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.

Pathology revealed a 3.6-cm tumor that was estrogen receptor positive, progesterone receptor positive, and HER2-neu negative, as well as three positive lymph nodes. She received adjuvant chemotherapy (docetaxel [Taxotere] plus doxorubicin and cyclophosphamide) and radiation therapy. She took tamoxifen for 3 years and is completing her second year of treatment with anastrozole (Arimidex). Her course of adjuvant chemotherapy was uneventful. She experienced brief episodes of anemia and neutropenia, which were treated with epoetin (Epogen, Procrit) and pegfilgrastim (Neulasta).

Prior to diagnosis Beatrice was active, worked full time, volunteered at a homeless shelter, walked her dog twice a day, and on the weekends went with friends on long hikes. During treatment she struggled to continue her normal routine but eventually found friends to walk her dog and gave up her volunteering and hiking. She did continue to work full time throughout treatment.

Now at age 59, she still complains of fatigue interfering with her daily activities and affecting plans for other activities. She states, “I feel flat and worn out all the time. I do have days when I feel more energetic but then I must do too much, because the following day I’m exhausted.” She consistently rates her fatigue at 6–8 on a 0-to-10 scale (with 0 being no fatigue and 10 being the worst fatigue).

At the long-term cancer survivor clinic, she underwent a thorough evaluation for the cause of her fatigue. Her blood work revealed no abnormalities. She denies depression and shows no outward signs of depression, although she expresses significant distress about the relentlessness of her fatigue. She states she needs to take a nap after work every day, and often sleeps for more than an hour, but reports difficulty falling asleep and staying asleep at night.

Even after a nap, she reports feeling too tired to do much around the house, and she spends most of the day and evening watching television. Since her diagnosis, Beatrice has gained 16 pounds and has not returned to her previous activity level. Comorbidities that have developed since her initial breast cancer diagnosis include hypertension, controlled with hydrochlorothiazide, and hyperlipidemia, managed with atorvastatin calcium.

Discussion
This case illustrates ongoing challenges of long-term cancer- related fatigue experienced by survivors. Beatrice’s health-care team did a comprehensive workup of treatable causes of fatigue, including a focused history and an in-depth assessment of other treatable contributing factors. Recurrence was ruled out, current medications were ruled out, and her blood work was within normal limits. Factors identified as contributing to Beatrice’s fatigue were prolonged inactivity, altered sleep patterns, weight gain, and emotional distress. Table 2 provides some practical tips for patient education.

Prolonged periods of inactivity cause declines in muscle strength and aerobic capacity. As these declines worsen, it becomes harder to perform the routine tasks of daily living. Everything a survivor does takes more energy and effort because his or her basic strength and fitness to complete the activity has diminished. Regular physical activity is critical to patients during treatment and well into survivorship. Exercise keeps survivors’ muscles strong, increases aerobic capacity, improves balance, and helps with weight control, ultimately helping to prevent and control comorbidities such as hypertension.

Survivors need to exercise at least every other day at a moderate pace for 20 to 30 minutes, as tolerated. Functional ability will dictate the exercise prescription. Debilitated survivors may need referral to physical therapy or a cancer rehabilitation program. Across the United States, the YMCA is developing cancer survivor exercise programs. These will be of key interest to healthcare practitioners for patient referrals to community-based programs.

Fatigue is a frustrating side effect in cancer survivors, because intuitively one thinks symptoms should improve with more rest, but that is not the case. Sleeping too much actually contributes to feelings of fatigue, and resting more to avoid fatigue actually increases declines in functional ability. Survivors need to be educated about maintaining a regular sleep pattern (regular bed time and rising time) and restricting the duration of naps to 20 to 30 minutes.

Long-term cancer survivors need ongoing education about living healthy lifestyles with a focus on wellness. Weight gain is a common side effect of many cancer treatments, and it increases risk of recurrence, leads to the development of other comorbidities (eg, hypertension, hyperlipidemia), and even increases the risk of death.

Nurses need to be aware of these risks, and should educate patients about weight control and healthy eating and maintain graphs of body weight and body mass index. Referral to a nutritionist may be appropriate for the patient who has not been aware of his or her nutritional intake, or needs more directed care and instruction in preparing and eating healthy, low-fat diets.

Psychological interventions should be recommended to survivors to reduce stress, anxiety, and depression. Interventions that have demonstrated efficacy include cognitive behavioral therapy, stress management, relaxation, and support groups. Support groups have the unique effect of helping survivors realize that they are not alone in their experience.

In the case study described, Beatrice was referred to a cancer rehabilitation program, where she began a supervised exercise program and received education on fatigue management, weight control, stress management, and wellness. After the rehabilitation program, she was referred to the YMCA cancer survivor exercise program. She started to nap for only 20 minutes after work, and then go out for a walk. Nurses can play a key role in the recovery of long-term survivors by advocating for community-based healthy lifestyle programs (eg, YMCA cancer survivor programs) and encouraging survivors to take a responsible and active role in their wellness.

References:

1. Minton O, Stone P: How common is fatigue in disease-free breast cancer survivors? A systematic review of the literature. Breast Cancer Res Treat 112(1):5–13, 2008.

2. Alexander S, Minton O, Andrews P, et al: A comparison of the characteristics of disease-free breast cancer survivors with or without cancer-related fatigue syndrome. Eur J Cancer 45(3):384–392, 2009.

3. Braun IM, Greenberg DB, Pirl WF: Evidence-based report on the occurrence of fatigue in long-term cancer survivors. J Natl Compr Cancer Netw 6(4):347–354, 2008.

4. Lavigne JE, Griggs JJ, Lerner DJ: Hot flashes, fatigue, treatment exposure and work productivity in breast cancer survivors. J Cancer Surviv 2(4):296–302, 2008.

5. Hansen JA, Feuerstein M, Clavio LC, et al: Breast cancer survivors at work. J Occup Environ Med 50(7):777–784, 2008.

6. Goedendorp MM, Gielisse MF, Peters ME, et al: Severe fatigue and related factors in cancer patients before the initiation of treatment. Br J Cancer 99(9):1408–1414, 2008.

7. Minton O, Stone P: A systematic review of the scales used for the measurement of cancer-related fatigue (CRF). Ann Oncol 20(1):17–25, 2009.8. Breitbart W, Alici Y: Pharmacologic treatment options for cancer-related fatigue: Current state of clinical research. Clin J Oncol Nurs 12(suppl 5):27–36, 2008.

9. Winters-Stone K, Bennett JA, Nail L, et al: Strength, physical activity, and age predict fatigue in older breast cancer survivors. Oncol Nurs Forum 35(5): 815–821, 2008.

10. Carson JW, Carson KM, Porter LS, et al: Yoga of Awareness program for menopausal symptoms in breast cancer survivors: Results from a randomized trial. Support Care Cancer Epub on Feb 12, 2009. Available at: http://www.springerlink.com/content/e4872w0203j52622/fulltext.pdf. Accessed on June 22, 2009.

11. National Comprehensive Cancer Network. NCCN Clinical practice guidelines in oncology. Cancer-related fatigue V.1.2009. Available at: http://www.nccn.org/professionals/physician_gls/PDF/fatigue.pdf. Accessed on April 19, 2009.