寰宇作業(yè)-代翻譯additional.Results符合入組條件的患者

AdditionalprognosticvalueoflymphnoderatioinstageIIICepithelialovariancancerwithnode-positiveinaSEERpopulation-basedstudyPurpose：ThepurposeofthisstudywastoassessthevalueoflymphnoderatioLNRinstageIIICepithelialovariancancer(EOC)withpositivenodesinaSEERpopulation-basedstudy.Methods:DatawereobtainedfromSEERfrom1990to2012,andyzedusingKaplan–MeiersurvivalandCoxregressionproportionalhazardmethods.TheprognosticimpactoftheLNRwithrespecttocancerspecificsurvival(CSS)andoverallsurvival(OS)wasyzed.Results:符合入組條件的患者6043例，中位numberofremovednodes（RLNs）10個(gè)（1-98個(gè)numberofpositivelymphnodes（PLNs）2個(gè)90個(gè)LNR0.36（0.01-1RLNcount,PLNcountandLNR為影響CSSOS的因素(allP0.05)LNRCSS和OS的獨(dú)立預(yù)后因素，隨著LNR的逐漸升高，患者的CSS(hazardratio[HR]1.955,95%confidenceinterval[CI]1.742-2.195,P<0.001)和OS(HR1.809,95%CI1.641-1.995,<0.001)RLNcountPLNcount10年CSS和OS分別為29.0%和25.3%淋比率≤0.25和>0.25的患者的10年OS分別為33.5%和19.7%（logrankP<0.001，淋比率≤0.25和>0.25的患者的10年CSS分別為37.6%22.9（logrankP<0.001。TheprognosticsignificanceofLNRpersistedirrespectivethenumberofRLNs,histologicaltype,andhistologicgrade.Conclusions:patientswithstageIIICEOC,LNRisanindependentprognosticfactor.LNRmightreducestagemigration,havemorepotentialforpredictingpatient es,andcompensatefordeficienciesincurrentstagingcategories.:Epithelialovariancancer,Lymphnoderatio,Positivelymphnode,Ovariancancerisahighlyfatalgynecologiccancerandthefifthleadingcauseofcancermortalityinwomen,with21,980newcasesand14,270deathsoccurringintheUnitedStatesin2014(1).Mostpatientswithovariancancerhaveadvanceddiseaseatthetimeofdiagnosisowingtoasymptomaticnatureforearlystagetumors,resultinginapoorlong-time(2,3).研究已發(fā)現(xiàn)癌的淋狀態(tài)會(huì)影響患者的生存(4,5)。目前淋狀態(tài)是癌InternationalFederationofGynecologyandObstetrics（FIGO）分期的重要指標(biāo)之一，patientswithpositiveretroperitoneallymphnodesarecategorizedasstageIIICregardlessofintraperitonealextentofthedisease(6,7).Recognizingtheimportanceoftheprognosticvalueoflymphnodemetastasis,thesystematiclymphadenectomywasincludedintheguidelinesinFIGOstagingsystem.Meta分析的結(jié)果顯示lymphadenectomycanimprovethesurvivalofepithelialovariancancer（EOC）patientswithadvancedstage(8).However,theroleoflymphadenectomy在EOC的價(jià)值仍有爭議(9-11).目前EOC的淋分期主要根據(jù)淋在stagingmigration淋比率（Lymphnodesratio，LNR）指的是陽性淋數(shù)和清掃淋數(shù)目的預(yù)后價(jià)值可能優(yōu)于目前的pN分期(12-19)，但是目前關(guān)于淋比率在EOC的預(yù)后價(jià)值資料stilllimited（20-22）.因此，在本研究中，我們采用apopulation-basedysisofLNR在EOC的預(yù)后價(jià)值usingSurveillance,Epidemiology,andEndResults(SEER)database,whichmaydecreasesthepotentialforselectionandsurveillancebiasesthatassociatedwithsingle-institutionPatientsandDatawereobtainedfromthecurrentSEERdatabase,whichconsistsof18population-basedcancerregistries.SEERdataareanopenaccessresourceforcancer-basedepidemiologyandsurvivalyses.SEER*StatsoftwarefromtheNationalCancerInstitute(SurveillanceResearchProgram,NationalCancerInstituteSEER*Stat)(Version8.2.1)wasusedtoidentifyeligiblepatients.PatientswithadiagnosisofEOCpatientswereidentifiedusingtheSEEdatabasefrom1990to2010,weobtainedpermissiontoaccessresearchdatafileswiththereferencenumber11252-Nov2014(23).Thefollowinginclusioncriteriawereutilizedforpatientselection:1)receivedsurgicalstagingincludinglymphadenectomy,2)stageIIICEOCwithnodal3)pathologicaldiagnosisofEOCwithhistologyofserous,mucinous,endometroidandclearcell,4)EOCasthefirstandonlycancerdiagnosis,5)knownageatdiagnosis.PathologicdiagnosiswasbasedontheprimarysiteusingtheInternationalClassificationofDiseaseforOncology,ThirdEdition(ICD-O-3).SEERdatabasedatadonotrequireinformedconsent,andthisstudywasapprovedbytheethicscommitteeoftheFirstaffiliatedHospitalofXiamenClinicopathologicalClinicopathologicalfactorswereusedtoassesstheriskofdeath.Factorsexaminedincludedage,race,histologicaltype,histologicgrade,tumorlocation,numberofremovedlymphnodes(RLN),numberofpositivelymphnodes(PLNs)andLNR.StatisticalUnivariateandmultivariateCoxregression ysesweregeneratedto yzeriskfactorsforcancerspecificsurvival(CSS)andoverallsurvival(OS).Multivariable yseswereperformedforfactorswhichweresignificantlyassociatedwithCSSandOSinunivariateyses.Theoptimumcut-offpointfortheLNRwasdeterminedbyuseofthereceiveroperatingcharacteristic(ROC)curve.CalculationofsurvivalrateswereplottedbytheKaplan-Meiermethod,andcomparedusingthelog-ranktest.AlldatawereyzedtheSPSSstatisticalsoftwarepackage,version17.0(IBMCorporation,Armonk,NY,USA).AvalueP<0.05wasconsideredstatisticallyPatient60431，86.9%（5252/6043）者為serousEOC，中位淋清掃數(shù)目10個(gè)（1-98個(gè)清掃淋數(shù)目1-10個(gè)，11-（39.8%2344（21.4%，所有患者中位陽性淋數(shù)目2個(gè)（1-90個(gè)，中位淋比率0.36（0.01-1ysisofage,grade,histologicaltype,tumorlocation,RLNcount,PLNcount,andLNR為影響CSSOS的因素(allP0.05)，race對預(yù)后無影響(2)。3為患者的多因素分析結(jié)果，提示LNR為影響CSSOS的獨(dú)立預(yù)后因素。隨著LNRCSS(hazardratio[HR]1.955,95%confidenceinterval[CI]1.742-2.195P0.001)OSHR1.80995%CI1.641-1.995,P0.001)更差，而RLNandtumorlocation.Identificationofoptimalcut-offpointsofTheoptimalcut-offpointsofLNRwereyzedusingROCcurve.Theresultsshowed0.26wastheoptimalcut-offpointforNLNs(AreaUnderrocCurve=0.572,P<0.001).Therefore,theoptimalcutoffvalueof0.25wasvalidatedasaprognosticfactorforysisoftheclinicaleffectofthenumberofNLNs.ysisoftheprognosticimpactoftheLNRonThemedianfollow-uptimewas33months(range,0-275months)inallthepatients,and42months(range0-275months)insurvivingpatients.510CSS分別為44.6%29.0%(Figure1A),510OS41.8%25.3%(Figure1B)。淋19.7（log2A)，淋比率≤0.25和>0.25的患者的10年CSS分別為37.6%和22.9%（logrank0.001）(Figure2B)WhethertheinfluenceofLNRonCSSandOSwasmodifiedbythenumberofRLNsdetermined.Incut-offpointofRLNcountwith1-10,11-20and>21,LNRwassignificantlyassociatedwithCSS(logrankP<0.001forRLNcount≤10,andP<0.001forRLNcount11-20,andP<0.001forRLNcount>21)andOS(logrankP<0.001forRLNcount≤10,andP<0.001forRLNcount11-20,andP<0.001forRLNcount>21).TheprognosticeffectoftheLNRaccordingtodifferenthistology(serousvs.non-serous)wasexamined.Inbothserousandnon-serousEOC,LNRwassignificantlyassociatedwithCSS(logrankp<0.001forseroushistology,andp<0.001fornon-seroushistology)andOS(logrankp<0.001forseroushistology,andp<0.001fornon-seroushistology).Thesurvivalratesofpatientsaccordingtohistologicgradewerecompared.TheeffectofLNRsignificantlydifferenceacrossanyhistologicgradegrouponCSS(logrankp=0.002forG1patients,p<0.001forG2patients,p<0.001forG3patients,andP<0.001forG4patients)andOS(logrankP=0.003forG1patients,p<0.001forG2patients,p<0.001forG3patients,andp<0.001forG4patients).在本研究中，我們探討了包括RLNcountPLNcountandLNR在stageIIICEOC的預(yù)后LNRCSSOSRLNcountandPLNcount。淋狀態(tài)是影響癌預(yù)后的最重要因一目前FIGO的分期把有淋陽性的患者歸入IIIc期（6.7）.。雖然根據(jù)淋的陽性或來判斷淋狀態(tài)的方法使部分患者存在stagingmigration，未能準(zhǔn)確反映患者的預(yù)后。LNR是陽性淋數(shù)目目前主要有三個(gè)研究來評價(jià)LNR在EOC的價(jià)值，Atasevenetal等入組的FIGOI-IV期的809例患者，其中398例為淋陽性，結(jié)果發(fā)現(xiàn)LNR是影響EOC患者OS的獨(dú)立預(yù)后因素（HR1.44,95%CI1.04-2.00，P=0.028，the5-year-OSrateswere42.5%forpatientswithLNR≤0.25,and18.0%forpatientswithLNR>0.25(p<0.001)(Baannetal分析95例IIIC期患者，結(jié)果提示increasingLNRleadstosignificantdecreasedOSP0.019)andsignificantbestOSwasassociatedwithLNR00.521,29).另外是采用SEER數(shù)據(jù)庫的研究，一共入組6310例淋陽性的IIIC-IV期EOC的研究發(fā)現(xiàn)increasingLNR(<10%,10–50%,and>50%)wasassociatedwithdecreasedsurvival(p<0.001),especiallyinpatientswithnomacroscopicperitonealdisease.LNRwasanindependentprognosticfactorforsurvivalonmultivariateysis(22).在本研究中，我們?nèi)虢M的為IIIC期淋陽性的患者，結(jié)果發(fā)現(xiàn)在這一特定人群當(dāng)中，LNR是影響生存的Itisstillunclearthetherapeuticvalueofsystematiclymphadenectomyinwomenwithadvancedstageovariancancer.Panicietal.performedthefirstmulticenterrandomizedclinicaltrial,whichshowedthatsystematiclymphadenectomywasassociatedwithsignificantimprovementofprogression-freesurvival,althoughOSwassimilarinthelymphadenectomyarmandthebulkynodesresectionarm(5).從Panicietal的研究結(jié)果來看似乎淋清掃數(shù)目不應(yīng)是影響患者預(yù)后的因素。但PereiraetalusedamathematicalmodeltopredicttheprobabilitytoobtainapositivenodeinEOCsurgicalstagingifatleast22lymphnodesbetweenpelvicandaorticlymphadenectomy(30).Chanetalusingdatabasetoconcerntheimpactoflymphnodedissectiononthesurvivalin13,918womenwithstageIII–IVEOC.OfthestageIIICpatientswithnodalmetastasis,theextentofnodalresection(1,2-5,6-10,11-20,and>20nodes)wasassociatedwithimprovedsurvivalof36.9,45.0,47.8,48.7,and51.1%,respectively(P=0.023),andtheextentoflymphnodedissectionandnumberofpositivenodesweresignificantindependentprognosticfactorsusingmultivariate(31).TheGermanAGOhasinitiatedthefirststudyinadvancedovariancancer(LION)comparethevalueofsystematiclymphnodedissectionwithnolymphnoderesectioninpatientswithoutanyvisibletumorresidualsinwhichsystematiclymphadenectomyisdefinedascomprisingatleast30(20pelviclymphnodesand10paraaorticlymphnodes)(20).的研究入組的淋清掃數(shù)目1-10個(gè)，11-20個(gè)和>20的患者分別39.8%，38.8%21.4%，發(fā)現(xiàn)LNR在不同的淋清掃數(shù)目患者中均具有預(yù)后價(jià)值，這也提示LNR可研究發(fā)現(xiàn)在不同的histologicaltype和grade的EOC中淋轉(zhuǎn)移概率不甚相同28，分析淋比率在不同histologicaltype和grade的EOC的預(yù)后價(jià)值結(jié)果亦提示LNR在不同的histologicaltype和grade具有顯著的預(yù)后價(jià)值。目前已把腫瘤部位和grade列為食管癌UICC/AJCCTNM分期的重要參考(32)。因此，在上皮性癌的淋分期中，亦應(yīng)不局限于目前只判斷是否淋陽性來進(jìn)行pN分期，根據(jù)我們的LNRRLNcountPLNcountLNREOC我們需要承認(rèn)本研究中存在局限性。First，基于SEER的數(shù)據(jù)庫缺少患者的相應(yīng)治療包括includingthevolumeofmetastaticdiseaseatdiagnosis,theextentand eofprimarysurgery,useandtypeofadjuvantchemotherapy.However,thestrengthofthisistheysisofdataonalargenumberofpatientswithnodepositiveEOCusingSEERcancerregistriesaresetuptobeabletoreflectpopulation-baseddata(33).Second，由于目前對于LNR在癌的研究尚少，仍沒有確切的LNRcut-offpoint標(biāo)準(zhǔn)，我們的研究中采用ROC0.25為LNR的cut-offpointcut-offpoint是否適用于其于RLNcount和PLNcount.InpatientswithEOC,LNRmightreducestagemigration,havemorepotentialforpredicting 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