Cancer-Related Fatigue: a multidimensional approach

Fatigue is experienced by cancer patients in all stages of the disease trajectory: from before diagnosis to years after completing treatment and also in advanced cancer. Fatigue has a greater negative influence on quality of life and daily activities than any other cancer-related symptom. Although both national and international guidelines have been developed to enhance the management of cancer-related fatigue, cancer-related fatigue is still poorly understood. This thesis describes research that has been performed in order to clarify some aspects of the multidimensional nature, pathogenesis, assessment and treatment of cancer-related fatigue. Concerning the multidimensional nature of fatigue, we investigated in a systematic review whether the physical and mental senses of fatigue are expressions of one symptom (multidimensional concept) or expressions of several phenomena which are all called fatigue but actually are separate symptoms (multiple symptom concept). We found some circumstantial evidence supporting the multiple symptom concept, for example a different trajectory during anti-tumor therapy. We also investigated in a cross-sectional study whether cancer patients in various stages of the disease trajectory have different fatigue experiences. We found that fatigue is more intense and that especially physical fatigue is more prominent in advanced cancer patients than in cancer survivors. With respect to the pathogenesis of fatigue, we found that several inflammatory markers were correlated to physical fatigue, but not to mental fatigue in advanced cancer patients, whereas no consistent association could be found between inflammation and fatigue in cancer survivors. On the assessment of fatigue, we investigated in a systematic review which the optimal cut points are on 0 to 10 Numeric Rating Scales for fatigue and other symptoms. Overall, using a score ≥4 for all symptoms as a trigger for a more comprehensive assessment seems to be justified in daily clinical practice. Concerning the treatment of fatigue, we performed a randomized controlled trial to investigate whether it is possible to alleviate fatigue in advanced cancer patients by optimizing treatment of other physical symptoms. Patients were randomized to protocolized patient-tailored treatment of physical symptoms (PPT) or care as usual (CAU). The patients randomized to PPT had four appointments with a nurse who assessed the severity of nine physical symptoms on an NRS. Patients received a nursing intervention for symptoms scored ≥1/10 and a medical intervention for symptoms scored ≥4/10. Seventy-six patients were randomized to each study arm. We found significant improvements over time in favor of PPT for the primary outcome General Fatigue (P=0.01). Improvements in favor of PPT were also found for the following secondary outcomes: fatigue dimensions Reduced Activity and Reduced Motivation, fatigue NRS, symptom burden, interference of fatigue with daily life and anxiety (all P≤0.03). We concluded that nurse-led monitoring and protocolized treatment of physical symptoms is effective in alleviating fatigue in advanced cancer patients.

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