Cancer-related fatigue is a symptom of fatigue that is experienced by nearly all cancer patients.

Among patients receiving cancer treatment other than surgery, it is essentially universal. Fatigue is a normal and expected side effect of most forms of chemotherapy, radiation therapy, and biotherapy.[1] On average, cancer-related fatigue is "more severe, more distressing, and less likely to be relieved by rest" than fatigue experienced by healthy people.[1] It can range from mild to severe, and may be either temporary or a long-term effect.

Fatigue may be a symptom of the cancer, or it may be the result of treatments for the cancer.

Pathophysiology

The pathophysiology of cancer-related fatigue is poorly understood. It may be caused by the cancer or the effects it has on the body, by the body's response to the cancer, or by the cancer treatments.

Fatigue is a common symptom of cancer.[2]

Some fatigue is caused by cancer treatments. This may show a characteristic pattern. For example, people on many chemotherapy regimens often feel more fatigue in the week after treatments, and less fatigue as they recover from that round of medications. People receiving radiation therapy, by contrast, often find their fatigue steadily increases until the end of treatment.[2]

Proposed mechanisms by which cancer can cause fatigue include an increase in pro-inflammatory cytokines, dysregulation of the hypothalamic-pituitary-adrenal axis, disruption of circadian rhythms, muscle loss and cancer wasting, and genetic problems.[1] Additionally, some forms of cancer may cause fatigue through more direct mechanisms, such as a leukemia that causes anemia by preventing the bone marrow from producing blood cells efficiently. A relationship between Interleukin 6 and fatigue has been observed in studies, albeit inconsistently. Increased markers of sympathetic nervous system activity are also associated with cancer related fatigue.[3]

Screening

The National Comprehensive Cancer Network recommends that every cancer patient be systematically screened for fatigue at the first visit with an oncologist, throughout treatment, and afterwards.[1] Screening typically involves a simple question, like "On a scale of one to ten, how tired have you felt during the last week?"

More detailed information may be collected in a symptom journal.

Diagnosis

Some causes of cancer-related fatigue are treatable, and evaluation is directed towards identifying these treatable causes. Treatable causes of cancer-related fatigue include: anemia, pain, emotional distress, sleep disturbances, nutritional disturbances, decreased physical fitness and activity, side effects from medications (e.g., sedatives), abuse of alcohol or other substances.[1] Additionally, other medical conditions, such as infections, heart disease, or endocrine dysfunction (e.g., hot flashes), can cause fatigue, and may also need treatment.

Definition

The National Comprehensive Cancer Network defines cancer-related fatigue as "a distressing persistent, subjective sense of physical, emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning".[1]

Cancer-related fatigue is a chronic fatigue (persistent fatigue not relieved by rest), but it is not related to chronic fatigue syndrome.[2]

Management

Treatment depends on the patient's overall situation. A patient who is in active treatment may have different priorities than a person who has completed treatment, or who is at the end of life.

Some management strategies may help all patients and could be supported by the work of an Occupational Therapist. These include scheduling high-priority tasks during the patient's best time of day, using labor-saving devices, delegating tasks to caregivers, and avoiding unimportant activities, so that the patient will have more energy available for other activities.

Patients who are not at the end of life may benefit from physical exercise or physical therapy. Engaging in physical activity may reduce fatigue.[1][4][5][6]

While antidepressants are ineffective at reducing fatigue in non-depressed cancer patients, psychostimulants such as methylphenidate and amphetamines may reduce fatigue in some patients.[1][7][8][9][10]

At the end of life, fatigue is usually associated with other symptoms, especially anemia, side effects from many medications and previous treatments, and poor nutritional status.[1] Pain, difficulty breathing, and fatigue form a common symptom cluster. Fatigue often increases as patients with advanced cancer approach death. As a result, people who are dying often sleep much more than a healthy person.

Addressing specific causes

If the fatigue is caused or exacerbated by a specific medical condition, such as anemia, then treatment of that medical condition should reduce the fatigue.

Prognosis

Fatigue caused by the cancer or its treatment often resolves if treatment is successful. However, some patients experience long-term or chronic fatigue. When strict definitions are used, about 20% of long-term, disease-free cancer survivors report fatigue.[1] Under looser definitions, up to half of cancer survivors report fatigue.[1] However, these studies are largely limited to patients with breast cancer, or peripheral stem cell transplant or bone marrow transplant patients, and the incidence may be different for survivors of other cancers.

Experiencing fatigue before treatment, being depressed or anxious, getting too little exercise, and having other medical conditions are all associated with higher levels of fatigue in post-treatment cancer survivors.[1] Receiving multiple types of treatments, such as chemotherapy and radiation, is associated with more fatigue.[2] Older adults have a higher risk of long-term fatigue.[2]

Cancer-related fatigue after treatment for childhood cancer.

Cancer-related fatigue has consistently been found to be one of the most prevalent and distressing symptoms in childhood cancer survivors.[14] The International Late Effects of Childhood Cancer Guidelines Harmonization Group (IGHG) has published recommendations regarding the surveillance of fatigue in survivors of childhood cancer. [15] These recommendations include regular screenings of fatigue in survivors of childhood cancer. Survivors of pediatric brain tumors report more fatigue after end of treatment than survivors of acute lymphoblastic leukemia, but both groups experience more fatigue than healthy children and adolescents.[16] While considered a long-term effect of the treatment, children and adolescents experience fatigue already during the treatment for acute lymphoblastic leukemia and this side-effect of treatment remains in some patients after the treatment has ended.[17] Fatigue after treatment for pediatric brain tumors does not automatically resolve itself, but requires surveillance and interventions.[18]

References

  1. ^ a b c d e f g h i j k l m "NCCN Clinical Practice Guidelines in Oncology: Cancer-Related Fatigue" (PDF) (Version 1.2010 ed.). National Comprehensive Cancer Network. 22 January 2010.
  2. ^ a b c d e f g h "Fatigue". National Cancer Institute. 1980-01-01. Retrieved 6 October 2010.
  3. ^ Saligan LN, Olson K, Filler K, Larkin D, Cramp F, Yennurajalingam S, et al. (August 2015). "The biology of cancer-related fatigue: a review of the literature". Supportive Care in Cancer. 23 (8): 2461–2478. doi:10.1007/s00520-015-2763-0. PMC 4484308. PMID 25975676.
  4. ^ Jose Stephy, Diwan Sanjay Kumar. Effect of standardized exercise program on reported fatigue in patients of cancer receiving chemotherapy. Clinical Cancer Investigation Journal 3(5): 373-376
  5. ^ Mishra, Shiraz I.; Scherer, Roberta W.; Geigle, Paula M.; Berlanstein, Debra R.; Topaloglu, Ozlem; Gotay, Carolyn C.; Snyder, Claire (2012-08-15). "Exercise interventions on health-related quality of life for cancer survivors". The Cochrane Database of Systematic Reviews. 2012 (8): CD007566. doi:10.1002/14651858.CD007566.pub2. ISSN 1469-493X. PMC 7387117. PMID 22895961.
  6. ^ a b Cramp F, Byron-Daniel J (November 2012). "Exercise for the management of cancer-related fatigue in adults". The Cochrane Database of Systematic Reviews. 11 (11): CD006145. doi:10.1002/14651858.CD006145.pub3. PMC 8480137. PMID 23152233.
  7. ^ Breitbart W, Alici Y (August 2010). "Psychostimulants for cancer-related fatigue". Journal of the National Comprehensive Cancer Network. 8 (8): 933–942. doi:10.6004/jnccn.2010.0068. PMID 20870637.
  8. ^ Minton O, Richardson A, Sharpe M, Hotopf M, Stone PC (April 2011). "Psychostimulants for the management of cancer-related fatigue: a systematic review and meta-analysis". Journal of Pain and Symptom Management. 41 (4): 761–767. doi:10.1016/j.jpainsymman.2010.06.020. PMID 21251796.
  9. ^ Gong S, Sheng P, Jin H, He H, Qi E, Chen W, et al. (2014). "Effect of methylphenidate in patients with cancer-related fatigue: a systematic review and meta-analysis". PLOS ONE. 9 (1): e84391. Bibcode:2014PLoSO...984391G. doi:10.1371/journal.pone.0084391. PMC 3885551. PMID 24416225.
  10. ^ Yennurajalingam S, Bruera E (2014). "Review of clinical trials of pharmacologic interventions for cancer-related fatigue: focus on psychostimulants and steroids". Cancer Journal. 20 (5): 319–324. doi:10.1097/PPO.0000000000000069. PMID 25299141. S2CID 29351114.
  11. ^ Brown JC, Huedo-Medina TB, Pescatello LS, Pescatello SM, Ferrer RA, Johnson BT (January 2011). "Efficacy of exercise interventions in modulating cancer-related fatigue among adult cancer survivors: a meta-analysis". Cancer Epidemiology, Biomarkers & Prevention. 20 (1): 123–133. doi:10.1158/1055-9965.epi-10-0988. PMID 21051654.
  12. ^ Kessels E, Husson O, van der Feltz-Cornelis CM (2018). "The effect of exercise on cancer-related fatigue in cancer survivors: a systematic review and meta-analysis". Neuropsychiatric Disease and Treatment. 14 (14): 479–494. doi:10.2147/ndt.s150464. PMC 5810532. PMID 29445285.
  13. ^ Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvão DA, Pinto BM, et al. (July 2010). "American College of Sports Medicine roundtable on exercise guidelines for cancer survivors". Medicine and Science in Sports and Exercise. 42 (7): 1409–1426. doi:10.1249/MSS.0b013e3181e0c112. PMID 20559064. S2CID 43598402.
  14. ^ Spathis A, Booth S, Grove S, Hatcher H, Kuhn I, Barclay S (March 2015). "Teenage and Young Adult Cancer-Related Fatigue Is Prevalent, Distressing, and Neglected: It Is Time to Intervene. A Systematic Literature Review and Narrative Synthesis". Journal of Adolescent and Young Adult Oncology. 4 (1): 3–17. doi:10.1089/jayao.2014.0023. PMC 4365509. PMID 25852970.
  15. ^ Christen S, Roser K, Mulder RL, Ilic A, Lie HC, Loonen JJ, et al. (December 2020). "Recommendations for the surveillance of cancer-related fatigue in childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group". Journal of Cancer Survivorship. 14 (6): 923–938. doi:10.1007/s11764-020-00904-9. PMC 7572340. PMID 32839902.
  16. ^ Irestorm E, Tonning Olsson I, Johansson B, Øra I (April 2020). "Cognitive fatigue in relation to depressive symptoms after treatment for childhood cancer". BMC Psychology. 8 (1): 31. doi:10.1186/s40359-020-00398-1. PMC 7146960. PMID 32272971.
  17. ^ Irestorm E, Steur LM, Kaspers GJ, Van Eijkelenburg NK, Van der Sluis IM, Dors N, et al. (December 2022). "Fatigue trajectories during pediatric ALL therapy are associated with fatigue after treatment: a national longitudinal cohort study". Supportive Care in Cancer. 31 (1): 1. doi:10.1007/s00520-022-07456-x. PMC 9747814. PMID 36512099.
  18. ^ Irestorm, Elin; van Gorp, Marloes; Twisk, Jos; Nijhof, Sanne; de Bont, Judith; Grootenhuis, Martha; van Litsenburg, Raphaele (2023-09-07). "Longitudinal development of fatigue after treatment for childhood cancer: a national cohort study". Acta Oncologica. 62 (10): 1309–1321. doi:10.1080/0284186X.2023.2254477. ISSN 0284-186X. PMID 37676687.