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Published in: Journal of Gastrointestinal Cancer 3/2019

01-09-2019 | Original Research

Comparison of Hematologic and Other Prognostic Markers in Metastatic Colorectal Cancer

Authors: Joey Mercier, Ioannis A. Voutsadakis

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

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Abstract

Background

Associations of thrombocytosis, neutrophilia, and lymphopenia with prognosis have been confirmed in many cancers. This study aims at comparing various prognostic indices based on blood counts in metastatic colorectal adenocarcinomas.

Patients and Methods

Records from 152 patients with metastatic colorectal cancer who were treated in our center were reviewed. Demographic and disease characteristics and hematologic parameters data were extracted and patients were stratified according to their scores of several hematologic ratios. Hematologic ratios and parameters considered included the platelet-neutrophil to lymphocyte ratio (PNLR), the platelet to lymphocyte ratio (PLR), the neutrophil to lymphocyte ratio (NLR), the Abnormal Hematological Markers Index (AHMI), and the neutrophil-platelet score (NPS). Optimal cutoffs were defined with the aid of an online tool. Baseline parameters of the two groups derived for each tool were evaluated and compared with the χ2 test. Univariate and multivariate Cox proportional-hazards regression analyses were performed on variables of interest.

Results

Progression-Free Survival (PFS) hazard ratios (HR) between the high-risk and low-risk groups derived from the multivariate analyses for each index were as follows: for PNLR 2.0 (95% CI 1.28–3.13), for PLR 1.74 (95% CI 1.13–2.67), for NLR 1.54 (95% CI 1.04–2.29), for AHMI 1.62 (95% CI 1.06–2.46), and for NPS 1.47 (95% CI 1.1–1.96). Overall Survival (OS) hazard ratios (HR) derived from the multivariate analyses for each index were as follows: for PNLR 2.23 (95% CI 1.36–3.66), for PLR 1.68 (95% CI 1.03–2.75), for NLR 1.62 (95% CI 1.06–2.49), for AHMI 1.7 (95% CI 1.07–2.69), and for NPS 1.53 (95% CI 1.11–2.11). Another prognostic index called PRONOPALL, which is based on ECOG PS (0–1 versus 2–3 versus 4), number of metastatic sites (≤ 1 versus ≥ 2), LDH (< 600 U/L versus ≥ 600 U/L), and albumin (≥ 33 g/L versus < 33 g/L), had HRs of 1.75 and 2.20 for PFS and OS, respectively, with a cutoff of < 4 versus ≥ 4. This score has a range of 0 to 10 and points are attributed for the presence of each of the four prognostic factors.

Conclusion

In this analysis of metastatic colorectal cancer patients, several ratios and other prognostic tools had prognostic value for both OS and PFS. While other variables held significance for poorer prognosis, PNLR had the highest HR and the highest significance in multivariate analysis for both PFS and OS. Thus, it represents a valid prognostic tool in metastatic colorectal cancer among the spectrum of hematologic parameter-constructed tools.
Literature
1.
go back to reference Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol Biomark Prev. 2015;25:16–27.CrossRef Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol Biomark Prev. 2015;25:16–27.CrossRef
3.
4.
go back to reference Shibutani M, Maeda K, Nagahara H, Iseki Y, Ikeya T, Hirakawa K. Prognostic significance of the preoperative lymphocyte-to-monoocyte ratio in patients with colorectal cancer. Oncol Lett. 2017;13:1000–6.CrossRefPubMed Shibutani M, Maeda K, Nagahara H, Iseki Y, Ikeya T, Hirakawa K. Prognostic significance of the preoperative lymphocyte-to-monoocyte ratio in patients with colorectal cancer. Oncol Lett. 2017;13:1000–6.CrossRefPubMed
5.
go back to reference Younes G, Segev Y, Begal J, Auslender R, Goldberg Y, Amit A, et al. The prognostic significance of hematological parameters in women with uterine serous papillary carcinoma (USPC). Eur J Gynecol Reprod Biol. 2016;199:16–20.CrossRef Younes G, Segev Y, Begal J, Auslender R, Goldberg Y, Amit A, et al. The prognostic significance of hematological parameters in women with uterine serous papillary carcinoma (USPC). Eur J Gynecol Reprod Biol. 2016;199:16–20.CrossRef
6.
go back to reference Su Z, Mao Y-P, Ou Yang P-Y, et al. Initial hyperleukocytosis and neutrophilia in nasopharyngeal carcinoma: incidence and prognostic impact. PLoS One. 2015;10:e0136752.CrossRefPubMedPubMedCentral Su Z, Mao Y-P, Ou Yang P-Y, et al. Initial hyperleukocytosis and neutrophilia in nasopharyngeal carcinoma: incidence and prognostic impact. PLoS One. 2015;10:e0136752.CrossRefPubMedPubMedCentral
7.
go back to reference Kaser A, Brandacher G, Steurer W, Kaser S, Offner FA, Zoller H, et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis. Blood. 2001;98:2720–5.CrossRefPubMed Kaser A, Brandacher G, Steurer W, Kaser S, Offner FA, Zoller H, et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis. Blood. 2001;98:2720–5.CrossRefPubMed
10.
go back to reference Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, et al. Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer. 2013;134:2403–13.CrossRef Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, et al. Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer. 2013;134:2403–13.CrossRef
11.
go back to reference Tan D, Fu Y, Su Q, Wand H. Prognostic role of platelet–lymphocyte ratio in colorectal cancer—a systematic review and meta-analysis. Medicine. 2016;24(e3837):95. Tan D, Fu Y, Su Q, Wand H. Prognostic role of platelet–lymphocyte ratio in colorectal cancer—a systematic review and meta-analysis. Medicine. 2016;24(e3837):95.
12.
go back to reference Mercier J, Voutsadakis IA. The platelets-neutrophils to lymphocytes ratio: a new prognostic marker in metastatic colorectal cancer. J Gastrointest Oncol. 2018; (in press) Mercier J, Voutsadakis IA. The platelets-neutrophils to lymphocytes ratio: a new prognostic marker in metastatic colorectal cancer. J Gastrointest Oncol. 2018; (in press)
13.
go back to reference Bourgeois H, Grudé F, Solal-Céligny P, Dupuis O, Voog E, Ganem G, et al. Clinical validation of a prognostic tool in a population of outpatients treated for incurable cancer undergoing anticancer therapy: PRONOPALL study. Ann Oncol. 2017;28:1612–7.CrossRefPubMed Bourgeois H, Grudé F, Solal-Céligny P, Dupuis O, Voog E, Ganem G, et al. Clinical validation of a prognostic tool in a population of outpatients treated for incurable cancer undergoing anticancer therapy: PRONOPALL study. Ann Oncol. 2017;28:1612–7.CrossRefPubMed
14.
go back to reference Renfro LA, Goldberg RM, Grothey A, Sobrero A, Adams R, Seymour MT, et al. Clinical calculator for early mortality in metastatic colorectal cancer: an analysis of patients from 28 clinical trials in the Aide et Recherche en Cancérologie Digestive Database. J Clin Oncol. 2017;35:1929–37.CrossRefPubMedPubMedCentral Renfro LA, Goldberg RM, Grothey A, Sobrero A, Adams R, Seymour MT, et al. Clinical calculator for early mortality in metastatic colorectal cancer: an analysis of patients from 28 clinical trials in the Aide et Recherche en Cancérologie Digestive Database. J Clin Oncol. 2017;35:1929–37.CrossRefPubMedPubMedCentral
15.
go back to reference Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10:7252–9.CrossRefPubMed Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10:7252–9.CrossRefPubMed
16.
go back to reference Balkwill FR, Capasso M, Hagemann T. The tumor microenvironment at a glance. J Cell Sci. 2012;125:5591–6.CrossRefPubMed Balkwill FR, Capasso M, Hagemann T. The tumor microenvironment at a glance. J Cell Sci. 2012;125:5591–6.CrossRefPubMed
18.
go back to reference Vogt Sionov R, Fridlender ZG, Granot Z. The multifaceted roles neutrophils play in the tumor microenvironment. Cancer Microenviron. 2015;8:125–58.CrossRef Vogt Sionov R, Fridlender ZG, Granot Z. The multifaceted roles neutrophils play in the tumor microenvironment. Cancer Microenviron. 2015;8:125–58.CrossRef
19.
go back to reference Diaz-Montero CM, Finke J, Montero AJ. Myeloid-derived suppressor cells in cancer: therapeutic, predictive, and prognostic implications. Semin Oncol. 2014;41:174–84.CrossRefPubMedPubMedCentral Diaz-Montero CM, Finke J, Montero AJ. Myeloid-derived suppressor cells in cancer: therapeutic, predictive, and prognostic implications. Semin Oncol. 2014;41:174–84.CrossRefPubMedPubMedCentral
20.
go back to reference Liang L, Zhu J, Jia H, et al. Predictive value of pretreatment lymphocyte count in stage II colorectal cancer and in high-risk patients treated with adjuvant chemotherapy. Oncotarget. 2015;7:1014–28.PubMedCentral Liang L, Zhu J, Jia H, et al. Predictive value of pretreatment lymphocyte count in stage II colorectal cancer and in high-risk patients treated with adjuvant chemotherapy. Oncotarget. 2015;7:1014–28.PubMedCentral
21.
22.
go back to reference Kim M, Chang H, Yang HC, Kim Y, Lee CT, Lee JH, et al. Preoperative thrombocytosis is a significant unfavorable prognostic factor for patients with resectable non-small cell lung cancer. World J Surg Oncol. 2014;12:37.CrossRefPubMedPubMedCentral Kim M, Chang H, Yang HC, Kim Y, Lee CT, Lee JH, et al. Preoperative thrombocytosis is a significant unfavorable prognostic factor for patients with resectable non-small cell lung cancer. World J Surg Oncol. 2014;12:37.CrossRefPubMedPubMedCentral
23.
go back to reference Steele M, Voutsadakis IA. Pre-treatment platelet counts as a prognostic and predictive factor in stage II and III rectal adenocarcinoma. World J Gastrointest Oncol. 2017;9:42–9.CrossRefPubMedPubMedCentral Steele M, Voutsadakis IA. Pre-treatment platelet counts as a prognostic and predictive factor in stage II and III rectal adenocarcinoma. World J Gastrointest Oncol. 2017;9:42–9.CrossRefPubMedPubMedCentral
24.
go back to reference Buergy D, Wenz F, Groden C, Brockmann MA. Tumor-platelet interaction in solid tumors. Int J Cancer. 2012;130:2747–60.CrossRefPubMed Buergy D, Wenz F, Groden C, Brockmann MA. Tumor-platelet interaction in solid tumors. Int J Cancer. 2012;130:2747–60.CrossRefPubMed
25.
go back to reference Ho-Tin-Noé B, Carbo C, Demers M, Cifuni SM, Goerge T, Wagner DD. Innate immune cells induce hemorrhage in tumors during thrombocytopenia. Am J Pathol. 2009;175:1699–708.CrossRefPubMedPubMedCentral Ho-Tin-Noé B, Carbo C, Demers M, Cifuni SM, Goerge T, Wagner DD. Innate immune cells induce hemorrhage in tumors during thrombocytopenia. Am J Pathol. 2009;175:1699–708.CrossRefPubMedPubMedCentral
26.
go back to reference Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 2011;20:576–90.CrossRefPubMedPubMedCentral Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 2011;20:576–90.CrossRefPubMedPubMedCentral
27.
go back to reference Kopp HG, Placke T, Salih HR. Platelet-derived transforming growth factor-beta down regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res. 2009;69:7775–83.CrossRefPubMed Kopp HG, Placke T, Salih HR. Platelet-derived transforming growth factor-beta down regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res. 2009;69:7775–83.CrossRefPubMed
28.
go back to reference Watt DG, Proctor MJ, Park JH, Horgan PG, McMillan DC. The neutrophil-platelet score (NPS) predicts survival in primary operable colorectal cancer and a variety of common cancers. PLoS One. 2015;10:e0142159.CrossRefPubMedPubMedCentral Watt DG, Proctor MJ, Park JH, Horgan PG, McMillan DC. The neutrophil-platelet score (NPS) predicts survival in primary operable colorectal cancer and a variety of common cancers. PLoS One. 2015;10:e0142159.CrossRefPubMedPubMedCentral
29.
go back to reference Dalerba P, Sahoo D, Paik S, Guo X, Yothers G, Song N, et al. CDX2 as a prognostic biomarker in stage II and stage III colon cancer. N Engl J Med. 2016;374:211–22.CrossRefPubMedPubMedCentral Dalerba P, Sahoo D, Paik S, Guo X, Yothers G, Song N, et al. CDX2 as a prognostic biomarker in stage II and stage III colon cancer. N Engl J Med. 2016;374:211–22.CrossRefPubMedPubMedCentral
Metadata
Title
Comparison of Hematologic and Other Prognostic Markers in Metastatic Colorectal Cancer
Authors
Joey Mercier
Ioannis A. Voutsadakis
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/s12029-018-0108-1

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