Iron Deficiency Anemia Coexists with Cancer Related Anemia and Adversely Impacts Quality of Life
Giridhar Kanuri, Ritica Sawhney, Jeeva Varghese, Madonna Britto, Arun Shet, Giridhar Kanuri, Ritica Sawhney, Jeeva Varghese, Madonna Britto, Arun Shet
Abstract
Cancer related anemia (CRA) adversely affects patient Quality of Life (QoL) and overall survival. We prospectively studied the prevalence, etiology and the impact of anemia on QoL in 218 Indian cancer patients attending a tertiary referral hospital. The study used the sTfR/log Ferritin index to detect iron deficiency anemia and assessed patient QoL using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) tool, standardized for language. Mean patient age was 51±13 years and 60% were female. The prevalence of cancer related anemia in this setting was 64% (n = 139). As expected, plasma ferritin did not differ significantly between anemic (n = 121) and non-anemic cancer patients (n = 73). In contrast, plasma sTfR levels were significantly higher in anemic cancer patients compared to non-anemic cancer patients (31 nmol/L vs. 24 nmol/L, p = 0.002). Among anemic cancer patients, using the sTfR/log Ferritin index, we found that 60% (n = 83) had iron deficiency anemia (IDA). Interestingly, plasma sTfR levels were significantly higher in cancer patients with CRA+IDA (n = 83) compared with patients having CRA (n = 38) alone (39 nmol/L vs. 20 nmol/L, p<0.001). There was a significant linear correlation between Hb and QoL (Spearman ρ = 0.21; p = 0.001) and multivariate regression analysis revealed that every gram rise in Hb was accompanied by a 3.1 unit increase in the QoL score (95% CI = 0.19-5.33; p = 0.003). The high prevalence of anemia in cancer patients, a major portion of which is due to iron deficiency anemia, the availability of sensitive and specific biomarkers of iron status to detect IDA superimposed on anemia of inflammation, suggests an urgent need to diagnose and treat such patients. Despite the potential negative consequences of increasing metabolically available plasma iron in cancer, our clinical data suggest that detecting and treating IDA in anemic cancer patients will have important consequences to their QoL and overall survival. Clinical trials of iron therapy in these patients will be able to demonstrate the potential for benefit or harm.
Conflict of interest statement
The authors declare they have no competing interests.
Figures
![Fig 1. Schematic representation of the study…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5040456/bin/pone.0163817.g001.jpg)
![Fig 2. Ferritin, sTfR levels in cancer…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5040456/bin/pone.0163817.g002.jpg)
Fig 3. Correlation analysis as well as…
Fig 3. Correlation analysis as well as FACT An scores in anemic and non-anemic cancer…
- Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.Skikne BS, Punnonen K, Caldron PH, Bennett MT, Rehu M, Gasior GH, Chamberlin JS, Sullivan LA, Bray KR, Southwick PC. Skikne BS, et al. Am J Hematol. 2011 Nov;86(11):923-7. doi: 10.1002/ajh.22108. Epub 2011 Aug 2. Am J Hematol. 2011. PMID: 21812017 Clinical Trial.
- Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants.Mupfudze TG, Stoltzfus RJ, Rukobo S, Moulton LH, Humphrey JH, Prendergast AJ; SHINE Trial Team; Jones AD, Manges A, Mangwadu G, Maluccio JA, Mbuya MN, Ntozini R, Tielsch JM. Mupfudze TG, et al. PLoS One. 2015 Aug 7;10(8):e0135227. doi: 10.1371/journal.pone.0135227. eCollection 2015. PLoS One. 2015. PMID: 26252205 Free PMC article.
- Diagnostic significance of serum soluble transferrin receptors in various anemic diseases: the first multi-institutional joint study in Japan.Matsuda A, Bessho M, Mori S, Takeuchi T, Abe T, Yawata Y, Mori H, Omine M, Nakamura Y, Furusawa S, Maeda T, Haginosita S, Hirasawa Y, Kinugasa E, Akizawa T, Kawakami N, Nagata A, Hirashima K. Matsuda A, et al. Haematologia (Budap). 2002;32(3):225-38. doi: 10.1163/15685590260461048. Haematologia (Budap). 2002. PMID: 12611483
- Biomarkers for Assessing and Managing Iron Deficiency Anemia in Late-Stage Chronic Kidney Disease [Internet].Chung M, Moorthy D, Hadar N, Salvi P, Iovin RC, Lau J. Chung M, et al. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Oct. Report No.: 12(13)-EHC140-EF. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Oct. Report No.: 12(13)-EHC140-EF. PMID: 23230575 Free Books & Documents. Review.
- Management of Anemia in Patients with Inflammatory Bowel Disease (IBD).Patel D, Trivedi C, Khan N. Patel D, et al. Curr Treat Options Gastroenterol. 2018 Mar;16(1):112-128. doi: 10.1007/s11938-018-0174-2. Curr Treat Options Gastroenterol. 2018. PMID: 29404920 Review.
- How to diagnose iron deficiency in chronic disease: A review of current methods and potential marker for the outcome.Rohr M, Brandenburg V, Brunner-La Rocca HP. Rohr M, et al. Eur J Med Res. 2023 Jan 9;28(1):15. doi: 10.1186/s40001-022-00922-6. Eur J Med Res. 2023. PMID: 36617559 Free PMC article. Review.
- Prognostic Value of Serum Transferrin Analysis in Patients with Ovarian Cancer and Cancer-Related Functional Iron Deficiency: A Retrospective Case-Control Study.Ivanova TI, Klabukov ID, Krikunova LI, Poluektova MV, Sychenkova NI, Khorokhorina VA, Vorobyev NV, Gaas MY, Baranovskii DS, Goryainova OS, Sachko AM, Shegay PV, Kaprin AD, Tillib SV. Ivanova TI, et al. J Clin Med. 2022 Dec 12;11(24):7377. doi: 10.3390/jcm11247377. J Clin Med. 2022. PMID: 36555993 Free PMC article.
- Iron Deficiency Anemia: Efficacy and Limitations of Nutritional and Comprehensive Mitigation Strategies.Kumar SB, Arnipalli SR, Mehta P, Carrau S, Ziouzenkova O. Kumar SB, et al. Nutrients. 2022 Jul 20;14(14):2976. doi: 10.3390/nu14142976. Nutrients. 2022. PMID: 35889932 Free PMC article. Review.
- Underdiagnosis of iron deficiency anemia among patients with colorectal cancer: an examination of electronic medical records.Bhurosy T, Jishan A, Boland PM, Lee YH, Heckman CJ. Bhurosy T, et al. BMC Cancer. 2022 Apr 21;22(1):435. doi: 10.1186/s12885-022-09542-z. BMC Cancer. 2022. PMID: 35449093 Free PMC article.
- Anemia requiring transfusion in breast cancer patients on dose-dense chemotherapy: Prevalence, risk factors, cost and effect on disease outcome.Sharma P, Georgy JT, Andrews AG, John AO, Joel A, Chacko RT, Premkumar PS, Singh A. Sharma P, et al. Support Care Cancer. 2022 Jun;30(6):5519-5526. doi: 10.1007/s00520-022-06970-2. Epub 2022 Mar 21. Support Care Cancer. 2022. PMID: 35314996 Free PMC article.
-
- Ludwig H, Van Belle S, Barrett-Lee P, Birgegard G, Bokemeyer C, Gascon P, et al. The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. European journal of cancer. 2004;40(15):2293–306. 10.1016/j.ejca.2004.06.019 . - DOI - PubMed
-
- Tchekmedyian NS. Anemia in cancer patients: significance, epidemiology, and current therapy. Oncology (Williston Park). 2002;16(9 Suppl 10):17–24. . - PubMed
-
- Caro JJ, Salas M, Ward A, Goss G. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer. 2001;91(12):2214–21. . - PubMed
- Full Text Sources
- Other Literature Sources
- Medical
- Research Materials
![Fig 3. Correlation analysis as well as…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5040456/bin/pone.0163817.g003.jpg)
References
- Ludwig H, Van Belle S, Barrett-Lee P, Birgegard G, Bokemeyer C, Gascon P, et al. The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. European journal of cancer. 2004;40(15):2293–306. 10.1016/j.ejca.2004.06.019 .
- Birgegard G, Aapro MS, Bokemeyer C, Dicato M, Drings P, Hornedo J, et al. Cancer-related anemia: pathogenesis, prevalence and treatment. Oncology. 2005;68 Suppl 1:3–11. 10.1159/000083128 .
- Tchekmedyian NS. Anemia in cancer patients: significance, epidemiology, and current therapy. Oncology (Williston Park). 2002;16(9 Suppl 10):17–24. .
- Caro JJ, Salas M, Ward A, Goss G. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer. 2001;91(12):2214–21. .
- Mercadante S, Gebbia V, Marrazzo A, Filosto S. Anaemia in cancer: pathophysiology and treatment. Cancer treatment reviews. 2000;26(4):303–11. 10.1053/ctrv.2000.0181 .
- Glaspy J. The impact of epoetin alfa on quality of life during cancer chemotherapy: a fresh look at an old problem. Seminars in hematology. 1997;34(3 Suppl 2):20–6. .
- Demetri GD, Kris M, Wade J, Degos L, Cella D. Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: results from a prospective community oncology study. Procrit Study Group. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 1998;16(10):3412–25. .
- Cella D. Factors influencing quality of life in cancer patients: anemia and fatigue. Seminars in oncology. 1998;25(3 Suppl 7):43–6. .
- Ludwig H, Strasser K. Symptomatology of anemia. Seminars in oncology. 2001;28(2 Suppl 8):7–14. .
- Grotto HZ. Anaemia of cancer: an overview of mechanisms involved in its pathogenesis. Medical oncology. 2008;25(1):12–21. 10.1007/s12032-007-9000-8 .
- Verdon F, Burnand B, Stubi CL, Bonard C, Graff M, Michaud A, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. Bmj. 2003;326(7399):1124 10.1136/bmj.326.7399.1124 .
- George John SS, Akhila Lakshmikantha, Arun Shet, editor Distribution of cancer anemia and its treatment in a limited resource setting. NCRI Cancer Conferences; 2010; Liverpool.
- WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity Vitamin and Mineral Nutrition Information System. World Health Organization; 2011;(WHO/NMH/NHD/MNM/11.1)
- Skikne BS, Punnonen K, Caldron PH, Bennett MT, Rehu M, Gasior GH, et al. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index. American journal of hematology. 2011;86(11):923–7. 10.1002/ajh.22108 .
- Steegmann JL, Sanchez Torres JM, Colomer R, Vaz A, Lopez J, Jalon I, et al. Prevalence and management of anaemia in patients with non-myeloid cancer undergoing systemic therapy: a Spanish survey. Clinical & translational oncology: official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2013;15(6):477–83. 10.1007/s12094-012-0953-5 .
- Merlini L, Carteni G, Iacobelli S, Stelitano C, Airoldi M, Balcke P, et al. Anemia prevalence and treatment practice in patients with non-myeloid tumors receiving chemotherapy. Cancer management and research. 2013;5:205–14. 10.2147/CMAR.S45236 .
- Verbeke N, Beguin Y, Wildiers H, Canon JL, Bries G, Bosly A, et al. High prevalence of anaemia and limited use of therapy in cancer patients: a Belgian survey (Anaemia Day 2008). Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer. 2012;20(1):23–8. 10.1007/s00520-010-1045-0 .
- Seshadri T, Prince HM, Bell DR, Coughlin PB, James PP, Richardson GE, et al. The Australian Cancer Anaemia Survey: a snapshot of anaemia in adult patients with cancer. The Medical journal of Australia. 2005;182(9):453–7. .
- Kitano T, Tada H, Nishimura T, Teramukai S, Kanai M, Nishimura T, et al. Prevalence and incidence of anemia in Japanese cancer patients receiving outpatient chemotherapy. International journal of hematology. 2007;86(1):37–41. 10.1532/IJH97.07040 .
- Parikh PM BA. Cancer related Anemia—Guidelines for Developing Countries. Parikh PM BA, editor. Mumbai: Elsevier; 2005.
- India TNFHSN-o. The National Family Health Survey (NFHS-4) of India. 2015–16.
- Aapro M, Osterborg A, Gascon P, Ludwig H, Beguin Y. Prevalence and management of cancer-related anaemia, iron deficiency and the specific role of i.v. iron. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO. 2012;23(8):1954–62. 10.1093/annonc/mds112 .
- Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood. 2010;116(23):4754–61. 10.1182/blood-2010-05-286260 .
- Weiss G, Goodnough LT. Anemia of chronic disease. The New England journal of medicine. 2005;352(10):1011–23. 10.1056/NEJMra041809 .
- Punnonen K, Irjala K, Rajamaki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood. 1997;89(3):1052–7..
- Margetic S, Topic E, Ruzic DF, Kvaternik M. Soluble transferrin receptor and transferrin receptor-ferritin index in iron deficiency anemia and anemia in rheumatoid arthritis. Clinical chemistry and laboratory medicine: CCLM / FESCC. 2005;43(3):326–31. 10.1515/CCLM.2005.056 .
- Thomas C, Thomas L. Anemia of chronic disease: pathophysiology and laboratory diagnosis. Laboratory hematology: official publication of the International Society for Laboratory Hematology. 2005;11(1):14–23. 10.1532/LH96.04049 .
- Zubrikhina GN, Blindar VN, Matveeva II. [Differential diagnosis of anemia in true and functional iron deficiency in patients with chronic diseases (malignant tumors)]. Terapevticheskii arkhiv. 2016;88(4):61–7. .
- Lind M, Vernon C, Cruickshank D, Wilkinson P, Littlewood T, Stuart N, et al. The level of haemoglobin in anaemic cancer patients correlates positively with quality of life. British journal of cancer. 2002;86(8):1243–9. 10.1038/sj.bjc.6600247 .
- Crawford J, Cella D, Cleeland CS, Cremieux PY, Demetri GD, Sarokhan BJ, et al. Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin alfa therapy. Cancer. 2002;95(4):888–95. 10.1002/cncr.10763 .
- Auerbach M, Ballard H, Trout JR, McIlwain M, Ackerman A, Bahrain H, et al. Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2004;22(7):1301–7. 10.1200/JCO.2004.08.119 .
- Wasada I, Eguchi H, Kurita M, Kudo S, Shishida T, Mishima Y, et al. Anemia affects the quality of life of Japanese cancer patients. The Tokai journal of experimental and clinical medicine. 2013;38(1):7–11. .
- Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. The New England journal of medicine. 2009;361(25):2436–48. 10.1056/NEJMoa0908355 .
- Pinnix ZK, Miller LD, Wang W, D'Agostino R Jr, Kute T, Willingham MC, et al. Ferroportin and iron regulation in breast cancer progression and prognosis. Science translational medicine. 2010;2(43):43ra56 10.1126/scisignal.3001127 .
Source: PubMed