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      Prognostic value of neutrophil-to-lymphocyte ratio in locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy

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          Abstract

          Purpose

          This study aimed to investigate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in patients with locally advanced non-small cell lung cancer (NSCLC) who received concurrent chemoradiotherapy (CCRT).

          Materials and Methods

          We retrospectively analyzed 66 patients with locally advanced NSCLC treated with definitive CCRT. Among these patients, 95% received paclitaxel/carboplatin or docetaxel/cisplatin. The median radiation dose was 66 Gy in 33 fractions. The NLR and PLR before/after CCRT were evaluated. The maximally selected log-rank test was used to obtain the cutoff values related to the overall survival (OS).

          Results

          Patients with high post-CCRT NLR (>3.12) showed worse OS, locoregional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS) than those with low NLR (2-year OS: 25.8% vs. 68.2%, p < 0.001; 2-year LRPFS: 12.9% vs. 33.8%, p = 0.010; 2-year DMFS: 22.6% vs. 38.2%, p = 0.030). Patients with high post-CCRT PLR (>141) showed worse OS and LRPFS than those with low PLR (2-year OS: 37.5% vs. 71.1%, p = 0.004; 2-year LRPFS: 16.5% vs. 40.3%, p = 0.040). Patients with high NLR change (>1.61) showed worse OS and LRPFS than those with low NLR change (2-year OS: 26.0% vs. 59.0%, p < 0.001; 2-year LRPFS: 6.8% vs. 31.8%, p = 0.004). The planning target volume (hazard ration [HR] = 2.05, p = 0.028) and NLR change (HR = 3.17, p = 0.025) were the significant factors for OS in the multivariate analysis.

          Conclusion

          NLR change after CCRT was associated with poor prognosis of survival in patients with locally advanced NSCLC. An elevated NLR after CCRT might be an indicator of an increased treatment failure risk.

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          Most cited references15

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          Neutrophils in cancer: neutral no more.

          Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets.
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            Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis.

            Matrix metalloprotease type 9 (MMP-9) has been functionally implicated in VEGF activation, the induction and maintenance of chronic angiogenesis, and early stage tumor growth in a number of mouse models of cancer. In this article, we have identified two inflammatory cell types that are major sources of MMP-9 in the angiogenic stages of pancreatic islet carcinogenesis that unfold in RIP1-Tag2 transgenic mice. MMP-9-expressing neutrophils were predominantly found inside angiogenic islet dysplasias and tumors, whereas MMP-9-expressing macrophages were localized along the periphery of such lesions. Transient depletion of neutrophils significantly suppressed VEGF:VEGF-receptor association, a signature of MMP-9 activity, and markedly reduced the frequency of initial angiogenic switching in dysplasias. Thus infiltrating neutrophils can play a crucial role in activating angiogenesis in a previously quiescent tissue vasculature during the early stages of carcinogenesis.
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              Bv8 regulates myeloid-cell-dependent tumour angiogenesis.

              Bone-marrow-derived cells facilitate tumour angiogenesis, but the molecular mechanisms of this facilitation are incompletely understood. We have previously shown that the related EG-VEGF and Bv8 proteins, also known as prokineticin 1 (Prok1) and prokineticin 2 (Prok2), promote both tissue-specific angiogenesis and haematopoietic cell mobilization. Unlike EG-VEGF, Bv8 is expressed in the bone marrow. Here we show that implantation of tumour cells in mice resulted in upregulation of Bv8 in CD11b+Gr1+ myeloid cells. We identified granulocyte colony-stimulating factor as a major positive regulator of Bv8 expression. Anti-Bv8 antibodies reduced CD11b+Gr1+ cell mobilization elicited by granulocyte colony-stimulating factor. Adenoviral delivery of Bv8 into tumours was shown to promote angiogenesis. Anti-Bv8 antibodies inhibited growth of several tumours in mice and suppressed angiogenesis. Anti-Bv8 treatment also reduced CD11b+Gr1+ cells, both in peripheral blood and in tumours. The effects of anti-Bv8 antibodies were additive to those of anti-Vegf antibodies or cytotoxic chemotherapy. Thus, Bv8 modulates mobilization of CD11b+Gr1+ cells from the bone marrow during tumour development and also promotes angiogenesis locally.
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                Author and article information

                Journal
                Radiat Oncol J
                Radiat Oncol J
                ROJ
                Radiation Oncology Journal
                The Korean Society for Radiation Oncology
                2234-1900
                2234-3164
                September 2019
                30 September 2019
                : 37
                : 3
                : 166-175
                Affiliations
                [1 ]Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
                [2 ]Department of Medical Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
                Author notes
                Correspondence: Yeon-Sil Kim, Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Korea. Tel: +82-2-2258-1526, Fax: +82-2-592-1532, E-mail: yeonkim7@ 123456catholic.ac.kr
                Author information
                http://orcid.org/0000-0003-1291-0821
                Article
                roj-2019-00220
                10.3857/roj.2019.00220
                6790800
                31591864
                b2acbf62-ea79-4e3d-9001-967c39188d9b
                Copyright © 2019 The Korean Society for Radiation Oncology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 April 2019
                : 20 June 2019
                : 8 July 2019
                Categories
                Original Article
                Clinical Investigations

                Oncology & Radiotherapy
                neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,non-small cell lung cancer,concurrent chemoradiotherapy

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