Skip to main content

Advertisement

Log in

Prevalence, predictors, and prognostic impact of fatigue among Brazilian outpatients with advanced cancers

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Purposes

The purposes of this study are to evaluate the impact of cancer-related fatigue (CRF) on quality of life (QoL), and to identify its clinical predictors. In addition, the authors investigated the prognostic impact of CRF and its relationship with the inflammatory marker C-reactive protein.

Method

Data regarding patient characteristics, symptom scores, and QoL indices were collected at the initial evaluation. At the same time, blood samples were collected in order to evaluate some laboratorial markers. Patients were followed by telephone interviews every 15 days until death. CRF was defined as ≥66.67 points on EORTC QLQ-C30 fatigue subscale.

Results

The examined patients had a median age of 61 years (range, 21–86 years) and 50.7 % were male. Median Karnofsky performance score (KPS) was 75.5 (SD, 15.1). The prevalence of CRF was 25 % (55 out of 221). Overall, patients with CRF presented higher symptom burden and also worst QoL scores. The following variables were independently associated with CRF: nausea (OR 1.22, p = 0.009), dyspnea (OR 1.33, p = 0.002), KPS (OR 0.96, p = 0.009), body mass index (OR 0.93, p = 0.046), and C-reactive protein (OR 1.08, p = 0.004). The median overall survival (OS) was lower in CRF patients (p < 0.0001). Only KPS (HR = 0.96, p < 0.001) and C-reactive protein (HR = 1.07, p < 0.001) were independent prognostic factors for OS.

Conclusions

Advanced cancer patients (ACP) with CRF had a higher burden of symptoms and impaired QoL. Our findings support the hypothesis that chronic inflammatory state (CIS) could play a role in the pathogenesis of fatigue in ACP. Moreover, CIS seems to have greater prognostic impact than the associated fatigue.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Butt Z, Rosenbloom SK, Abernethy AP, Beaumont JL, Paul D, Hampton D, Jacobsen PB, Syrjala KL, Von Roenn JH, Cella D (2008) Fatigue is the most important symptom for advanced cancer patients who have had chemotherapy. J Natl Compr Canc Netw 6(5):448–455

    PubMed  Google Scholar 

  2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Cancer-Related Fatigue. (2012). http://www.nccn.org/professionals/physician_gls/pdf/fatigue.pdf. Accessed 8 June 2012

  3. Cavalli Kluthcovsky AC, Urbanetz AA, de Carvalho DS, Pereira Maluf EM, Schlickmann Sylvestre GC, Bonatto Hatschbach SB (2012) Fatigue after treatment in breast cancer survivors: prevalence, determinants and impact on health-related quality of life. Support Care Cancer 20(8):1901–1909

    Article  Google Scholar 

  4. Cheng KK, Lee DT (2011) Effects of pain, fatigue, insomnia, and mood disturbance on functional status and quality of life of elderly patients with cancer. Crit Rev Oncol Hematol 78(2):127–137

    Article  PubMed  Google Scholar 

  5. Kawaguchi T, Iwase S, Koinuma M, Onodera Y, Takeuchi H, Umeda M, Matsunaga T, Unezaki S, Nagumo Y (2012) Determinants affecting quality of life: implications for pharmacist counseling for patients with breast cancer in Japan. Biol Pharm Bull 35(1):59–64

    Article  PubMed  CAS  Google Scholar 

  6. Gray NM, Hall SJ, Browne S, Macleod U, Mitchell E, Lee AJ, Johnston M, Wyke S, Samuel L, Weller D, Campbell NC (2011) Modifiable and fixed factors predicting quality of life in people with colorectal cancer. Br J Cancer 104(11):1697–1703

    Article  PubMed  CAS  Google Scholar 

  7. Shi Q, Smith TG, Michonski JD, Stein KD, Kaw C, Cleeland CS (2011) Symptom burden in cancer survivors 1 year after diagnosis: a report from the American Cancer Society’s Studies of Cancer Survivors. Cancer 117(12):2779–2790

    Article  PubMed  Google Scholar 

  8. Scott JA, Lasch KE, Barsevick AM, Piault-Louis E (2011) Patients’ experiences with cancer-related fatigue: a review and synthesis of qualitative research. Oncol Nurs Forum 38(3):E191–E203

    Article  PubMed  Google Scholar 

  9. Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, Johnson DH, Miaskowski C, Scherr SL, Portenoy RK, Vogelzang NJ (2000) Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition. Oncologist 5(5):353–360

    Article  PubMed  CAS  Google Scholar 

  10. Gupta D, Lis CG, Grutsch JF (2007) The relationship between cancer-related fatigue and patient satisfaction with quality of life in cancer. J Pain Symptom Manage 34(1):40–47

    Article  PubMed  Google Scholar 

  11. Vogelzang NJ, Breitbart W, Cella D, Curt GA, Groopman JE, Horning SJ, Itri LM, Johnson DH, Scherr SL, Portenoy RK (1997) Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The Fatigue Coalition Semin Hematol 34(3 Suppl 2):4–12

    CAS  Google Scholar 

  12. Oh HS, Seo WS (2011) Systematic review and meta-analysis of the correlates of cancer-related fatigue. Worldviews Evid Based Nurs 8(4):191–201

    Article  PubMed  Google Scholar 

  13. Bower JE, Ganz PA, Aziz N, Olmstead R, Irwin MR, Cole SW (2007) Inflammatory responses to psychological stress in fatigued breast cancer survivors: relationship to glucocorticoids. Brain Behav Immun 21(3):251–258

    Article  PubMed  CAS  Google Scholar 

  14. Schubert C, Hong S, Natarajan L, Mills PJ, Dimsdale JE (2007) The association between fatigue and inflammatory marker levels in cancer patients: a quantitative review. Brain Behav Immun 21(4):413–427

    Article  PubMed  CAS  Google Scholar 

  15. Jager A, Sleijfer S, van der Rijt CC (2008) The pathogenesis of cancer related fatigue: could increased activity of pro-inflammatory cytokines be the common denominator? Eur J Cancer 44(2):175–181

    Article  PubMed  CAS  Google Scholar 

  16. Bower JE, Ganz PA, Irwin MR, Kwan L, Breen EC, Cole SW (2011) Inflammation and behavioral symptoms after breast cancer treatment: do fatigue, depression, and sleep disturbance share a common underlying mechanism? J Clin Oncol 29(26):3517–3522

    Article  PubMed  Google Scholar 

  17. Bruera E, Kuehn N, Miller MJ, Selmser P, Macmillan K (1991) The Edmonton Symptom Assessment System (ESAS): a simple method for the assessment of palliative care patients. J Palliat Care 7(2):6–9

    PubMed  CAS  Google Scholar 

  18. Chang VT, Hwang SS, Feuerman M (2000) Validation of the Edmonton Symptom Assessment Scale. Cancer 88(9):2164–2171

    Article  PubMed  CAS  Google Scholar 

  19. Franceschini J, Jardim JR, Fernandes AL, Jamnik S, Santoro IL (2010) Reproducibility of the Brazilian Portuguese version of the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire used in conjunction with its lung cancer-specific module. J Bras Pneumol 36(5):595–602

    Article  PubMed  Google Scholar 

  20. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC et al (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85(5):365–376

    Article  PubMed  CAS  Google Scholar 

  21. Minton O, Stone P (2009) A systematic review of the scales used for the measurement of cancer-related fatigue (CRF). Ann Oncol 20(1):17–25

    Article  PubMed  CAS  Google Scholar 

  22. Stone P, Richards M, A’Hern R, Hardy J (2000) A study to investigate the prevalence, severity and correlates of fatigue among patients with cancer in comparison with a control group of volunteers without cancer. Ann Oncol 11(5):561–567

    Article  PubMed  CAS  Google Scholar 

  23. Minton O, Strasser F, Radbruch L, Stone P (2012) Identification of factors associated with fatigue in advanced cancer: a subset analysis of the European palliative care research collaborative computerized symptom assessment data set. J Pain Symptom Manage 43(2):226–235

    Article  PubMed  Google Scholar 

  24. Bower JE, Ganz PA, Desmond KA, Bernaards C, Rowland JH, Meyerowitz BE, Belin TR (2006) Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer 106(4):751–758

    Article  PubMed  Google Scholar 

  25. Hofman M, Ryan JL, Figueroa-Moseley CD, Jean-Pierre P, Morrow GR (2007) Cancer-related fatigue: the scale of the problem. Oncologist 12(Suppl 1):4–10

    Article  PubMed  Google Scholar 

  26. Lawrence DP, Kupelnick B, Miller K, Devine D, Lau J (2004) Evidence report on the occurrence, assessment, and treatment of fatigue in cancer patients. J Natl Cancer Inst Monogr 32:40–50

    Article  PubMed  Google Scholar 

  27. Storey DJ, Waters RA, Hibberd CJ, Rush RW, Cargill AT, Wall LR, Fallon MT, Strong VA, Walker J, Sharpe M (2007) Clinically relevant fatigue in cancer outpatients: the Edinburgh Cancer Centre symptom study. Ann Oncol 18(11):1861–1869

    Article  PubMed  CAS  Google Scholar 

  28. Bruera E (2010) Cancer-related fatigue: a multidimensional syndrome. J Support Oncol 8(4):175–176

    PubMed  Google Scholar 

  29. Barsevick A, Frost M, Zwinderman A, Hall P, Halyard M (2010) I’m so tired: biological and genetic mechanisms of cancer-related fatigue. Qual Life Res 19(10):1419–1427

    Article  PubMed  Google Scholar 

  30. Barbera L, Seow H, Howell D, Sutradhar R, Earle C, Liu Y, Stitt A, Husain A, Sussman J, Dudgeon D (2010) Symptom burden and performance status in a population-based cohort of ambulatory cancer patients. Cancer 116(24):5767–5776

    Article  PubMed  Google Scholar 

  31. Walsh D, Rybicki L (2006) Symptom clustering in advanced cancer. Support Care Cancer 14(8):831–836

    Article  PubMed  Google Scholar 

  32. Tisdale MJ (2002) Cachexia in cancer patients. Nat Rev Cancer 2(11):862–871

    Article  PubMed  CAS  Google Scholar 

  33. Kilgour RD, Vigano A, Trutschnigg B, Hornby L, Lucar E, Bacon SL, Morais JA (2010) Cancer-related fatigue: the impact of skeletal muscle mass and strength in patients with advanced cancer. J Cachexia Sarcopenia Muscle 1(2):177–185

    Article  PubMed  Google Scholar 

  34. Scott HR, McMillan DC, Forrest LM, Brown DJ, McArdle CS, Milroy R (2002) The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer. Br J Cancer 87(3):264–267

    Article  PubMed  CAS  Google Scholar 

  35. Hwang JE, Kim HN, Kim DE, Choi HJ, Jung SH, Shim HJ, Bae WK, Hwang EC, Cho SH, Chung IJ (2011) Prognostic significance of a systemic inflammatory response in patients receiving first-line palliative chemotherapy for recurred or metastatic gastric cancer. BMC Cancer 11:489

    Article  PubMed  CAS  Google Scholar 

  36. Gueron G, De Siervi A, Vazquez E (2012) Advanced prostate cancer: reinforcing the strings between inflammation and the metastatic behavior. Prostate Cancer Prostatic Dis 15(3):213–221

    Article  PubMed  CAS  Google Scholar 

  37. Saligan LN, Kim HS (2012) A systematic review of the association between immunogenomic markers and cancer-related fatigue. Brain Behav Immun 26(6):830–848

    Article  PubMed  CAS  Google Scholar 

  38. Wang XS, Williams LA, Krishnan S, Liao Z, Liu P, Mao L, Shi Q, Mobley GM, Woodruff JF, Cleeland CS (2012) Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing chemoradiation therapy. Brain Behav Immun 26(5):699–705

    Article  PubMed  CAS  Google Scholar 

  39. Zimmerman MA, Selzman CH, Cothren C, Sorensen AC, Raeburn CD, Harken AH (2003) Diagnostic implications of C-reactive protein. Arch Surg 138(2):220–224

    Article  PubMed  Google Scholar 

  40. Orre IJ, Reinertsen KV, Aukrust P, Dahl AA, Fossa SD, Ueland T, Murison R (2011) Higher levels of fatigue are associated with higher CRP levels in disease-free breast cancer survivors. J Psychosom Res 71(3):136–141

    Article  PubMed  Google Scholar 

  41. Alexander S, Minton O, Andrews P, Stone P (2009) A comparison of the characteristics of disease-free breast cancer survivors with or without cancer-related fatigue syndrome. Eur J Cancer 45(3):384–392

    Article  PubMed  CAS  Google Scholar 

  42. Trajkovic-Vidakovic M, de Graeff A, Voest EE, Teunissen SC (2012) Symptoms tell it all: a systematic review of the value of symptom assessment to predict survival in advanced cancer patients. Crit Rev Oncol Hematol 84(1):130–148. doi:10.1016/j.critrevonc.2012.02.011

    Article  PubMed  Google Scholar 

  43. Ehrsson YT, Hellstrom PM, Brismar K, Sharp L, Langius-Eklof A, Laurell G (2010) Explorative study on the predictive value of systematic inflammatory and metabolic markers on weight loss in head and neck cancer patients undergoing radiotherapy. Support Care Cancer 18(11):1385–1391. doi:10.1007/s00520-009-0758-4

    Article  PubMed  Google Scholar 

  44. Wang G, Jiang Z, Zhao K, Li G, Liu F, Pan H, Li J (2012) Immunologic response after laparoscopic colon cancer operation within an enhanced recovery program. J Gastrointest Surg 16(7):1379–1388. doi:10.1007/s11605-012-1880-z

    Article  PubMed  Google Scholar 

  45. Mills PJ, Ancoli-Israel S, Parker B, Natarajan L, Hong S, Jain S, Sadler GR, von Kanel R (2008) Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer. Brain Behav Immun 22(1):98–104

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the Learning and Research Institute of Barretos Cancer Hospital for revising the English text and also the Researcher Support Center of Barretos Cancer Hospital for the help in data collection.

Conflict of interest

The authors have full control over the primary data and agree to allow the journal to review the data if requested. In addition, they declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carlos Eduardo Paiva.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paiva, C.E., Paiva, B.S.R. Prevalence, predictors, and prognostic impact of fatigue among Brazilian outpatients with advanced cancers. Support Care Cancer 21, 1053–1060 (2013). https://doi.org/10.1007/s00520-012-1625-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-012-1625-2

Keywords

Navigation