NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines?)PediatricHodgkinLymphomaersionMarchVersion3.2021,03/18/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:08:58AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexJamieEFlerlage,MD,MS/Chair€St.JudeChildren'sResearchHospital/TheUniversityofTennesseeHealthScienceCenter*SusanM.Hiniker,MD/ViceChair§StanfordCancerInstitute*SaroArmenian,DO,MPH€?CityofHopeNationalMedicalCenterEllenC.Benya,MDфAnn&RobertH.LurieChildren'sHospitalofChicago/RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityAdamJ.Bobbey,MDфeOhioStateUniversityComprehensivecerCenterJamesCancerHospitaldSoloveResearchInstituteVivianChang,MD€UCLAJonssonComprehensiveCancerCentercyCooperMDeSidneyKimmelComprehensiverCenteratJohnsHopkinsDonW.Coulter,MD€Fred&PamelaBuffettCancerCentervanMD*BradfordS.Hoppe,MD,MPH§CancerCenterLeidyIsenalumhe,MD,MS€?MoffittCancerCenterComprehensiveCancerCenterKersunMDMSCEMSEdfPhiladelphiaAbramsonheUniversityofPennsylvaniaAdamJ.Lamble,MD€CancerResearchCenterianceALarrierMDMScstituteJeffreyMagee,Md,PhD€?SitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolof*KwadwoOduro,MD,PhD≠?rehensiveCancerCenterUniversitysSeidmanCancerCenterandtuteMarthaPachecoMD€nsComprehensiveenterloanKetteringCancerCenterKennethB.Roberts,MD§YaleCancerCenter/SmilowCancerHospital*ChristineM.Smith,MD€?Vanderbilt-IngramCancerCenter*AliyahR.Sohani,MD≠ttsGeneralHospitalCancerCenterErinM.Trovillion,MD€?UCSanDiegoMooresCancerCenter*EmilyWalling,MD,MPHS€UniversityofMichiganRogelCancerCenterAnaC.Xavier,MD€O'NealComprehensiveCancerCenteratUABJenniferBurnsCampbellPhDesPanelDisclosures?Hematology/Hematologyoncology€PediatriconcologyфDiagnosticradiology≠Pathology§Radiotherapy/Radiationoncology*DiscussionSectionWritingCommitteeVersion3.2021,03/18/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:08:58AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexlievesthatthebestmanagementlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.tNCCNutionsclickhereinicaltrialsmemberpxofEvidenceanddationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.yoftheGuidelinesUpdatesDiagnosisandWorkup(PHL-1)ClinicalStagingofClassicHodgkinLymphoma(PHL-2)PrimaryTreatmentofCHL?Low-RiskDisease(PHL-3)?Intermediate-RiskDisease(PHL-4)?High-RiskDisease(PHL-5)Follow-upAfterCompletionofTreatmentandMonitoringforLateEffects(PHL-6)SuspectedRelapsed/RefractoryCHL(PHL-7)PrinciplesofCriteriaforResponse-AdaptedRadiationTherapy(PHL-A)PrinciplesofPathology(PHL-B)PrinciplesofImaging(PHL-C)PrinciplesofStaging(PHL-D)PrinciplesofSystemicTherapy(PHL-E)PrinciplesofRadiationTherapy(PHL-F)Staging(ST-1)TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNationalComprehensiveCancerNetworkAllrightsreservedTheNCCNGuidelinesandtheillustrationshereinmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2021.Version3.2021,03/18/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion3.2021,03/18/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:08:58AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexheNCCNGuidelinesforPediatricHodgkinLymphomafromVersioninclude?TheDiscussionsectionwasadded.heNCCNGuidelinesforPediatricHodgkinLymphomafromVersionincludePHL-E(2of3)?Footnotefmodified:PembrolizumabisindicatedforthetreatmentofadultandpediatricpatientswithrefractoryCHL,orwhohaverelapsedafter32ormorepriorlinesoftherapy.PHL-E(3of3)?Referenceadded:GeoergerB,KangHJ,Yalon-OrenM,etal.PembrolizumabinpaediatricpatientswithadvancedmelanomaoraPD-L1-positive,advanced,relapsed,orrefractorysolidtumourorlymphoma(KEYNOTE-051):interimanalysisofanopen-label,single-arm,phase1–2trial.LancetOncol.2020;21:121–33.PrintedbyMinTangon3/14/20227:08:58AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexConsultationwithcentersparticipatinginpediatriccooperativegrouptrialsisencouragedTherecommendationsintheseGuidelinesarefromthepreviousandmostrecentlypublishedtrials.?Referraltocurrentclinicaltrialsisencouragedwhereavailable.ThepediatricHodgkinlymphomaHL)panelconsiders“pediatric”toincludeanypatientaged≤18years,andmaybeapplicabletoesareintendedtoincludeAYApatientscologysettingsForgeneraloncologiccareofAYApatientsseetheNCCNGuidelinesTheguidelinesdonotcurrentlyaddressnodularlymphocyte-predominantHodgkinlymphoma(NLPHL),asdataarelimitedinpediatricpatients.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.INTRO-1Version3.2021,03/18/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.ionalbiopsya?Immunohisto-evaluationbErythrocytesedimentationrateESR)and/orC-reactiveprotein(CRP)mprehensivemetabolicpanelEchocardiogramespeciallyifanthracycline-basedchemotherapyisindicated)stxrayposteroanteriorPAandlateralviewsifcrossionalbiopsya?Immunohisto-evaluationbErythrocytesedimentationrateESR)and/orC-reactiveprotein(CRP)mprehensivemetabolicpanelEchocardiogramespeciallyifanthracycline-basedchemotherapyisindicated)stxrayposteroanteriorPAandlateralviewsifcrosssectionalimagingnotavailableornecessitatedtodeterminebulkofdiseaseforaclinicaltrial)c?k/chest/abdomen/pelviswithcontrastorCTchestandMRIneck/abdomen/?PET/CTscandorPET/MRIscand(whole-body)cPregnancytestforwomenofchildbearingagecapacityDLCOifbleomycinindicatedfOnlyconsiderbilateralbonemarrowbiopsyiftherearecytopeniasandnegativePETgalpresentationofHodgkinlymphomaorifthereisanunusualHLForchildrenwhoareunabletocooperateforPFTsthethoughttobesecondarytocytokinerelease)bonemarrowinvolvementisnotsweatsorweightloss>10%ofbodyweightwithin6monthsofdiagnosis)dexDIAGNOSISionalWORKUPEssential:tifferentialgifferentialgFertilitysmokingdrugcessationpsychosocialSeeNCCNGuidelinesilitypreservatione?ECGilitypreservatione?ECG?HIVandhepatitisB/Ctesting(encouraged)CLINICALPRESENTATIONHodgkinlicalaCoreneedlebiopsymaybeadequateifitisdiagnostic.Fine-needleaCoreneedlebiopsymaybeadequateifitisdiagnostic.Fine-needlePrinciplesofPathology(PHL-B).y,dihiior.toallowforstagingandriskassignment.Consultationwithradiationoncologistwhenconsideringtreatmentoptionsandadequacyofimagingforpotentialfutureradiationtherapyisstronglyrecommended.dIncasesofPETpositivitywheresitesofdiseaseareinconsistentwithSeePrinciplesofImaging(PHL-dIncasesofPETpositivitywheresitesofdiseaseareinconsistentwithdiseasepresentation(ie,HIV),additionalclinicalevaluationmayberequiredtostagethepatient.SeePrinciplesofStaging(PHL-D).IfPETnegativeforanatomiclesionsofconcern,biopsyshouldbeconsidered.eFertilitypreservationisanoptionforsomepatients.RefertofertilityclinicforfurtherfIngeneralFEV1/FVC>60%byPFTforfIngeneralFEV1/FVC>60%byPFTforuseofbleomycin,unlessduetolargecriteriaare:noevidenceofdyspneaatrest,noexerciseintolerance,andapulsegInmostinstancesifthePET/CTgInmostinstancesifthePET/CTdisplaysahomogeneouspatternofmarrowuptakeassumed.Iftherearemultifocal(>2–3)skeletalPETlesionswithoutcorticaldestructiononCT,marrowinvolvementmaybeassumedandabonemarrowbiopsyisnotneeded(LDHL),andlymphocyte-rich(LRHL)subtypes.Ifgrey-zone,seeNCCNGuidelinesforB-CellLymphomas.ManagementofNLPHLisnotincludedintheseguidelines.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.PHL-1Version3.2021,03/18/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.ageNoLowrisk(perEuroNet-PHL-C1l)PrintedbyMinTangon3/14/20227:08:58AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?ageNoLowrisk(perEuroNet-PHL-C1l)dexCLINICALSTAGINGOFCLASSICHODGKINLYMPHOMARiskstratificationisevolvingThistablerepresentsclinicaltrialswithpublisheddataConsiderconsultationwithacenterofexpertiseforpatientmanagementenrollmentinaclinicaltrialispreferredClinicaltrialstagingmaydifferfromthistable,andcloseattentiontotrialeligibilityandstagingshouldbefollowed.EE-lesionsj(SeePHL-D)Lowrisk(perEuroNet-PHL-CIntermediaterisk(perAHOD0031) YesYesIntermediaterisk(perEuroNet-PHL-C1lorAHOD0031)IBAnyNoLowrisk(perEuroNet-PHL-C1l) AnyAnyIntermediaterisk(perAHOD0031)NoNoIntermediaterisk(perAHOD0031orEuroNet-PHL-C1l)NoYesorIIBiHighNoYesorIIBiHighrisk(perEuroNet-PHL-C1l)YesAnyHighrisk(perAHOD1331l) YesYesHighrisk(perEuroNet-PHL-C1l)AnyNoIntermediaterisk(perAHOD0031orEuroNet-PHL-C1l)AnyYesor Highrisk(perAnyYesor Highrisk(perEuroNet-PHL-C1l)IIIB,IVAnyAnyHighrisk(AHOD1331lorEuroNet-PHL-C1l)LowRiskDiseasermediateRiskhRiskiOnlyIIBwithbulkwasupstagedtohighriskinthemostrecentseriesofCOGclinicaltrials.Thepanelacknowledgesthatcurrenttrialshavemodifiedthesegroupings.kGPOH-HD-2002:Mauz-K?rholzC,etal.JClinOncol2010;28:3680-3686;EuroNet-PHL-C1:Landman-ParkerJ,etal.Hematologica/ISHL10,jE-lesionsaredefinedbytheHD10studyaslocalizedinvolvementofextralymphatictissue(bycontiguousgrowthfromaninvolvedlymphnodeorincloseanatomicrelation)thatistreatablebyirradiation.(EngertA,etal.NEnglJMed2010;363:640-652;ListerTA,etal.JClinOncol1989;7:1630-1636.)2016[Abstract#P064];101:35;AHOD0031:FriedmanDL,etal.JClinOncol2014;32:3651-3658;AHOD1331:KellyKM,etal.BrJHaematol2019;187:39-48;CastellinoSM,etal.KlinPadiatr2020;232(02):82-83.lStudyiscompleteanddataareemerging.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.PHL-2Version3.2021,03/18/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:08:58AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexCLINICALPRESENTATION:mphomaRESPONSEpPRIMARYTREATMENTmRESPONSEpOngoingclinicaltrialAdequatePHLClPHLClntontoISRTqtoallsitesandboosttositesofinadequateresponseEndofntntoABVDSeeNCCNGuidelinesforHodgkinLymphoma(Adult)orUsefulincertaincircumstancesAdequatecellularityntontoEndofntntolStudyiscompleteanddataareemerging.mRegimensarebasedoffofstudieswithpediatricdata.nSeePrinciplesofSystemicTherapy(PHL-E).oFDG-PET/CTorPET/MRIandcontrast-enhanceddiagnosticCTorMRIoforiginalsitesofdiseaseifnotincludedwithPET.pSeePrinciplesofCriteriaforResponse-AdaptedRadiationTherapy(PHL-A).qSeePrinciplesofRadiationTherapy(PHL-F).FollowupPHLSeeFollow-up(PHL-6)orIfconcernforpersistentdisease,seeTherapyforRelapsedorRefractoryDisease(PHL-7)eeFollowupPHLSeeFollow-up(PHL-6)orIfconcernforpersistentdisease,seeTherapyforRelapsedorRefractoryDisease(PHL-7)Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version3.2021,03/18/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PHL-3PrintedbyMinTangon3/14/20227:08:58AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexCLINICALPRESENTATION:mphomaPRIMARYTREATMENTm,nclinicaltrialABVE-PCx2cyclesPHLClPHLClOtherrecommendedABVDRESPONSEo,pADDITIONALTREATMENTn,pntontoAdequateInadequatex2cyclesassessmento,pABVE-PCEndx2cyclesassessmento,p ISRT ISRTq,sx2cyclesrapyntolowuprapyntoRTqRTqstoesntonto COPDACx2cyclesEndofntntox2cyclesISRTqtoallsitesandboosttositesofinadequateresponseGuidelinesforHodgkinLymphomaAdultSeeFollow-up(PHL-6)orIfconcernforpersistentdisease,seeTherapyforRelapsedorRefractoryDisease(PHL-7)lStudyiscompleteanddataareemerging.mRegimensarebasedoffofstudieswithpediatricdata.nSeePrinciplesofSystemicTherapy(PHL-E).oFDG-PET/CTorPET/MRIandcontrast-enhanceddiagnosticCTorMRIoforiginalsitesofdiseaseifnotincludedwithPET.pSeePrinciplesofCriteriaforResponse-AdaptedRadiationTherapy(PHL-A).qSeePrinciplesofRadiationTherapy(PHL-F).rRER=Rapidearlyresponders;SER=Slowearlyresponders.sISRTcansafelyreplaceIFRT(seePHL-F).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.PHL-4Version3.2021,03/18/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:08:58AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexCLINICALPRESENTATION:mphomaPRIMARYRESPONSEpADDITIONALTREATMENTm,pTREATMENTm,noABVE-PCx2cyclesResponseISRTqtoEndofeeHighriskTherapyforAdequateRelapsedorCxcyclesABVE-PCx2cyclesResponseISRTqtoEndofeeHighriskTherapyforAdequateRelapsedorCxcyclesresponseRefractoryUsefulincertaincircumstancesresponsepororSeeNCCNGuidelinesforHodgkinLymphoma(Adult)ommendationsforABVEPCarebasedonemergingdatafromAHODCyclophosphamidedosinginAHODdiffersfromAHOD1331.AHODCyclophosphamidedosinginAHODdiffersfromAHOD1331.SeePrinciplesofSystemicTherapy(PHL-E).uBEACOPPhasbeenstudiedinpediatrictrialsieCCGuBEACOPPhasbeenstudiedinpediatrictrialsieCCG59704).ConsideronlyforselectpatientswithextensivediseasegivenconcernsforacuteandonlyforselectpatientswithextensivediseasegivenconcernsforacuteandxicityriskSeeNCCNGuidelinesforHodgkinLymphomawhereoFDG-PET/CTorPET/MRIandcontrast-enhanceddiagnosticCTorMRIofregimenswithreducednumberofcyclesofBEACOPPhavebeenregimenswithreducednumberofcyclesofBEACOPPhavebeendeveloped.vRRLRapidlyrespondinglesionsSRLSlowrespondinglesionsLMA=pSeevRRLRapidlyrespondinglesionsSRLSlowrespondinglesionsLMA=naladenopathyqSeePrinciplesofRadiationTherapy(PHL-naladenopathyNote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.PHL-5Version3.2021,03/18/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrinciplesofPathologyandSeeTherapyforRelapsed/RefractoryDisease(PHL-7)PrintedbyMinTangon3/14/20227:08:58AM.Forpersonaluseonly.NotPrinciplesofPathologyandSeeTherapyforRelapsed/RefractoryDisease(PHL-7)dexFOLLOW-UPAFTERCOMPLETIONOFTREATMENTANDMONITORINGFORLATEEFFECTSlanceFollow-upAfterCompletionofTreatmentInterimHPpEvery3–4monthsfor1–2years,pthenevery6–12monthsuntilyear3,pthenannuallyuntil5years?Laboratorystudies:pCBCwithdifferential,ESRorCRP,chemistryprofileasclinicallyindicated.pThyroid-stimulatinghormone(TSH)atleastannuallyifRTtoneck.?ConsiderPFTs(ifbleomycin,pulmonaryRT,significantpulmonaryinvolvement,orotherclinicalconcerns)?ImagingpConsiderendoftherapyECHO.pImagingstudiesareonlyrecommendedwhenrelapseissuspected,becausemostpatientswillclinicallydeclarethemselvesandthereisnosurvivaladvantageinpre-emptiveimaging.pIfclinicalconcern,CTwithcontrastorMRIoforiginalsitesofdiseasemaybeperformedandfollowedat3-to6-mointervalsupto2yfollowingcompletionoftherapy.pMRIisacceptableinplaceofCTscanforneck/abdomen/pelvis,butnotforchest;diagnosticCTofchestisneeded.pPET/CTorPET/MRIifpreviousPETwaspositive(Deauville3–5),toconfirmcompleteresponse(CR)atendofallprescribedtherapyincludingRT.Oncenegative,repeatPETshouldnotbedoneunlessevaluatingsuspiciousfindingsonH&PorCTorMRI.?Waitatleast8–12weeksafterendofRTtoperformPETtominimizefalse-positiveresults.?SurveillancePETisnotrecommendedduetoriskforfalsepositives.pIfconcernforrelapse,managementdecisionsshouldnotbebasedonPETscanalone;clinicalandpathologiccorrelationisneeded.SeePrinciplesofPathology(PHL-B)andSeeTherapyforRelapsed/RefractoryDisease(PHL-7).?ImmunizationspAnnualinfluenzavaccineisrecommended,ev