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      Effectiveness and Safety of Chemotherapy Combined with Dendritic Cells Co-Cultured with Cytokine-Induced Killer Cells in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

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          Abstract

          Background

          Lung cancer, particularly non-small-cell lung cancer (NSCLC) is the leading cause of cancer mortality. Chemotherapy combined dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) immunotherapy has been applied in advanced NSCLC patients' treatment, but couldn't provide consistent beneficial results. Therefore, it is necessary to evaluate the efficiency and safety of combination therapy to promote the application.

          Methods

          A literature search for randomized controlled trials of NSCLC was conducted in PubMed database. Before meta-analysis was performed, studies were evaluated heterogeneity. Pooled risk ratios (RRs) were estimated and 95% confidence intervals (CIs) were calculated using a fixed-effect model. Sensitivity analysis was also performed.

          Results

          Six eligible trials were enrolled. Efficiency and safety of chemotherapy followed by DC-CIK immunotherapy (experimental group) and chemotherapy alone (control group) were compared. 1-year overall survival (OS) ( P = 0.02) and progression free survival (PFS) ( P = 0.005) in the experimental group were significantly increased compared with the control. Disease control rate (DCR) ( P = 0.006) rose significantly in experimental group. However, no significant differences between the two groups were observed in 2-year OS ( P = 0.21), 2-year PFS ( P = 0.10), overall response rate (ORR) ( P = 0.76) and partial response (PR) ( P = 0.22). Temporary fever, anemia, leukopenia and nausea were the four major adverse events (AEs) treated by chemotherapy. The incidence of anemia, leukopenia and nausea in the experimental group was obviously lower than the control group. Temporary fever rate was higher in experimental group than that in the control, but could be alleviated by taking sufficient rest.

          Conclusions

          Chemotherapy combined with DC-CIK immunotherapy showed superiority in DCR, 1-year OS and PFS, and no more AEs appeared, however, there was no significant improvement in ORR, PR, 2-year OS and PFS. As a whole, the combination therapy is safer but modest in efficacy for advanced NSCLC patients.

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          Most cited references28

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          Global cancer statistics

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            Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

            Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I 2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R 2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I 2, which we call . We also provide a multivariate H 2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I 2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd.
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              Two hundred years of cancer research.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                30 September 2014
                : 9
                : 9
                : e108958
                Affiliations
                [1 ]First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
                [2 ]Tianjin University of Traditional Chinese Medicine, Tianjin, China
                Shanghai Jiao Tong University School of Medicine, China
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Performed the experiments: YJJ JCY. Analyzed the data: RXH PP. Contributed reagents/materials/analysis tools: RXH XL PP. Wrote the paper: RXH XL PP.

                Article
                PONE-D-13-54665
                10.1371/journal.pone.0108958
                4182599
                25268709
                b881b067-0289-42a7-a9bc-adff34446d13
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 December 2013
                : 6 September 2014
                Page count
                Pages: 8
                Funding
                This work was supported by National Natural Science Foundation of China (No. 81273937), Key Project of Anti-Cancer of Tianjin (12ZCDZSY15800), Science and Technology Developing and Supporting Program from Tianjin (12CDZSY17000), Specialized Research Fund for the Doctoral Program of Higher Education (20121210110010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Immunology
                Clinical Immunology
                Immunotherapy
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Lung and Intrathoracic Tumors
                Non-Small Cell Lung Cancer
                Cancer Treatment
                Clinical Trials (Cancer Treatment)
                Cytokine Therapy
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Research Design
                Clinical Research Design

                Uncategorized
                Uncategorized

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