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To be or not to be physically active? The role of exercise in Cancer Cachexia

The following scenario took place in an outpatient clinic at a leading UK cancer centre, 2010.

Cancer patient (stepping off weighing scales): 'I'm losing a lot of weight...I don't know why, I'm eating. What should I do nurse?'
Nurse: 'Are you doing exercise?'
Cancer patient: 'Well, not really...I walk to the local shop in the mornings.'
Nurse: 'Well, there you are! Stop exercising, that's why you're losing weight.'

Was this good advice?
Involuntary weight loss is a defining characteristic of cancer cachexia, a debilitating syndrome characterised by loss of skeletal muscle mass1 and patient impact that includes decline in physical strength and function. Moreover, weight loss in cancer is associated not only with physical function, but also with mortality, treatment tolerance and other morbidities, such as fatigue. Arresting weight loss could thus have survival benefit and improve the experience of living with cancer.
Exercise is physical activity performed repeatedly with the goal of improving fitness or health2. Physical activity is defined as any bodily movement produced by skeletal muscles that requires energy expenditure3. Since exercise is successful in sustaining and building muscle mass, an important question is whether or not it has any health benefit for people with or at risk of cancer cachexia. The evidence available to answer this question suggests that it may be important to differentiate between three different patient groups: long-term survivorship, patients undergoing potentially curative treatment and patients with incurable (advanced) cancer.

Physical activity and cancer survivorship
Systematic reviews of research evidence identify the benefits of physical activity in people who have completed treatment with curative intent for cancer. Epidemiological studies of breast and colorectal cancer patients demonstrate there is survival benefit for those who incorporate regular resistance training exercise into their routine, and manage their weight effectively by following a healthy low fat diet high in fibre, fruit and vegetables4. Interventions are effective in improving physical activity levels in cancer survivors5. Patients in this group may have been affected by cancer cachexia although it is reversible.

Physical activity during cancer treatment
From the point of diagnosis, physical activity may be an important form of self-management of cancer symptoms and treatment of side effects. Systematic reviews have found beneficial effects of physical activity during treatment, although the majority of studies have been limited to patients with early stage breast and prostate cancer.  These benefits include improvement in physical activity level, aerobic fitness, muscular strength, functional quality of life, anxiety, and self-esteem6. Aerobic and resistance exercise, or a combination of both, have been found to improve upper and lower body strength in comparison to usual care7. Stene also identifies some, although weak, evidence that resistance exercise is more effective than aerobic exercise in improving both muscle mass and strength.

Some reviews of exercise interventions include patients both in treatment and post-cancer therapy.  Findings include positive effects on depressive symptoms8 and reduction in fatigue for those with breast and prostate cancers9.

Although benefits of exercise have been demonstrated both during and following cancer treatment, outcomes may be dependent on stage of disease, nature of medical treatment and lifestyle of the patient10. There is uncertainty about the optimal type, intensity and timing of exercise intervention required to regain muscle mass and hence counter cancer cachexia. Furthermore, we need a better understanding of how to support patients in the uptake and maintenance of physical activity and exercise programmes. Since cancer cachexia adversely affects muscle strength and endurance, these factors may limit patients’ ability to exercise. Maddocks found that only half of cancer patients offered an exercise programme completed it11. Moreover, exercise may not be advisable in certain sub-groups of patients with cachexia, such as those with anaemia12.

Although there is uncertainty whether there are the same benefits of physical activity during and following cancer treatment for weight-stable and weight-losing cancer patients, there is currently optimism that it will have a future role in the management of cancer cachexia.

Exercise, by virtue of its anti-inflammatory effect, is shown to be effective at counteracting the muscle catabolism by increasing protein synthesis and reducing protein degradation, thus successfully improving muscle strength, physical function and quality of life in patients with non-cancer-related cachexia. Therefore, by implementing appropriate exercise interventions upon diagnosis and at various stages of treatment, it may be possible to reverse protein degradation, while increasing protein synthesis and lean body mass, thus counteracting the wasting seen in cachexia13.

Physical activity and incurable or advanced cancer
There has been limited study of the effects of physical activity in people with advanced cancer. In 2009, Beaton et al. conducted a systematic review about exercise in advanced cancer and found evidence from three randomised control trials of benefit to quality of life. This review also looked for adverse effects but found none, although it acknowledged very few researchers have reported on these14.
More recent studies, Oldervoll et al.15 and Chevilleet al. 16 also report no adverse event in studies of exercise interventions in patients with incurable and advanced disease. Oldervoll et al. compared patients with mixed site metastatic cancer over an 8-week period randomised to a physical exercise group (n=78) or a usual care group (n=85). There were clinically and statistically significant differences between the groups in hand grip strength and shuttle walk test, but not fatigue. 15 Chevelle et al. tested a home exercise program called REST over an 8-week period in a group of patients with stage IV lung and colorectal cancers randomised to an intervention group (n=26 ) or a usual care group (n=30). REST is a one-to-one instruction session, a pedometer-based walking programme plus home-based strength training, with bimonthly telephone follow-up calls to review and advance the programme. At 8 weeks there were statistically significant differences between groups favouring the intervention in respect of mobility, sleep quality and fatigue16.

To be or not to be physically active when living with cancer?
A strong body of evidence supports the benefit of exercise in survivorship (post curative treatment). It reduces the risk of cancer recurrence and other morbidity.
For people with advanced disease accompanied by refractory cachexia the benefits of physical activity remain uncertain.  Physical activity may help with self-management of symptoms and enhance quality of life.
Research investigating physical activity/exercise in cancer patients undergoing treatment demonstrates improvement in physical performance, fatigue and functional quality of life. However, it is unclear if these benefits are experienced by patients with cancer cachexia.

Physical activity as a component of multimodal therapy
Physical activity alone is unlikely to maintain muscle mass and improve outcomes in cancer cachexia. Nutrients are also likely to be required. In the future, it would seem most likely that the optimisation of physical function in cancer will require a combination of physical activity, nutritional support and perhaps appetite stimulants (or similar interventions). However, this idea of a multimodal approach has yet to be demonstrated effective. Patient compliance with such an approach may be affected by the nature of physical activity and other interventions and may therefore be enhanced if embedded within an education component that supports health behaviour change. These are all factors that which should be tested clinically.

Jane Hopkinson. Professor of Nursing, Cardiff University.


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