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      Prognostic value of pretreatment platelet counts in lung cancer: a systematic review and meta-analysis

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          Abstract

          Background

          The prognostic value of elevated pretreatment platelet counts remains controversial in lung cancer patients. We performed the present meta-analysis to determine its precise role in these patients.

          Methods

          We employed a multiple search strategy in the PubMed, EMBASE and Cochrane Library databases to identify eligible studies. Disease-free survival (DFS)/progression-free survival (PFS)/time to progression (TTP) and overall survival (OS) were used as outcomes with hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity among the studies and publication bias were also evaluated.

          Results

          A total of 40 studies including 16,696 lung cancer patients were eligible for the analysis. Overall, the pooled analysis showed that compared with normal platelet counts, elevated pretreatment platelet counts were associated with poorer OS (HR = 1.54, 95% CI: 1.37–1.72, P < 0.001) and poorer DFS/PFS/TTP (HR = 1.62, 95% CI: 1.33–1.98, P < 0.001) in patients with lung cancer. In subgroup analyses, elevated pretreatment platelet counts were also associated with poorer OS and DFS/PFS/TTP in most subgroups. There was no evidence of publication bias.

          Conclusions

          This meta-analysis revealed that elevated pretreatment platelet counts were an independent predictor of OS and DFS/PFS/TTP in lung cancer patients. Large-scale prospective studies and a validation study are warranted.

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          Most cited references55

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          Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA.

          S. Bauer, V Groh, J. Wu … (1999)
          Stress-inducible MICA, a distant homolog of major histocompatibility complex (MHC) class I, functions as an antigen for gammadelta T cells and is frequently expressed in epithelial tumors. A receptor for MICA was detected on most gammadelta T cells, CD8+ alphabeta T cells, and natural killer (NK) cells and was identified as NKG2D. Effector cells from all these subsets could be stimulated by ligation of NKG2D. Engagement of NKG2D activated cytolytic responses of gammadelta T cells and NK cells against transfectants and epithelial tumor cells expressing MICA. These results define an activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses.
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            Paraneoplastic thrombocytosis in ovarian cancer.

            Rebecca L. Stone, Alpa Nick, Iain A McNeish … (2012)
            The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear. We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained. Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis. These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. (Funded by the National Cancer Institute and others.).
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              A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study.

              Michael Proctor, David Morrison, Dinesh Talwar … (2011)
              Components of the systemic inflammatory response, combined to form inflammation-based prognostic scores (modified Glasgow Prognostic Score (mGPS), Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI), Prognostic Nutritional Index (PNI)) have been associated with cancer specific survival. The aim of the present study was to compare the prognostic value of these scores. Patients (n=27,031) who had an incidental blood sample taken between 2000 and 2007 for C-reactive protein, albumin, white cell, neutrophil, lymphocyte and platelet counts, as well as a diagnosis of cancer (Scottish Cancer Registry) were identified. Of this group 8759 patients who had been sampled within two years following their cancer diagnosis were studied. On follow up, there were 5163 deaths of which 4417 (86%) were cancer deaths. The median time from blood sampling to diagnosis was 1.7 months. An elevated mGPS, NLR, PLR, PI and PNI were predictive of a reduced cancer specific survival independent of age, sex and deprivation and tumour site (all p<0.001). The area under the receiver operator curves was greatest for mGPS and PI. Specifically, in colorectal cancer, an elevated mGPS and PI were predictive of a reduced cancer specific survival independent of age, sex, deprivation and tumour stage (both p<0.001). The results of the present study show that systemic inflammation-based scores, in particular the mGPS and PI, have prognostic value in cancer independent of tumour site. Based on the present results and the existing validation literature, the mGPS should be included in the routine assessment of all patients with cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Yingying Qian: qianyyvic@126.com
                Journal
                Journal ID (nlm-ta): BMC Pulm Med
                Journal ID (iso-abbrev): BMC Pulm Med
                Title: BMC Pulmonary Medicine
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2466
                Publication date (Electronic): 20 April 2020
                Publication date PMC-release: 20 April 2020
                Publication date Collection: 2020
                Volume: 20
                Electronic Location Identifier: 96
                Affiliations
                [1 ]Department of Respiratory and Critical Care Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle road, Nanjing, 210006 Jiangsu China
                [2 ]ISNI 0000 0000 9255 8984, GRID grid.89957.3a, Department of Pulmonary and Critical Care Medicine, , The Affiliated Jiangning Hospital of Nanjing Medical University, ; Nanjing, 210006 Jiangsu China
                Article
                Publisher ID: 1139
                DOI: 10.1186/s12890-020-1139-5
                PMC ID: 7171794
                PubMed ID: 32312252
                SO-VID: 4c05569b-476c-4ec8-bf35-d2799e91fcb5
                Copyright © © The Author(s). 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                Date received : 16 October 2019
                Date accepted : 7 April 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100014718, Innovative Research Group Project of the National Natural Science Foundation of China;
                Award ID: 81601998
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2020

                ScienceOpen disciplines: Respiratory medicine
                Keywords: lung cancer,platelet count,prognosis,meta-analysis
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: lung cancer, platelet count, prognosis, meta-analysis

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