Effect of exercise on cancer-related fatigue: moving forward

Abstract

Fatigue is a common and disabling symptom in patients with cancer. Meta-analyses have shown that exercise has significant beneficial effects on cancer-related fatigue, both during and post-treatment. However, the majority of research so far has been performed in women with breast cancer, and has focused on the general effects of exercise on fatigue. To promote implementation in clinical practice, it is important to move research efforts forward and expand the current knowledge on exercise effects on fatigue. To this aim, in Part I of this thesis we studied effects of exercise in patients with other cancers than breast cancer. In the multicenter Physical Activity during Cancer Treatment (PACT) study, we found that an 18-week combined aerobic and resistance exercise program during chemotherapy for colon cancer had beneficial effects on general fatigue, physical fatigue and physical functioning. The observed differences in effect sizes compared to patients with breast cancer underscore the importance of expanding research to other subgroups with cancer. Exercise effects in the more rare, but increasingly common, esophageal cancer are yet unknown. Therefore, we designed and described the randomized controlled Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study, to investigate effects of a 12-week supervised exercise program in the first year after esophagectomy. The second aim of the thesis (Part II: Moving forward) was to expand our knowledge beyond the general effects of exercise on fatigue. We showed that exercise during adjuvant treatment for breast cancer had beneficial effects on several dimensions of fatigue, with largest effects on physical fatigue, indicating that this is the fatigue dimension most sensitive to exercise. Second, in a pooled analysis of the PACT study and German Bewegung und Entspannung als Therapie gegen Erschöpfung (BEATE) study, we observed that inflammatory markers (interleukin [IL]-6 and IL-6/IL-1 receptor antagonist ratio) had strong responses to adjuvant chemotherapy. Supervised exercise training did not counteract the increase in inflammatory markers, suggesting that beneficial effects of exercise on fatigue during adjuvant chemotherapy are not essentially mediated by these markers. Hence, future research is required to further disentangle the working mechanisms of exercise. Third, in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, we used individual patient data from 31 exercise oncology trials to assess moderators of exercise effects on fatigue. We found significant beneficial effects on fatigue, across patients with different demographic and clinical characteristics, supporting a role for exercise in clinical practice. In addition, our findings indicated that supervised exercise interventions have the largest effects. Last, we interviewed esophageal cancer patients participating in the exercise program of the PERFECT study. Together with their own, positive attitudes towards exercise, supervision of a physiotherapist was the most important facilitator perceived by the patients. Exercise programs may be further optimized by incorporating intervention-related characteristics that yield the largest benefits and by taking into account patientperceived barriers and facilitators.