Cancer-Related Fatigue
Quick Facts
- CRF is one of the most common and complex symptoms experienced by patients with cancer
- CRF occurs across the continuum of cancer treatment from prediagnosis to long-term survivorship
- Assessment of fatigue is not performed routinely in many oncology practice settings
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Background
The National Comprehensive Cancer Network (NCCN) defines cancer-related fatigue (CRF) as “a distressing, persistent, subjective sense of tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.”1
Compared with fatigue reported by healthy people, CRF is described as more distressing, as interfering with usual functioning, and as less likely to be relieved by rest. Most importantly, if left untreated, CRF is a major factor in patient quality of life scores.2
Prevalence
Although reported by 60% to 100% of patients undergoing therapy for CRC, fatigue is still considered an underreported symptom for which there are multiple overlappingetiologies, confounding an explanation of its specific pathophysiologic mechanisms.3 CRF may be more prevalent in patients undergoing multimodality treatment,2such as chemoradiotherapy for rectal carcinoma. CRF may continue for years after treatment is completed, even when the cancer has been cured.4
Possible Causes of CRF
CRF has a complex etiology, possibly regulated by physiologic, psychologic, and situational factors3:
- Changes in the production and balance of muscle proteins, glucose, electrolytes, and hormones4
- A catabolic process resulting from decreased daily energy expenditure and bed rest5
- Disease-related and treatment-induced anemia4
- Distinguishing between fatigue and depression is an important aspect of fatigue evaluation
Complex interplay exists between etiologic factors such as cancer treatment, infection, concomitant medications, and susceptibility of the patient to CRF.4
Table 1. Etiology of CRF
Tumor-Related Causes
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Treatment-Related Causes
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Disease site
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Surgery and postoperative recovery
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Paraneoplastic syndrome
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Psychological distress
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Increased cytokine production
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Chemotherapy and chemotherapy effects
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Decreased availability of metabolic substrates
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Radiotherapy and radiotherapy effects
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Cachexia
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Anemia
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Pain
|
Pain
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Data from Wang et al.4
Risk Factors
Multiple risk factors, rather than a single risk factor, appear to put patients with cancer at risk for CRF.4 Risk factors for CRF include3-7
- Poor nutrition
- Sleep disorders
- Stress
- Comorbidities: cardiac, pulmonary, renal, liver, neurologic, thyroid, and endocrine, and associated medications
- Hypoxia
- Pain
- Infection
- Deconditioning
- Ongoing therapy
Tests for Comorbidities
Comorbidities, such as anemia or endocrine abnormalities, may contribute to CRF. The results of tests for causative factors may be helpful and direct further testing or evaluation.
-
Tests for anemia
- Complete blood count
- Iron studies
- Total iron-binding capacity (TIBC)
- Ferritin
- Transferrin
- Tests for other causative factors
- Endocrine
- Thyroid function studies
- Folic acid
- Vitamin B12
- Blood glucose (to rule out diabetes)
- Pulmonary function studies
- Liver function studies
- Electrolytes
- Renal
- Blood urea nitrogen
- Creatinine clearance
- Glomerular filtration rate (GFR)
Assessment of the Impact of CRF on Quality of Life
CRF is a subjective experience that must be assessed on a regular basis, using the patient’s self-report or perception of fatigue in addition to other objective measures.8 Because fatigue is believed to be multifactorial and is experienced physically, emotionally, and spiritually, nurses must first focus their assessment of the impact of CRF on quality of life by asking some simple questions7-8: Accessed January 27, 2010.
Assessment Tools
A comprehensive listing of assessment tools for CRF is available in Piper et al. Clin J Oncol Nurs. 2008;12(5 suppl):37-47. PubMed abstract available athttp://www.ncbi.nlm.nih.gov/pubmed/18842523. Accessed January 27, 2010.
Table 2. National Cancer Institute Common Terminology Criteria for Adverse Events
(NCI CTCAE 4.02) Grading Scale[
CTCAE v 4.02 for Fatigue9
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Grade 1
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Grade 2
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Grade 3
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Grade 4
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Grade 5
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Fatigue relieved by rest
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Fatigue not relieved by rest; limiting instrumental ADLs
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Fatigue not relieved by rest; limiting self-care
ADL
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- |
-
|
Table 3. Fatigue Scale
Fatigue Assessment Survey8,10-11
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0
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1, 2, 3
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4, 5, 6
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7, 8, 9
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10
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Energetic,
not tired
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Mild
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Moderate
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Extreme
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Total exhaustion
|
Table 4. National Comprehensive Cancer Network (NCCN) Guidelines
NCCN Guidelines: Cancer-Related Fatigue1
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0
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1-3
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4-6
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7-9
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10
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No fatigue
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Mild
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Moderate*
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Severe*
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Worse fatigue imagined*
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Instruction about fatigue and ways to manage it
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Primary evaluation based on history and assessment of factors contributing to fatigue
|
|
Patient History
Disease state and treatment and current medications, system assessment, fatigue assessment
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Contributing Treatable Factors (use interventions for active treatment, long-term follow-up, or end-of-life)
Pain (NCCN guideline); emotional distress (NCCN guideline); sleep; anemia (NCCN guideline); nutrition; activity (deconditioning) level; comorbidities (system review)
|
*Progressive decrease in physical functioning from 4-9. Score is based on patient’s description.
- Are you experiencing any fatigue?
- If yes, how severe has it been on a scale of 0 to 10 (10 being the highest) during an average day?
- How is fatigue interfering with your ability to function?
Additional questions may elicit whether fatigue worsens at certain times of the day or occurs during certain days of the chemotherapy regimen. A printable version of thePiper Fatigue Assessment tool is available at http://www.propax.com/survey/PFS.PDF
Clinical Practice Guidelines for Fatigue and Anemia
National Comprehensive Cancer Network (NCCN)
http://www.nccn.org/professionals/physician_gls/PDF/fatigue.pdf. Version 1.2010. Accessed January 27, 2010.
http://www.nccn.org/professionals/physician_gls/PDF/anemia.pdf. Version 2.2010. Accessed January 27, 2010.
Web Resources
Oncology Nursing Society (ONS)
Putting Evidence into Practice® (PEP) resources are available through the ONS Web site or on pocket cards for purchase. Clinical practice questions, suggested interventions, and practice recommendations are based on a level of evidence. To learn more about evidence-based information for fatigue, click here. Accessed January 27, 2010.
American Cancer Society
Patient-friendly Web site with information on identifying and managing fatigue: http://www.cancer.org/docroot/MIT/MIT_2_2x_Fatigue.asp Accessed January 27, 2010.
National Cancer Institute
This NCI Web site provides both professional and patient pages with peer-reviewed information on the pathophysiology and treatment of fatigue: http://www.cancer.gov/cancertopics/pdq/supportivecare/fatigue/HealthProfessional/page1. Updated January 8, 2010. Accessed January 27, 2010.
http://www.cancer.gov/cancertopics/pdq/supportivecare/fatigue/Patient Updated June 9, 2009. Accessed January 27, 2010.
Management of CRF
CRF can be one of the most difficult and frustrating symptoms to treat. Apart from treating anemia or correcting endocrine abnormalities, offering energy conservation tips, and treating depression related to CRF, little information has been available to assist patients through this distressing experience. Although CRF is prevalent, it is often not discussed with the patient and is underassessed in many oncology settings.4
CRF is a multifactorial symptom, and management strategies are influenced by the patient’s clinical status, disease stage, and contributing factors.12 Guidelines and resources for management of CRF are available through the NCCN and ONS (see above). None of the pharmacologic interventions listed in the table below have indications for CRF, and many have not been studied in this setting. The benefits of antidepressant use are unclear in patients with CRF without a depressive mood disorder.13
Table 5. Interventions for Management of CRF
Nonpharmacologic Strategies
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Nursing Considerations
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Components
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Exercise
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·Consider patient condition and goal of cancer care (curative vs palliative)
·Weigh risk-benefit ratio for all patients
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·Low-intensity exercise
·Aerobic interval training with monitoring
·Strength-resistance exercise
|
Education and counseling
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·Should be included for all patients with cancer
|
·Teach CRF coping strategies
·Energy conservation
·Activity management
·Balance rest and activity
|
Cognitive behavior interventions
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·Goals include
·Distress reduction
·Stress reduction
·Improved sleep behaviors
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·Progressive muscle relaxation
·Relaxed breathing techniques
·Improve sleep hygiene habits
·Consider referral to psychologist, psychiatrist, or sleep specialist
|
Pharmacologic Strategy
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Agent
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Approved Indication
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CNS stimulant
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Methylphenidate
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ADHD
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CNS stimulant
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Modafinil
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Daytime sleepiness secondary to narcolepsy, sleep apnea
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CNS stimulant
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Dextroamphetamine
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Not studied in CRF
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Cholinesterase inhibitor
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Donepezil
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Alzheimer dementia
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Antidepressant
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Bupropion sustained release
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Smoking cessation
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Antidepressant
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SSRIs
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Depression
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Amino acid supplement
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Levocarnitine
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None
|
Nutraceutical
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Adenosine 5'-triphosphate
|
None
|
Based on information from Barsevick et al12 and Breitbart and Alici.13
ADHD = attention deficit hyperactivity disorder; CNS = central nervous system; CRF = cancer-related fatigue; SSRI = selective serotonin reuptake inhibitor.
Nursing Implications
Routine and ongoing systematic assessment of CRF in patients throughout the continuum of CRC care is essential to improving physical and psychological quality of life. Nurses should be proactive in discussing fatigue and assessing the severity of this common side effect of therapy. Patients often assume that fatigue is an inevitable part of cancer and cancer therapy and may not offer information voluntarily. In an NCCN study of barriers to implementation of the CRF guidelines, the most frequent patient-related barrier was the patient’s belief that the health care practitioner would ask about fatigue if it was important, followed by the patient’s desire to play the “good patient” role.14
References
- NCCN Clinical Practice Guidelines in Oncology: Cancer-Related Fatigue, v1.2010. http://www.nccn.org/professionals/physician_gls/PDF/fatigue.pdf. Accessed January 27, 2010, . Page 22. Accessed January 27, 2010.
- Given B. Cancer-related fatigue: a brief overview of current nursing perspectives and experiences. Clin J Oncol Nurs. 2008;12(5 suppl):7-9.
- Fu MR, McDaniel RW, Rhodes, VA. Fatigue. In: Yarbro CH, Frogge MH, Goodman M, Groenwald SL, eds. Cancer Nursing: Principles and Practice, 6th ed. Sudbury, Mass: Jones & Bartlett; 2005:741-760.
- Wang XS. Pathophysiology of cancer-related fatigue. Clin J Oncol Nurs. 2008;12(5 suppl):11-20.
- Winningham ML. The foundation of energetics: fatigue, fuel, and functioning. In: Winningham ML, Barton-Burke M, eds. Fatigue in Cancer. Sudbury, Mass: Jones & Bartlett; 2000.
- Madden J, Newton S. Why am I so tired all the time? Understanding cancer-related fatigue. Clin J Oncol Nurs. 2006;10:659-661.
- Portenoy RK, Itri LM. Cancer-related fatigue: guidelines for evaluation and management. Oncologist. 1999;4:1-10.
- Piper BF, Borneman T, Sun VC-Y et al. Cancer-related fatigue: role of oncology nurses in translating National Comprehensive Cancer Network assessment guidelines into practice. Clin J Oncol Nurs. 2008;12(5 suppl): 37-47.
- Cancer Therapy Evaluation Program, National Cancer Institute. Common Terminology Criteria for Adverse Events, v4.02, page 22.http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.02_2009-09-15_QuickReference_8.5x11.pdf
- Polovich M, White J, Kelleher L, eds. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 3rd ed. Pittsburgh, Pa: Oncology Nursing Society; 2009.
- Quick M, Fonteyn M. Development and implementation of a clinical survey for cancer-related fatigue assessment. Clin J Oncol Nurs. 2005;4:435-439. ]Pub Med[
- Barsevick AM, Newhall T, Brown S. Management of cancer-related fatigue. Clin J Oncol Nurs. 2008;12(5 suppl):21-25.
- Breitbart W, Alici Y. Pharmacologic treatment options for cancer-related fatigue: current state of clinical research. Clin J Oncol Nurs. 2008;12(5 suppl):27-36.
- Borneman T, Piper BF, Sun VC et al. Implementing the fatigue guidelines at one NCCN member institution: process and outcomes. J Natl Compr Canc Netw. 2007;5:1092-1101.
Key Definitions
catabolic—destructive metabolism involving the release of energy and resulting in the breakdown of complex materials within the organism
deconditioning—a loss of physical fitness
etiologies—causing or contributing to the cause of a disease or condition
ferritin—a crystalline iron-containing protein that functions in the storage of iron and is found especially in the liver and spleen
hypoxia—a deficiency of oxygen reaching the tissues of the body
total iron-binding capacity (TIBC)—a blood test that measures the total iron binding capacity (TIBC) as an indirect measure of transferrin
transferrin—a plasma protein that transports iron through the blood to the liver, spleen, and bone marrow. Transferrin levels are abnormally high in iron-deficiency anemia
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