Questions About Cancer? 1-800-4-CANCER
  • View entire document
  • Print
  • Email
  • Facebook
  • Twitter
  • Google+
  • Pinterest

Fatigue (PDQ®)


Assessment of fatigue is multidimensional in nature,[1] and a number of tools originally developed for fatigue research have also been used in clinical practice. Most of these tools include symptom dimensions other than fatigue intensity, such as the impact or consequences of fatigue, timing of fatigue, related symptoms, and self-care actions.[2-10] Research has also contributed a validated 10-item measure for children.[11]

However, much of the time in clinical practice, because of perceived provider/patient burden, screening most often relies on a single-item fatigue intensity rating.[12-15] According to National Comprehensive Cancer Network (NCCN) guidelines, ratings of fatigue of 4 or higher on a scale of 0 to 10 (where 10 is very severe fatigue) are further evaluated for known contributing factors such as pain, emotional distress, anemia, sleep, nutrition, and level of activity. These comorbidities are then treated.[16] One study of ambulatory outpatients with solid tumors (N = 148) evaluated the usefulness of single-item screening for symptoms such as fatigue and pain.[12] Investigators found that the single-item assessment can assist as a first screening step to identify patients requiring comprehensive assessment of symptoms. Patients identified by using single-item screening tools undergo comprehensive assessments to detect clinically relevant symptomatology.[12,13]

Multiple-Item Tools

Ambiguous literature and a previous lack of specific tools to measure fatigue have created difficulties in establishing assessment and management guidelines. Comprehensive assessment of the fatigued patient starts with obtaining a careful history to characterize the individual’s fatigue pattern and to identify all factors that contribute to its development. The following may be included in the initial assessment:

  • Self-report of fatigue pattern, including onset, duration, intensity, and aggravating and alleviating factors.
  • Type and degree of disease- and of treatment-related symptoms and/or side effects.
  • Treatment history.
  • Current medications.
  • Sleep and/or rest patterns, relaxation habits, customs, and rituals.
  • Nutrition intake and any appetite or weight changes.
  • Effects of fatigue on activities of daily living and lifestyle.
  • Psychiatric evaluation, including evaluation for depression.
  • Complete physical examination, including gait, posture, and range of motion.
  • Compliance with treatment.
  • Job performance.
  • Financial resources.
  • Other contributing factors (e.g., anemia, dyspnea, muscle wasting).

Specific attention is paid to underlying factors that contribute to fatigue and may be correctable, including the following:[17,18]

  • Anemia.
  • Depression.
  • Anxiety.
  • Pain.
  • Dehydration.
  • Nutritional deficiencies (e.g., protein, calories, vitamins).
  • Sedating medications (e.g., opioids, benzodiazepines).
  • Neurotoxic therapies.
  • Infection.
  • Fever.
  • Sleep disturbances.
  • Immobility.

Proposed criteria for cancer-related fatigue (CRF) are listed below. These criteria have been adopted for inclusion in the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification (ICD-10-CM).[19]

Defining CRF as a diagnostic syndrome has some potential advantages and disadvantages.[20] One of the possible advantages is that it would enable clinicians to document the presence or absence of fatigue in a reproducible fashion. It may also be useful in establishing appropriate reimbursement for management of this finding. The potential disadvantage of this approach is that it may deter management of fatigue that does not reach the threshold for ICD-10 diagnosis. The alternative to the syndrome-based approach (commonly used for depression) is a symptom-based approach, which is commonly used for phenomena such as pain and nausea. The utility of the following ICD-10 criteria for CRF has not been validated.

ICD-10 Criteria for Cancer-related Fatigue

The following symptoms have been present every day or nearly every day during the same 2-week period in the past month:

  1. Significant fatigue, diminished energy, or increased need to rest, disproportionate to any recent change in activity level, plus five or more of the following:
    1. Complaints of generalized weakness, limb heaviness.
    2. Diminished concentration or attention.
    3. Decreased motivation or interest to engage in usual activities.
    4. Insomnia or hypersomnia.
    5. Experience of sleep as unrefreshing or nonrestorative.
    6. Perceived need to struggle to overcome inactivity.
    7. Marked emotional reactivity (e.g., sadness, frustration, or irritability) to feeling fatigued.
    8. Difficulty completing daily tasks attributed to feeling fatigued.
    9. Perceived problems with short-term memory.
    10. Postexertional fatigue lasting several hours.
  2. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  3. There is evidence from the history, physical examination, or laboratory findings that the symptoms are a consequence of cancer or cancer therapy.
  4. The symptoms are not primarily a consequence of comorbid psychiatric disorders such as major depression, somatization disorder, somatoform disorder, or delirium.

As with other self-reported symptoms such as pain, it may be necessary to encourage the patient and other family members to report symptoms of fatigue to the medical staff. Information regarding the potential for fatigue due to the underlying disease or treatments, possible options for management, and the importance of reporting these symptoms is given to patients at the initiation of treatment.[17] Patients may not mention the fatigue they experience unless they are prompted by a health professional.

Several barriers hamper appropriate management of CRF. Some of these barriers were identified in phase 1 of an ongoing three-phase project related to the implementation of evidence-based (NCCN) guidelines for fatigue management.[21] The most commonly identified barriers were the following:[21,22]

  • Patient’s belief that the physician would introduce the subject of fatigue if it was important (patient barrier).
  • Lack of fatigue documentation (professional barrier).
  • Lack of supportive care referrals (system barrier).

Although there is no universally accepted standard for the measurement of fatigue, there are a variety of instruments that have been developed to assess fatigue and related sequelae.[2-6][Level of evidence: II];[7-10] Fatigue is also commonly assessed in multidimensional quality-of-life instruments. Selected instruments for assessing fatigue are listed below.

  • Brief Fatigue Inventory.[4]
  • The Functional Assessment of Cancer Therapy-Anemia.[7]
  • The Functional Assessment of Cancer Therapy-Fatigue.[8]
  • The Piper Fatigue Scale (long and short versions).[3,23]
  • The Schwartz Cancer Fatigue Scale.[9]
  • Fatigue Symptom Inventory.[6]
  • The Profile of Mood States Fatigue/Inertia Subscale.[10]
  • Lee’s Visual Analogue Scale for Fatigue.[2]
  • Cancer Fatigue Scale.[5]
  • Multidimensional Fatigue Symptom Inventory-Short Form.[24]

Evaluation of Anemia

The proper evaluation of anemia in cancer patients includes the following:

  • A careful history and physical examination.
  • An evaluation of the complete blood count and red blood cell indices.
  • An examination of the peripheral blood smear.

In combination, the information from these investigations is often diagnostic.

One commonly used method for classifying anemia is to categorize the anemia by the size of the red blood cell as measured by the mean corpuscular volume (MCV). Microcytic anemias are associated with an MCV of 79 fL or lower and include iron-deficiency anemia, thalassemia, and anemia of chronic disease. Macrocytic anemias are associated with an MCV higher than 101 fL and include anemias related to vitamin B12 or folate deficiency, myelodysplasia, and liver disease. Most anemias are normocytic, meaning that the MCV is in the normal range. This category includes the following:[25]

  • Myelophthisic anemia (i.e., anemia due to neoplastic replacement of the bone marrow).
  • Most chemotherapy-related anemias.
  • Anemia due to renal or hepatic dysfunction.
  • Hemolytic anemia.
  • Aplastic anemia.

However, a mixed red blood cell population consisting of both microcytic and macrocytic cells (anisocytosis) may indicate a combined etiology, for example, chronic blood loss (microcytic) with resultant reticulocytosis (macrocytic). In this situation, the MCV may be in the normal range, but the red blood cell size distribution width would be elevated.

The peripheral blood smear examination, though often overlooked, remains an important step in the evaluation of anemia. For example, nucleated blood cells and teardrop-shaped red blood cells suggest myelophthisic anemia. Macro-ovalocytes and hypersegmented neutrophils often indicate megaloblastic anemia. Small target cells and basophilic stippling are associated with thalassemia.

Additional studies that are sometimes required to characterize anemia in a given patient include testing of vitamin B12 or folate levels; serum iron, transferrin, and ferritin levels; erythropoietin level, the direct and indirect Coombs test, and/or examination of a bone marrow aspirate and biopsy. In cancer patients, the underlying etiology is often multifactorial.


  1. Portenoy RK, Miaskowski C: Assessment and management of cancer-related fatigue. In: Berger A, Portenoy RK, Weissman DE, eds.: Principles and Practice of Supportive Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 1998, pp 109-18.
  2. Lee KA, Hicks G, Nino-Murcia G: Validity and reliability of a scale to assess fatigue. Psychiatry Res 36 (3): 291-8, 1991. [PUBMED Abstract]
  3. Piper BF, Dibble SL, Dodd MJ, et al.: The revised Piper Fatigue Scale: psychometric evaluation in women with breast cancer. Oncol Nurs Forum 25 (4): 677-84, 1998. [PUBMED Abstract]
  4. Mendoza TR, Wang XS, Cleeland CS, et al.: The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer 85 (5): 1186-96, 1999. [PUBMED Abstract]
  5. Okuyama T, Akechi T, Kugaya A, et al.: Development and validation of the cancer fatigue scale: a brief, three-dimensional, self-rating scale for assessment of fatigue in cancer patients. J Pain Symptom Manage 19 (1): 5-14, 2000. [PUBMED Abstract]
  6. Hann DM, Denniston MM, Baker F: Measurement of fatigue in cancer patients: further validation of the Fatigue Symptom Inventory. Qual Life Res 9 (7): 847-54, 2000. [PUBMED Abstract]
  7. Cella D: The Functional Assessment of Cancer Therapy-Anemia (FACT-An) Scale: a new tool for the assessment of outcomes in cancer anemia and fatigue. Semin Hematol 34 (3 Suppl 2): 13-9, 1997. [PUBMED Abstract]
  8. Cella D: Manual of the Functional Assessment of Chronic Illness Therapy (FACIT) Scales. Version 4. Evanston, Ill: Evanston Northwestern Healthcare, 1997.
  9. Schwartz AL: The Schwartz Cancer Fatigue Scale: testing reliability and validity. Oncol Nurs Forum 25 (4): 711-7, 1998. [PUBMED Abstract]
  10. McNair D, Lorr M, Droppelman L, et al.: Profile of Mood States. San Diego, Calif: Educational and Industrial Testing Service, 1971.
  11. Hinds PS, Yang J, Gattuso JS, et al.: Psychometric and clinical assessment of the 10-item reduced version of the Fatigue Scale-Child instrument. J Pain Symptom Manage 39 (3): 572-8, 2010. [PUBMED Abstract]
  12. Butt Z, Wagner LI, Beaumont JL, et al.: Use of a single-item screening tool to detect clinically significant fatigue, pain, distress, and anorexia in ambulatory cancer practice. J Pain Symptom Manage 35 (1): 20-30, 2008. [PUBMED Abstract]
  13. Kirsh KL, Passik S, Holtsclaw E, et al.: I get tired for no reason: a single item screening for cancer-related fatigue. J Pain Symptom Manage 22 (5): 931-7, 2001. [PUBMED Abstract]
  14. Strasser F, Müller-Käser I, Dietrich D: Evaluating cognitive, emotional, and physical fatigue domains in daily practice by single-item questions in patients with advanced cancer: a cross-sectional pragmatic study. J Pain Symptom Manage 38 (4): 505-14, 2009. [PUBMED Abstract]
  15. Temel JS, Pirl WF, Recklitis CJ, et al.: Feasibility and validity of a one-item fatigue screen in a thoracic oncology clinic. J Thorac Oncol 1 (5): 454-9, 2006. [PUBMED Abstract]
  16. Berger AM, Abernethy AP, Atkinson A, et al.: Cancer-related fatigue. J Natl Compr Canc Netw 8 (8): 904-31, 2010. [PUBMED Abstract]
  17. Cella D, Peterman A, Passik S, et al.: Progress toward guidelines for the management of fatigue. Oncology (Huntingt) 12 (11A): 369-77, 1998. [PUBMED Abstract]
  18. Groopman JE: Fatigue in cancer and HIV/AIDS. Oncology (Huntingt) 12 (3): 335-44; discussion 345-6, 351, 1998. [PUBMED Abstract]
  19. Portenoy RK, Itri LM: Cancer-related fatigue: guidelines for evaluation and management. Oncologist 4 (1): 1-10, 1999. [PUBMED Abstract]
  20. Sadler IJ, Jacobsen PB, Booth-Jones M, et al.: Preliminary evaluation of a clinical syndrome approach to assessing cancer-related fatigue. J Pain Symptom Manage 23 (5): 406-16, 2002. [PUBMED Abstract]
  21. 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 5 (10): 1092-101, 2007. [PUBMED Abstract]
  22. Passik SD, Kirsh KL, Donaghy K, et al.: Patient-related barriers to fatigue communication: initial validation of the fatigue management barriers questionnaire. J Pain Symptom Manage 24 (5): 481-93, 2002. [PUBMED Abstract]
  23. Reeve BB, Stover AM, Alfano CM, et al.: The Piper Fatigue Scale-12 (PFS-12): psychometric findings and item reduction in a cohort of breast cancer survivors. Breast Cancer Res Treat 136 (1): 9-20, 2012. [PUBMED Abstract]
  24. Stein KD, Jacobsen PB, Blanchard CM, et al.: Further validation of the multidimensional fatigue symptom inventory-short form. J Pain Symptom Manage 27 (1): 14-23, 2004. [PUBMED Abstract]
  25. Armitage JO: Management of anemia in patients with cancer. Clinical Oncology Updates 1: 1-12, 1998.
  • Updated: August 28, 2014