Skip to main content

Advertisement

SpringerLink
Log in

Neoadjuvant chemoradiotherapy of rectal carcinoma

Baseline hematologic parameters influencing outcomes

Neoadjuvante Radiochemotherapie bei Rektumkarzinom

Einfluss hämatologischer Ausgangswerte auf den Therapieerfolg

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Background

The link between the blood count and a systemic inflammatory response (SIR) is indisputable and well described. Pretreatment hematological parameters may predict the overall clinical outcomes in many types of cancer. Thus, this study aims to systematically evaluate the relationship between baseline blood count levels and treatment response in rectal cancer patients treated with neoadjuvant chemoradiotherapy.

Patients and methods

From 2009–2015, 173 patients with locally advanced rectal cancer were retrospectively enrolled in the study and analyzed. The baseline blood count was recorded in all patients 1 week before chemoradiation. Tumor response was evaluated through pathologic findings. Blood count levels which included RBC (red blood cells), Hb (hemoglobin), PLT (platelet count), neutrophil count, WBC (white blood cells), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio) were analyzed in relation to tumor downstaging, pCR (pathologic complete response), OS (overall survival), and DFS (disease-free survival).

Results

Hb levels were associated with a response in logistic regression analysis: pCR (p = 0.05; OR 1.04, 95 % CI 1.00–1.07); T downstaging (p = 0.006; OR 1.03, 95 % CI 1.01–1.05); N downstaging (p = 0.09; OR 1.02, 95 % CI 1.00–1.04); T or N downstaging (p = 0.007; OR 1.04, 95 % CI 1.01–1.07); T and N downstaging (p = 0.02; OR 1.02, 95 % CI 1.00–1.04); Hb and RBC were the most significant parameters influencing OS; PLT was a negative prognostic factor for OS and DFS (p = 0.008 for OS); an NLR value of 2.8 was associated with the greatest significance for OS (p = 0.03) and primary tumor downstaging (p = 0.02).

Conclusion

Knowledge of pretreatment hematological parameters appears to be an important prognostic factor in patients with rectal carcinoma.

Zusammenfassung

Hintergrund

Die Verbindung zwischen dem Blutbild und der systemischen Entzündungsreaktion („systemic inflammatory response“, SIR) ist unbestreitbar und gut beschrieben. Aufgrund der prätherapeutischen Blutparameter ist bei vielen Krebsarten das klinische Gesamtergebnis nach Therapie möglicherweise voraussagbar. Ziel dieser Studie ist die systematische Bewertung der Beziehung zwischen den Ausgangswerten im Blutbild und dem Therapieerfolg bei Patienten mit Rektumkarzinom, die präoperativ mit Radiochemotherapie behandelt wurden.

Patienten und Methoden

Zwischen den Jahren 2009 und 2015 wurden die Daten von insgesamt 173 Patienten mit lokal fortgeschrittenem Rektumkarzinom retrospektiv analysiert. Das Ausgangsblutbild wurde bei allen Patienten eine Woche vor dem Beginn der Radiochemotherapie erstellt. Die Tumorantwort wurde anhand der pathologischen Veränderungen ermittelt. Die zellulären Blutbestandteile wie Erythrozyten („red blood cells“, RBC), Leukozyten („white blood cells“, WBC), Thrombozyten („platelets“, PLT) und weitere Parameter wie Hämoglobin (Hb), der Neutrophilen-Lymphozyten-Quotient („neutrophil-to-lymphocyte ratio“, NLR) und der Thrombozyten-Lymphozyten-Quotient („platelet-to-lymphocyte ratio“, PLR) wurden im Zusammenhang mit Tumor-Downstaging, pathologisch kompletter Remission („pathologic complete response“, pCR), dem Gesamtüberleben („overall survival“, OS) und rezidivfreiem Überleben („disease-free survival“, DFS) analysiert.

Ergebnisse

Der Hb-Wert und das Ansprechen auf die Therapie wurde anhand der logistischen Regressionsanalyse in einen Zusammenhang gestellt: pCR (p = 0,05; OR: 1,04; 95 %-KI: 1,00–1,07); T‑Downstaging (p = 0,006; OR: 1,03; 95 %-KI: 1,01–1,05); N‑Downstaging (p = 0,09; OR: 1,02; 95 %-KI: 1,00–1,04); T‑ oder N‑Downstaging (p = 0,007; OR: 1,04; 95 %-KI: 1,01–1,07); T‑ und N‑Downstaging (p = 0,02; OR: 1,02; 95 %-KI: 1,00–1,04); Hämoglobin und RBC waren die Parameter mit dem stärksten Einfluss auf das OS; die Thrombozytenzahl war ein negativer prognostischer Faktor für das OS und DFS (p = 0,008 für OS); ein NLR-Wert von 2,8 wies die größte Signifikanz für das OS (p = 0,03) und ein Tumor-Downstaging des primären Tumors auf (p = 0,02).

Schlussfolgerungen

Die Kenntnis der prätherapeutischen hämatologischen Parameter scheint einen wichtigen prognostischen Faktor für Patienten mit Rektumkarzinom darzustellen.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–545

    Article  CAS  PubMed  Google Scholar 

  2. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454(7203):436–444

    Article  CAS  PubMed  Google Scholar 

  3. McMillan DC (2009) Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care 12(3):223–226

    Article  PubMed  Google Scholar 

  4. American College of Chest Physicians, Society of Critical Care Medicine (1992) American college of chest physicians/society of critical care medicine consensus conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20(6):864–874

    Article  Google Scholar 

  5. Roxburgh CS, McMillan DC (2010) Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol 6(1):149–163

    Article  CAS  PubMed  Google Scholar 

  6. McMillan DC (2013) The systemic inflammation-based Glasgow prognostic score: a decade of experience in patients with cancer. Cancer Treat Rev 39(5):534–540

    Article  PubMed  Google Scholar 

  7. Choi KW, Hong SW, Chang YG, Lee WY, Lee B, Paik IW, Lee H (2014) Inflammation-based score (Glasgow prognostic score) as an independent prognostic factor in colorectal cancer patients. Ann Surg Treat Res 86(6):309–313

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lee SD, Park JW, Park KS, Lim SB, Chang HJ, Kim DY, Jeong SY, Choi HS, Oh JH (2009) Influence of anemia on tumor response to preoperative chemoradiotherapy for locally advanced rectal cancer. Int J Colorectal Dis 24(12):1451–1458

    Article  PubMed  Google Scholar 

  9. Carruthers R, Tho LM, Brown J, Kakumanu S, McCartney E, McDonald AC (2012) Systemic inflammatory response is a predictor of outcome in patients undergoing preoperative chemoradiation for locally advanced rectal cancer. Colorectal Dis 14(10):e701–707

    Article  CAS  PubMed  Google Scholar 

  10. Kawai K, Kitayama J, Tsuno NH, Sunami E, Watanabe T (2013) Thrombocytosis before pre-operative chemoradiotherapy predicts poor response and shorter local recurrence-free survival in rectal cancer. Int J Colorectal Dis 28(4):527–535

    Article  PubMed  Google Scholar 

  11. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Terzic J, Grivennikov S, Karin E, Karin M (2010) Inflammation and colon cancer. Gastroenterology 138(6):2101–2114

    Article  CAS  PubMed  Google Scholar 

  13. Pernot S, Terme M, Voron T, Colussi O, Marcheteau E, Tartour E, Taieb J (2014) Colorectal cancer and immunity: what we know and perspectives. World J Gastroenterol 20(14):3738–3750

    Article  PubMed  PubMed Central  Google Scholar 

  14. Proctor MJ, McMillan DC, Morrison DS, Fletcher CD, Horgan PG, Clarke SJ (2012) A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Br J Cancer 107(4):695–699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocana A, Leibowitz-Amit R, Sonpavde G, Knox JJ, Tran B, Tannock IF, Amir E (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106(6):dju124

    Article  PubMed  Google Scholar 

  16. Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ (2013) The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol 88(1):218–230

    Article  PubMed  Google Scholar 

  17. Dvorak J, Sitorova V, Ryska A, Sirak I, Richter I, Hatlova J, Ferko A, Melichar B, Petera J (2012) Prognostic significance of changes of tumor epidermal growth factor receptor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma. Strahlenther Onkol 188(9):833–838

    Article  CAS  PubMed  Google Scholar 

  18. Kumar P (2000) Impact of anemia in patients with head and neck cancer. Oncologist 5(Suppl 2):13–18

    Article  Google Scholar 

  19. Grogan M, Thomas GM, Melamed I, Wong FL, Pearcey RG, Joseph PK, Portelance L, Crook J, Jones KD (1999) The importance of hemoglobin levels during radiotherapy for carcinoma of the cervix. Cancer 86(8):1528–1536

    Article  CAS  PubMed  Google Scholar 

  20. Khan AA, Klonizakis M, Shabaan A, Glynne-Jones R (2013) Association between pretreatment haemoglobin levels and morphometric characteristics of the tumour, response to neoadjuvant treatment and long-term outcomes in patients with locally advanced rectal cancers. Colorectal Dis 15(10):1232–1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang F, Cheng F, Cao L, Wang S, Zhou W, Ma W (2014) A retrospective study: the prevalence and prognostic value of anemia in patients undergoing radiotherapy for esophageal squamous cell carcinoma. World J Surg Oncol 12:244

    Article  PubMed  PubMed Central  Google Scholar 

  22. Park SH, Lee J, Lee SH, Park JO, Kim K, Kim WS, Jung CW, Park YS, Kang WK, Park K, Kim S, Bang SM, Cho EK, Shin DB, Lee JH (2006) Anemia is the strongest prognostic factor for outcomes of 5‑fluorouracil-based first-line chemotherapy in patients with advanced gastric cancer. Cancer Chemother Pharmacol 57(1):91–96

    Article  CAS  PubMed  Google Scholar 

  23. Dunst J (2004) Management of anemia in patients undergoing curative radiotherapy. Erythropoietin, transfusions, or better nothing? Strahlenther Onkol 180(11):671–681

    Article  PubMed  Google Scholar 

  24. Hoff CM (2012) Importance of hemoglobin concentration and its modification for the outcome of head and neck cancer patients treated with radiotherapy. Acta Oncol (Madr) 51(4):419–432

    Article  CAS  Google Scholar 

  25. Smyth SS, McEver RP, Weyrich AS, Morrell CN, Hoffman MR, Arepally GM, French PA, Dauerman HL, Becker RC, Platelet Colloquium Participants (2009) Platelet functions beyond hemostasis. J Thromb Haemost 7(11):1759–1766

    Article  CAS  PubMed  Google Scholar 

  26. Bambace NM, Holmes CE (2011) The platelet contribution to cancer progression. J Thromb Haemost 9(2):237–249

    Article  CAS  PubMed  Google Scholar 

  27. Sasaki K, Kawai K, Tsuno NH, Sunami E, Kitayama J (2012) Impact of preoperative thrombocytosis on the survival of patients with primary colorectal cancer. World J Surg 36(1):192–200

    Article  PubMed  Google Scholar 

  28. Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, Dong J, Cheng JW, Liu ZW, Ma L, Lv Y (2014) Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer 134(10):2403–2413

    Article  CAS  PubMed  Google Scholar 

  29. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313(5795):1960–1964

    Article  CAS  PubMed  Google Scholar 

  30. Kadota K, Nitadori J, Ujiie H, Buitrago DH, Woo KM, Sima CS, Travis WD, Jones DR, Adusumilli PS (2015) Prognostic impact of immune microenvironment in lung squamous cell carcinoma: tumor-infiltrating CD10+ neutrophil/CD20+ lymphocyte ratio as an independent prognostic factor. J Thorac Oncol 10(9):1301–1310

    Article  CAS  PubMed  Google Scholar 

  31. Wang J, Jia Y, Wang N, Zhang X, Tan B, Zhang G, Cheng Y (2014) The clinical significance of tumor-infiltrating neutrophils and neutrophil-to-CD8+ lymphocyte ratio in patients with resectable esophageal squamous cell carcinoma. J Transl Med 12:7

    Article  PubMed  PubMed Central  Google Scholar 

  32. Malietzis G, Giacometti M, Kennedy RH, Athanasiou T, Aziz O, Jenkins JT (2014) The emerging role of neutrophil to lymphocyte ratio in determining colorectal cancer treatment outcomes: a systematic review and meta-analysis. Ann Surg Oncol 21(12):3938–3946

    Article  PubMed  Google Scholar 

  33. Shen L, Zhang H, Liang L, Li G, Fan M, Wu Y, Zhu J, Zhang Z (2014) Baseline neutrophil-lymphocyte ratio (≥2.8) as a prognostic factor for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation. Radiat Oncol 9:295

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kitayama J, Yasuda K, Kawai K, Sunami E, Nagawa H (2010) Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer. Radiat Oncol 5:47

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by Charles University Faculty of Medicine in Hradec Králové grant PRVOUK [PRVOUK-P 37/06].

Author information

Authors and Affiliations

  1. Department of Oncology and Radiotherapy, University Hospital in Hradec Králové, Sokolská 581, 500 05, Hradec Králové, Czech Republic

    Miroslav Hodek M.D., Igor Sirák M.D., Ph.D., Petr Paluska M.Sc., Jindřich Kopecký M.D., Ph.D.,  Jiří Petera M.D., Ph.D. & Milan Vošmik M.D., Ph.D.

  2. Department of Surgery, University Hospital in Hradec Králové, Hradec Králové, Czech Republic

    Alexander Ferko M.D., Ph.D. & Július Örhalmi M.D.

  3. Fingerland Department of Pathology, University Hospital in Hradec Králové, Hradec Králové, Czech Republic

    Eva Hovorková M.D. & Dimitar Hadži Nikolov M.D., Ph.D.

Authors
  1. Miroslav Hodek M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Igor Sirák M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander Ferko M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Július Örhalmi M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eva Hovorková M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dimitar Hadži Nikolov M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Petr Paluska M.Sc.
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jindřich Kopecký M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jiří Petera M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Milan Vošmik M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Miroslav Hodek M.D..

Ethics declarations

Conflict of interest

M. Hodek, I. Sirák, A. Ferko, J. Orhalmi, E. Hovorková, D. Hadži Nikolov, P. Paluska, J. Kopecký, J. Petera, and M. Vošmik state that there are no conflicts of interest.

The accompanying manuscript does not include studies on humans or animals.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hodek, M., Sirák, I., Ferko, A. et al. Neoadjuvant chemoradiotherapy of rectal carcinoma. Strahlenther Onkol 192, 632–640 (2016). https://doi.org/10.1007/s00066-016-0988-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-016-0988-6

Keywords

Schlüsselwörter

Search

Navigation