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      The role of the systemic inflammatory response in predicting outcomes in patients with operable cancer: Systematic review and meta-analysis

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          Abstract

          Cancer remains a leading causes of death worldwide and an elevated systemic inflammatory response (SIR) is associated with reduced survival in patients with operable cancer. This review aims to examine the evidence for the role of systemic inflammation based prognostic scores in patients with operable cancers. A wide-ranging literature review using targeted medical subject headings for human studies in English was carried out in the MEDLINE, EMBASE, and CDSR databases until the end of 2016. The SIR has independent prognostic value, across tumour types and geographical locations. In particular neutrophil lymphocyte ratio (NLR) (n = 158), platelet lymphocyte ratio (PLR) (n = 68), lymphocyte monocyte ratio (LMR) (n = 21) and Glasgow Prognostic Score/ modified Glasgow Prognostic Score (GPS/mGPS) (n = 60) were consistently validated. On meta-analysis there was a significant relationship between elevated NLR and overall survival (OS) (p < 0.00001)/ cancer specific survival (CSS) (p < 0.00001), between elevated LMR and OS (p < 0.00001)/CSS (p < 0.00001), and elevated PLR and OS (p < 0.00001)/CSS (p = 0.005). There was also a significant relationship between elevated GPS/mGPS and OS (p < 0.00001)/CSS (p < 0.00001). These results consolidate the prognostic value of the NLR, PLR, LMR and GPS/mGPS in patients with resectable cancers. This is particularly true for the NLR/GPS/mGPS which should form part of the routine preoperative and postoperative workup.

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          Inflammation and cancer.

          Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.
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            Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis.

            Inflammation may play an important role in cancer progression, and a high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a poor prognostic indicator in several malignancies. Here we quantify the prognostic impact of this biomarker and assess its consistency in solid tumors. A systematic review of electronic databases was conducted to identify publications exploring the association of blood NLR and clinical outcome in solid tumors. Overall survival (OS) was the primary outcome, and cancer-specific survival (CSS), progression-free survival (PFS), and disease-free survival (DFS) were secondary outcomes. Data from studies reporting a hazard ratio and 95% confidence interval (CI) or a P value were pooled in a meta-analysis. Pooled hazard ratios were computed and weighted using generic inverse-variance and random-effect modeling. All statistical tests were two-sided. One hundred studies comprising 40559 patients were included in the analysis, 57 of them published in 2012 or later. Median cutoff for NLR was 4. Overall, NLR greater than the cutoff was associated with a hazard ratio for OS of 1.81 (95% CI = 1.67 to 1.97; P < .001), an effect observed in all disease subgroups, sites, and stages. Hazard ratios for NLR greater than the cutoff for CSS, PFS, and DFS were 1.61, 1.63, and 2.27, respectively (all P < .001). A high NLR is associated with an adverse OS in many solid tumors. The NLR is a readily available and inexpensive biomarker, and its addition to established prognostic scores for clinical decision making warrants further investigation. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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              The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer.

              Since the initial work, a decade ago that the combination of C-reactive protein and albumin, the Glasgow Prognostic Score (GPS), had independent prognostic value in patients with cancer, there have been more than 60 studies (>30,000 patients) that have examined and validated the use of the GPS or the modified GPS (mGPS) in a variety of cancer scenarios. The present review provides a concise overview of these studies and comments on the current and future clinical utility of this simple objective systemic inflammation-based score. The GPS/mGPS had independent prognostic value in (a) unselected cohorts (4 studies, >19,400 patients) (b) operable disease (28 studies, >8,000 patients) (c) chemo/radiotherapy (11 studies, >1500 patients) (d) inoperable disease (11 studies, >2,000 patients). Association studies (15 studies, >2,000 patients) pointed to an increased GPS/mGPS being associated with increased weight and muscle loss, poor performance status, increased comorbidity, increased pro-inflammatory and angiogenic cytokines and complications on treatment. These studies have originated from 13 different countries, in particular the UK and Japan. A chronic systemic inflammatory response, as evidenced by the GPS/mGPS, is clearly implicated in the prognosis of patients with cancer in a variety of clinical scenarios. The GPS/mGPS is the most extensively validated of the systemic inflammation-based prognostic scores and therefore may be used in the routine clinical assessment of patients with cancer. It not only identifies patients at risk but also provides a well defined therapeutic target for future clinical trials. It remains to be determined whether the GPS has prognostic value in other disease states. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Ross.Dolan@glasgow.ac.uk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                1 December 2017
                1 December 2017
                2017
                : 7
                : 16717
                Affiliations
                Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK
                Author information
                http://orcid.org/0000-0002-5272-5906
                http://orcid.org/0000-0003-4260-5334
                Article
                16955
                10.1038/s41598-017-16955-5
                5711862
                29196718
                5eeb0f16-c669-4b2c-a941-20e7a4864f67
                © The Author(s) 2017

                Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 June 2017
                : 17 November 2017
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