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Physiological and psychosocial correlates of cancer-related fatigue

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Abstract

Purpose

Cancer-related fatigue (CRF) is a common and distressing symptom of cancer that may persist for years following treatment completion. However, little is known about the pathophysiology of CRF. Using a comprehensive group of gold-standard physiological and psychosocial assessments, this study aimed to identify correlates of CRF in a heterogenous group of cancer survivors.

Methods

Using a cross-sectional design to determine the physiological and psychosocial correlates of CRF, ninety-three cancer survivors (51 fatigued, 42 non-fatigued) completed assessments of performance fatigability (i.e. the decline in muscle strength during cycling), cardiopulmonary exercise testing, venous blood samples for whole blood cell count and inflammatory markers and body composition. Participants also completed questionnaires measuring demographic, treatment-related, and psychosocial variables.

Results

Performance fatigability, time-to-task-failure, peak oxygen uptake (V̇O2peak), tumor necrosis factor-α (TNF-α), body fat percentage, and lean mass index were associated with CRF severity. Performance fatigability, V̇O2peak, TNF-α, and age explained 35% of the variance in CRF severity. Those with clinically-relevant CRF reported more pain, more depressive symptoms, less perceived social support, and were less physically active than non-fatigued cancer survivors.

Conclusions

The present study utilised a comprehensive group of gold-standard physiological and psychosocial assessments and the results give potential insight into the mechanisms underpinning the association between physical inactivity, physical deconditioning and CRF.

Implications for Cancer Survivors

Given the associations between CRF and both physiological and psychosocial measures, this study identifies targets that can be measured by rehabilitation professionals and used to guide tailored interventions to reduce fatigue.

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Data availability

Data available upon request.

Code availability

Not applicable.

References

  1. Berger AM, Mooney K, Alvarez-Perez A, Breitbart WS, Carpenter KM, Cella D, et al. Cancer-Related Fatigue, Version 2.2015. J Natl Compr Canc Netw JNCCN. 2015;13(8):1012–39. https://doi.org/10.6004/jnccn.2015.0122.

    Article  PubMed  Google Scholar 

  2. Lawrence DP, Kupelnick B, Miller K, Devine D, Lau J. Evidence report on the occurrence, assessment, and treatment of fatigue in cancer patients. J Natl Cancer Inst Monogr. 2004;32:40–50. https://doi.org/10.1093/jncimonographs/lgh027.

    Article  Google Scholar 

  3. Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, et al. Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition. Oncologist. 2000;5(5):353–60. https://doi.org/10.1634/theoncologist.5-5-353.

    Article  CAS  PubMed  Google Scholar 

  4. Goedendorp MM, Gielissen MF, Verhagen CA, Bleijenberg G. Development of fatigue in cancer survivors: a prospective follow-up study from diagnosis into the year after treatment. J Pain Symptom Manage. 2013;45(2):213–22. https://doi.org/10.1016/j.jpainsymman.2012.02.009.

    Article  PubMed  Google Scholar 

  5. Jones JM, Olson K, Catton P, Catton CN, Fleshner NE, Krzyzanowska MK, et al. Cancer-related fatigue and associated disability in post-treatment cancer survivors. J Cancer Surviv. 2016;10(1):51–61. https://doi.org/10.1007/s11764-015-0450-2.

    Article  PubMed  Google Scholar 

  6. Bower JE, Ganz PA, Desmond KA, Rowland JH, Meyerowitz BE, Belin TR. Fatigue in Breast Cancer Survivors: Occurrence, Correlates, and Impact on Quality of Life. J Clin Oncol. 2000;18(4):743. https://doi.org/10.1200/jco.2000.18.4.743.

    Article  CAS  PubMed  Google Scholar 

  7. Goldstein D, Bennett BK, Webber K, Boyle F, de Souza PL, Wilcken NR, et al. Cancer-related fatigue in women with breast cancer: outcomes of a 5-year prospective cohort study. J Clin Oncol. 2012;30(15):1805–12. https://doi.org/10.1200/jco.2011.34.6148.

    Article  PubMed  Google Scholar 

  8. Islam T, Dahlui M, Majid HA, Nahar AM, Mohd Taib NA, Su TT. Factors associated with return to work of breast cancer survivors: a systematic review. BMC Public Health. 2014;14(Suppl 3):S8. https://doi.org/10.1186/1471-2458-14-s3-s8.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69(5):363–85. https://doi.org/10.3322/caac.21565.

    Article  PubMed  Google Scholar 

  10. McNeely ML, Courneya KS. Exercise programs for cancer-related fatigue: evidence and clinical guidelines. J Natl Compr Canc Netw JNCCN. 2010;8(8):945–53. https://doi.org/10.6004/jnccn.2010.0069.

    Article  PubMed  Google Scholar 

  11. Carpenter JS, Elam JL, Ridner SH, Carney PH, Cherry GJ, Cucullu HL. Sleep, fatigue, and depressive symptoms in breast cancer survivors and matched healthy women experiencing hot flashes. Oncol Nurs Forum. 2004;31(3):591–5598. https://doi.org/10.1188/04.onf.591-598.

    Article  PubMed  Google Scholar 

  12. Kuhnt S, Ernst J, Singer S, Rüffer JU, Kortmann RD, Stolzenburg JU, et al. Fatigue in cancer survivors–prevalence and correlates. Onkologie. 2009;32(6):312–7. https://doi.org/10.1159/000215943.

    Article  PubMed  Google Scholar 

  13. Servaes P, Verhagen C, Bleijenberg G. Fatigue in cancer patients during and after treatment: prevalence, correlates and interventions. Eur J Cancer. 2002;38(1):27–43. https://doi.org/10.1016/s0959-8049(01)00332-x.

    Article  CAS  PubMed  Google Scholar 

  14. Beck SL, Dudley WN, Barsevick A. Pain, sleep disturbance, and fatigue in patients with cancer: using a mediation model to test a symptom cluster. Oncol Nurs Forum. 2005;32(3):542. https://doi.org/10.1188/04.onf.e48-e55.

    Article  PubMed  Google Scholar 

  15. Martin T, Twomey R, Medysky ME, Temesi J, Culos-Reed SN, Millet GY. The Relationship between Fatigue and Actigraphy-Derived Sleep and Rest-Activity Patterns in Cancer Survivors. Curr Oncol. 2021;28(2):1170–82. https://doi.org/10.3390/curroncol28020113.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Servaes P, Verhagen S, Bleijenberg G. Determinants of chronic fatigue in disease-free breast cancer patients: a cross-sectional study. Ann Oncol. 2002;13(4):589–98. https://doi.org/10.1093/annonc/mdf082.

    Article  CAS  PubMed  Google Scholar 

  17. Gielissen MF, Verhagen S, Witjes F, Bleijenberg G. Effects of cognitive behavior therapy in severely fatigued disease-free cancer patients compared with patients waiting for cognitive behavior therapy: a randomized controlled trial. J Clin Oncol. 2006;24(30):4882–7. https://doi.org/10.1200/jco.2006.06.8270.

    Article  PubMed  Google Scholar 

  18. Corbett TK, Groarke A, Devane D, Carr E, Walsh JC, McGuire BE. The effectiveness of psychological interventions for fatigue in cancer survivors: systematic review of randomised controlled trials. Syst Rev. 2019;8(1):324. https://doi.org/10.1186/s13643-019-1230-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Saligan LN, Olson K, Filler K, Larkin D, Cramp F, Yennurajalingam S, et al. The biology of cancer-related fatigue: a review of the literature. Support Care Cancer. 2015;23(8):2461–78. https://doi.org/10.1007/s00520-015-2763-0.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Neil SE, Klika RJ, Garland SJ, McKenzie DC, Campbell KL. Cardiorespiratory and neuromuscular deconditioning in fatigued and non-fatigued breast cancer survivors. Support Care Cancer. 2013;21(3):873–81. https://doi.org/10.1007/s00520-012-1600-y.

    Article  PubMed  Google Scholar 

  21. Yavuzsen T, Davis MP, Ranganathan VK, Walsh D, Siemionow V, Kirkova J, et al. Cancer-related fatigue: central or peripheral? J Pain Symptom Manage. 2009;38(4):587–96. https://doi.org/10.1016/j.jpainsymman.2008.12.003.

    Article  PubMed  Google Scholar 

  22. Kilgour RD, Vigano A, Trutschnigg B, Hornby L, Lucar E, Bacon SL, et al. Cancer-related fatigue: the impact of skeletal muscle mass and strength in patients with advanced cancer. J Cachexia Sarcopenia Muscle. 2010;1(2):177–85. https://doi.org/10.1007/s13539-010-0016-0.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Enoka RM, Duchateau J. Translating Fatigue to Human Performance. Med Sci Sports Exerc. 2016;48(11):2228–38. https://doi.org/10.1249/mss.0000000000000929.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kisiel-Sajewicz K, Davis MP, Siemionow V, Seyidova-Khoshknabi D, Wyant A, Walsh D, et al. Lack of muscle contractile property changes at the time of perceived physical exhaustion suggests central mechanisms contributing to early motor task failure in patients with cancer-related fatigue. J Pain Symptom Manage. 2012;44(3):351–61. https://doi.org/10.1016/j.jpainsymman.2011.08.007.

    Article  PubMed  Google Scholar 

  25. Twomey R, Aboodarda SJ, Kruger R, Culos-Reed SN, Temesi J, Millet GY. Neuromuscular fatigue during exercise: Methodological considerations, etiology and potential role in chronic fatigue. Neurophysiol Clin. 2017;47(2):95–110. https://doi.org/10.1016/j.neucli.2017.03.002.

    Article  PubMed  Google Scholar 

  26. Andrykowski MA, Donovan KA, Laronga C, Jacobsen PB. Prevalence, predictors, and characteristics of off-treatment fatigue in breast cancer survivors. Cancer. 2010;116(24):5740–8. https://doi.org/10.1002/cncr.25294.

    Article  PubMed  Google Scholar 

  27. Reinertsen KV, Cvancarova M, Loge JH, Edvardsen H, Wist E, Fosså SD. Predictors and course of chronic fatigue in long-term breast cancer survivors. J Cancer Surviv. 2010;4(4):405–14. https://doi.org/10.1007/s11764-010-0145-7.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Greenberg DB, Gray JL, Mannix CM, Eisenthal S, Carey M. Treatment-related fatigue and serum interleukin-1 levels in patients during external beam irradiation for prostate cancer. J Pain Symptom Manage. 1993;8(4):196–200. https://doi.org/10.1016/0885-3924(93)90127-h.

    Article  CAS  PubMed  Google Scholar 

  29. Lutgendorf SK, Weinrib AZ, Penedo F, Russell D, DeGeest K, Costanzo ES, et al. Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients. J Clin Oncol. 2008;26(29):4820–7. https://doi.org/10.1200/jco.2007.14.1978.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bower JE, Ganz PA, Irwin MR, Kwan L, Breen EC, Cole SW. Inflammation and behavioral symptoms after breast cancer treatment: do fatigue, depression, and sleep disturbance share a common underlying mechanism? J Clin Oncol. 2011;29(26):3517–22. https://doi.org/10.1200/jco.2011.36.1154.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Collado-Hidalgo A, Bower JE, Ganz PA, Cole SW, Irwin MR. Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin Cancer Res. 2006;12(9):2759–66. https://doi.org/10.1158/1078-0432.ccr-05-2398.

    Article  CAS  PubMed  Google Scholar 

  32. Bower JE, Ganz PA, Aziz N, Fahey JL. Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom Med. 2002;64(4):604–11. https://doi.org/10.1097/00006842-200207000-00010.

    Article  PubMed  Google Scholar 

  33. Kisiel-Sajewicz K, Siemionow V, Seyidova-Khoshknabi D, Davis MP, Wyant A, Ranganathan VK, et al. Myoelectrical manifestation of fatigue less prominent in patients with cancer related fatigue. PLoS ONE. 2013;8(12): e83636. https://doi.org/10.1371/journal.pone.0083636.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Twomey R, Martin T, Temesi J, Culos-Reed SN, Millet GY. Tailored exercise interventions to reduce fatigue in cancer survivors: study protocol of a randomized controlled trial. BMC Cancer. 2018;18(1):757. https://doi.org/10.1186/s12885-018-4668-z.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Veni T, Boyas S, Beaune B, Bourgeois H, Rahmani A, Landry S, et al. Handgrip fatiguing exercise can provide objective assessment of cancer-related fatigue: a pilot study. Support Care Cancer. 2019;27(1):229–38. https://doi.org/10.1007/s00520-018-4320-0.

    Article  CAS  PubMed  Google Scholar 

  36. Bower JE. Cancer-related fatigue: links with inflammation in cancer patients and survivors. Brain Behav Immun. 2007;21(7):863–71. https://doi.org/10.1016/j.bbi.2007.03.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Brown LF, Kroenke K. Cancer-related fatigue and its associations with depression and anxiety: a systematic review. Psychosomatics. 2009;50(5):440–7. https://doi.org/10.1176/appi.psy.50.5.440.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Oh HS, Seo WS. Systematic review and meta-analysis of the correlates of cancer-related fatigue. Worldviews Evid Based Nurs. 2011;8(4):191–201. https://doi.org/10.1111/j.1741-6787.2011.00214.x.

    Article  PubMed  Google Scholar 

  39. Bower JE, Ganz PA, Desmond KA, Rowland JH, Meyerowitz BE, Belin TR. Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life. J Clin Oncol. 2000;18(4):743–53. https://doi.org/10.1200/jco.2000.18.4.743.

    Article  CAS  PubMed  Google Scholar 

  40. Mardanian-Dehkordi L, Kahangi L. The Relationship between Perception of Social Support and Fatigue in Patients with Cancer. Iran J Nurs Midwifery Res. 2018;23(4):261–6. https://doi.org/10.4103/ijnmr.IJNMR_63_17.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Karakoç T, Yurtsever S. Relationship between social support and fatigue in geriatric patients receiving outpatient chemotherapy. Eur J Oncol Nurs Soc. 2010;14(1):61–7. https://doi.org/10.1016/j.ejon.2009.07.001.

    Article  Google Scholar 

  42. Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E. Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J Pain Symptom Manage. 1997;13(2):63–74. https://doi.org/10.1016/s0885-3924(96)00274-6.

    Article  CAS  PubMed  Google Scholar 

  43. Van Belle S, Paridaens R, Evers G, Kerger J, Bron D, Foubert J, et al. Comparison of proposed diagnostic criteria with FACT-F and VAS for cancer-related fatigue: proposal for use as a screening tool. Support Care Cancer. 2005;13(4):246–54. https://doi.org/10.1007/s00520-004-0734-y.

    Article  PubMed  Google Scholar 

  44. Cella D, Peterman A, Passik S, Jacobsen P, Breitbart W. Progress toward guidelines for the management of fatigue. Oncology (Williston Park). 1998;12(11A):369–77.

    CAS  Google Scholar 

  45. Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol. 1993;11(3):570–9. https://doi.org/10.1200/jco.1993.11.3.570.

    Article  CAS  PubMed  Google Scholar 

  46. Radloff LS. The CES-D Scale: A Self-Report Depression Scale for Research in the General Population. Appl Psychol Meas. 1977;1(3):385–401. https://doi.org/10.1177/014662167700100306.

    Article  Google Scholar 

  47. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore. 1994;23(2):129–38.

    CAS  PubMed  Google Scholar 

  48. Cutrona CE, Russel D. The provisions of social relationships and adaptation to stress. In: WH J, D P, editors. Adv. Pers. Relationships. Greenwich: JAI Press; 1987. p. 37–67.

  49. Godin G, Shephard RJ. A simple method to assess exercise behavior in the community. Can J Appl Sport Sci. 1985;10(3):141–6.

    CAS  PubMed  Google Scholar 

  50. Beaver WL, Wasserman K, Whipp BJ. A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol (Bethesda, Md: 1985). 1986;60(6):2020–7. https://doi.org/10.1152/jappl.1986.60.6.2020.

    Article  CAS  Google Scholar 

  51. Whipp BJ, Davis JA, Wasserman K. Ventilatory control of the “isocapnic buffering” region in rapidly-incremental exercise. Respir Physiol. 1989;76(3):357–67. https://doi.org/10.1016/0034-5687(89)90076-5.

    Article  CAS  PubMed  Google Scholar 

  52. Doyle-Baker D, Temesi J, Medysky ME, Holash RJ, Millet GY. An Innovative Ergometer to Measure Neuromuscular Fatigue Immediately after Cycling. Med Sci Sports Exerc. 2018;50(2):375–87. https://doi.org/10.1249/mss.0000000000001427.

    Article  PubMed  Google Scholar 

  53. Merton PA. Voluntary strength and fatigue. J Physiol. 1954;123(3):553–64. https://doi.org/10.1113/jphysiol.1954.sp005070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Team RDC. R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna2011

  55. Kowarik A, Templ M. Imputation with the R Package VIM. J Stat Softw. 2016;74(7):1–16.

    Article  Google Scholar 

  56. Tibshirani R. Regression Shrinkage and Selection via the Lasso. J Roy Stat Soc: Ser B (Methodol). 1996;58(1):267–88.

    Google Scholar 

  57. Friedman J, Hastle T, Tibshirani R. Regularization Paths for Generalized Linear Models via Coordinate Descent. J Stat Softw. 2010;33(1):1–22.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Benjamini Y, Hochberg Y. On the Adaptive Control of the False Discovery Rate in Multiple Testing With Independent Statistics. J Educ Behav Stat. 2000;25(1):60–83. https://doi.org/10.3102/10769986025001060.

    Article  Google Scholar 

  59. Cohen J. CHAPTER 1 - The Concepts of Power Analysis. In: Cohen J, editor. Statistical Power Analysis for the Behavioral Sciences. Academic Press; 1977. p. 1–17.

    Google Scholar 

  60. Place N, Millet GY. Quantification of Neuromuscular Fatigue: What Do We Do Wrong and Why? Sports Med (Auckland, NZ). 2020;50(3):439–47. https://doi.org/10.1007/s40279-019-01203-9.

    Article  Google Scholar 

  61. Taul-Madsen L, Dalgas U, Kjølhede T, Hvid LG, Petersen T, Riemenschneider M. A Head-to-Head Comparison of an Isometric and a Concentric Fatigability Protocol and the Association With Fatigue and Walking in Persons With Multiple Sclerosis. Neurorehabil Neural Repair. 2020;34(6):523–32. https://doi.org/10.1177/1545968320920250.

    Article  PubMed  Google Scholar 

  62. Lavigne C, Lau H, Francis G, Culos-Reed SN, Millet GY, Twomey R. Neuromuscular function and fatigability in people diagnosed with head and neck cancer before versus after treatment. Eur J Appl Physiol. 2020;120(6):1289–304. https://doi.org/10.1007/s00421-020-04362-0.

    Article  PubMed  Google Scholar 

  63. Berger AM. Patterns of fatigue and activity and rest during adjuvant breast cancer chemotherapy. Oncol Nurs Forum. 1998;25(1):51–62.

    CAS  PubMed  Google Scholar 

  64. Winters-Stone KM, Bennett JA, Nail L, Schwartz A. Strength, physical activity, and age predict fatigue in older breast cancer survivors. Oncol Nurs Forum. 2008;35(5):815–21. https://doi.org/10.1188/08.onf.815-821.

    Article  PubMed  Google Scholar 

  65. Marcora SM, Bosio A, de Morree HM. Locomotor muscle fatigue increases cardiorespiratory responses and reduces performance during intense cycling exercise independently from metabolic stress. Am J Physiol Regul Integr Comp Physiol. 2008;294(3):R874–83. https://doi.org/10.1152/ajpregu.00678.2007.

    Article  CAS  PubMed  Google Scholar 

  66. Myers J, Kaminsky LA, Lima R, Christle JW, Ashley E, Arena R. A Reference Equation for Normal Standards for VO2 Max: Analysis from the Fitness Registry and the Importance of Exercise National Database (FRIEND Registry). Prog Cardiovasc Dis. 2017;60(1):21–9. https://doi.org/10.1016/j.pcad.2017.03.002.

    Article  PubMed  Google Scholar 

  67. Mitchell SA, Hoffman AJ, Clark JC, DeGennaro RM, Poirier P, Robinson CB, et al. Putting evidence into practice: an update of evidence-based interventions for cancer-related fatigue during and following treatment. Clin J Oncol Nurs. 2014;18(Suppl):38–58. https://doi.org/10.1188/14.cjon.s3.38-58.

    Article  PubMed  Google Scholar 

  68. Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, et al. Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable. Med Sci Sports Exerc. 2019;51(11):2375–90. https://doi.org/10.1249/mss.0000000000002116.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Doyle C, Kushi LH, Byers T, Courneya KS, Demark-Wahnefried W, Grant B, et al. Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices. CA Cancer J Clin. 2006;56(6):323–53. https://doi.org/10.3322/canjclin.56.6.323.

    Article  PubMed  Google Scholar 

  70. Ottenbacher A, Yu M, Moser RP, Phillips SM, Alfano C, Perna FM. Population Estimates of Meeting Strength Training and Aerobic Guidelines, by Gender and Cancer Survivorship Status: Findings From the Health Information National Trends Survey (HINTS). J Phys Act Health. 2015;12(5):675–9. https://doi.org/10.1123/jpah.2014-0003.

    Article  PubMed  Google Scholar 

  71. Courneya KS, Katzmarzyk PT, Bacon E. Physical activity and obesity in Canadian cancer survivors: population-based estimates from the 2005 Canadian Community Health Survey. Cancer. 2008;112(11):2475–82. https://doi.org/10.1002/cncr.23455.

    Article  PubMed  Google Scholar 

  72. Bellizzi KM, Rowland JH, Jeffery DD, McNeel T. Health behaviors of cancer survivors: examining opportunities for cancer control intervention. J Clin Oncol. 2005;23(34):8884–93. https://doi.org/10.1200/jco.2005.02.2343.

    Article  PubMed  Google Scholar 

  73. Bower JE. Cancer-related fatigue–mechanisms, risk factors, and treatments. Nat Rev Clin Oncol. 2014;11(10):597–609. https://doi.org/10.1038/nrclinonc.2014.127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9(1):46–56. https://doi.org/10.1038/nrn2297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Larson SJ, Dunn AJ. Behavioral effects of cytokines. Brain Behav Immun. 2001;15(4):371–87. https://doi.org/10.1006/brbi.2001.0643.

    Article  CAS  PubMed  Google Scholar 

  76. Trudel-Fitzgerald C, Savard J, Ivers H. Which symptoms come first? Exploration of temporal relationships between cancer-related symptoms over an 18-month period. Ann Behav Med. 2013;45(3):329–37. https://doi.org/10.1007/s12160-012-9459-1.

    Article  PubMed  Google Scholar 

  77. Ho SY, Rohan KJ, Parent J, Tager FA, McKinley PS. A longitudinal study of depression, fatigue, and sleep disturbances as a symptom cluster in women with breast cancer. J Pain Symptom Manage. 2015;49(4):707–15. https://doi.org/10.1016/j.jpainsymman.2014.09.009.

    Article  PubMed  Google Scholar 

  78. Ryan JL, Carroll JK, Ryan EP, Mustian KM, Fiscella K, Morrow GR. Mechanisms of cancer-related fatigue. Oncologist. 2007;12(Suppl 1):22–34. https://doi.org/10.1634/theoncologist.12-S1-22.

    Article  CAS  PubMed  Google Scholar 

  79. Visser MR, Smets EM. Fatigue, depression and quality of life in cancer patients: how are they related? Support Care Cancer. 1998;6(2):101–8. https://doi.org/10.1007/s005200050142.

    Article  CAS  PubMed  Google Scholar 

  80. Morrow GR, Hickok JT, Roscoe JA, Raubertas RF, Andrews PL, Flynn PJ, et al. Differential effects of paroxetine on fatigue and depression: a randomized, double-blind trial from the University of Rochester Cancer Center Community Clinical Oncology Program. J Clin Oncol. 2003;21(24):4635–41. https://doi.org/10.1200/jco.2003.04.070.

    Article  CAS  PubMed  Google Scholar 

  81. Tibubos AN, Ernst M, Brähler E, Fischbeck S, Hinz A, Blettner M, et al. Fatigue in survivors of malignant melanoma and its determinants: a register-based cohort study. Support Care Cancer. 2019;27(8):2809–18. https://doi.org/10.1007/s00520-018-4587-1.

    Article  PubMed  Google Scholar 

  82. Goedendorp MM, Gielissen MF, Verhagen CA, Peters ME, Bleijenberg G. Severe fatigue and related factors in cancer patients before the initiation of treatment. Br J Cancer. 2008;99(9):1408–14. https://doi.org/10.1038/sj.bjc.6604739.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bower JE, Ganz PA, Dickerson SS, Petersen L, Aziz N, Fahey JL. Diurnal cortisol rhythm and fatigue in breast cancer survivors. Psychoneuroendocrinology. 2005;30(1):92–100. https://doi.org/10.1016/j.psyneuen.2004.06.003.

    Article  CAS  PubMed  Google Scholar 

  84. Fagundes CP, Murray DM, Hwang BS, Gouin JP, Thayer JF, Sollers JJ 3rd, et al. Sympathetic and parasympathetic activity in cancer-related fatigue: more evidence for a physiological substrate in cancer survivors. Psychoneuroendocrinology. 2011;36(8):1137–47. https://doi.org/10.1016/j.psyneuen.2011.02.005.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Charalambous A, Berger AM, Matthews E, Balachandran DD, Papastavrou E, Palesh O. Cancer-related fatigue and sleep deficiency in cancer care continuum: concepts, assessment, clusters, and management. Support Care Cancer. 2019;27(7):2747–53. https://doi.org/10.1007/s00520-019-04746-9.

    Article  PubMed  Google Scholar 

  86. Fiorentino L, Rissling M, Liu L, Ancoli-Israel S. The Symptom Cluster of Sleep, Fatigue and Depressive Symptoms in Breast Cancer Patients: Severity of the Problem and Treatment Options. Drug Discov Today Dis Model. 2011;8(4):167–73. https://doi.org/10.1016/j.ddmod.2011.05.001.

    Article  Google Scholar 

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Acknowledgements

The authors would like to thank the Canadian Cancer Society for funding the study (grant #704208-1). The authors would also like to acknowledge and sincerely thank Dr. Renata Krüger for her assistance with phlebotomy and the careful storage of blood samples, and Doug Doyle-Baker for his assistance with data collection. Finally, the authors would like to thank the participants—without them, this research would not be possible.

Funding

The study was funded by the Canadian Cancer Society (grant #704208–1).

Author information

Authors and Affiliations

  1. Inter-University Laboratory of Human Movement Biology, Univ Lyon, UJM-Saint-Etienne, 7424, F-42023, Saint-Etienne, EA, France

    Callum G. Brownstein & Guillaume Y. Millet

  2. Faculty of Kinesiology, University of Calgary, Calgary, Canada

    Rosemary Twomey, John Temesi, James G. Wrightson, Tristan Martin, Mary E. Medysky, S. Nicole Culos-Reed & Guillaume Y. Millet

  3. Ohlson Research Initiative, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4Z6, Canada

    Rosemary Twomey

  4. O’Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4Z6, Canada

    Rosemary Twomey

  5. Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, UK

    John Temesi

  6. Department of Clinical Neurosciences, University of Calgary, Calgary, Canada

    James G. Wrightson

  7. Movement-Interactions, Performance, Le Mans University, MIP, 4334, Le Mans, EA, France

    Tristan Martin

  8. Faculty of Sciences and Technologies, Avenue Olivier Messiaen, 72000, Le Mans, France

    Tristan Martin

  9. Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Canada

    S. Nicole Culos-Reed

  10. Institut Universitaire de France (IUF), Paris, France

    Guillaume Y. Millet

  11. Laboratoire Interuniversitaire de Biologie de La Motricité, Bâtiment IRMIS, 10 rue de la Marandière, 42270, Saint Priest en Jarez, France

    Guillaume Y. Millet

Authors
  1. Callum G. Brownstein
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  2. Rosemary Twomey
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  3. John Temesi
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  4. James G. Wrightson
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  5. Tristan Martin
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  6. Mary E. Medysky
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  7. S. Nicole Culos-Reed
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  8. Guillaume Y. Millet
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Contributions

G.Y.M conceived and designed the study; R.T, J.T, T.M and M.M performed experiments; C.G.B, R.T, J.T and J.G.W analysed data; C.G.B, G.Y.M, R.T interpreted results of experiment; C.G.B drafted manuscript; R.T, J.T, J.G.W, T.M, M.M, N.C.R and G.Y.M edited and revised manuscript. C.G.B, R.T, J.T, J.G.W, T.M, M.M, N.C.R and G.Y.M approved final version of manuscript.

Corresponding author

Correspondence to Guillaume Y. Millet.

Ethics declarations

Ethics approval

Approval for all procedures was obtained by the Conjoint Health Research Ethics Board and the Health Research Ethics Board of Alberta Cancer Committee (REB14-0398 and HREBA.CC-16–10-10, respectively). The study was conducted in accordance with all aspects of the Declaration of Helsinki, apart from registration in a database.

Consent to participate

All participants provided written informed consent to take part in the study.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no competing interests.

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Brownstein, C.G., Twomey, R., Temesi, J. et al. Physiological and psychosocial correlates of cancer-related fatigue. J Cancer Surviv 16, 1339–1354 (2022). https://doi.org/10.1007/s11764-021-01115-6

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  • DOI: https://doi.org/10.1007/s11764-021-01115-6

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