Clinical Review

Clinical Assessment and Management of Cancer-Related Fatigue


 

References

Other Hypotheses

Several other hypotheses for CRF pathogenesis have been proposed. Activation of latent viruses such as Epstein-Barr virus, lack of social support [22], genetic alterations in immune pathway [23], epigenetic changes [24], accumulation of neurotoxic metabolites and depletion of serotonin by indoleamine 2,3-dioxygenase pathway activation [25], elevated vascular endothelial growth factor levels [26], and hypoxia-related organ dysfunction due to anemia or hemoglobin dysfunction [13] all have been postulated to cause CRF.

Approach to Evaluation and Treatment

The evaluation and treatment of CRF involve 4 steps ( Figure). First, patients are screened for fatigue, and in the second step those who have fatigue undergo primary evaluation to assess for potential precipitating causes. The third step is implementation of pharmacologic and non-pharmacologic interventions aimed at alleviating or mitigating fatigue. The fourth step involves re-evaluating patients at periodic intervals to recognize and manage changes in fatigue levels. A multidisciplinary approach involving nursing, physical therapy, social work, and nutrition is critical in managing fatigue in these patients. Education and counselling of patients and involvement of the family are essential for effective management.

Screening

Because patients and health care professionals may be unaware of the treatment options available for CRF, patients may not report fatigue levels to their clinicians, and clinicians may not understand the impact of fatigue on their patients’ quality of life. This leads to underrecognition of the problem. The NCCN recommends screening every cancer patient and post-treatment survivor for fatigue [2]. Patients should be screened at their first visit and then at periodic intervals during and after cancer treatment.

Many scales are available to screen patients for CRF in clinical practice and clinical trials [27]. A single item that asks patients to rate their fatigue on a scale from 0 to 10—in which 0 indicates no fatigue, 1 to 3 indicates mild fatigue, 4 to 6 indicates moderate fatigue, 7 to 9 indicates severe fatigue, and 10 indicates the worst fatigue imaginable—is commonly used to screen for CRF [2]. This scale was adapted from the MD Anderson Symptom Inventory scale and is based on a large nationwide study of cancer patients and survivors [28]. The statistically derived cutoff points in this study are consistent with other scales such as the Brief Fatigue Inventory (BFI) and support the cutoff points (4–6 for moderate and ≥ 7 for severe fatigue) used in various fatigue management guidelines. Furthermore, studies of fatigue in cancer patients have revealed a marked decrease in physical function at levels of 7 or higher, suggesting 7 as an optimal cutoff to identify severe fatigue [29,30]. The Visual Analog Scale is another simple-to-use tool that helps in understanding variations in fatigue throughout the course of the day [31]. The 9-item BFI is often used in clinical trials [29]. It measures the severity of fatigue over the previous 24 hours and has been validated in non-English speaking patients [32].

CRF affects not only the somatic domain, but also the cognitive, behavioral, and affective domains; therefore, multidimensional scales have been developed for screening. One such tool is the Multidimensional Fatigue Inventory, which measures general, physical, mental, and emotional fatigue domains as well as activity and compares them with those of individuals without cancer [33,34]. The Functional Assessment of Cancer Therapy for Fatigue (FACT-F) is a 13-item questionnaire that has been used to measure CRF in clinical trials as well as in patients receiving various treatments [35].

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