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      Prognostic value of neutrophil-to-lymphocyte ratio in advanced nasopharyngeal carcinoma: a large institution-based cohort study from an endemic area

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          Abstract

          Background

          Findings remain unclear whether neutrophil-to-lymphocyte ratio (NLR) detrimentally affects advanced nasopharyngeal carcinoma (NPC) prognosis. We aim to evaluate the prognostic value of NLR in patients with NPC based on a large-scale cohort from an endemic area.

          Methods

          We selected patients retrospectively from a cohort examining long-term cancer outcomes following diagnosis. Neutrophil counts and lymphocyte counts were assessed prior to treatment. Kaplan–Meier method and log-rank test were used to calculate and compare survival outcomes. Additionally, Cox proportional hazards model was utilized to carry out univariate and multivariate analyses.

          Results

          Between October 2009 and August 2012, we enrolled 1550 consecutive NPC patients staged II-IVB. The median value of NLR was 2.27 (interquartile range [IQR], 1.71–3.12). Determined by operating characteristic curve using overall survival (OS) as an endpoint, the cutoff value for NLR was 2.50. At 5 years, NLR > 2.50 was associated with inferior OS (90.3% vs 82.5%; P < 0.001), distant metastasis-free survival (DMFS, 89.4% vs 85.0%; P = 0.014), and progression-free survival (PFS, 80.9% vs 76.5%; P = 0.031) than NLR ≤2.50. In multivariate analysis, NLR was found to be a significant prognostic factor for OS (HR, 1.72; 95% CI, 131–2.24; P < 0.001), DMFS (HR, 1.45; 95% CI, 1.10–1.92; P = 0.009), and PFS (HR, 1.29; 95% CI, 1.04–1.59; P = 0.021).

          Conclusion

          Pretreatment NLR independently affects survival. Our findings suggest that NLR measurements will be of great clinical significance in the management of NPC.

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          Most cited references18

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          The meaning and use of the area under a receiver operating characteristic (ROC) curve.

          A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.
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            Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine.

            The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to the quality of the information provided by the classification device and should be distinguished from the usefulness, or actual practical value, of the information. Receiver-operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. Furthermore, ROC plots occupy a central or unifying position in the process of assessing and using diagnostic tools. Once the plot is generated, a user can readily go on to many other activities such as performing quantitative ROC analysis and comparisons of tests, using likelihood ratio to revise the probability of disease in individual subjects, selecting decision thresholds, using logistic-regression analysis, using discriminant-function analysis, or incorporating the tool into a clinical strategy by using decision analysis.
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              Cytokine patterns in patients with cancer: a systematic review.

              Active, but dysfunctional, immune responses in patients with cancer have been studied in several tumour types, but owing to the heterogeneity of cancer theories of common reaction mechanisms seem to be obsolete. In this Review of published clinical studies of patients with cancer, expression and interplay of the following cytokines are examined: interleukin 2, interleukin 6, interleukin 8, interleukin 10, interleukin 12, interleukin 18, tumour necrosis factor α (TNFα), transforming growth factor β (TGFβ), interferon-γ, HLA-DR, macrophage migration inhibitory factor (MIF), and C-X-C motif chemokine receptor 4 (CXCR4). Clinical data were analysed in a non-quantitative descriptive manner and interpreted with regard to experimentally established physiological cytokine interactions. The clinical cytokine pattern that emerged suggests that simultaneous immunostimulation and immunosuppression occur in patients with cancer, with increased concentrations of the cytokines MIF, TNFα, interleukin 6, interleukin 8, interleukin 10, interleukin 18, and TGFβ. This specific cytokine pattern seems to have a prognostic effect, since high interleukin 6 or interleukin 10 serum concentrations are associated with negative prognoses in independent cancer types. Although immunostimulatory cytokines are involved in local cancer-associated inflammation, cancer cells seem to be protected from immunological eradication by cytokine-mediated local immunosuppression and a resulting defect of the interleukin 12-interferon-γ-HLA-DR axis. Cytokines produced by tumours might have a pivotal role in this defect. A working hypothesis is that the cancer-specific and histology-independent uniform cytokine cascade is one of the manifestations of the underlying paraneoplastic systemic disease, and this hypothesis links the stage of cancer with both the functional status of the immune system and the patient's prognosis. Neutralisation of this cytokine pattern could offer novel and so far unexploited treatment approaches for cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                yaojj@sysucc.org.cn
                zhuft@sysucc.org.cn
                dongjun1@sysucc.org.cn
                liangzb@mail.sysu.edu.cn
                13631201672@163.com
                csy0319@163.com
                wzhang27@albany.edu
                wlawrence@albany.edu
                zhangfan26@mail.sysu.edu.cn
                13570608929@163.com
                +86-20-87343816 , sunying@sysucc.org.cn
                +86-20-87343816 , zhougq@sysucc.org.cn
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                8 January 2019
                8 January 2019
                2019
                : 19
                : 37
                Affiliations
                [1 ]ISNI 0000 0004 1803 6191, GRID grid.488530.2, Department of Radiation Oncology, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, , Sun Yat-sen University Cancer Center, ; Guangzhou, 510060 Guangdong Province People’s Republic of China
                [2 ]GRID grid.452859.7, Department of Head and Neck Oncology, , The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, ; Zhuhai, 519001 Guangdong Province China
                [3 ]ISNI 0000 0004 1803 6191, GRID grid.488530.2, Department of Imaging Diagnosis and Interventional Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, , Sun Yat-sen University Cancer Center, ; Guangzhou, 510060 Guangdong Province People’s Republic of China
                [4 ]ISNI 0000 0004 1803 6191, GRID grid.488530.2, Department of VIP Region, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, , Sun Yat-sen University Cancer Center, ; Guangzhou, 510060 People’s Republic of China
                [5 ]GRID grid.452859.7, Department of thoracic oncology, , the cancer center of the fifth affiliated hospital of Sun Yat-sen University, ; Zhuhai, 519001 Guangdong Province China
                [6 ]GRID grid.452859.7, Department of abdominal oncology, , the cancer center of the fifth affiliated hospital of Sun Yat-sen University, ; Zhuhai, 519001 Guangdong Province China
                [7 ]ISNI 0000 0001 2360 039X, GRID grid.12981.33, Department of Medical Statistics and Epidemiology & Health Information Research Center & Guangdong Key Laboratory of Medicine, School of Public Health, , Sun Yat-sen University, ; Guangzhou, 510080 Guangdong Province China
                [8 ]ISNI 0000 0001 2151 7947, GRID grid.265850.c, Department of Environmental Health Sciences, School of Public Health, , University at Albany, State University of New York, ; New York, Rensselaer 12144 USA
                Author information
                http://orcid.org/0000-0002-5888-2929
                Article
                5236
                10.1186/s12885-018-5236-2
                6325732
                30621619
                aa895e5d-131c-4bdc-a328-eacd3e2ae942
                © The Author(s). 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 December 2017
                : 20 December 2018
                Funding
                Funded by: the Health and Medical Collaborative Innovation Project of Guangzhou City, China
                Award ID: 201604020003
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: No. 81402532
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                nasopharyngeal carcinoma, advanced,neutrophil-to-lymphocyte ratio,prognosis

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