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Cancer-related fatigue

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Cancer-related fatigue is a symptom of fatigue that is experienced by nearly all cancer patients.[1]

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.[2] On average, cancer-related fatigue is "more severe, more distressing, and less likely to be relieved by rest" than fatigue experienced by healthy people.[2] 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

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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.[3]

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.[3]

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.[2] 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.[4]

Screening

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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.[2] 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

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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.[2] 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

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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".[2]

Cancer-related fatigue is a chronic fatigue (persistent fatigue not relieved by rest), but it is not related to chronic fatigue syndrome.[3] Cancer-related fatigue occurs in a significant proportion of cancer survivors, both during and after cancer treatment.[5] A review of current evidence indicates that exercise is the most effective way of ameliorating cancer-related fatigue.[5]

Prostate cancer

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Cancer related fatigue is common in patients undergoing treatment for prostate cancer.[6] A systematic review of the prevalence of cancer-related fatigue in men with prostate cancer was performed.[7] The analysis indicated that fatigue is a common symptom, occurring in about 40% of men with prostate cancer especially among those using hormone therapy.[7]

Management

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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.[8]

Patients who are not at the end of life may benefit from physical exercise or physical therapy. Engaging in physical activity may reduce fatigue.[2][9][10][11] Forms of exercise that have been proven to be most effective are more aerobic exercise such as walking, running, cycling, and swimming. These forms of activity can be done at various levels of intensity and have been proven as an effective way of improving QOL for cancer patients.[12]

While antidepressants are ineffective at reducing fatigue in non-depressed cancer patients, psychostimulants such as methylphenidate and amphetamines may reduce fatigue in some patients.[2][13][14][15][16] The findings of a study conducted by researchers from reputable universities in the UK indicate that methylphenidate may be effective in the management of CRF (Cancer Related Fatigue). If methylphenidate were to be used in patients with CRF, it would be prudent to restrict its use to patients with advanced disease or for short-term use in patients on active treatment. The clear advantage of methylphenidate in cancer is its rapid onset of action within 24–48 hours, and so the drug can be discontinued if ineffective.[17]

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.[2] 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.[18][19]

Addressing specific causes

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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.

  • Anemia: Loss of oxygen-carrying red blood cells is a common cause of fatigue. Medications to improve blood production or blood transfusions frequently reduce fatigue.
  • Pain: A variety of approaches to managing cancer pain may be used, particularly analgesic medications.
  • Emotional distress: Anxiety and depression are strongly associated with fatigue in cancer patients. Psychosocial treatments directed at reducing stress and increasing coping skills may reduce fatigue. Additionally, some patients in active treatment worry that the fatigue indicates treatment failure, and this anxiety may increase their fatigue in a vicious cycle. Education about fatigue as a normal side effect can reassure the patient.[2] Up to 25% of cancer patients will experience depression.[3]
  • Sleep disturbances: Patients who do not sleep well are more tired than others. Cancer patients commonly experience insomnia or hypersomnia. Sleep disturbances may be caused by sleeping too much during the day, by restless leg syndrome, by pain, by anxiety, or by other medical conditions, like obstructive sleep apnea or menopause. Practicing good sleep hygiene may reduce fatigue by improving sleep quality.
  • Nutritional disturbances: Patients may have difficulty eating, may not be absorbing food well, or may have chosen an extreme diet as an alternative cancer treatment. Loss of appetite, diarrhea and vomiting may result in the patient consuming too few calories or becoming dehydrated.[3]
  • Lack of physical activity: Decreased physical activity can make fatigue worse by reducing endurance and muscle strength. Participating in regular aerobic[11] and muscle-strengthening[20] physical activity both during and after cancer treatment may reduce cancer-related fatigue. Current physical activity guidelines recommend adults with cancer to engage in at least 150 minutes per week of moderate- intensity or 75 minutes per week of vigorous-intensity aerobic physical activity, or an equivalent combination. It is also recommended to perform muscle-strengthening physical activity two to three times a week, although there are studies showing that aerobic training is better at mitigating symptoms of cancer-related fatigue and reduces the risk of post exercise malaise.[21] Physical activities should be tailored to individual needs and physical abilities.[22]
  • Side effects from medications: Fatigue and sleepiness are known side effects with some kinds of medications. Sometimes a change of medication, the dose, or the timing of the medication may result in less fatigue. For example, an antihistamine might be taken shortly before sleep, rather than in the middle of the day.
  • Substance abuse: Alcohol, marijuana, and many other drugs can produce fatigue as a side effect.
  • Other medical conditions: Cancer and its treatment usually put intense physical stress on the body, which can exacerbate other medical conditions. Additionally, fatigue may result from an infection.[3]

Prognosis

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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.[2] Under looser definitions, up to half of cancer survivors report fatigue.[2] 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.[2] Receiving multiple types of treatments, such as chemotherapy and radiation, is associated with more fatigue.[3] Older adults have a higher risk of long-term fatigue.[3]

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Cancer-related fatigue has consistently been found to be one of the most prevalent and distressing symptoms in childhood cancer survivors.[23] The International Late Effects of Childhood Cancer Guidelines Harmonization Group (IGHG) has published recommendations regarding the surveillance of fatigue in survivors of childhood cancer.[24] 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.[25] 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.[26] Fatigue after treatment for pediatric brain tumors does not automatically resolve itself, but requires surveillance and interventions.[27]

References

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  1. ^ Hofman, Maarten; Ryan, Julie L.; Figueroa-Moseley, Colmar D.; Jean-Pierre, Pascal; Morrow, Gary R. (2007-05-01). "Cancer-Related Fatigue: The Scale of the Problem". The Oncologist. 12 (S1): 4–10. doi:10.1634/theoncologist.12-s1-4. ISSN 1083-7159. PMID 17573451.
  2. ^ 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.
  3. ^ a b c d e f g h "Fatigue". National Cancer Institute. 1980-01-01. Retrieved 6 October 2010.
  4. ^ 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.
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  6. ^ Randall J, Haque W, Butler EB, Teh BS (March 2019). "Cancer related fatigue in prostate cancer". Translational Andrology and Urology. 8 (Suppl 1): S106–S108. doi:10.21037/tau.2018.12.06. PMC 6511691. PMID 31143682.
  7. ^ a b Luo YH, Yang YW, Wu CF, Wang C, Li WJ, Zhang HC (July 2021). "Fatigue prevalence in men treated for prostate cancer: A systematic review and meta-analysis". World J Clin Cases. 9 (21): 5932–5942. doi:10.12998/wjcc.v9.i21.5932. PMC 8316927. PMID 34368311.
  8. ^ Wallis, Amy; Meredith, Pamela; Stanley, Mandy (April 2020). "Cancer care and occupational therapy: A scoping review". Australian Occupational Therapy Journal. 67 (2): 172–194. doi:10.1111/1440-1630.12633. ISSN 0045-0766. PMID 31957031.
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  12. ^ Thompson, Paul D.; Arena, Ross; Riebe, Deborah; Pescatello, Linda S. (July–August 2013). "ACSM's New Preparticipation Health Screening Recommendations from ACSM's Guidelines for Exercise Testing and Prescription". Current Sports Medicine Reports. 12 (4) (Ninth ed.): 215–217. doi:10.1249/JSR.0b013e31829a68cf. ISSN 1537-8918. PMID 23851406.
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  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ Minton, Ollie; Richardson, Alison; Sharpe, Michael; Hotopf, Matthew; Stone, Patrick C. (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. ISSN 0885-3924. PMID 21251796.
  18. ^ Lin, Shuanglan; Chen, Yanhan; Yang, Liu; Zhou, Jianrong (May 2013). "Pain, fatigue, disturbed sleep and distress comprised a symptom cluster that related to quality of life and functional status of lung cancer surgery patients". Journal of Clinical Nursing. 22 (9–10): 1281–1290. doi:10.1111/jocn.12228. ISSN 0962-1067. PMID 23574291.
  19. ^ Klasson, Caritha; Helde Frankling, Maria; Lundh Hagelin, Carina; Björkhem-Bergman, Linda (January 2021). "Fatigue in Cancer Patients in Palliative Care—A Review on Pharmacological Interventions". Cancers. 13 (5): 985. doi:10.3390/cancers13050985. ISSN 2072-6694. PMC 7956665. PMID 33652866.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ 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.
  24. ^ 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.
  25. ^ 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.
  26. ^ 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.
  27. ^ 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.
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