Excision Repair Cross-Complementation Group 1 (ERCC1) Status and Lung Cancer Outcomes A Meta-Analysis of Published Studies and Recommendations 英文参考文献.docVIP

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Excision Repair Cross-Complementation Group 1 (ERCC1) Status and Lung Cancer Outcomes A Meta-Analysis of Published Studies and Recommendations 英文参考文献.doc

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Excision Repair Cross-Complementation Group 1 (ERCC1) Status and Lung Cancer Outcomes A Meta-Analysis of Published Studies and Recommendations 英文参考文献

ExcisionRepairCross-ComplementationGroup1(ERCC1) StatusandLungCancerOutcomes:AMeta-Analysisof PublishedStudiesandRecommendations RichardA.Hubner1,RichardD.Riley2,LucindaJ.Billingham3,4,SanjayPopat5,6 * 1Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, United Kingdom, 2Department of Public Health, Epidemiology and Biostatistics, University of Birmingham, Birmingham, United Kingdom, 3Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom, 4MRC MidlandHubforTrialsMethodologyResearch,UniversityofBirmingham,Birmingham,UnitedKingdom,5DepartmentofMedicine,RoyalMarsdenNHSFoundationTrust, London,UnitedKingdom,6MolecularGeneticsGroup,ImperialCollege,London,UnitedKingdom Abstract Purpose:Despitediscrepantresultsonclinicalutility,severaltrialsarealreadyprospectivelyrandomizingnon-smallcelllung cancer (NSCLC) patients by ERCC1 status. We aimed to characterize the prognostic and predictive effect of ERCC1 by systematicreviewandmeta-analysis. Methods: Eligible studies assessed survival and/or chemotherapy response in NSCLC or SCLC by ERCC1 status. Effect measures of interest were hazard ratio (HR) for survival or relative risk (RR) for chemotherapy response. Random-effects meta-analyses were used to account for between-study heterogeneity, with unadjusted/adjusted effect estimates consideredseparately. Results:23eligiblestudiesprovidedsurvivalresultsin2,726patients.Substantialheterogeneitywasobservedinallmeta- analyses (I2 always .30%), partly due to variability in thresholds defining ‘low’ and ‘high’ ERCC1. Meta-analysis of unadjusted estimates showed high ERCC1 was associated with significantly worse overall survival in platinum-treated NSCLC(averageunadjustedHR=1.61,95%CI:1.23–2.1,p=0.014),butnotinNSCLCuntreatedwithchemotherapy(average unadjustedHR=0.82,95%CI:0.51–1.31).Meta-analysisofadjustedestimateswaslimitedbyvariablechoiceofadjustment factorsandpotentialpublicationbias(Egger’sp,0.0001).Therewasevidencethat