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Published in: Journal of Gastrointestinal Cancer 3/2019

01-09-2019 | Original Research

Hematologic Markers of Lung Metastasis in Stage IV Colorectal Cancer

Authors: Mohammad Abu-Shawer, Osama Abu-Shawer, Mamoun Souleiman, Mohammad Akkawi, Osama Alshakhatreh, Tamer Altamimi, Amal Al-Omari, Maysa Al-Hussaini

Published in: Journal of Gastrointestinal Cancer | Issue 3/2019

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Abstract

Background

Many studies showed an association between absolute neutrophil count (ANC), absolute monocyte count (AMC), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) with poor overall survival (OS) in patients with cancer. However, only a few studies were conducted to further investigate this association in colorectal cancer (CRC).

Methods

Clinical data from 299 stage IV CRC patients treated at King Hussein Cancer Center from 2004 to 2012 have been retrospectively reviewed. We examined the association between ANC, AMC, MLR, PLR, and NLR with lung metastasis in stage IV CRC. Receiver Operating Characteristic (ROC) curve analysis was operated to determine the optimal NLR cutoff value. Univariate and multivariate analysis were performed.

Results

The ROC value of 3.4 was determined as the cutoff value of NLR to study the association. Univariate and multivariate analysis showed that patients with high baseline NLR (≥ 3.4) had more baseline lung metastasis than patients with low NLR (< 3.4) (p = 0.0001, p = 0.0151, respectively). Also, baseline NLR correlated significantly with the presence of lymphovascular invasion (p = 0.001). In patients with no baseline lung metastasis, high post-treatment NLR was associated with consequent development of lung metastasis (p = 0.0227). Other markers including ANC, AMC, MLR, and PLR were significantly associated with lung metastasis at time of diagnosis (p = 0.0006, p = 0.0006, p = 0.0187, and p = 0.001, respectively).

Conclusion

Results are suggesting that different hematologic markers obtained from a cheap test (CBC) could potentially be used to predict the likelihood of lung metastasis in stage IV CRC. Prospective studies are needed to further assess the immune cells’ role in tumor metastasis promotion.
Literature
6.
go back to reference Nagasaki T, Akiyoshi T, Fujimoto Y, Konishi T, Nagayama S, Fukunaga Y, Ueno M Prognostic impact of neutrophil-to-lymphocyte ratio in patients with advanced low rectal cancer treated with preoperative chemoradiotherapy. Dig Surg 2015;32(6):496–503. Epub 2015/11/07. https://doi.org/10.1159/000441396. PubMed. Nagasaki T, Akiyoshi T, Fujimoto Y, Konishi T, Nagayama S, Fukunaga Y, Ueno M Prognostic impact of neutrophil-to-lymphocyte ratio in patients with advanced low rectal cancer treated with preoperative chemoradiotherapy. Dig Surg 2015;32(6):496–503. Epub 2015/11/07. https://​doi.​org/​10.​1159/​000441396. PubMed.
7.
go back to reference Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, Dong J, Cheng JW, Liu ZW, Ma L, Lv Y Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer 2014;134(10):2403–2413. Epub 2014/01/29. https://doi.org/10.1002/ijc.28536. PubMed. Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, Dong J, Cheng JW, Liu ZW, Ma L, Lv Y Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer 2014;134(10):2403–2413. Epub 2014/01/29. https://​doi.​org/​10.​1002/​ijc.​28536. PubMed.
10.
go back to reference Liu H, Liu G, Bao Q, Sun W, Bao H, Bi L, Wen W, Liu Y, Wang Z, Yin X, Bai Y, Hu X The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in rectal carcinoma. J Gastrointest Cancer 2010;41(2):116–120. https://doi.org/10.1007/s12029-009-9125-4. PubMed. Liu H, Liu G, Bao Q, Sun W, Bao H, Bi L, Wen W, Liu Y, Wang Z, Yin X, Bai Y, Hu X The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in rectal carcinoma. J Gastrointest Cancer 2010;41(2):116–120. https://​doi.​org/​10.​1007/​s12029-009-9125-4. PubMed.
11.
go back to reference Gondo T, Nakashima J, Ohno Y, Choichiro O, Horiguchi Y, Namiki K, Yoshioka K, Ohori M, Hatano T, Tachibana M Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology 2012;79(5):1085–1091. Epub 2012/03/23. https://doi.org/10.1016/j.urology.2011.11.070. PubMed. Gondo T, Nakashima J, Ohno Y, Choichiro O, Horiguchi Y, Namiki K, Yoshioka K, Ohori M, Hatano T, Tachibana M Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology 2012;79(5):1085–1091. Epub 2012/03/23. https://​doi.​org/​10.​1016/​j.​urology.​2011.​11.​070. PubMed.
12.
go back to reference Stotz M, Gerger A, Eisner F, Szkandera J, Loibner H, Ress AL, et al. Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer. Br J Cancer. 2013;109(2):416–21. Epub 2013/06/25. https://doi.org/10.1038/bjc.2013.332. PubMed PMID: 23799847; PubMed Central PMCID: PMCPMC3721392. Stotz M, Gerger A, Eisner F, Szkandera J, Loibner H, Ress AL, et al. Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer. Br J Cancer. 2013;109(2):416–21. Epub 2013/06/25. https://​doi.​org/​10.​1038/​bjc.​2013.​332. PubMed PMID: 23799847; PubMed Central PMCID: PMCPMC3721392.
13.
14.
go back to reference Szkandera J, Absenger G, Liegl-Atzwanger B, Pichler M, Stotz M, Samonigg H, et al. Elevated preoperative neutrophil/lymphocyte ratio is associated with poor prognosis in soft-tissue sarcoma patients. Br J Cancer. 2013;108(8):1677–83. Epub 2013/04/04. https://doi.org/10.1038/bjc.2013.135. PubMed PMID: 23558897; PubMed Central PMCID: PMCPMC3668478. Szkandera J, Absenger G, Liegl-Atzwanger B, Pichler M, Stotz M, Samonigg H, et al. Elevated preoperative neutrophil/lymphocyte ratio is associated with poor prognosis in soft-tissue sarcoma patients. Br J Cancer. 2013;108(8):1677–83. Epub 2013/04/04. https://​doi.​org/​10.​1038/​bjc.​2013.​135. PubMed PMID: 23558897; PubMed Central PMCID: PMCPMC3668478.
15.
go back to reference Ying HQ, Deng QW, He BS, Pan YQ, Wang F, Sun HL, Chen J, Liu X, Wang SK The prognostic value of preoperative NLR, d-NLR, PLR and LMR for predicting clinical outcome in surgical colorectal cancer patients. Med Oncol 2014;31(12):305. Epub 2014/10/30. https://doi.org/10.1007/s12032-014-0305-0. PubMed. Ying HQ, Deng QW, He BS, Pan YQ, Wang F, Sun HL, Chen J, Liu X, Wang SK The prognostic value of preoperative NLR, d-NLR, PLR and LMR for predicting clinical outcome in surgical colorectal cancer patients. Med Oncol 2014;31(12):305. Epub 2014/10/30. https://​doi.​org/​10.​1007/​s12032-014-0305-0. PubMed.
16.
go back to reference Koh YW, Choi JH, Ahn MS, Choi YW, Lee HW. Baseline neutrophil-lymphocyte ratio is associated with baseline and subsequent presence of brain metastases in advanced non-small-cell lung cancer. Sci Rep. 2016;6:38585. Epub 2016/12/07. https://doi.org/10.1038/srep38585. PubMed PMID: 27924837; PubMed Central PMCID: PMCPMC5141478. Koh YW, Choi JH, Ahn MS, Choi YW, Lee HW. Baseline neutrophil-lymphocyte ratio is associated with baseline and subsequent presence of brain metastases in advanced non-small-cell lung cancer. Sci Rep. 2016;6:38585. Epub 2016/12/07. https://​doi.​org/​10.​1038/​srep38585. PubMed PMID: 27924837; PubMed Central PMCID: PMCPMC5141478.
18.
go back to reference van der Geest LG, Lam-Boer J, Koopman M, Verhoef C, Elferink MA, de Wilt JH. Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases. Clin Exp Metastasis 2015;32(5):457–465. Epub 2015/04/22. https://doi.org/10.1007/s10585-015-9719-0. PubMed. van der Geest LG, Lam-Boer J, Koopman M, Verhoef C, Elferink MA, de Wilt JH. Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases. Clin Exp Metastasis 2015;32(5):457–465. Epub 2015/04/22. https://​doi.​org/​10.​1007/​s10585-015-9719-0. PubMed.
19.
go back to reference Noone AM, Cronin KA, Altekruse SF, Howlader N, Lewis DR, Petkov VI, et al. Cancer incidence and survival trends by subtype using data from the Surveillance Epidemiology and End Results Program, 1992–2013. Cancer Epidemiol Biomarkers Prev. 2017;26(4):632–41. Epub 2016/12/12. https://doi.org/10.1158/1055-9965.EPI-16-0520. PubMed PMID: 27956436; PubMed Central PMCID: PMCPMC5380602. Noone AM, Cronin KA, Altekruse SF, Howlader N, Lewis DR, Petkov VI, et al. Cancer incidence and survival trends by subtype using data from the Surveillance Epidemiology and End Results Program, 1992–2013. Cancer Epidemiol Biomarkers Prev. 2017;26(4):632–41. Epub 2016/12/12. https://​doi.​org/​10.​1158/​1055-9965.​EPI-16-0520. PubMed PMID: 27956436; PubMed Central PMCID: PMCPMC5380602.
27.
go back to reference Yuan A, Chen JJ, Yang PC. Pathophysiology of tumor-associated macrophages. Adv Clin Chem 2008;45:199–223. PubMed. Yuan A, Chen JJ, Yang PC. Pathophysiology of tumor-associated macrophages. Adv Clin Chem 2008;45:199–223. PubMed.
28.
go back to reference Kitayama J, Yasuda K, Kawai K, Sunami E, Nagawa H. Circulating lymphocyte is an important determinant of the effectiveness of preoperative radiotherapy in advanced rectal cancer. BMC Cancer. 2011;11:64. Epub 2011/02/10. https://doi.org/10.1186/1471-2407-11-64. PubMed PMID: 21306650; PubMed Central PMCID: PMCPMC3041780. Kitayama J, Yasuda K, Kawai K, Sunami E, Nagawa H. Circulating lymphocyte is an important determinant of the effectiveness of preoperative radiotherapy in advanced rectal cancer. BMC Cancer. 2011;11:64. Epub 2011/02/10. https://​doi.​org/​10.​1186/​1471-2407-11-64. PubMed PMID: 21306650; PubMed Central PMCID: PMCPMC3041780.
31.
go back to reference Ogino S, Nosho K, Irahara N, Meyerhardt JA, Baba Y, Shima K, et al. Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. Clin Cancer Res. 2009;15(20):6412–20. Epub 2009/10/13. https://doi.org/10.1158/1078-0432.CCR-09-1438. PubMed PMID: 19825961; PubMed Central PMCID: PMCPMC2771425. Ogino S, Nosho K, Irahara N, Meyerhardt JA, Baba Y, Shima K, et al. Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. Clin Cancer Res. 2009;15(20):6412–20. Epub 2009/10/13. https://​doi.​org/​10.​1158/​1078-0432.​CCR-09-1438. PubMed PMID: 19825961; PubMed Central PMCID: PMCPMC2771425.
32.
go back to reference Templeton AJ, Knox JJ, Lin X, Simantov R, Xie W, Lawrence N, Broom R, Fay AP, Rini B, Donskov F, Bjarnason GA, Smoragiewicz M, Kollmannsberger C, Kanesvaran R, Alimohamed N, Hermanns T, Wells JC, Amir E, Choueiri TK, Heng DYC Change in neutrophil-to-lymphocyte ratio in response to targeted therapy for metastatic renal cell carcinoma as a prognosticator and biomarker of efficacy. Eur Urol 2016;70(2):358–364. Epub 2016/02/28. https://doi.org/10.1016/j.eururo.2016.02.033. PubMed. Templeton AJ, Knox JJ, Lin X, Simantov R, Xie W, Lawrence N, Broom R, Fay AP, Rini B, Donskov F, Bjarnason GA, Smoragiewicz M, Kollmannsberger C, Kanesvaran R, Alimohamed N, Hermanns T, Wells JC, Amir E, Choueiri TK, Heng DYC Change in neutrophil-to-lymphocyte ratio in response to targeted therapy for metastatic renal cell carcinoma as a prognosticator and biomarker of efficacy. Eur Urol 2016;70(2):358–364. Epub 2016/02/28. https://​doi.​org/​10.​1016/​j.​eururo.​2016.​02.​033. PubMed.
34.
go back to reference Riihimäki M, Hemminki A, Sundquist J, Hemminki K. Patterns of metastasis in colon and rectal cancer. Sci Rep. 2016;6:29765. Epub 2016/07/15. doi: https://doi.org/10.1038/srep29765. PubMed PMID: 27416752; PubMed Central PMCID: PMCPMC4945942. Riihimäki M, Hemminki A, Sundquist J, Hemminki K. Patterns of metastasis in colon and rectal cancer. Sci Rep. 2016;6:29765. Epub 2016/07/15. doi: https://​doi.​org/​10.​1038/​srep29765. PubMed PMID: 27416752; PubMed Central PMCID: PMCPMC4945942.
35.
go back to reference Shoenfeld Y, Gurewich Y, Gallant LA, Pinkhas J. Prednisone-induced leukocytosis. Influence of dosage, method and duration of administration on the degree of leukocytosis. Am J Med 1981;71(5):773–778. PubMed. Shoenfeld Y, Gurewich Y, Gallant LA, Pinkhas J. Prednisone-induced leukocytosis. Influence of dosage, method and duration of administration on the degree of leukocytosis. Am J Med 1981;71(5):773–778. PubMed.
36.
go back to reference Nakagawa M, Terashima T, D’yachkova Y, Bondy GP, Hogg JC, van Eeden SF. Glucocorticoid-induced granulocytosis: contribution of marrow release and demargination of intravascular granulocytes. Circulation 1998;98(21):2307–2313. PubMed. Nakagawa M, Terashima T, D’yachkova Y, Bondy GP, Hogg JC, van Eeden SF. Glucocorticoid-induced granulocytosis: contribution of marrow release and demargination of intravascular granulocytes. Circulation 1998;98(21):2307–2313. PubMed.
Metadata
Title
Hematologic Markers of Lung Metastasis in Stage IV Colorectal Cancer
Authors
Mohammad Abu-Shawer
Osama Abu-Shawer
Mamoun Souleiman
Mohammad Akkawi
Osama Alshakhatreh
Tamer Altamimi
Amal Al-Omari
Maysa Al-Hussaini
Publication date
01-09-2019
Publisher
Springer US
Published in
Journal of Gastrointestinal Cancer / Issue 3/2019
Print ISSN: 1941-6628
Electronic ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-018-0089-0

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