Prinsen, H., Bleijenberg, G., Heijmen, L., Zwarts, M. J., Leer, J. W., Heerschap, A., . . . van Laarhoven, H. W. (2013). The role of physical activity and physical fitness in postcancer fatigue: a randomized controlled trial. Supportive Care in Cancer, 21, 2279–2288.

To examine the effect of cognitive-behavioral therapy (CBT) on fatigue and to examine whether the effect on fatigue is mediated by physical activity and/or physical fitness.

Patients referred for CBT were randomly assigned to the intervention group or to a wait-list control group. The CBT intervention was provided in six modules focusing on coping, rear of disease recurrence, dysfunctional cognitions related to fatigue, activity management, dysregulation of sleep, social support, and negative social interactions. Material was adapted to the individual patients. All patients set a baseline level of physical activity and, once set, began an activity program of cycling or walking five to 10 minutes twice daily. This was increased to a maximum of 120 minutes daily. Study measures were obtained at baseline and six-month follow-up. Physical activity was measured for two weeks prior to study entry.

• Thirty-seven patients (48.6% male and 51.4% female) were included.            
• Mean age was 49.5 years.
• Patients had various disease types of solid tumors or non-Hodgkin lymphoma.  
• All patients had completed initial antitumor therapy. 
• At baseline, average time since diagnosis was 52 months for the intervention group and 45 months for the control group.
• Patients with psychological problems or treatment and those with depression were excluded.

• Single site  
• Setting not specified    
• Netherlands

Patients were undergoing the late effects and survivorship phase of care.

This was a randomized, controlled trial.

• Checklist Individual Strength (CIS) fatigue severity subscale
• Sickness Impact Profile (SIP)
• Actigraphy:  resting and activity oxygen consumption, ventilation, respiratory quotient, and maximal oxygen consumption

Forty-six percent of patients in the intervention were lost to follow-up. The CBT group had a significantly greater improvement in fatigue scores than control patients (p < 0.001). There was significantly greater improvement in functional impairment in the CBT group compared to controls (p = 0.009). Fatigue and impairment improved over the six-month period in both groups. There were no significant differences between groups in physical activity or physical fitness measures at baseline or follow-up. Analysis showed no mediation effect of physical activity or physical fitness.

Findings suggested that CBT was effective in reducting cancer-related fatigue and sickness impact scores. Findings suggested that this effect was not mediated by physical activity or fitness.

• The study had a small sample size, with less than 100 patients.
• Baseline sample/group differences were of import. 
• The study had risks of bias due to no blinding and no appropriate attentional control condition.
• Unintended interventions or applicable interventions that would influence the results were not described.
• Key sample group differences could influence the results.
• Measurement validity/reliability was questionable.
• Patient withdrawals were 10% or greater.
• Physical activity was only measured at baseline, and activity levels in both groups over the course of the study period were not measured and reported. This suggests that findings regarding the potential mediation of CBT effects by activity were not valid. 
• More patients in the control group had a combination of surgery, chemotherapy, and radiation therapy, which may have had a greater impact on fatigue. 
• The large drop-out rate in the intervention group was a limitation of findings. 
• There was no analysis of differences between those who were lost to follow-up and others.

Findings supported the potential effectiveness of CBT for fatigue management in cancer care. These findings were in patients about four years after completion of treatment, suggesting benefits even long after active treatment. There were several study limitations that reduced the strength of this evidence.