This article includes a succinct review of current research into exercise in the cancer setting and a discussion of the American College of Sports Medicine exercise recommendations for cancer survivors. Common acute, long-term, and late effects of cancer and its treatment are also described in the context of ways in which these side effects impact the ability to exercise.
Oncology (Williston Park). 31(10):711–717.
Figure.
Table 1. American College of Sports Medicine (ACSM) Exercise Guidelines for Cancer Survivors
Table 2. Goals of Exercise for Cancer Survivors
Exercise is associated with significant reductions in the recurrence and mortality rates of several common cancers. Cancer survivors who exercise can potentially benefit from reduced levels of fatigue, and improved quality of life, physical function, and body composition (ie, healthier ratios of lean body mass to fat mass). The amount of activity required to achieve protective effects is moderate (eg, walking 30 minutes per day at 2.5 miles per hour). However, many healthcare providers report a lack of awareness of the appropriate exercise recommendations across the phases of cancer survivorship, considerations regarding the timing of exercise interventions, and the ability to refer patients to exercise programs specifically aimed at cancer survivors. The American College of Sports Medicine notes that exercise is generally safe for most cancer survivors, and inactivity should be avoided. Their guidelines for exercise call for 150 minutes of moderate or 75 minutes of vigorous aerobic activity per week, and 2 days per week of resistance training (eg, with exercise bands or light weights). Survivors with lymphedema, peripheral neuropathy, breast reconstruction, central lines, and ostomies should follow specific precautions. Providing health professionals with the training and tools needed to provide adequate recommendations to their patients is essential to improving patient outcomes. To facilitate adherence among communities with the greatest need and poor access to services, cultural and environmental adaptations are critical.
The purpose of this article is to discuss exercise recommendations for cancer survivors at different stages of survivorship. The survivorship period for patients with cancer is defined by the National Cancer Institute as beginning on the day of cancer diagnosis and continuing through the end of life. This definition is broad and includes people with no tumor burden as well as those in the final stages of multiple organ failure at the end of life. Clearly, exercise regimens need to be tailored to address individual needs and abilities at various points along the survivorship trajectory. This article includes a succinct review of current research into exercise in the cancer setting and a discussion of the American College of Sports Medicine (ACSM) exercise recommendations for cancer survivors.[1] Common acute, long-term, and late effects of cancer and its treatment are also described in the context of ways in which these side effects impact the ability to exercise. We conclude with a brief discussion of ongoing exercise programs in the community, at cancer centers, and in culturally adapted programs that have been developed for specific underserved communities.
Cancer treatment causes profound debilitation that leads to reduced physical function and impairs quality of life. Negative sequelae have been observed across a range of treatment types-from surgery, to radiation, to hormonal treatment and targeted therapies.[1] For example, aerobic capacity, an important indicator of physical fitness and function, has been shown to decrease by 10% to 33% over a 12-week period of chemotherapy for breast and other cancers.[2-4] Almost one-third of breast cancer survivors have aerobic capacity below the minimum physiologic threshold required for functional independence. Peak oxygen consumption, which has been found to be reduced in patients with breast cancer across the survivorship continuum, may also be an independent predictor of survival in those patients with metastatic disease.[5]
The declines in physical abilities and physiologic function that are commonly observed in cancer patients can be minimized or prevented with a well-thought-out progressive program of restorative exercise. A substantial body of evidence demonstrates that exercise improves a variety of objectively measured and self-reported outcomes. Exercise during and following treatment has been associated with reductions in cancer recurrence and disease-specific mortality rates of 30% to 60% in breast and colorectal cancers.[6-8] Exercise also has been found to prevent or ameliorate many treatment-related negative effects-such as fatigue, muscle weakness, declines in cardiovascular function and overall functional ability, neuropathy, altered body composition, and reduced quality of life.[1,2,9-19]
The aforementioned treatment-related effects are observed across different tumor types (eg, in breast, prostate, colorectal, and lung cancer patients; in the setting of bone marrow transplant; and in other clinical scenarios), during and after treatment, and at different stages. Among breast cancer survivors, for example, the incidence rate of lymphedema has been reported to range from 6% to 70%. Risk factors include extent of axillary surgery and treatment with radiation therapy and/or chemotherapy. However, a study of breast cancer survivors showed that those who engaged in a slow, progressive program of resistance exercise (weight lifting) not only strengthened their affected arms but also had a lower incidence and severity of lymphedema.[15] Similar benefits have been observed in multiple studies of prostate cancer survivors receiving androgen deprivation therapy-which has a profound impact on skeletal muscle mass and strength, as well as body composition. Men who exercised gained muscle strength; improved their body composition, physical function, and quality of life; and experienced reductions in fatigue.[16-19]
Only a moderate amount of physical activity is required to achieve many of the protective benefits of exercise. Walking for 30 minutes 5 days a week at a speed of about 2.5 miles per hour conveys health benefits and is an attainable goal for most cancer survivors.[6] During a period when we expect patients to become debilitated, simple exercises such as walking 3 or 4 days per week can prevent the typical declines and, in many cases, improve functional ability.
Despite a rapidly growing body of evidence for the benefits of exercise for cancer survivors, 80% of oncology care providers (nurses and physicians) have reported being unaware of the availability of exercise guidelines in this setting and lack knowledge about when to implement them and where to refer survivors for exercise programs.[20] As a result, few cancer survivors receive formal information about exercise, a referral to rehabilitation or physical therapy, or even direction to an appropriate community-based exercise program. Notably, oncology care providers who are physically active themselves and meet the national exercise guidelines are significantly more likely to discuss exercise with their patients and provide a referral.[20]
To provide optimal care during and following treatment, healthcare providers should refer cancer survivors to programs of restorative exercise to reduce their fatigue, weakness, pain, and (in some patients) risk for lymphedema, and to improve their overall functional ability. The facility to which a survivor is referred for physical rehabilitation may be based on the individual’s level of physical function, previous experience with exercise, degree of debilitation, and number and types of comorbidities. Initially, a survivor with severe debilitation and other comorbidities that greatly limit his or her physical abilities may achieve the greatest benefit from working with a physical therapist. Survivors who are able to perform activities of daily living and are not experiencing any specific deficit(s) (eg, lymphedema, peripheral neuropathy, pain, muscle weakness) that significantly compromise their physical abilities will benefit from a community-based program directed by a cancer exercise specialist, such as the exercise programs offered by LIVESTRONG at the YMCA.[21]
In 2009, the ACSM convened a multidisciplinary group of experts to review cancer exercise research and develop guidelines for survivors.[1,9] In many ways the ACSM Exercise Guidelines for Cancer Survivors (summarized in Table 1) mirror the US Department of Health and Human Services Physical Activity Guidelines for Americans, but specific recommendations are given for different sites of cancer; stages of disease; types of treatment; and acute, long-term, and late treatment effects. The overwhelming message to convey to all cancer survivors is that inactivity should be avoided and any level of physical activity may provide some degree of health benefit.
The ACSM guidelines recommend that all cancer survivors engage in at least 150 minutes of moderate or 75 minutes of vigorous aerobic activity per week and 2 days per week of resistance exercise at a moderate to high intensity for all major muscle groups.[1] In addition, the guidelines recommend flexibility exercises for the eight major muscle groups. Exercises to improve balance are recommended for older adults, and there is little downside to including them in a survivor regimen for individuals of any age, especially for survivors at increased risk of falling. The guidelines make explicit exercise recommendations for cancer-specific conditions such as lymphedema, peripheral neuropathy, breast reconstruction, and central lines, as well as for colorectal cancer survivors who should avoid excess abdominal pressure, because of ostomies. While there are limitations on the generalizability of the research to date, which does not include all cancer populations, the overall findings are strong enough to recommend that exercise is safe and should be encouraged, whereas inactivity should be avoided. Table 2 highlights the goals of exercise programs for cancer survivors.
Acute treatment-related side effects are those that occur during active treatment for cancer, when patients are often immunocompromised. During this period, they may be learning to cope with myriad physical and emotional disturbances, including nausea, vomiting, fatigue, skin rashes, peripheral neuropathy, hair loss, pain, anxiety, depression, and changes in self-esteem and body image-all of which can negatively impact their overall well-being, quality of life, and daily function.
Exercise is possible during active treatment, but patients need to learn to manage their side effects before they escalate from mild to severe. Any planned exercise program should be adapted to the individual’s abilities and should focus on improving specific physical limitations. Many studies have demonstrated that engaging in exercise during active treatment improves fatigue, weakness, nausea, depression, anxiety, and quality of life.[1,9,11,14,15,22-25] The Figure illustrates the ways in which exercise programs can ameliorate certain acute and late effects of cancer and its treatment.
Oncology professionals need to help patients manage their side effects to enable them to exercise and function at the highest possible level. To optimize performance outcomes and benefits, it is important that exercise professionals guide patients in learning to adapt a particular exercise regimen to their physical state, the side effects they are experiencing, and their degree of fatigue.
Long-term effects of cancer treatment are side effects that begin during treatment and linger many months or years after the completion of treatment. Examples are lymphedema, fatigue, peripheral neuropathy, infertility, premature menopause, and changes in body composition. Long-term effects often necessitate adapting an individualized restorative exercise program to minimize the risk of injury or lymphedema. The goal is to adapt exercise regimens while still helping the survivor to achieve the greatest possible benefits from exercise. For example, the presence of lymphedema does not preclude exercise, but exercise precautions-such as wearing compression garments and beginning an exercise program with very light weights (eg, 1 pound)-must be observed to avoid a flare-up while still increasing muscle strength and range of motion. Gradual, progressive resistance exercise is safe and recommended to reduce the risk and severity of lymphedema.[14,15,26]
Cancer-related fatigue continues to be a persistent problem for approximately 33% of long-term breast cancer survivors.[27-29] Fatigue is exacerbated by other symptoms. Fatigue levels increase with neuropathy, with Raynaud syndrome–like symptoms, and with anxiety and depression. Rest and a sedentary lifestyle compound fatigue by accelerating debilitation. Data demonstrate that physical activity reduces fatigue.[1,12,13,16,17,24] Exercise programs for long-term cancer survivors must be developed slowly and gradually. Gradual increases in levels of physical activity can provide significant cardiovascular benefits.[30] Survivors may initially be shocked by their degree of debilitation, but with regular exercise they quickly see gains in muscle strength and cardiovascular endurance.
Peripheral neuropathy, a side effect of many chemotherapy agents, plagues a staggering 60% of patients up to 3 months post treatment; unfortunately, in as many as 30% of patients, this condition persists for 6 months or more after completion of treatment.[31] Some preliminary studies suggest that exercise may improve peripheral neuropathy, although no interventions have been discovered that reverse or prevent the neurologic damage.[25] When long-term cancer survivors begin exercising, their balance may be impaired due to peripheral neuropathy and general weakness. It is important to tailor an exercise prescription not only to improve muscle strength and aerobic capacity, but also to improve and restore balance. Physical therapy or a community-based exercise program should focus on core muscle and pelvic girdle strength. One easy exercise that can be performed at home is to balance on one foot while holding onto a stable object (eg, chair or table) nearby. Improving balance not only reduces the risk of falls and bone fracture, but also builds self-confidence regarding movement.
Cardiopulmonary complications of cancer treatment can emerge during active treatment but generally become problematic at later stages of survivorship for a wide range of malignancies, including breast cancer, non-Hodgkin lymphoma, Hodgkin lymphoma, and testicular cancer.[32,33] Heart failure is an adverse effect that may occur during treatment with certain chemotherapeutic agents (eg, trastuzumab, doxorubicin), but which also may present years later. Other cardiac complications in cancer patients and survivors include hypertension, arrhythmia, arterial stenosis, conduction disorders, and valvular heart disease. Pulmonary effects from chemotherapy and/or radiation therapy may include radiation pneumonitis, pulmonary fibrosis, and a reduction in pulmonary function. Breast cancer survivors demonstrate such severe declines in cardiac function that they actually experience accelerated aging; fortunately, these cardiac declines can largely be reversed with physical activity.[6]
Ongoing studies are examining the hypothesis that a program of structured exercise may prevent cardiovascular disease in survivors of testicular cancer.[34] While more research is needed to determine the optimal level, duration, and timing of exercise intervention, there is growing evidence to support the notion that progressive restorative exercise programs may not only reverse, but may also mitigate, specific cancer treatment–related cardiopulmonary complications.[35-37]
Late effects of cancer treatment can develop years after treatment has ended and may impair the survivor’s functional ability and ability to exercise. Osteoporosis and cardiovascular disease[13,32,38] are two common examples of late effects of chemotherapy and hormonal therapy.
The late cardiac effects of cancer treatment have a profound impact on survivors, who have up to a 70% higher risk for developing cardiovascular disease compared with people without cancer.[5,32,34] The most common cardiovascular conditions seen in this population are myocardial dysfunction and heart failure, coronary artery disease, valvular heart disease, arrhythmias, arterial hypertension, thromboembolic disease, peripheral vascular disease and stroke, pulmonary hypertension, and pericardial problems. Common classes of chemotherapy drugs that can cause left ventricular dysfunction include anthracyclines, alkylating agents, antimetabolites, antimicrotubule agents, monoclonal antibodies, and small-molecule tyrosine kinase inhibitors. Radiation therapy administered alone or concurrently with a cardiotoxic chemotherapy can predispose a survivor to interstitial myocardial fibrosis, diastolic dysfunction, and heart failure. Trastuzumab-induced cardiotoxicity has been reported to occur in up to one-third of patients with breast cancer when associated with anthracycline therapy.[39] In patients treated with mantle field radiation, these cardiac effects are often not seen for 15 to 20 years after treatment. Survivors of Hodgkin lymphoma who have undergone treatment with mantle field radiation and cardiotoxic drugs have a twofold to sevenfold increased risk of myocardial infarction.[40,41]
Women with early-stage breast cancer are at increased risk for coronary artery disease and heart failure, and cardiovascular disease is the leading cause of mortality in this population.[35,36] Preliminary evidence suggests that exercise may have the potential benefit of modulating cardiovascular disease risk factors in survivors of early-stage breast cancer; the authors of a longitudinal prospective study of nearly 3,000 women with nonmetastatic breast cancer noted that women who adhered to the national exercise guidelines for adult cancer patients (≥ 9 MET [metabolic equivalent of task] hours per week) had a 23% adjusted reduced risk of cardiovascular events, compared with women who did not follow the guidelines (P = .0002).[36]
Along with the growing body of research into exercise in the oncology setting, there is now greater availability of community-based exercise programs for cancer survivors. Many physical and occupational therapists offer restorative exercise programs, which are fully reimbursable by insurance for indications such as fatigue, muscle weakness, muscle spasms, osteoporosis, pain, connective tissue disorders (scars and fibrosis), cardiopulmonary conditions, and lymphedema. These programs may focus on improving overall function or specifically on managing or preventing lymphedema, and on improving functional ability, reducing weakness, and increasing the patient’s range of motion. LIVESTRONG at the YMCA is a community-based exercise program led by ACSM-certified Cancer Exercise Trainers.[21] These individuals have received formal training to work with cancer survivors during and following cancer treatment, and they understand how to structure and adapt exercise plans for survivors with different diagnoses, treatment types, and disease stages. Many other community programs exist that are more loosely structured. Online programs, such as Restwise, an online recovery awareness program, help survivors learn to interpret their symptoms and understand when to rest and how hard to exercise in order to maximize benefits.[37]
It is particularly important to focus on cancer exercise interventions for vulnerable populations with traditionally poorer access to care, since research has consistently demonstrated poorer screening rates (and therefore presentation with more advanced disease) and lower survival rates in these groups. For example, compared with white populations, African-American men and women have a 25% higher death rate and a significantly lower 5-year survival rate for almost all cancers.[42] Native American populations have the lowest 5-year survival rates of any population (59.0%) in the United States, and were the only group that did not see reductions in cancer mortality from 1999 to 2010.[43]
In order to reach these at-risk populations, it is important to adapt programs that have demonstrated efficacy. To date, most culturally adapted programs target education and screening, not survivorship.[44-46] An example of a physical activity intervention for Native American populations is Restoring Balance, a cancer survivor exercise program developed specifically for Native Americans. The program follows the ACSM Exercise Guidelines for Cancer Survivors and is culturally tailored to meet the specific needs and preferences of Native American cancer survivors.[47] An important part of tailoring the intervention was to ensure that the individuals working with survivors had specialized training in working with Native American populations. These caregivers learned the cultural nuances of discussing cancer and its treatment with these groups, as well as common barriers to access and uptake, and environmental circumstances and historical context of this population. For example, limitations in the accessibility of facilities may require flexibility in scheduling and a combination of face-to-face and home-based exercise regimens. In addition, all activities and materials were vetted to ensure alignment with traditional cultural preferences and feasibility in the environment.[47]
Regardless of the medical history and background of the cancer patient or survivor under consideration for an exercise intervention, it is important to provide clear and succinct information about exercise at every visit and emphasize that inactivity should be avoided. Survivors need to know that exercise is safe and beneficial at all stages of survivorship, with the caveat that exercise should begin slowly and progress gradually to increase volume (time spent) and intensity of the regimen. Individuals with specific limitations (as outlined previously in this article) should be referred to a program of physical or occupational therapy, and survivors with few limitations should be directed to community-based programs. It is important to remind survivors to start slowly and progress slowly with their exercise routines. A simple handout with ACSM exercise recommendations will make educating the survivor both simple and time-efficient.
It is time that we change our thinking about caring for cancer survivors and become proactive advocates for restorative exercise during and following treatment. Ideally, restorative exercise should begin as soon as possible after diagnosis to enable the cancer patient to improve his or her tolerance of treatment, and to reap the physical and emotional benefits of exercise.[1,3] However, it is never too late to refer a survivor to an exercise program. Exercise at any point in the survivorship trajectory helps to maintain and improve functional ability, body composition, and quality of life.
Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.
Acknowledgment: Research reported in this publication was supported by the National Cancer Institute under the awards for the Partnership for Native American Cancer Prevention U54CA143924 (University of Arizona Cancer Center) and U54CA143925 (Northern Arizona University).
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Efficacy and Safety of Zolbetuximab in Gastric Cancer
Zolbetuximab’s targeted action, combined with manageable adverse effects, positions it as a promising therapy for advanced gastric cancer.
These data support less restrictive clinical trial eligibility criteria for those with metastatic NSCLC. This is especially true regarding both targeted therapy and immunotherapy treatment regimens.
