Exercise Mechanisms to Reduce Fatigue in Cancer Survivors

Cancer-related fatigue (CRF) is one of the most prevalent long-term side effects of cancer and its treatment, severely impacting a patient’s quality of life. The pathogenesis of CRF is multifactorial and poorly understood, hampering effective management. Exercise is an effective non-pharmacological treatment to reduce CRF. However, the exact mechanisms underlying this beneficial effect remain unclear. Knowledge of underlying mechanisms might further improve exercise interventions. PURPOSE: To examine underlying behavioral and physiological factors mediating the effect of a 4-month walking exercise program on CRF. METHODS: Cancer survivors who were at least moderately fatigued (score of >27 on the Checklist Individual Strength; CIS) and finished treatment between 6 - 36 months ago, were included. This quasi-experimental interrupted time-series design compared a 4-month baseline period with a 4-month walking intervention period, in which patients act as their own controls. Measurements of fatigue (CIS-score), physical activity, fitness and muscle contractile properties (muscle fatiguability, early- and half relaxation time, and maximal force rise assessed by electrical stimulation) were performed at baseline (T0); pre-intervention (T1) and post-intervention (T2). Associations were examined using linear mixed model analyses. RESULTS: In total, 27 patients with CRF (59 ± 15 years; 63% male; BMI 27 ± 5 kg/m2) were included. CRF decreased from a CIS-score of 35 ± 8 at T0 to 28 ± 13 at T1, and 25 ± 12 at T2. Increases in step count (β per 100 steps = -0.1 [95% CI -0.2 – -0.07]) and moderate-to-vigorous physical activity per week (β per minute = -0.2 [95% CI -0.3 – -0.1]) were associated with reductions in CRF. Additionally, patients who increased leg strength (1 repetition maximum; β per kg = -0.08 [95% CI -0.12 – -0.04]) and maximal voluntary contraction of the quadriceps muscle (β per Newton = -0.05 [95% CI -0.07 – -0.03]) showed reduced CRF. Changes in aerobic capacity and muscle contractile properties were not associated with CRF. CONCLUSION: Increasing physical activity and muscle strength may reduce CRF. The lack of associations between muscle contractile properties and fatigue suggests that peripheral muscle abnormalities have a limited role in CRF. Funded by Hypatia Fellowship grant from Radboudumc to L.M.B.