恶性淋巴瘤疗效评价标准.ppt

“REVISEDRESPONSECRITERIAFORMALIGNANTLYMPHOMA”,JClinOncol25:579-586.2019byAmericanSocietyofClinicalOncology,Chesonetal,JClinOncol17:1244,2019,In2019,anInternationalWorkingGroup(IWG)ofclinicians,radiologists,andpathologistswithexpertiseintheevaluationandmanagementofpatientswithLymphomapublishedguidelinesforresponseassessmentandoutcomesmeasurement.,ResponseCriteriaforLymphoma,DefinitionsofEndPointsforClinicalTrials,Standardizedresponsecriteriaprovideuniformendpointsforclinicaltrials:,AllowingforcomparisonsamongstudiesFacilitatingtheidentificationofmoreeffectivetherapies,ThewidelyusedIWGcriteriaforresponseassessmentoflymphomaarebasedpredominantlyonCT.ItbecameclearthattheInternationalWorkingGroupcriteriawarrantedrevision,becauseofidentifiedlimitationsandtheincreaseduseof:,18Ffluorodeoxyglucose-positronemissiontomography(PET),immunohistochemistry(IHC),flowcytometry,molecularbiology,“REVISEDRESPONSECRITERIAFORMALIGNANTLYMPHOMA”,JClinOncol25:579-586.2019byAmericanSocietyofClinicalOncology,TheCompetenceNetworkMalignantLymphomaconvenedanInternationalHarmonizationProjectatwhich5subcommitteeswereformed:,ResponseCriteriaEndPointsforClinicalTrialsImagingClinicalFeaturesPathology/Biology,UseofPositronEmissionTomographyforResponseAssessmentofLymphoma:ConsensusoftheImagingSubcommitteeofInternationalHarmonizationProjectinLymphoma,JClinOncol25:571-578.2019byAmericanSocietyofClinicalOncology,PET-PET/CT,PETusing18Ffluorodeoxyglucose(FDG,aradioactivederivativeofglucose,isanadvancedimagingtool,basedontheincreasedglucoseconsumptionofcancercells),hasemergedasapowerfulfunctionalimagingtoolforstaging,restaging,andresponseassessmentoflymphomas.TheadvantageofPEToverconventionalimagingtechniques,suchasTCorRMN,isitsabilitytodistinguishbetweenviabletumorandnecrosisorfibrosisinresidualmass(es)oftenpresentaftertreatment.ArecentlydevelopedintegratedPET/CTsystem,whichcombinesaPETcameraandCTscannerinasinglesession,hasovercomethesedrawbacksbyprovidingbothanatomicalandfunctionalimagingatthesameposition.PET/CThasbecomethenewstandardapproachtoimaginginthediagnosisandmanagementofmanycancerpatients.,StandardizationofPETandCTImagingParameters,PatientsundergoingPETimagingshouldreceiveanFDGdoseof3.5to8MBq/kgofbodyweight,withaminimumdoseof185MBqinadults(5mCi)and18.5MBq(0.5mCi)inchildren.Patientsshouldhavefastedforatleast4hoursbeforeFDGinjection.Bloodglucoselevelshouldnotexceed200mg/dLatthetimeofFDGinjection.Ifthebloodglucoseexceedsthislevel,theFDG-PETstudyshouldberescheduledandanattemptmadetocontrolthebloodsugar.Whole-bodyacquisitionusingaPETorPET/CTsystemshouldencompassatleasttheregionbetweenthebaseoftheskullandthemedthigh,andcanbeacquiredineithertwo-orthree-dimensionalmode.Whole-bodyimagingshouldbegin50-70minutesaftertheadministrationofFDG.ThereconstructedPETorPET/CTimagesmustbedisplayedonacomputerworkstationsothattransaxial,sagittal,andcoronalimagescanbeviewedsimultaneously.,PET,False-positive:-Thymichyperplasia-Infection-Inflammation-Sarcoidosis-BrownfatOthercausesoffalse-positivescansshouldberuledout.False-negative:-Resolutionoftheequipmentandtechnique-VariabilityofFDGavidityamonghistologicsubtypes,Juweidetal.evaluatedtheimpactofintegratingPETintotheIWGcriteriainaretrospectivestudyof54patientswithdiffuselargeB-cellNHLwhohadbeentreatedwithananthracycline-basedregimen.PET:Increasedthenumberofcompleteremission(CR)patients,EliminatedtheCRucategoryEnhancedtheabilitytodiscernthedifferenceinprogression-freesurvival(PFS)betweenpatientsexperiencingCRandPR,RecommendationsfortheuseofPETorPET/CT,PETisstronglyrecommendedbeforetreatmentforpatientswithroutinelyFDG-avid,potentiallycurablelymphomas(eg,diffuselargeB-celllymphomaDLBCL,Hodgkinslymphoma)tobetterdelineatetheextentofdisease.2.PETisessentialforthepost-treatmentassessmentofDLBCLandHodgkinslymphomabecauseacompleteresponseisrequiredforacurativeoutcome.Basedonthe“meta-analysisbyZijlstraetal”,pooledsensitivityandspecificityofFDG-PETfordetectionofresidualdiseaseaftercompletionoffirst-linetherapywere84%and90%,respectively,forHL,and72%and100%,respectively,foraggressiveNHL.,RecommendationsfortheuseofPETorPET/CT,3.However,PETisrecommendedintheother,incurablehistologiesonlyiftheywerePETpositivebeforetreatmentandifresponserateisaprimaryendpointofaclinicalstudy.4.NumerousstudieshavedemonstratedthatPETperformedafter1to4cyclesofmultiagentchemotherapypredictstherapeuticoutcome;however,nocurrentlyavailabledatademonstrateimprovementinresultsbyalteringtreatmentbasedonthisinformation.TheroleofPETforresponseassessmentofaggressiveNHLsubtypesotherthanDLBCLandofindolentandmantle-celllymphomas,islessclear.ForthesegenerallyincurableNHLs,progression-freeoroverallsurvivalisusuallytheprimaryendpointinclinicaltrialsevaluatingtheirresponsetotreatment.,RequirementforPretherapyPETScanforResponseAssessmentofLymphomaattheConclusionofTherapy,notobligatoryforassessmentofresponseaftertreatmentofpatientswithHL,DLBCL,follicularlymphoma,ormantle-celllymphomabecausetheselymphomasroutinelyareFDGavid.However,itisstronglyencouragedforthesesubtypesbecauseitcanfacilitatetheinterpretationofpost-therapyPET.mandatoryforvariablyFDG-avidlymphomas,ifPETisusedtoassesstheirresponsetotreatment.TheseincludeaggressiveNHLsubtypesotherthanDLBCL,suchasT-celllymphomas,andallsubtypesofindolentNHLotherthanfollicularlymphoma,suchasextranodalmarginalzonelymphomaofmucosaassociatedlymphoidtissueandsmalllymphocyticlymphoma.IfPETistobeusedforresponseassessmentofpatientswiththesehistologicsubtypes,thereneedstobedocumentationthatPETwaspositiveatalldiseasesites1.5cmindiameternotedbyCT.,TimingofPETPerformedforResponseAssessmentattheConclusionofTherapy,PETshouldnotbeperformedbeforeatleast3weeksafterchemotherapyandpreferably8to12weeksaftercompletionofradiotherapy.,REVISEDRESPONSECRITERIA,2019,Endpoint,OverallSurvivalisdefinedasthetimefromentryontotheclinicaltrialuntildeathasaresultofanycause.ProgressionFreeSurvivalisdefinedasthetimefromentryontoastudyuntillymphomaprogressionordeathasaresultofanycause.PFSisoftenconsideredthepreferredendpointinlymphomaclinicaltrials,itreflectstumorgrowth,andthereforeisinterpretableearlierthantheendpointofoverallsurvival.Event-FreeSurvivalismeasuredfromthetimefromstudyentrytoanytreatmentfailureincludingdiseaseprogression,ordiscontinuationoftreatmentforanyreason(eg,diseaseprogression,toxicity,patientpreference,initiationofnewtreatmentwithoutdocumentedprogression,ordeath).Itmaybeusefulintheevaluationofsometherapiessuchasthosethatarehighlytoxic.TimetoProgressionisdefinedasthetimefromstudyentryuntildocumentedlymphomaprogressionordeathasaresultoflymphoma.Disease-FreeSurvivalismeasuredfromthetimeofoccurrenceofdisease-freestateorattainmentofaCRtodiseaserecurrenceordeathasaresultoflymphomaoracutetoxicityoftreatment.,Endpoint,ResponseDuratioisfromthetimewhencriteriaforresponse(ie,CRorPR)aremet,forwhichtheeventisthefirstdocumentationofrelapseorprogression.Lymphoma-SpecificSurvival(eg,disease-specificsurvival,causespecificsurvival)isdefinedastimefromstudyentrytodeathasaresultoflymphoma.TimetoNextTreatmentisdefinedasthetimetonextlymphomatreatmentmaybeofinterest,andisdefinedastimefromtheendofprimarytreatmentuntiltheinstitutionofthenexttherapy.ClinicalBenefitisoneofthemostimportantendpointsforpatientsaswellasfordrugapprovalbyregulatoryagencieshasbeenevidenceofclinicalbenefit.Clinicalbenefitmayreflectimprovementin:qualityoflife,reductioninpatientsymptoms,transfusionrequirements,frequentinfections,otherparameters.Timetoreappearanceorprogressionoflymphoma-relatedsymptomscanalsobeusedinthisendpoint.,Follow-UpEvaluation,-Goodclinicaljudgmentandacarefulhistory-Physicalexamination-CBCandserumchemistriesThereisnoevidencetosupportregularsurveillanceCTscans,giventhatthepatientorphysicianidentifiestherelapsemorethan80%ofthetimewithouttheneedforimagingstudies.DatawithPETarealsoinsufficienttorecommendroutineproceduresatthistime.Inaclinicaltrial,uniformityofreassessmentisnecessarytoensurecomparabilityamongstudieswithrespecttothemajorendpointsof:event-freesurvival,disease-freesurvivalprogressionfreesurvivalOnerecommendationhasbeentoassesspatientsonclinicaltrialsaftercompletionoftreatmentataminimumofevery3monthsfor2years,thenevery6monthsfor3years,andthenannuallyforatleast5years.Theseintervalsmayvarywith:-specifictreatments-durationoftreatment-protocols-uniquedrugcharacteristics,Follow-UpEvaluation,Recently,theNationalComprehensiveCancerNetworkpublishedrecommendationsforfollow-upofpatientswithHodgkinsandNHL:forpatientswithHodgkinslymphomainaninitialCR,aninterimhistoryandphysicalexaminationevery2to4monthsfor1to2years,thenevery3to6monthsforthenext3to5years,withannualmonitoringforlateeffectsafter5years.ForfollicularorotherindolenthistologylymphomapatientsinaCR,therecommendationforfollow-upwasevery3monthsforayearthenevery3to6mo