are evaluated by a medical provider and also a physical therapist before participation to identify functional deficits and any late and lingering side effects that may impact their ability to exercise. The 12 week exercise intervention includes twice weekly supervised aerobic and resistance training with recommendations to perform aerobic activity on additional days. The aerobic component is generally brisk walking and resistance training focuses on upper and lower extremity strength though modification in exercise choice is based on initial evaluation. Education sessions focusing on nutrition and stress management are also provided. To date we have collected baseline and post exercise intervention data on over 500 participants. The majority of participants are well below average for strength³⁰ and fitness³¹ at baseline compared to reference standards. After 12 weeks aerobic capacity increases by 9.8% and by 22.8% from baseline as measured by peak VO2 and the 6 minute walk test respectively. Upper extremity strength increases by 40.4% and lower extremity strength by 24.4% from baseline. Patient reported outcomes including fatigue, depression and anxiety scores also improve significantly.

Over the past 8 years we have learned valuable lessons about making clinically based exercise programs available for cancer survivors. From a systems perspective it is important to align key stake holders including cardiologists and cardiac rehabilitation staff, rehabilitative therapy providers, oncologists, and cancer center staff. Further, the program must have a champion at the cancer center whether this is an oncologist or an advanced practice provider. Given competing priorities in the care of cancer survivors, it helps to have reminders from a colleague to include rehabilitation and exercise as a key component of supportive care. Nurses, other providers and patients must be empowered to facilitate the referral. If adequate exercise opportunities are available, the “opt out” referral suggestion in the AHA statement eliminates the need to refer and expands the number of cancer survivors offered exercise opportunities. Spend time promoting the program by presenting at grand rounds for different medical disciplines including primary care and providing community talks for cancer survivors.

Supervised exercise for cancer survivors results in better compliance than recommendations to exercise³² or home based programs.³³ The reasons for improved compliance are multifactorial. Similar to individuals who have experienced a cardiac event, our program participants often express fear about starting to exercise after cancer treatment especially if they were not physically active prior. The exercise trainers and the location close to medical facilities help them feel safe. We use a safety checklist similar to that recommended by the AHA statement. The exercise trainers provide needed encouragement and help participants stay accountable by progressing their exercise and calling if they stop coming. Cancer survivors form strong bonds within the group. However; social support doesn’t necessarily have to come from another cancer survivor. Cardiac, pulmonary and oncology patients share the same space and cancer survivors see that other cancer survivors are thriving and that individuals without cancer are also overcoming medical struggles. This is important for programs that may be too small to provide exercise for cancer survivors only.

Additional research needed to support growth of CORE spans the translational research continuum. Basic studies are needed to evaluate the impact of the growing number of new oncology drugs on cardiac function and muscle and exercise interventions to ameliorate the impact. The authors correctly acknowledge the challenges of exercising during therapy and predict most participation will be after cancer treatment. However, it may be more valuable to prevent loss of fitness and strength rather than regain strength and fitness. Data suggests cardiovascular and muscle function^34,35 is preserved or improved when exercise occurs during chemotherapy compared to no exercise. Pragmatic effectiveness trials of CORE dissemination to multiple centers, academic and community will be essential to be sure impacts of exercise found in tightly controlled studies translate to environments where the exercise will be delivered such as cardiac rehabilitation. Not all cancer centers have cardiac rehabilitation nearby especially in rural areas. Additionally, some cardiac rehabilitation sites have insufficient space to accommodate a new population. Research in to the value of “distantly supervised” exercise through the use of interactive monitoring and wearable technology has the potential to greatly expand cancer survivor access to exercise.

Dr Gilchrist and her co-authors have done cancer survivors a huge favor by creating a road map to provide clinically delivered exercise interventions for cardiovascular risk reduction. While additional research is needed there is no reason to wait to provide interventions we know are safe and effective. The AHA statement provides enough detail to immediately begin program development. At the University of Vermont Medical Center, we are fortunate to have a forward thinking cardiac rehabilitation medical director and rehabilitative services manager and cardiac and oncology rehabilitation have combined exceptionally well. Nonetheless we have depended on creative funding strategies to make the program free for cancer survivors. Programs shouldn’t have to depend on bake sales to fund interventions that are in the best interest of cancer survivors. Insurance reimbursement is a necessary next step. Do we need overall survival data from a randomized control trial? I hope not. Other outcome improvements such as function and improvement in patient reported outcomes are starting to be recognized as valuable end points for obtaining insurance coverage.^36.37 The next decade should see CORE become standard of care for cancer survivors and the AHA statement is a promising first step.