2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)課件

2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)“REVISEDRESPONSECRITERIAFORMALIGNANTLYMPHOMA”2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)Chesonetal,JClinOncol17:1244,1999 In1999,anInternationalWorkingGroup(IWG)ofclinicians,radiologists,andpathologistswithexpertiseintheevaluationandmanagementofpatientswithLymphomapublishedguidelinesforresponseassessmentandoutcomesmeasurement.2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)ResponseCriteriaforLymphomaReappearanceNeworincreasedNeworincreasedEnlargingliver/spleen;newsitesRelapse/progressionIrrelevant≥50%decrease≥50%decreaseDecreaseinliver/spleenIrrelevant≥50%decrease≥50%decreaseNormalPositiveNormalNormalNormalPRNormalorindeterminate>75%decreaseNormalNormalIndeterminateNormalNormalNormalCRuNormalNormalNormalNormalCRBoneMarrowLymphNodeMassesLymphNodesPhysicalExaminationResponseCategory2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)DefinitionsofEndPointsforClinicalTrials

DeathDeathrelatedtoNHLAllpatientsCause-specificdeathEntryontotrialTimewhennewtreatmentisneededAllpatientsTimetonexttreatmentFirstdocumentationofresponseTimetorelapseorprogressionCR,CRu,PRResponsedurationFirstdocumentationofresponseTimetorelapseCR,CRuDisease-freesurvivalEntryontotrialDiseaseprogressionordeathfromNHLAllpatientsProgression-freesurvivalEntryontotrialFailureordeathfromanycauseCR,CRu,PREvent-freesurvivalEntryontotrialDeathfromanycauseAllpatientsOverallsurvivalPointofMeasurementDefinitionResponseCategoryEndPoint2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)Standardizedresponsecriteriaprovideuniformendpointsforclinicaltrials:AllowingforcomparisonsamongstudiesFacilitatingtheidentificationofmore effectivetherapies2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)ThewidelyusedIWGcriteriaforresponseassessmentoflymphomaarebasedpredominantlyonCT.

ItbecameclearthattheInternationalWorkingGroupcriteriawarrantedrevision,becauseofidentifiedlimitationsandtheincreaseduseof:[18F]fluorodeoxyglucose-positronemissiontomography(PET),

immunohistochemistry(IHC),flowcytometry,molecularbiology2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)“REVISEDRESPONSECRITERIAFORMALIGNANTLYMPHOMA”JClinOncol25:579-586.?2007byAmericanSocietyofClinicalOncology2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)TheCompetenceNetworkMalignantLymphomaconvenedanInternationalHarmonizationProjectatwhich5subcommitteeswereformed:ResponseCriteriaEndPointsforClinicalTrialsImagingClinicalFeaturesPathology/Biology2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)UseofPositronEmissionTomographyforResponseAssessmentofLymphoma:ConsensusoftheImagingSubcommitteeofInternationalHarmonizationProjectinLymphoma JClinOncol25:571-578.?2007byAmericanSocietyofClinicalOncology2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)PET-PET/CTPETusing[18F]fluorodeoxyglucose(FDG,aradioactivederivativeofglucose,isanadvancedimagingtool,basedontheincreasedglucoseconsumptionofcancercells),hasemergedasapowerfulfunctionalimagingtoolforstaging,restaging,andresponseassessmentoflymphomas.TheadvantageofPEToverconventionalimagingtechniques,suchasTCorRMN,isitsabilitytodistinguishbetweenviabletumorandnecrosisorfibrosisinresidualmass(es)oftenpresentaftertreatment.ArecentlydevelopedintegratedPET/CTsystem,whichcombinesaPETcameraandCTscannerinasinglesession,hasovercomethesedrawbacksbyprovidingbothanatomicalandfunctionalimagingatthesameposition.PET/CThasbecomethenewstandardapproachtoimaginginthediagnosisandmanagementofmanycancerpatients.2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)StandardizationofPETandCTImagingParametersPatientsundergoingPETimagingshouldreceiveanFDGdoseof3.5to8MBq/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.2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)PETFalse-positive: -Thymichyperplasia -Infection -Inflammation -Sarcoidosis -Brownfat Othercausesoffalse-positivescansshould beruledout.False-negative: -Resolutionoftheequipmentandtechnique -VariabilityofFDGavidityamonghistologicsubtypes2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)Juweidetal.evaluatedtheimpactofintegratingPETintotheIWGcriteriainaretrospectivestudyof54patientswithdiffuselargeB-cellNHLwhohadbeentreatedwithananthracycline-basedregimen.PET:Increasedthenumberofcompleteremission(CR)patients,EliminatedtheCRucategoryEnhancedtheabilitytodiscernthedifferenceinprogression-freesurvival(PFS)betweenpatientsexperiencingCRandPR2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)RecommendationsfortheuseofPETorPET/CTPETisstronglyrecommendedbeforetreatmentforpatientswithroutinelyFDG-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.2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)RecommendationsfortheuseofPETorPET/CT3. However,PETisrecommendedintheother,incurablehistologiesonlyiftheywerePETpositivebeforetreatmentandifresponserateisaprimaryendpointofaclinicalstudy. 4. NumerousstudieshavedemonstratedthatPETperformedafter1to4cyclesofmultiagentchemotherapypredictstherapeuticoutcome;however,nocurrentlyavailabledatademonstrateimprovementinresultsbyalteringtreatmentbasedonthisinformation.TheroleofPETforresponseassessmentofaggressiveNHLsubtypesotherthanDLBCLandofindolentandmantle-celllymphomas,islessclear.ForthesegenerallyincurableNHLs,progression-freeoroverallsurvivalisusuallytheprimaryendpointinclinicaltrialsevaluatingtheirresponsetotreatment.2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)RequirementforPretherapyPETScanforResponseAssessmentofLymphomaattheConclusionofTherapynotobligatoryforassessmentofresponseaftertreatmentofpatientswithHL,DLBCL,follicularlymphoma,ormantle-celllymphomabecausetheselymphomasroutinelyareFDGavid.However,itisstronglyencouragedforthesesubtypesbecauseitcanfacilitatetheinterpretationofpost-therapyPET.mandatoryforvariablyFDG-avidlymphomas,ifPETisusedtoassesstheirresponsetotreatment. TheseincludeaggressiveNHLsubtypesotherthanDLBCL,suchasT-celllymphomas,andallsubtypesofindolentNHLotherthanfollicularlymphoma,suchasextranodalmarginalzonelymphomaofmucosaassociatedlymphoidtissueandsmalllymphocyticlymphoma. IfPETistobeusedforresponseassessmentofpatientswiththesehistologicsubtypes,thereneedstobedocumentationthatPETwaspositiveatalldiseasesites≥1.5cmindiameternotedbyCT.2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)TimingofPETPerformedforResponseAssessment

attheConclusionofTherapyPETshouldnotbeperformedbeforeatleast3weeksafterchemotherapyandpreferably8to12weeksaftercompletionofradiotherapy.2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)REVISEDRESPONSECRITERIA,2007Neworrecurrentinvolvement>50%increasefromnadirintheSPDofanypreviouslesionsAppearanceofanewlesion(s)>1.5cminanyaxis,≥50%increaseinSPDofmorethanonenode,or≥50%increaseinlongestdiameterofapreviouslyidentifednode>1cminshortaxisLesionPETpositiveifFDG-avidlymphomaorPETpositivepriortherapyAnynewlesionorincreaseby≥50%ofpreviouslyinvolvedsitesfromnadirPD(a)FDG-avidorPETpositivepriortotherapy;PETpositivepriorsitesofdiseaseandnonewsitesonCTorPET(b)VariablyFDG-avidorPETnegative;nochangeinsizeofpreviouslesionsonCTFailuretoattainCR/PRorPDSDIrrelevantifpositivepriortotherapy;celltypeshouldbespecified≥50%decreaseinSPDofnodules;noincreaseinsizeofliverorspleen≥50%decreaseinSPDofupto6largestdominantmasses;noincreaseinsizeofothernodes(a)FDG-avidorPETpositivepriortotherapy;oneormorePETpositiveatpreviouslyinvolvedsite(b)VariablyFDG-avidorPETnegative;regressiononCTRegressionofmeasuablediseaseandnonewsitesPRInfiltrateclearedonrepeatbiopsy;ifindeterminatebymorphology,immunohistochemistryshouldbenegativeNotpalpable,nodulesdisappearedFDG-avidorPETpositivepriortotherapy;massofanysizepermittedifPETnegative-VariablyFDG-avidorPETnegative;regressiontonormalsizeonCTDisappearanceofallevidenceofdiseaseCRBONEMARROWSPLEEN,LIVERNODALMASSESDEFINITIONRESPONSE2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)EndpointOverallSurvivalisdefinedasthetimefromentryontotheclinicaltrialuntildeathasaresultofanycause.ProgressionFreeSurvivalisdefinedasthetimefromentryontoastudyuntillymphomaprogressionordeathasaresultofanycause. PFSisoftenconsideredthepreferredendpointinlymphomaclinicaltrials,itreflectstumorgrowth,andthereforeisinterpretableearlierthantheendpointofoverallsurvival.Event-FreeSurvivalismeasuredfromthetimefromstudyentrytoanytreatmentfailureincludingdiseaseprogression,ordiscontinuationoftreatmentforanyreason(eg,diseaseprogression,toxicity,patientpreference,initiationofnewtreatmentwithoutdocumentedprogression,ordeath). Itmaybeusefulintheevaluationofsometherapiessuchasthosethatarehighlytoxic.

TimetoProgressionisdefinedasthetimefromstudyentryuntildocumentedlymphomaprogressionordeathasaresultoflymphoma.

Disease-FreeSurvivalismeasuredfromthetimeofoccurrenceofdisease-freestateorattainmentofaCRtodiseaserecurrenceordeathasaresultoflymphomaoracutetoxicityoftreatment.

2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)EndpointResponseDuratioisfromthetimewhencriteriaforresponse(ie,CRorPR)aremet,forwhichtheeventisthefirstdocumentationofrelapseorprogression.Lymphoma-SpecificSurvival(eg,disease-specificsurvival,causespecificsurvival)isdefinedastimefromstudyentrytodeathasaresultoflymphoma.TimetoNextTreatmentisdefinedasthetimetonextlymphomatreatmentmaybeofinterest,andisdefinedastimefromtheendofprimarytreatmentuntiltheinstitutionofthenexttherapy.ClinicalBenefitisoneofthemostimportantendpointsforpatientsaswellasfordrugapprovalbyregulatoryagencieshasbeenevidenceofclinicalbenefit.Clinicalbenefitmayreflectimprovementin:qualityoflife,reductioninpatientsymptoms,transfusionrequirements,frequentinfections,otherparameters.Timetoreappearanceorprogressionoflymphoma-relatedsymptomscanalsobeusedinthisendpoint.2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)Follow-UpEvaluation

-Goodclinicaljudgmentandacarefulhistory -Physicalexamination -CBCandserumchemistries

ThereisnoevidencetosupportregularsurveillanceCTscans,giventhatthepatientorphysicianidentifiestherelapsemorethan80%ofthetimewithouttheneedforimagingstudies.DatawithPETarealsoinsufficienttorecommendroutineproceduresatthistime.Inaclinicaltrial,uniformityofreassessmentisnecessarytoensurecomparabilityamongstudieswithrespecttothemajorendpointsof: event-freesurvival, disease-freesurvival progressionfreesurvivalOnerecommendationhasbeentoassesspatientsonclinicaltrialsaftercompletionoftreatmentataminimumofevery3monthsfor2years,thenevery6monthsfor3years,andthenannuallyforatleast5years.Theseintervalsmayvarywith:-specifictreatments-durationoftreatment-protocols-uniquedrugcharacteristics2007年惡性淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn)Follow-UpEvaluationRecently,theNationalComprehensiveCancerNetworkpublishedrecommendationsforfollow-upofpatientswithHodgkin’sandNHL:forpatientswithHodgkin’slymphomainaninitialCR,aninterimhistoryandphysicalexaminationevery2to4monthsfor1to2years,thenevery3to6monthsforthenext3to