Potential mechanisms underlying the effect of walking exercise on cancer-related fatigue in cancer survivors

Purpose: Cancer-related fatigue (CRF) is a common and debilitating long-term side effect of cancer and its treatment. While exercise has been shown to effectively reduce CRF, the underlying mechanisms are not fully clear. Therefore, the aim of this study was to explore the effects of a 4-month walking exercise program on fatigue severity and to explore potential underlying physiological, behavioral, and psychological mechanisms of action. Methods: We included 27 cancer survivors (59 ± 15 years, 37% female) with variable cancer diagnoses who were at least moderately fatigued and finished treatment between 6 and 36 months ago. This study with a quasi-experimental interrupted time-series design compared a 4-month walking intervention period with a 4-month control period. Measurements of fatigue and physiological, behavioral, and psychological factors were performed, supplemented with participants’ perceptions on how exercise influenced their fatigue. Results: A significant and clinically relevant decrease in fatigue severity was found over time (β = − 8.1, 95% CI = − 12.1; − 4.2), but could not be attributed directly to the walking exercise intervention. Increases in muscle strength (β = − 0.07, 95% CI = − 0.12; − 0.02), physical activity (β = − 0.1, 95% CI = − 0.2; − 0.04), and sleep quality (β = 1.1, 95% CI = 0.3; 1.9), as well as decreases in muscle relaxation times (β = 0.09, 95% CI = 0.02; 0.16) and psychological distress (β = 1.1, 95% CI = 0.8; 1.3) were associated with reductions in fatigue severity. Resilience and physical well-being were perceived as most important constructs explaining the walking exercise effects on fatigue. Conclusion: Our findings reveal potential physiological, behavioral, and psychological mechanisms underlying the multidimensional effects of exercise on fatigue severity. Implications for Cancer Survivors.: Incorporating resistance exercise and addressing resilience and physical well-being might improve the efficacy of exercise interventions for cancer survivors.