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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Effect of surgery and radiotherapy on complete blood count, lymphocyte subsets and inflammatory response in patients with advanced oral cancer

Authors: Tadej Dovšak, Alojz Ihan, Vojko Didanovič, Andrej Kansky, Miha Verdenik, Nataša Ihan Hren

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

The immune system has a known role in the aetiology, progression and final treatment outcome of oral squamous cell cancers. The aim of this study was to evaluate the influence of radical surgery and radiotherapy on advanced oral squamous cell carcinoma blood counts, lymphocyte subsets and levels of acute inflammatory response markers.

Methods

Blood samples were obtained from 56 patients 5 days before and 10 days after surgery, 30 days and 1 year after radiotherapy. The whole blood count, lymphocyte subsets and inflammatory response markers (C-reactive protein, erythrocyte sedimentation rate, leukocyte count, expression of index CD64 and index CD163 on neutrophils and monocytes) were measured, statistically analysed and correlated with clinical treatment outcomes.

Results

The post-operative period was characterised by the onset of anaemia, thrombocytosis, lymphopenia with reduced B lymphocyte, T helper cell and NK cell counts, and a rise in acute phase reactants. Immediately after radiotherapy, the anaemia improved, the lymphopenia worsened, and thrombocyte levels returned to pre-treatment values. There was a drop in counts across the T and B cell lines, including a reduction in B lymphocytes, naïve and memory T cells with reduced CD4+ and CD8+ counts and a decreased CD4/CD8 ratio. One year after radiotherapy all the lymphocyte subsets remained depressed, the only exception being NK cells, whose levels returned to pre-treatment values.

Conclusions

We concluded that surgery resulted in a stronger acute phase response than radiotherapy, while radiotherapy caused a long-lasting reduction in lymphocyte counts. There was no correlation between any of the pre-treatment parameters and the clinical outcome.
Literature
1.
2.
go back to reference Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4-5):309–16.CrossRefPubMed Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4-5):309–16.CrossRefPubMed
3.
go back to reference Amit M, Yen TC, Liao CT, Chaturvedi P, Agarwal JP, Kowalski LP, Ebrahimi A, Clark JR, Kreppel M, Zoller J, et al. Improvement in survival of patients with oral cavity squamous cell carcinoma: an international collaborative study. Cancer. 2013;119(24):4242–8.CrossRefPubMed Amit M, Yen TC, Liao CT, Chaturvedi P, Agarwal JP, Kowalski LP, Ebrahimi A, Clark JR, Kreppel M, Zoller J, et al. Improvement in survival of patients with oral cavity squamous cell carcinoma: an international collaborative study. Cancer. 2013;119(24):4242–8.CrossRefPubMed
5.
go back to reference Lee JJ, Lin CL, Chen THH, Kok SH, Chang MC, Jeng JH. Changes in peripheral blood lymphocyte phenotypes distribution in patients with oral cancer/oral leukoplakia in Taiwan. Int J Oral Maxillofac Surg. 2010;39(8):806–14.CrossRefPubMed Lee JJ, Lin CL, Chen THH, Kok SH, Chang MC, Jeng JH. Changes in peripheral blood lymphocyte phenotypes distribution in patients with oral cancer/oral leukoplakia in Taiwan. Int J Oral Maxillofac Surg. 2010;39(8):806–14.CrossRefPubMed
6.
go back to reference Gildener-Leapman N, Ferris RL, Bauman JE. Promising systemic immunotherapies in head and neck squamous cell carcinoma. Oral Oncol. 2013;49(12):1089–96.CrossRefPubMedPubMedCentral Gildener-Leapman N, Ferris RL, Bauman JE. Promising systemic immunotherapies in head and neck squamous cell carcinoma. Oral Oncol. 2013;49(12):1089–96.CrossRefPubMedPubMedCentral
7.
go back to reference Badoual C, Sandoval F, Pere H, Hans S, Gey A, Merillon N, Van Ryswick C, Quintin-Colonna F, Bruneval P, Brasnu D, et al. Better understanding tumor-host interaction in head and neck cancer to improve the design and development of immunotherapeutic strategies. Head Neck. 2010;32(7):946–58.PubMed Badoual C, Sandoval F, Pere H, Hans S, Gey A, Merillon N, Van Ryswick C, Quintin-Colonna F, Bruneval P, Brasnu D, et al. Better understanding tumor-host interaction in head and neck cancer to improve the design and development of immunotherapeutic strategies. Head Neck. 2010;32(7):946–58.PubMed
8.
9.
go back to reference Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL. Imbalance in absolute counts of T lymphocyte subsets in patients with head and neck cancer and its relation to disease. Adv Otorhinolaryngol. 2005;62:161–72.PubMed Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL. Imbalance in absolute counts of T lymphocyte subsets in patients with head and neck cancer and its relation to disease. Adv Otorhinolaryngol. 2005;62:161–72.PubMed
10.
go back to reference Greenfeld K, Avraham R, Benish M, Goldfarb Y, Rosenne E, Shapira Y, Rudich T, Ben-Eliyahu S. Immune suppression while awaiting surgery and following it: dissociations between plasma cytokine levels, their induced production, and NK cell cytotoxicity. Brain Behav Immun. 2007;21(4):503–13.CrossRefPubMed Greenfeld K, Avraham R, Benish M, Goldfarb Y, Rosenne E, Shapira Y, Rudich T, Ben-Eliyahu S. Immune suppression while awaiting surgery and following it: dissociations between plasma cytokine levels, their induced production, and NK cell cytotoxicity. Brain Behav Immun. 2007;21(4):503–13.CrossRefPubMed
11.
go back to reference Purdy J, Klein E. External photon beam dosimetry and treatment planning. Princ Pract Radiat Ther. 1997;3:308–12. Purdy J, Klein E. External photon beam dosimetry and treatment planning. Princ Pract Radiat Ther. 1997;3:308–12.
12.
go back to reference Verastegui EL, Morales RB, Barrera-Franco JL, Poitevin AC, Hadden J. Long-term immune dysfunction after radiotherapy to the head and neck area. Int Immunopharmacol. 2003;3(8):1093–104.CrossRefPubMed Verastegui EL, Morales RB, Barrera-Franco JL, Poitevin AC, Hadden J. Long-term immune dysfunction after radiotherapy to the head and neck area. Int Immunopharmacol. 2003;3(8):1093–104.CrossRefPubMed
13.
go back to reference Dovšak T, Ihan A, Didanovič V, Kansky A, Hren N. Influence of surgical treatment and radiotherapy of the advanced intraoral cancers on complete blood count, body mass index, liver enzymes and leukocyte CD64 expression. Radiol Oncol. 2009;43(4):282–92. Dovšak T, Ihan A, Didanovič V, Kansky A, Hren N. Influence of surgical treatment and radiotherapy of the advanced intraoral cancers on complete blood count, body mass index, liver enzymes and leukocyte CD64 expression. Radiol Oncol. 2009;43(4):282–92.
14.
go back to reference Neeman E, Ben-Eliyahu S. Surgery and stress promote cancer metastasis: new outlooks on perioperative mediating mechanisms and immune involvement. Brain Behav Immun. 2013;30(Suppl):S32–40.CrossRefPubMed Neeman E, Ben-Eliyahu S. Surgery and stress promote cancer metastasis: new outlooks on perioperative mediating mechanisms and immune involvement. Brain Behav Immun. 2013;30(Suppl):S32–40.CrossRefPubMed
15.
go back to reference Omura K. Current status of oral cancer treatment strategies: surgical treatments for oral squamous cell carcinoma. Int J Clin Oncol. 2014;19(3):423–30.CrossRefPubMed Omura K. Current status of oral cancer treatment strategies: surgical treatments for oral squamous cell carcinoma. Int J Clin Oncol. 2014;19(3):423–30.CrossRefPubMed
16.
go back to reference Scott SN, Boeve TJ, McCulloch TM, Fitzpatrick KA, Karnell LH. The effects of Epoetin alfa on transfusion requirements in head and neck cancer patients: a prospective, randomized, placebo-controlled study. Laryngoscope. 2002;112(7):1221–9.CrossRefPubMed Scott SN, Boeve TJ, McCulloch TM, Fitzpatrick KA, Karnell LH. The effects of Epoetin alfa on transfusion requirements in head and neck cancer patients: a prospective, randomized, placebo-controlled study. Laryngoscope. 2002;112(7):1221–9.CrossRefPubMed
17.
go back to reference Grau C, Overgaard J. Significance of hemoglobin concentration for treatment outcome. In: Molls M. Vaupel P, editors. Blood perfusion and microenviroment of human tumors. Berlin: Springer; 1998. p. 101–112. Grau C, Overgaard J. Significance of hemoglobin concentration for treatment outcome. In: Molls M. Vaupel P, editors. Blood perfusion and microenviroment of human tumors. Berlin: Springer; 1998. p. 101–112.
18.
go back to reference Leaver HA, Craig SR, Yap PL, Walker WS. Lymphocyte responses following open and minimally invasive thoracic surgery. Eur J Clin Investig. 2000;30(3):230–8.CrossRef Leaver HA, Craig SR, Yap PL, Walker WS. Lymphocyte responses following open and minimally invasive thoracic surgery. Eur J Clin Investig. 2000;30(3):230–8.CrossRef
19.
go back to reference Brigden ML. Clinical utility of the erythrocyte sedimentation rate. Am Fam Physician. 1999;60(5):1443–50.PubMed Brigden ML. Clinical utility of the erythrocyte sedimentation rate. Am Fam Physician. 1999;60(5):1443–50.PubMed
20.
go back to reference Giannoudis PV, Smith MR, Evans RT, Bellamy MC, Guillou PJ. Serum CRP and IL-6 levels after trauma: not predictive of septic complications in 31 patients. Acta Orthop Scand. 1998;69(2):184–8.CrossRefPubMed Giannoudis PV, Smith MR, Evans RT, Bellamy MC, Guillou PJ. Serum CRP and IL-6 levels after trauma: not predictive of septic complications in 31 patients. Acta Orthop Scand. 1998;69(2):184–8.CrossRefPubMed
21.
go back to reference Khandavilli SD, Ceallaigh PO, Lloyd CJ, Whitaker R. Serum C-reactive protein as a prognostic indicator in patients with oral squamous cell carcinoma. Oral Oncol. 2009;45(10):912–4.CrossRefPubMed Khandavilli SD, Ceallaigh PO, Lloyd CJ, Whitaker R. Serum C-reactive protein as a prognostic indicator in patients with oral squamous cell carcinoma. Oral Oncol. 2009;45(10):912–4.CrossRefPubMed
22.
23.
go back to reference Mohammed FF, Poon I, Zhang L, Elliott L, Hodson ID, Sagar SM, Wright J. Acute-phase response reactants as objective biomarkers of radiation-induced mucositis in head and neck cancer. Head Neck. 2012;34(7):985–93.CrossRefPubMed Mohammed FF, Poon I, Zhang L, Elliott L, Hodson ID, Sagar SM, Wright J. Acute-phase response reactants as objective biomarkers of radiation-induced mucositis in head and neck cancer. Head Neck. 2012;34(7):985–93.CrossRefPubMed
24.
go back to reference Chethana RPS, Madathil LP, Rao S, Shetty P, Patidar M. Quantitative analysis of acute phase proteins in post chemo-radiation mucositis. J Clin Diagn Res. 2015;9(10):Zc28–31.PubMedPubMedCentral Chethana RPS, Madathil LP, Rao S, Shetty P, Patidar M. Quantitative analysis of acute phase proteins in post chemo-radiation mucositis. J Clin Diagn Res. 2015;9(10):Zc28–31.PubMedPubMedCentral
25.
go back to reference Qureshi S, Lewis S, Gant V, Treacher D, Davis B, Brown K. Increased distribution and expression of CD64 on blood polymorphonuclear cells from patients with the systemic inflammatory response syndrome (SIRS). Clin Exp Immunol. 2001;125(2):258–65.CrossRefPubMedPubMedCentral Qureshi S, Lewis S, Gant V, Treacher D, Davis B, Brown K. Increased distribution and expression of CD64 on blood polymorphonuclear cells from patients with the systemic inflammatory response syndrome (SIRS). Clin Exp Immunol. 2001;125(2):258–65.CrossRefPubMedPubMedCentral
26.
go back to reference Zuwała-Jagiełło J. Haemoglobin scavenger receptor: function in relation to disease. Acta Biochim Pol. 2005;53(2):257–68. Zuwała-Jagiełło J. Haemoglobin scavenger receptor: function in relation to disease. Acta Biochim Pol. 2005;53(2):257–68.
27.
go back to reference Fjaertoft G, Douhan Håkansson L, Pauksens K, Sisask G, Venge P. Neutrophil CD64 (FcγRI) expression is a specific marker of bacterial infection: a study on the kinetics and the impact of major surgery. Scand J Infect Dis. 2007;39(6-7):525–35.CrossRefPubMed Fjaertoft G, Douhan Håkansson L, Pauksens K, Sisask G, Venge P. Neutrophil CD64 (FcγRI) expression is a specific marker of bacterial infection: a study on the kinetics and the impact of major surgery. Scand J Infect Dis. 2007;39(6-7):525–35.CrossRefPubMed
28.
go back to reference Olkowski ZL, Wilkins SA Jr. T-lymphocyte levels in the peripheral blood of patients with cancer of the head and neck. Am J Surg. 1975;130(4):440–4.CrossRefPubMed Olkowski ZL, Wilkins SA Jr. T-lymphocyte levels in the peripheral blood of patients with cancer of the head and neck. Am J Surg. 1975;130(4):440–4.CrossRefPubMed
29.
go back to reference Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL. Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck. Clin Cancer Res. 2004;10(11):3755–62.CrossRefPubMed Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL. Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck. Clin Cancer Res. 2004;10(11):3755–62.CrossRefPubMed
30.
go back to reference Ogawa K, Hirai M, Katsube T, Murayama M, Hamaguchi K, Shimakawa T, Naritake Y, Hosokawa T, Kajiwara T. Suppression of cellular immunity by surgical stress. Surgery. 2000;127(3):329–36.CrossRefPubMed Ogawa K, Hirai M, Katsube T, Murayama M, Hamaguchi K, Shimakawa T, Naritake Y, Hosokawa T, Kajiwara T. Suppression of cellular immunity by surgical stress. Surgery. 2000;127(3):329–36.CrossRefPubMed
31.
go back to reference Graboyes EM, Garrett-Mayer E, Sharma AK, Lentsch EJ, Day TA. Adherence to National Comprehensive Cancer Network guidelines for time to initiation of postoperative radiation therapy for patients with head and neck cancer. Cancer. 2017;123(14):2651–60.CrossRefPubMed Graboyes EM, Garrett-Mayer E, Sharma AK, Lentsch EJ, Day TA. Adherence to National Comprehensive Cancer Network guidelines for time to initiation of postoperative radiation therapy for patients with head and neck cancer. Cancer. 2017;123(14):2651–60.CrossRefPubMed
33.
go back to reference Kuss I, Donnenberg AD, Gooding W, Whiteside TL. Effector CD8+CD45RO-CD27-T cells have signalling defects in patients with squamous cell carcinoma of the head and neck. Br J Cancer. 2003;88(2):223–30.CrossRefPubMedPubMedCentral Kuss I, Donnenberg AD, Gooding W, Whiteside TL. Effector CD8+CD45RO-CD27-T cells have signalling defects in patients with squamous cell carcinoma of the head and neck. Br J Cancer. 2003;88(2):223–30.CrossRefPubMedPubMedCentral
34.
go back to reference Caserta S, Kleczkowska J, Mondino A, Zamoyska R. Reduced functional avidity promotes central and effector memory CD4 T cell responses to tumor-associated antigens. J Immunol. 2010;185(11):6545–54.CrossRefPubMed Caserta S, Kleczkowska J, Mondino A, Zamoyska R. Reduced functional avidity promotes central and effector memory CD4 T cell responses to tumor-associated antigens. J Immunol. 2010;185(11):6545–54.CrossRefPubMed
35.
36.
go back to reference Tabi Z, Spary LK, Coleman S, Clayton A, Mason MD, Staffurth J. Resistance of CD45RA- T cells to apoptosis and functional impairment, and activation of tumor-antigen specific T cells during radiation therapy of prostate cancer. J Immunol. 2010;185(2):1330–9.CrossRefPubMed Tabi Z, Spary LK, Coleman S, Clayton A, Mason MD, Staffurth J. Resistance of CD45RA- T cells to apoptosis and functional impairment, and activation of tumor-antigen specific T cells during radiation therapy of prostate cancer. J Immunol. 2010;185(2):1330–9.CrossRefPubMed
37.
go back to reference Brown JS, Blackburn TK, Woolgar JA, Lowe D, Errington RD, Vaughan ED, Rogers SN. A comparison of outcomes for patients with oral squamous cell carcinoma at intermediate risk of recurrence treated by surgery alone or with post-operative radiotherapy. Oral Oncol. 2007;43(8):764–73.CrossRefPubMed Brown JS, Blackburn TK, Woolgar JA, Lowe D, Errington RD, Vaughan ED, Rogers SN. A comparison of outcomes for patients with oral squamous cell carcinoma at intermediate risk of recurrence treated by surgery alone or with post-operative radiotherapy. Oral Oncol. 2007;43(8):764–73.CrossRefPubMed
38.
go back to reference Uchida K, Veeramachaneni R, Huey B, Bhattacharya A, Schmidt BL, Albertson DG. Investigation of HOXA9 promoter methylation as a biomarker to distinguish oral cancer patients at low risk of neck metastasis. BMC Cancer. 2014;14:353.CrossRefPubMedPubMedCentral Uchida K, Veeramachaneni R, Huey B, Bhattacharya A, Schmidt BL, Albertson DG. Investigation of HOXA9 promoter methylation as a biomarker to distinguish oral cancer patients at low risk of neck metastasis. BMC Cancer. 2014;14:353.CrossRefPubMedPubMedCentral
39.
go back to reference Kissun D, Magennis P, Lowe D, Brown JS, Vaughan ED, Rogers SN. Timing and presentation of recurrent oral and oropharyngeal squamous cell carcinoma and awareness in the outpatient clinic. Br J Oral Maxillofac Surg. 2006;44(5):371–6.CrossRefPubMed Kissun D, Magennis P, Lowe D, Brown JS, Vaughan ED, Rogers SN. Timing and presentation of recurrent oral and oropharyngeal squamous cell carcinoma and awareness in the outpatient clinic. Br J Oral Maxillofac Surg. 2006;44(5):371–6.CrossRefPubMed
40.
go back to reference Fang HY, Huang XY, Chien HT, Chang JT, Liao CT, Huang JJ, Wei FC, Wang HM, Chen IH, Kang CJ, et al. Refining the role of preoperative C-reactive protein by neutrophil/lymphocyte ratio in oral cavity squamous cell carcinoma. Laryngoscope. 2013;123(11):2690–9.CrossRefPubMed Fang HY, Huang XY, Chien HT, Chang JT, Liao CT, Huang JJ, Wei FC, Wang HM, Chen IH, Kang CJ, et al. Refining the role of preoperative C-reactive protein by neutrophil/lymphocyte ratio in oral cavity squamous cell carcinoma. Laryngoscope. 2013;123(11):2690–9.CrossRefPubMed
41.
go back to reference Bobdey S, Ganesh B, Mishra P, Jain A. Role of monocyte count and neutrophil-to-lymphocyte ratio in survival of oral cancer patients. Int Arch Otorhinolaryngol. 2017;21(1):21–7.PubMed Bobdey S, Ganesh B, Mishra P, Jain A. Role of monocyte count and neutrophil-to-lymphocyte ratio in survival of oral cancer patients. Int Arch Otorhinolaryngol. 2017;21(1):21–7.PubMed
42.
go back to reference Lu CC, Chang KW, Chou FC, Cheng CY, Liu CJ. Association of pretreatment thrombocytosis with disease progression and survival in oral squamous cell carcinoma. Oral Oncol. 2007;43(3):283–8.CrossRefPubMed Lu CC, Chang KW, Chou FC, Cheng CY, Liu CJ. Association of pretreatment thrombocytosis with disease progression and survival in oral squamous cell carcinoma. Oral Oncol. 2007;43(3):283–8.CrossRefPubMed
Metadata
Title
Effect of surgery and radiotherapy on complete blood count, lymphocyte subsets and inflammatory response in patients with advanced oral cancer
Authors
Tadej Dovšak
Alojz Ihan
Vojko Didanovič
Andrej Kansky
Miha Verdenik
Nataša Ihan Hren
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4136-9

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