恶性淋巴瘤疗效评价标准PPT课件

REVISEDRESPONSECRITERIAFORMALIGNANTLYMPHOMA JClinOncol25 579 586 2007byAmericanSocietyofClinicalOncology 1 Chesonetal JClinOncol17 1244 1999 In1999 anInternationalWorkingGroup IWG ofclinicians radiologists andpathologistswithexpertiseintheevaluationandmanagementofpatientswithLymphomapublishedguidelinesforresponseassessmentandoutcomesmeasurement 2 3 4 ResponseCriteriaforLymphoma 5 DefinitionsofEndPointsforClinicalTrials 6 Standardizedresponsecriteriaprovideuniformendpointsforclinicaltrials AllowingforcomparisonsamongstudiesFacilitatingtheidentificationofmoreeffectivetherapies 7 ThewidelyusedIWGcriteriaforresponseassessmentoflymphomaarebasedpredominantlyonCT ItbecameclearthattheInternationalWorkingGroupcriteriawarrantedrevision becauseofidentifiedlimitationsandtheincreaseduseof 18F fluorodeoxyglucose positronemissiontomography PET immunohistochemistry IHC flowcytometry molecularbiology 8 REVISEDRESPONSECRITERIAFORMALIGNANTLYMPHOMA JClinOncol25 579 586 2007byAmericanSocietyofClinicalOncology 9 TheCompetenceNetworkMalignantLymphomaconvenedanInternationalHarmonizationProjectatwhich5subcommitteeswereformed ResponseCriteriaEndPointsforClinicalTrialsImagingClinicalFeaturesPathology Biology 10 UseofPositronEmissionTomographyforResponseAssessmentofLymphoma ConsensusoftheImagingSubcommitteeofInternationalHarmonizationProjectinLymphoma JClinOncol25 571 578 2007byAmericanSocietyofClinicalOncology 11 PET PET CT PETusing 18F fluorodeoxyglucose FDG aradioactivederivativeofglucose isanadvancedimagingtool basedontheincreasedglucoseconsumptionofcancercells hasemergedasapowerfulfunctionalimagingtoolforstaging restaging andresponseassessmentoflymphomas TheadvantageofPEToverconventionalimagingtechniques suchasTCorRMN isitsabilitytodistinguishbetweenviabletumorandnecrosisorfibrosisinresidualmass es oftenpresentaftertreatment ArecentlydevelopedintegratedPET CTsystem whichcombinesaPETcameraandCTscannerinasinglesession hasovercomethesedrawbacksbyprovidingbothanatomicalandfunctionalimagingatthesameposition PET CThasbecomethenewstandardapproachtoimaginginthediagnosisandmanagementofmanycancerpatients 12 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 13 PET False positive Thymichyperplasia Infection Inflammation Sarcoidosis BrownfatOthercausesoffalse positivescansshouldberuledout False negative Resolutionoftheequipmentandtechnique VariabilityofFDGavidityamonghistologicsubtypes 14 Juweidetal evaluatedtheimpactofintegratingPETintotheIWGcriteriainaretrospectivestudyof54patientswithdiffuselargeB cellNHLwhohadbeentreatedwithananthracycline basedregimen PET Increasedthenumberofcompleteremission CR patients EliminatedtheCRucategoryEnhancedtheabilitytodiscernthedifferenceinprogression freesurvival PFS betweenpatientsexperiencingCRandPR 15 RecommendationsfortheuseofPETorPET CT PETisstronglyrecommendedbeforetreatmentforpatientswithroutinelyFDG avid potentiallycurablelymphomas eg diffuselargeB celllymphoma DLBCL Hodgkin slymphoma tobetterdelineatetheextentofdisease 2 PETisessentialforthepost treatmentassessmentofDLBCLandHodgkin slymphomabecauseacompleteresponseisrequiredforacurativeoutcome Basedonthe meta analysisbyZijlstraetal pooledsensitivityandspecificityofFDG PETfordetectionofresidualdiseaseaftercompletionoffirst linetherapywere84 and90 respectively forHL and72 and100 respectively foraggressiveNHL 16 RecommendationsfortheuseofPETorPET CT 3 However PETisrecommendedintheother incurablehistologiesonlyiftheywerePETpositivebeforetreatmentandifresponserateisaprimaryendpointofaclinicalstudy 4 NumerousstudieshavedemonstratedthatPETperformedafter1to4cyclesofmultiagentchemotherapypredictstherapeuticoutcome however nocurrentlyavailabledatademonstrateimprovementinresultsbyalteringtreatmentbasedonthisinformation TheroleofPETforresponseassessmentofaggressiveNHLsubtypesotherthanDLBCLandofindolentandmantle celllymphomas islessclear ForthesegenerallyincurableNHLs progression freeoroverallsurvivalisusuallytheprimaryendpointinclinicaltrialsevaluatingtheirresponsetotreatment 17 RequirementforPretherapyPETScanforResponseAssessmentofLymphomaattheConclusionofTherapy notobligatoryforassessmentofresponseaftertreatmentofpatientswithHL DLBCL follicularlymphoma ormantle celllymphomabecausetheselymphomasroutinelyareFDGavid However itisstronglyencouragedforthesesubtypesbecauseitcanfacilitatetheinterpretationofpost therapyPET mandatoryforvariablyFDG avidlymphomas ifPETisusedtoassesstheirresponsetotreatment TheseincludeaggressiveNHLsubtypesotherthanDLBCL suchasT celllymphomas andallsubtypesofindolentNHLotherthanfollicularlymphoma suchasextranodalmarginalzonelymphomaofmucosaassociatedlymphoidtissueandsmalllymphocyticlymphoma IfPETistobeusedforresponseassessmentofpatientswiththesehistologicsubtypes thereneedstobedocumentationthatPETwaspositiveatalldiseasesites 1 5cmindiameternotedbyCT 18 TimingofPETPerformedforResponseAssessmentattheConclusionofTherapy PETshouldnotbeperformedbeforeatleast3weeksafterchemotherapyandpreferably8to12weeksaftercompletionofradiotherapy 19 REVISEDRESPONSECRITERIA 2007 20 Endpoint OverallSurvivalisdefinedasthetimefromentryontotheclinicaltrialuntildeathasaresultofanycause ProgressionFreeSurvivalisdefinedasthetimefromentryontoastudyuntillymphomaprogressionordeathasaresultofanycause PFSisoftenconsideredthepreferredendpointinlymphomaclinicaltrials itreflectstumorgrowth andthereforeisinterpretableearlierthantheendpointofoverallsurvival Event FreeSurvivalismeasuredfromthetimefromstudyentrytoanytreatmentfailureincludingdiseaseprogression ordiscontinuationoftreatmentforanyreason eg diseaseprogression toxicity patientpreference initiationofnewtreatmentwithoutdocumentedprogression ordeath Itmaybeusefulintheevaluationofsometherapiessuchasthosethatarehighlytoxic TimetoProgressionisdefinedasthetimefromstudyentryuntildocumentedlymphomaprogressionordeathasaresultoflymphoma Disease FreeSurvivalismeasuredfromthetimeofoccurrenceofdisease freestateorattainmentofaCRtodiseaserecurrenceordeathasaresultoflymphomaoracutetoxicityoftreatment 21 Endpoint ResponseDuratioisfromthetimewhencriteriaforresponse ie CRorPR aremet forwhichtheeventisthefirstdocumentationofrelapseorprogression Lymphoma SpecificSurvival eg disease specificsurvival causespecificsurvival isdefinedastimefromstudyentrytodeathasaresultoflymphoma TimetoNextTreatmentisdefinedasthetimetonextlymphomatreatmentmaybeofinterest andisdefinedastimefromtheendofprimarytreatmentuntiltheinstitutionofthenexttherapy ClinicalBenefitisoneofthemostimportantendpointsforpatientsaswellasfordrugapprovalbyregulatoryagencieshasbeenevidenceofclinicalbenefit Clinicalbenefitmayreflectimprovementin qualityoflife reductioninpatientsymptoms transfusionrequirements frequentinfections otherparameters Timetoreappearanceorprogressionoflymphoma relatedsymptomscanalsobeusedinthisendpoint 22 Follow UpEvaluation Goodclinicaljudgmentandacarefulhistory Physicalexamination CBCandserumchemistriesThereisnoevidencetosupportregularsurveillanceCTscans giventhatthepatientorphysicianidentifiestherelapsemorethan80 ofthetimewithouttheneedforimagingstudies DatawithPETarealsoinsufficienttorecommendroutineproceduresatthistime Inaclinicaltrial uniformityofreassessmentisnecessarytoensurecomparabilityamongstudieswithrespecttothemajorendpointsof event freesurvival disease freesurvivalprogressionfreesurvivalOnerecommendationhasbeentoassesspatientsonclinicaltrialsaftercompletionoftreatmentataminimumofevery3monthsfor2years thenevery6monthsfor3years andthenannuallyforatleast5years Theseintervalsmayvarywith specifictreatments durationoftreatment protocols uniquedrugcharacteristics 23 Follow UpEvaluation Recently theNationalComprehensiveCancerNetworkpublishedrecommendationsforfollow upofpatientswithHodgkin sandNHL forpatientswithHodgkin slymphomainaninitialCR aninterimhistoryandphysicalexaminationevery2to4monthsfor1to2years thenevery3to6monthsforthenext3to5years withannualmonitoringforlateeffectsafter5years ForfollicularorotherindolenthistologylymphomapatientsinaCR therecommendationforfollow upwasevery3monthsforayearthenevery3to