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Fatigue in Long-Term Cancer Survivors

Fatigue in Long-Term Cancer Survivors

Cancer-related fatigue is a common side effect during cancer treatment, and research demonstrates that it is a troubling, lingering side effect for many long-term survivors. Long-term cancer survivor fatigue is under-reported, underdiagnosed, and undertreated.[1] Studies suggest that the prevalence of fatigue in breast cancer survivors may be as high as 30%,[2] and that fatigue levels are higher in cancer survivors than in healthy controls,[3] even as long as 5 years after treatment.[1]

Fatigue that lingers long into survivorship affects quality of life, mood, and work productivity.[4,5] A patient’s fatigue level at time of diagnosis may increase risk for fatigue problems after completion of treatment. Factors that contribute to severe fatigue in survivors include low levels of physical activity, depressed mood, impaired sleep and rest, and feelings of fatigue for as long as 1 year prior to diagnosis.[6] Some physiologic factors may also influence fatigue after completion of treatment. These include elevated white blood cell count and low sodium levels.

The exact etiology of fatigue is still debated. Hypotheses include hypokinesia, proinflammatory cytokine changes, serotonin alterations, vagal afferent activation, anemia, and adenosine triphosphate depletion. While all of these hypotheses are plausible, only the correction of anemia and hypokinesia (debilitation from physical disuse) have demonstrated a clear correlation with fatigue.

Hypokinesia has been examined in exercise studies that consistently demonstrate that regular, moderate exercise improves aerobic capacity and muscle strength and decreases fatigue. Basically, as one gets physically stronger, it is easier to perform desirable activities without becoming fatigued.

The importance of assessing fatigue in long-term survivors should not be overlooked. Though specific measures to assess fatigue in long-term survivors have not been developed, scales that measure fatigue during treatment appear to be psychometrically sound in the long-term survivor setting. The most efficient and relevant clinical measure of fatigue continues to be a 10-point scale (ie, 0-to-10 scale), which is easy to administer and is easily understood by patients.[7] Moderate to severe fatigue scores (4–10 on a 10-point scale) warrant further evaluation of underlying disease. As clinicians, it is important to look for other treatable and reversible common causes of fatigue, including anemia, depression, anxiety, and hypothyroidism.

While there is some evidence that treatment with methylphenidate is effective, exercise programs appear to have the greatest benefit in reducing fatigue experienced by cancer survivors.[8] Studies demonstrate that women with greater lower-extremity strength, higher aerobic capacity, higher levels of physical activity, and advanced age report less fatigue.[9] Exercise intervention studies demonstrate the efficacy of weight lifting, aerobic exercises, and yoga.[10]

The National Comprehensive Cancer Network (NCCN) 2009 Practice Guidelines for Cancer-Related Fatigue include a treatment and intervention algorithm for long-term survivors.[11] After ruling out treatable contributing factors such as pain, emotional disorders, anemia, sleep disturbances, and medication side effects, the guidelines specify strategies for fatigue management. These begin with energy conservation and progress to distraction techniques and exercise rehabilitation programs and psychosocial interventions, such as cognitive behavioral therapy, stress management, and support groups.

The recommended interventions are classified as “Category 1 or 2A,” meaning there is evidence for the proposed recommendations and they have uniform NCCN consensus.

Case Study
Beatrice M. was a 54-year-old high school art teacher when she was diagnosed with stage II infiltrating ductal carcinoma. She underwent sentinel node biopsy, followed by modified radical mastectomy.


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