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Baseline anaemia increases locally advanced rectal cancer mortality in older patients undergoing preoperative chemoradiation

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Abstract

Purpose

The median diagnosis age of rectal cancer (RC) is 70 years old. The standard of care for locally advanced RC (LARC) is preoperative chemoradiation (CRT) followed by surgery. Anaemia is a frequent condition in older patients but is not a pure consequence of ageing.

Methods

The patients aged 65 years or over, with clinical stage II/III LARC, and treated with preoperative concurrent CRT were retrospectively reviewed. Baseline haemoglobin (Hb) levels were collected.

Results

One hundred and seven patients enrolled in this study, but 17 were excluded in relation with treatment disruption. Fifty-seven (63.3%) males and 33 (36.7%) females completed preoperative CRT whose median age at diagnosis was 73. Twenty-five (27.8%) patients presented with anaemia at rectal cancer diagnosis, and median Hb was 13.5 g/dL (IQR = 1.45) and 11.2 g/dL (IQR = 1.35), for non-anaemic and anaemic patients, respectively. For the enrolled older population, only 2 patients reported acute grade 3 toxicity. Baseline anaemia tended to decrease the LARC-free interval and was associated with a significantly higher hazard of all-cause and LARC mortality, approximately 5 times (HR = 5.25; 95% CI 1.48–18.66) and 10 times (HR = 10.09; 95% CI 2.40–42.48), respectively. Patients older than 75 presented a significantly negative impact on overall survival (OS) and LARC-specific survival (HR = 6.20, 95% CI 2.00–19.22; and HR = 7.61, 95% CI 2.08–27.87, respectively). Conversely, no significant impact was found for age-adjusted Charlson comorbidity index on OS, LARC-specific survival and LARC-free interval.

Conclusions

Overall and LARC-specific survival were significantly lower for the baseline anaemic older patients and for those aged 75 years or over.

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References

  1. GLOBOCAN (2018) Estimated number of new cases in 2018, Europe. https://gco.iarc.fr/today/online-analysis-table. Accessed 10.11.2019

  2. Wang SJ, Hathout L, Malhotra U, Maloney-Patel N, Kilic S, Poplin E, Jabbour SK (2018) Decision-making strategy for rectal Cancer management using radiation therapy for elderly or comorbid patients. Int J Radiat Oncol Biol Phys 100(4):926–944. https://doi.org/10.1016/j.ijrobp.2017.12.261

    Article  PubMed  Google Scholar 

  3. Fiscon V, Portale G, Migliorini G, Frigo F (2010) Laparoscopic resection of colorectal cancer in elderly patients. Tumori 96(5):704–708

    Article  Google Scholar 

  4. Ausili Cefaro G, Genovesi D, Vinciguerra A, Augurio A, Di Tommaso M, Marchese R, Borzillo V, Tasciotti L, Taraborrelli M, Innocenti P, Colecchia G, Di Nicola M (2012) Effects of preoperative radiochemotherapy with capecitabine for resectable locally advanced rectal cancer in elderly patients. Tumori 98(5):622–629. https://doi.org/10.1700/1190.13204

    Article  PubMed  Google Scholar 

  5. Jung B, Pahlman L, Johansson R, Nilsson E (2009) Rectal cancer treatment and outcome in the elderly: an audit based on the Swedish Rectal Cancer Registry 1995-2004. BMC Cancer 9:68. https://doi.org/10.1186/1471-2407-9-68

    Article  PubMed  PubMed Central  Google Scholar 

  6. Hathout L, Maloney-Patel N, Malhotra U, Wang SJ, Chokhavatia S, Dalal I, Poplin E, Jabbour SK (2018) Management of locally advanced rectal cancer in the elderly: a critical review and algorithm. J Gastrointest Oncol 9(2):363–376. https://doi.org/10.21037/jgo.2017.10.10

    Article  PubMed  PubMed Central  Google Scholar 

  7. Montroni I, Ugolini G, Saur NM, Spinelli A, Rostoft S, Millan M, Wolthuis A, Daniels IR, Hompes R, Penna M, Furst A, Papamichael D, Desai AM, Cascinu S, Gerard JP, Myint AS, Lemmens V, Berho M, Lawler M, De Liguori CN, Potenti F, Nanni O, Altini M, Beets G, Rutten H, Winchester D, Wexner SD, Audisio RA (2018) Personalized management of elderly patients with rectal cancer: expert recommendations of the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology, and American College of Surgeons Commission on Cancer. Eur J Surg Oncol 44(11):1685–1702. https://doi.org/10.1016/j.ejso.2018.08.003

    Article  PubMed  Google Scholar 

  8. Halawi R, Moukhadder H, Taher A (2017) Anemia in the elderly: a consequence of aging? Expert Rev Hematol 10(4):327–335. https://doi.org/10.1080/17474086.2017.1285695

    Article  CAS  PubMed  Google Scholar 

  9. Väyrynen JP, Tuomisto A, Väyrynen SA, Klintrup K, Karhu T, Mäkelä J, Herzig KH, Karttunen TJ, Mäkinen MJ (2018) Preoperative anemia in colorectal cancer: relationships with tumor characteristics, systemic inflammation, and survival. Sci Rep 8(1):1126. https://doi.org/10.1038/s41598-018-19572-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Smaniotto D, Luzi S, Morganti AG, Cellini N (2000) Prognostic significance of anemia and role of erythropoietin in radiation therapy. Tumori 86(1):17–23

    Article  CAS  Google Scholar 

  11. Horsman MR, Van der Kogel AJ (2009) Therapeutic approaches to tumour hypoxia. In: Joiner MKA (ed) Basic clinical radiobiology, 4th edn. Edward Arnold, London, pp 233–245

    Chapter  Google Scholar 

  12. Charlson M, Szatrowski TP, Peterson J, Gold J (1994) Validation of a combined comorbidity index. J Clin Epidemiol 47(11):1245–1251. https://doi.org/10.1016/0895-4356(94)90129-5

    Article  CAS  PubMed  Google Scholar 

  13. WHO (2011) Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. WHO. https://www.who.int/vmnis/indicators/haemoglobin.pdf. Accessed 09/11/2019

  14. U.S.Department-of-Health-and-Human-Services (2017) Common terminology criteria for adverse events (CTCAE) version 5.0 https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf. Accessed 09/11/2019

  15. Pasetto LM, Friso ML, Pucciarelli S, Basso U, Falci C, Bortolami A, Toppan P, Agostini M, Rugge M, Serpentini S, Nitti D, Monfardini S (2006) Rectal cancer neoadjuvant treatment in elderly patients. Anticancer Res 26(5B):3913–3923

    PubMed  Google Scholar 

  16. Guimas V, Boustani J, Schipman B, Lescut N, Puyraveau M, Bosset JF, Servagi-Vernat S (2016) Preoperative chemoradiotherapy for rectal Cancer in patients aged 75 years and older: acute toxicity, compliance with treatment, and early results. Drugs Aging 33(6):419–425. https://doi.org/10.1007/s40266-016-0367-0

    Article  CAS  PubMed  Google Scholar 

  17. Nishikawa T, Kawai K, Hata K, Emoto S, Murono K, Sasaki K, Tanaka T, Nozawa H, Ishihara S (2019) Clinical outcomes of preoperative chemoradiotherapy in octogenarian with locally advanced rectal cancer. Mol Clin Oncol 11(2):181–188. https://doi.org/10.3892/mco.2019.1873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Correia CMFFV (2016) Análise de sobrevivência ao cancro colo-retal nos períodos 2000–2001 e 2007–2008 na região norte de Portugal. Master’s Degree, Universidade Aberta, Portugal

  19. Liu SL, O'Brien P, Zhao Y, Hopman WM, Lamond N, Ramjeesingh R (2018) Adjuvant treatment in older patients with rectal cancer: a population-based review. Curr Oncol 25(6):e499–e506. https://doi.org/10.3747/co.25.4102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. McGrane JM, Humes DJ, Acheson AG, Minear F, Wheeler JMD, Walter CJ (2017) Significance of anemia in outcomes after neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Clin Colorectal Cancer 16(4):381–385. https://doi.org/10.1016/j.clcc.2017.03.016

    Article  PubMed  Google Scholar 

  21. Lee H, Park HC, Park W, Choi DH, Kim YI, Park YS, Park JO, Chun HK, Lee WY, Kim HC, Yun SH, Cho YB, Park YA (2012) Negative impact of pretreatment anemia on local control after neoadjuvant chemoradiotherapy and surgery for rectal cancer. Radiat Oncol J 30(3):117–123. https://doi.org/10.3857/roj.2012.30.3.117

    Article  PubMed  PubMed Central  Google Scholar 

  22. McSorley ST, Johnstone M, Steele CW, Roxburgh CSD, Horgan PG, McMillan DC, Mansouri D (2019) Normocytic anaemia is associated with systemic inflammation and poorer survival in patients with colorectal cancer treated with curative intent. Int J Color Dis 34(3):401–408. https://doi.org/10.1007/s00384-018-3211-7

    Article  Google Scholar 

  23. Tian Y, Jian Z, Xu B, Liu H (2017) Age-adjusted Charlson comorbidity index score as predictor of survival of patients with digestive system cancer who have undergone surgical resection. Oncotarget 8(45):79453–79461. https://doi.org/10.18632/oncotarget.18401

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kostek O, Bozkaya Y, Hacioglu MB, Yildirim Ozdemir N, Yilmaz E, Demircan NC, Erdogan B, Uzunoglu S, Cicin I, Zengin N (2019) Is the Charlson comorbidity index a prognostic Indicator for toxicity and mortality in elderly patients with locally advanced rectal cancer? Arch Iran Med 22(5):236–241

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiotherapy, Centro Hospitalar Universitário de São João, E.P.E., 4200–319, Porto, Portugal

    Darlene Rodrigues, Fátima Aires & Margarida Marques

  2. Department of Medical Oncology, Centro Hospitalar Universitário de São João, E.P.E., 4200–319, Porto, Portugal

    Joana Simões, Catarina Fernandes, Cármen Rey & Cristina Sarmento

  3. Departamento de Estudo de Populações, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Porto, Portugal

    Laetitia Teixeira

  4. CINTESIS, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313, Porto, Portugal

    Laetitia Teixeira

  5. EPIUnit Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, n° 135, 4050-600, Porto, Portugal

    Laetitia Teixeira

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  1. Darlene Rodrigues
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  4. Fátima Aires
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  8. Margarida Marques
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Darlene Rodrigues, Joana Simões and Laetitia Teixeira. The first draft of the manuscript was written by Darlene Rodrigues, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Darlene Rodrigues.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the Ethics Committee of the Centro Hospitalar Universitário de São João, E.P.E. (reference number: 204/19).

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Formal consent was not required as the article was based on the Radiotherapy Department’s electronic health records.

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Rodrigues, D., Simões, J., Teixeira, L. et al. Baseline anaemia increases locally advanced rectal cancer mortality in older patients undergoing preoperative chemoradiation. Support Care Cancer 29, 1403–1411 (2021). https://doi.org/10.1007/s00520-020-05618-3

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  • DOI: https://doi.org/10.1007/s00520-020-05618-3

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