肺癌筛查对新发结节的研究.pptx

Occurrence and lung cancer probability of new solid nodules at incidence screening with low-dose CT:analysis of data from the randomised,controlled NELSON trial2of39l Lung cancer is a leading cause of death worldwide.l US guidelines now recommend lung cancer screening with low-dose CT for high-risk individuals.l So far,most research has focused on lung nodules detected during baseline screening.Introduction3of39Introductionl Reports of new nodules after baseline screening have been scarce and are inconsistent because of differences in definitions used.l Because these nodules developed within a short time-interval,Lung cancers found in incidence screening rounds tend to be more aggressive than those detected at baseline.4of39l Up to now,no study has focused on new solid nodules found during lung cancer screening.l We aimed to identify the occurrence of new solid nodules and their probability of being lung cancer at incidence screening rounds in the Dutch-Belgian Randomized Lung Cancer Screening Trial(NELSON).Introduction5of39Dutch Belgian randomised lung cancer screening trial(NELSON)Overall trial start date16/08/2003Overall trial end date31/12/20156of39l Organisation：Erasmus Medical Centre(Netherlands)l Participating centres:University Medical Centre Groningen,University Medical Centre Utrecht,Kennemer Gasthuis Haarlem(the Netherlands),and University Hospital Leuven(Belgium).Dutch Belgian randomised lung cancer screening trial(NELSON)7of39Dutch Belgian randomised lung cancer screening trial(NELSON)studyaims：1.Toinvestigatewhetherscreeninginahigh-riskpopulationleadstoareductioninlungcancerdeathsofatleast25%;2.Toestimatetheimpactoflungcancerscreeningonhealth-relatedqualityoflifeandsmokingcessation3.Toestimatecost-effectivenessoflungcancerscreeningforsubgroups.8of39lParticipant inclusion criteria1.Bornbetween1928and1956（50-75years）2.Smoked:2.1.Morethan15cigarettesperdayformorethan25years,or2.2.Morethan10cigarettesperdayformorethan30years3.Currentorformersmokerswhoquitsmokinglessthanorequalto10yearsagol Participant exclusion criteria1.Moderateorbadself-reportedhealthwhowereunabletoclimbtwoflightsofstairs2.Bodyweightgreaterthanorequalto140kg3.Currentorpastrenalcancer,melanomaorbreastcancer4.Lungcancer,diagnosedlessthanfiveyearsagoorgreaterthanorequaltofiveyearsbutstillundertreatment5.HadachestCTexaminationlessthanoneyearDutch Belgian randomised lung cancer screening trial(NELSON)9of39lIntervention1.Screenarm:1.1.16-detectormulti-slicecomputedtomographyofthechestinyearone,twoandfourofthestudy1.2.Pulmonaryfunctiontest1.3.Bloodsampling1.4.Questionnaires1.5.Smokingcessationadviceforcurrentsmokers2.Controlarm:Smokingcessationadviceforcurrentsmokers.Dutch Belgian randomised lung cancer screening trial(NELSON)Methods-Study design and participants10 of39Intheongoing,multicentre,randomisedcontrolledNELSONtrial,betweenDec23,2003,andJuly6,2006.15822participantswereenrolledandrandomlyassignedtoreceiveeitherscreeningwithlow-doseCT(n=7915)ornoscreening(n=7907).7557individualsunderwentbaseline;7295participantsunderwentsecondandthirdscreeningrounds.Methods-Study design and participants11 of39Thesecondscreeningroundtookplace1yearafterthebaselinescan(annualscreen).Thethirdscreeningroundtookplace2yearsafterthesecondscreeningscan(biannualscreen).Resultsofthefourthscreeninground,done55yearsafterbaseline(25yearscreeninginterval).Methods-Study design and participants12 of39Weincludedallparticipantswithsolidnon-calcifiednodules,registeredbytheNELSONradiologistsasneworsmallerthan15mm3(studydetectionlimit)atpreviousscreens.Methods-Procedures13 of39Nodulevolumewasgeneratedsemiautomaticallybysoftware.Thesemiautomatedvolumetricsoftware(LungCARE,versionSomaris/5VA70C-W,SiemensMedicalSolutions,Forchheim,Germany).Onthebasisofthethree-dimensionalnodulevolume,thissoftwarealsosimulatedlongestandperpendicularnodulediameterintheaxialplane.Methods-Procedures14 of39ForsubsequentCTscans,noduleswereindividuallymatchedonpreviousscansbythesoftwaresmatchingalgorithm(dependingonconsistency,size,andlocation),andvisuallycheckedbytheradiologists.Methods-Procedures15 of39Atfirstdetection,solidnoduleswereassessedbasedonvolume.Becausenewnoduleswereconsideredfast-growing,theirfollow-upstrategydifferedfrombaselinenodules.Newnodulesmeasuring1550mm3withoutbenigncharacteristicswereconsideredindeterminate(follow-uplow-doseCTafter1year),newnodulesmeasuring50500mm3werealsoconsideredindeterminate(follow-uplow-doseCTwithin68weeks),andnewnodulesmeasuring500mm3ormorewereconsideredpositive(immediatereferraltopulmonologist).Methods-Procedures16 of39lAfterinitialdetection,subsequentevaluationofanodulewasbasedongrowthandvolumedoublingtime.lWecalculatedthemaximumvolumedoublingtimefornoduleswithanestimatedpercentagevolumechangeof25%ormore.17 of39Methods-ProceduresIn theory,the actual volume doubling time in the examined time interval might have been faster,but not slower,than the calculated maximum time.Methods-Procedures18 of39lFornoduleseventuallydiagnosedascancer,wesupplementeddatawithcancer-specificinformationobtainedatdiagnosis,suchashistologyandstage.lMalignancy was based on histology,and benignity was based on histology or stable size for at least 2 years.Methods-Statistical analysis19 of39NormalitytestingforcontinuousvariableswasdonewiththeKolmogorovSmirnovtest.ContinuousvariableswereanalysedwiththeMannWhitneyUtestandarepresentedasmediansandIQRs.WeusedFishersexacttesttoanalysenominalvariables.Methods-Statistical analysis20 of39Receiveroperatingcharacteristic(ROC)analysiswasdonefornodulevolumewitheventuallungcancerdiagnosisastheoutcometoevaluatetheirperformanceaspredictorsoflungcancerandtoestimatecutoffvalues.Wederivedcutoffvalueswithapredefinedoverallsensitivityof95%.Methods-Statistical analysis21 of39Wedevelopedariskpredictionmodeltoassesswhethertheestablishedrelationbetweenvolumeofanewsolidnoduleandlungcancerdiagnosisremainedsignificantindependentofotherriskfactors(ie,age,sex,pack-years,smokingstatus,timesincepreviousscan,solidnodulecountatbaseline,andnoduleimagingandvolume).Results22 of39Weanalyseddataforparticipantswithatleastonesolidnon-calcifiednoduleatthesecondorthirdscreeninground.Inthetwoincidencescreeningrounds,theNELSONradiologistsregistered1222newsolidnodulesin787(11%)participants.23 of39Table1showscharacteristicsofincludedparticipants.Ahighernumberofpack-yearssmokedandalowernumberofsolidnodulesatbaselinescreeningsignificantlyincreasedtheprobabilityofanewsolidnodulebeinglungcancer.Increasedagewasnotsignificantlyassociatedwithlungcancer.Results24 of39In49(6%)participantswithnewsolidnodules,anewsolidnodulewaslungcancer.Oneparticipantwasdiagnosedwithsynchronousdoubletumoursintwonewnodules.Intotal,50lungcancerswerefound,representing4%ofallnewsolidnodules.25 of39Table 2:New solid new nodules detected during second and third screening rounds(N=1222;1172 benign nodules and 50 lung cancer nodules).Results26 of39Nodule volume had a high discriminatory power(area under the receiver operating curve 0795 95%CI 07280862;p00001).27 of39Results28 of39Nodulessmallerthan27mm3hadalowprobabilityoflungcancer(two05%of417nodules;lungcancerprobability05%95%CI0019),noduleswithavolumeof27mm3upto206mm3hadanintermediateprobability(1731%of542nodules;lungcancerprobability31%1950),andnodulesof206mm3orgreaterhadahighprobability(29169%of172nodules;lungcancerprobability169%120232).Avolumecutoffvalueof27mm3orgreaterhadmorethan95%sensitivityforlungcancer.29 of39Results30 of39Lessthanhalfofscreen-detectedlungcancersinnewsolidnoduleswere500mm3ormoreatfirstnoduledetection.Histologically,mostlungcancerswereadenocarcinomas,squamous-cellcarcinomas,orsmall-celllungcarcinomas.Mostsmall-celllungcarcinomasandsquamous-cellcarcinomashadvolumesgreaterthan500mm3atfirstnoduledetection.However,fewadenocarcinomasinitiallypresentedwithvolumesof500mm3andmore,whereasroughlytwo-fifthsweresmallerthan50mm3atfirstdetection.MostlungcancerswerediagnosedatstageI.Inabouthalfthelungcancercases,participantswerereferredimmediatelyafterfirstnewsolidnoduledetection.Adenocarcinomastendedtobereferredlater.Discussion31 of39Fewstudiesoflungcancerscreeninghavepublisheddetaileddataregardingnewnodulesatincidencescreeningrounds.Furthermore,toourknowledge,thisisthefirsttimenodulevolumecutoffvalueshavebeenestablishedasaguideforfurthermanagementofnewsolidnodules.1.Discussion32 of392.meredetectionofanewsolidnoduleduringincidencescreeningmightcarrythesamelungcancerprobabilityasasuspicioustestresultduringbaselinescreening(6%vs5%;p=025).Discussion33 of393.Atthesetinynodulesizes,growthdetectionbasedontwo-dimensionaldiameterevaluationisunreliable,favouringvolumetry.Discussion34 of39Agewasnotsignificantlyassociatedwithnewnodulelungcancer.Possibleexplanationscouldbethatthenumberofcaseswastoolowtoshowthecorrelation,orperhapsfastnodulegrowthislessassociatedwithage,possiblyevenwithaconverserelation,witholderindividualshavinglessfast-growingnodules.4.Discussion35 of395.Themaximumvolumedoublingtimewassignificantlylowerinnewnodulelungcancersthaninbenignnewsolidnodules.Notably,themedianmaximumvolumedoublingtimeofadenocarcinomas(191daysIQR146348)andsquamous-cellcarcinomas(133days105182)wassimilartopreviouslypublishedvolumedoublingtimeoffast-growingbaselinecancersintheNELSONtrialofthesamehistologicaltype(196daysIQR135250and142days91178,respectively).Discussion36 of396.Comparedwiththeoverallscreeningresultsofthefirstthreerounds,newsolidnodulecancercomprised11(19%)of58cancersfoundinthesecondscreening;and34(44%)of77cancerseveninthethirdscreening;Thus,managementofnewsolidnoduleshasagreatimpactontheoutcomeofalungcancerscreeningprogramme.Discussion37 of397.limitationsWeexcludednodulessmallerthan15mm3,WecannotexcludethepossibilitythattheactualnumberofnewnodulesissomewhathigherthanwereportbasedontheNELSONmanagementsysteminformation.Weincludedonlysolidnodules,withexclusionofpart-solidandpureground-glassnodules.Calculationofamaximumvolumedoublingtimefornewnodulesisanewandnotyetvalidatedapproach,andsoneedsfurtherinvestigation.Ratesofnewsolidnodulesandcancerdifferedbetweentheincidencescreeningrounds.Discussion38 of39Ourstudyshowsthatnewsolidnodulesaredetectedateachscreeningroundin57%ofindividualswhoundergoscreeningforlungcancerwithlow-doseCT.Thesenewnoduleshaveahighprobabilityofmalignancyevenatasmallsize.Thesefindingsshouldbeconsideredinfuturescreeningguidelines.Newsolidnodulesshouldbefollowedupmoreaggressivelythannodulesdetectedatbaselinescreening,forexamplebyusinglowervolumecutoffvalues(27mm3,27mm3to206mm3,206mm3)withasensitivityofmorethan95%.THANK YOU