NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines?)AmpullaryAdenocarcinomarsionMarchVersion1.2022,03/09/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:27:24AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ocarcinomadex*MargaretA.Tempero,MD/Chair??UCSFHelenDillerFamilyComprehensiveCancerCenternternter**StephenW.Behrman,MD/Co-Lead?TheUniversityofTennesseeeCenter**E.GabrielaChiorean,MD/Co-Lead?FredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceyofMichiganRogelyofMichiganRogelCancerCenter**AlB.BensonIII,MD?RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityngramCancerCenterVincentChung,MDngramCancerCenterVincentChung,MD?yofHopeNationalMedicalCenter**BrianCzito,MD§DukeCancerInstituteofColoradoCancerCenterChiaroofColoradoCancerCenterMaryDillhoff,MD,MS?TheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandSoloveResearchInstituteTimothyR.Donahue,MD?UCLAJonssonComprehensiveCancerCenterEfratDotan,MD?FoxChaseCancerCenterCristinaR.Ferrone,MD?MassachusettsGeneralHospitalCancerCenteresPanelDisclosuresChristosFountzilas,MD?RoswellParkComprehensiveCancerCenterJeffreyHardacre,MD?CaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussigCancerInstitutemanCancerCenteratBarnesmanCancerCenteratBarnesJewishHospitaltonUniversitySchoolofMedicineEdwardJ.Kim,MD,PhD?UCDavisComprehensiveCancerCenterfettCancerfettCancerCenterAndrewH.Ko,MD?UCSFHelenDillerFamilyComprehensiveCancerCenternterSmilowCancerHospitalnterSmilowCancerHospital**NoelleLoConte,MD?UniversityofWisconsinCarboneCancerCenter**AndrewM.Lowy,MD?UCSanDiegoMooresCancerCenterMoravekPancreaticCancerActionNetworkPatricioM.Polanco,MD?UTSouthwesternSimmonsComprehensiveCancerCenterONealComprehensiveCancerCenterONealComprehensiveCancerCenteratUABMarshaReyngold,MD,PhD§MemorialSloanKetteringCancerCenterrInstituteattherInstituteatthefUtah**JeanneShen,MD≠StanfordCancerInstituteMarkJ.Truty,MD,MS?MayoClinicCancerCenterAbramsonCancerCenterattheAbramsonCancerCenteratthensylvaniaandWomensnMWolpinandWomensenterghRNBSghRNBSenPhDUCSFHelenDillerFamilyComprehensiveCancerCenterAmolK.Narang,MD§TheSidneyKimmelComprehensiveosticgyosticgy¤Gastroenterology?Hematology/Hematologyoncology?Medicaloncology≠Pathology￥Patientadvocacy§Radiotherapy/Radiationoncology?Surgery/Surgicaloncology*Discussionsectionwritingcommittee**Development/writingsubcommittee**JorgeObando,MD¤stituteVersion1.2022,03/09/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.AmpullaryAdenocarcinomaPanelMembersofAmpullaryNeoplasmAMPyAdenomaAMPAdenocarcinoma(AMP-3)LocalizedDisease(AMP-4)PostoperativeAdjuvantTherapy(AMP-5)seaseAmpullaryAdenocarcinomaPanelMembersofAmpullaryNeoplasmAMPyAdenomaAMPAdenocarcinoma(AMP-3)LocalizedDisease(AMP-4)PostoperativeAdjuvantTherapy(AMP-5)seaseAMPssionAMPPrinciplesofDiagnosis,Imaging,andStaging(AMP-A)PancreaticCancerRadiologyReportingTemplate(AMP-A,5of8)PrinciplesofStentManagement(AMP-B)PrinciplesofSurgicalTechnique(AMP-C)PathologicAnalysis:SpecimenOrientation,HistologicSections,andReporting(AMP-D)PrinciplesofSystemicTherapy(AMP-E)PrinciplesofRadiationTherapy(AMP-F)PrinciplesofPalliationandSupportiveCare(AMP-G)ocarcinomadexdNCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2022.Version1.2022,03/09/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:27:24AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ocarcinomadexCLINICALWORKUPTREATMENTPRESENTATIONcionymprotocolCTandpelvisandpelvisa?Esophagogastroduodenoscopy(EGD)±endoscopicultrasound(EUS)withbiopsy?ColonoscopyifnotpreviouslyperformedaccordingtoestablishedguidelinesHigh-gradedysplasiaSeeAmpullaryAdenoma(AMP-2)denocarcinomaAdenocarcinoma(AMP-3)aSeePrinciplesofDiagnosis,Imaging,andStaging(AMP-A).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2022,03/09/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.AMP-1PrintedbyMinTangon3/14/20227:27:24AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ocarcinomadexCLINICALPRESENTATIONTREATMENTmpullaryNegativemarginsampullectomyampullectomybNegativemargins Pancreatoduodenectomy PancreatoduodenectomybtomybampullectomyampullectomybNegativemarginssrPancreatoduodenectomybtomybEndoscopicsurveillanceillanceEndoscopicsurveillanceillancebSeePrinciplesofSurgicalTechnique(AMP-C).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2022,03/09/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.AMP-2rfunctionstbaselineACEA?ConsiderERCP/PTCasclinicallyindicated?Considerestingforinheritedmutationsc?MultidisciplinaryondPrintedbyMinTangon3/14/20227:27:24AM.ForpersonalrfunctionstbaselineACEA?ConsiderERCP/PTCasclinicallyindicated?Considerestingforinheritedmutationsc?MultidisciplinaryondocarcinomadexCLINICALPRESENTATIONAdenocarcinomaWORKUP?CTchest,andpancreasprotocolCTofMetastaticTREATMENT?ConsiderMRIforindeterminateliverlesionsasclinicallyindicated?HistologicsubtypepancreatobiliaryversusintestinalifpossibletepreferredeonsidermoleculartepreferredeonsidermolecularprofilingfoftumortissueasallyindicatedaSeePrinciplesofDiagnosis,Imaging,andStaging(AMP-A).cGenetictestingforinheritedmutationsisrecommendedforanypatientwithconfirmedampullarycancer,usingcomprehensivegenepanelsforhereditarycancersyndromes.Geneticcounselingisrecommendedforpatientswhotestpositiveforapathogenicmutation(ATM,BRCA1,BRCA2,CDKN2A,MLH1,MSH2,MSH6,PALB2,PMS2,STK11,andTP53)orforpatientswithapositivefamilyhistoryofcancer,especiallypancreatic/ampullarycancer,regardlessofmutationstatus.SeeNCCNGuidelinesforGenetic/FamilialHighRiskAssessment:Breast,Ovarian,andPancreatic.dMultidisciplinaryreviewshouldconsiderinvolvingexpertisefromdiagnosticimaging,interventionalendoscopy,medicaloncology,radiationoncology,surgery,pathology,geriatricmedicine,geneticcounseling,andpalliativecare(seePrinciplesofPalliationandSupportiveCare[AMP-G]).Considerconsultationwitharegistereddietitian.SeeNCCNGuidelinesforOlderAdultOncologyandNCCNGuidelinesforPalliativeCare.eCorebiopsyisrecommended,ifpossible,toobtainadequatetissueforpossibleancillarystudies.fTumor/somaticmolecularprofilingisrecommendedforpatientswithlocallyadvanced/metastaticdiseasewhoarecandidatesforanti-cancertherapytoidentifyuncommonmutations.Considerspecificallytestingforpotentiallyactionablesomaticfindingsincluding,butnotlimitedto:fusions(ALK,NRG1,NTRK,ROS1,FGFR2,RET),mutations(BRAF,BRCA1/2,KRAS,PALB2),amplifications(HER2),microsatelliteinstability(MSI)and/ormismatchrepair(MMR)deficiency.Testingontumortissueispreferred;however,cell-freeDNAtestingcanbeconsiderediftumortissuetestingisnotfeasible.SeeDiscussion.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.AMP-3Version1.2022,03/09/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.icularlyinighriskpatientsiPrintedbyMinTangon3/14/20227:27:24AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.icularlyinighriskpatientsiocarcinomadexCLINICALPRESENTATIONTREATMENTProceedtosurgerywithoutneoadjuvanttherapy)SurgerygProceedtosurgerywithoutroradiationhjoradiationhjkstentlifstentlifclinicallyTorMRIResectableSurgerygUnresectablePeMetastaticDiseaseAMPgSeePrinciplesofSurgicalTechnique(AMP-C)andPathologicAnalysis:SpecimenOrientation,HistologicSections,andReporting(AMP-D).hSeePrinciplesofSystemicTherapy(AMP-E).iHigh-riskfeaturesincludeimagingfindings,markedlyelevatedCA19-9,markedlyelevatedcarcinoembryonicantigen(CEA),largeprimarytumors,largeregionallymphnodes,excessiveweightloss,andextremepain.jThereislimitedevidencetorecommendspecificneoadjuvantregimensoff-study,andpracticesvarywithregardtotheuseofchemotherapyandchemoradiation.kSeePrinciplesofRadiationTherapy(AMP-F).lSeePrinciplesofStentManagement(AMP-B).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.AMP-4Version1.2022,03/09/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.kSeePrinciplesofRadiationTherapy(AMP-F).mInitiationofadjuvantsystemictherapyisrecommendedwithin12weeksofsurgeryifthepatientismedicallyfit.TheoptimaldurationoftreatmentiskSeePrinciplesofRadiationTherapy(AMP-F).mInitiationofadjuvantsystemictherapyisrecommendedwithin12weeksofsurgeryifthepatientismedicallyfit.Theoptimaldurationoftreatmentis4to6months.ocarcinomadexPOSTOPERATIVEADJUVANTTREATMENTTREATMENTSURVEILLANCEyobservationSystemictherapyh,m±StageIobservationSystemictherapyh,m±observationStageIIchemoradiationh,k,mobservationStageIIIStageIIISystemictherapyh,m±StageIVSeeMetastaticDisease(AMP-6)Surveillanceevery3-6monthsfor2years,thenevery6-12monthsion?Historyandphysicalexamination(H&P)?ChestCTandCTorMRIoftrastaabdomenandpelvistrastahSeePrinciplesofSystemicTherapy(AMP-E).aSeePrinciplesofhSeePrinciplesofSystemicTherapy(AMP-E).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.AMP-5Version1.2022,03/09/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:27:24AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ocarcinomadexMETASTATICDISEASETREATMENTtictestingforinheritedmutations,ifnotlecularproilingoftumortissue,ifnotGoodPSnPoorPStionhktionhkcctherapyhllowedllowedbyrpalliativeSystemicSystemictherapyhfollowedbylocal-directedtherapytoliverorlungtastasesforselectpatientswithligometastaticdiseaseandresponsetablediseasetosystemictherapyprogressionSeeAMP-7PalliativeandbestsupportivecareoystemictherapyhTargetedtherapyhbasedonmolecularproilingfasclinicallyindicatedliativeliativeRTkdGenetictestingforinheritedmutationsisrecommendedforanypatientwithconfirmedampullarycancer,usingcomprehensivegenepanelsforhereditarycancersyndromes.Geneticcounselingisrecommendedforpatientswhotestpositiveforapathogenicmutation(ATM,BRCA1,BRCA2,CDKN2A,MLH1,MSH2,MSH6,PALB2,PMS2,STK11,andTP53)orforpatientswithapositivefamilyhistoryofcancer,especiallypancreatic/ampullarycancer,regardlessofmutationstatus.SeeNCCNGuidelinesforGenetic/FamilialHighRiskAssessment:Breast,Ovarian,andPancreatic.fTumor/somaticmolecularprofilingisrecommendedforpatientswithlocallyadvanced/metastaticdiseasewhoarecandidatesforanti-cancertherapytoidentifyuncommonmutations.Considerspecificallytestingforpotentiallyactionablesomaticfindingsincluding,butnotlimitedto:fusions(ALK,NRG1,NTRK,ROS1,FGFR2,RET),mutations(BRAF,BRCA1/2,KRAS,PALB2),amplifications(HER2),microsatelliteinstability(MSI)and/ormismatchrepair(MMR)deficiency.Testingontumortissueispreferred;however,cell-freeDNAtestingcanbeconsiderediftumortissuetestingisnotfeasible.SeeDiscussion.hSeePrinciplesofSystemicTherapy(AMP-E).kSeePrinciplesofRadiationTherapy(AMP-F).nDefinedasECOG0–1,withgoodbiliarydrainageandadequatenutritionalintake.oSeePrinciplesofPalliationandSupportiveCare(AMP-G).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.AMP-6Version1.2022,03/09/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:27:24AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ocarcinomadexDISEASEPROGRESSIONSUBSEQUENTTHERAPYpmolecularproiling,fasclinicallymolecularproiling,fasclinicallyindicatedSystemicSystemictherapyhorpossiblytargetedtherapyf,hbasedonPalliativeRTkforseverepainrefractorytoanalgesictherapyPalliativerialPalliativeandbestsupportivecareoystemictherapyhTargetedtherapyf,hbasedonmolecularproiling,fasclinicallyindicatediativeiativeRTkfTumorsomaticmolecularprofilingisrecommendedforpatientswithlocallyadvancedmetastaticdiseasewhoarecandidatesforanti-cancertherapytoidentifyuncommonmutationsConsiderspecificallytestingforpotentiallyactionablesomaticfindingsincludingbutnotlimitedto:fusions(ALK,NRG1,onsBRAFBRCAKRASPALBamplifications(HER2),microsatelliteinstability(MSI)and/ormismatchrepairrredhowevercellfreeDNAtestingcanbeconsiderediftumortissuetestingisnotfeasible.SeeDiscussion.hSeePrinciplesofSystemicTherapy(AMP-E).kSeePrinciplesofRadiationTherapy(AMP-F).nDefinedasECOG0–1,withgoodbiliarydrainageandadequatenutritionalintake.oSeePrinciplesofPalliationandSupportiveCare(AMP-G).pSerialimagingasindicatedtoassessdiseaseresponse.SeePrinciplesofDiagnosis,Imaging,andStaging(AMP-A).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.AMP-7Version1.2022,03/09/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.AMP-AOF8institutionalpreferencesMultiplanarreconstructionispreferredasitallowsprecisevisualizationoftherelationshipoftheprimarytumorPrintedbyMinTangon3/14/20227:27:24AM.ForAMP-AOF8institutionalpreferencesMultiplanarreconstructionispreferredasitallowsprecisevisualizationoftherelationshipoftheprimarytumorocarcinomadexPRINCIPLESOFDIAGNOSIS,IMAGING,ANDSTAGINGDecisionsaboutdiagnosticmanagementandresectabilityshouldinvolvemultidisciplinaryconsultationatahigh-volumecenterwithreferencetoappropriatehighqualityimagingstudiestoevaluatetheextentofdiseaseResectionsshouldbedoneatinstitutionsthatperformalargenumberatleastofpancreaticresectionsand/orendoscopicandsurgicalampullectomyannually.Highqualitydedicatedimagingoftheampullaryregionshouldbeperformedatpresentation(evenifstandardCTimagingisalreadyavailablepreferablywithinweeksofsurgeryandfollowingneoadjuvanttreatmenttoprovideadequatestagingandassessmentofresectabilitystatus.Imagingshouldbedonepriortostenting,whenpossible.?ImagingshouldincludededicatedpancreaticCTofabdomen(preferred)orMRIwithcontrast.pMultidetectorcomputedtomography(MDCT)angiography,performedbyacquiringthin,preferablysub-millimeter,axialsectionsusingaimagingtoolfordedicatedpancreaticimaging.aScancoveragecanbeextendedtocoverthechestandpelvisforcompletestagingasimagingtoolfordedicatedpancreaticimaging.aScancoveragecanbeextendedtocoverthechestandpelvisforcompletestagingaspertothemesentericvasculatureaswellasdetectionofsubcentimetermetastaticdeposits.SeeMDCTPancreaticAdenocarcinomaProtocol,PANC-A(3of8).pMRIismostcommonlyusedasaproblem-solvingtool,particularlyforcharacterizationofCT-indeterminateliverlesionsorwhencontrast-enhancedCTcannotbeobtained(asincaseswithsevereallergytoiodinatedintravenouscontrastmaterial).ThispreferenceforusingMDCTasthemainimagingtoolinmanyhospitalsandimagingcentersismainlyduetothehighercostandlackofwidespreadavailabilityofMRIcomparedtoCT.SeeMRIPancreaticAdenocarcinomaProtocol,AMP-A(4of8).?Thedecisionregardingresectabilitystatusshouldbemadebyconsensusatmultidisciplinarymeetings/discussionsfollowingthecompleteassessmentandreportingofallimagingcriteriaessentialforoptimalstaging,whichwillimprovethedecision-makingprocess.aacquisitionofcompleteassessmentandreportingofallimagingcriteriaessentialforoptimalstaging,whichwillimprovethedecision-makingprocess.aSeePancreaticCancerRadiologyReportingTemplateAMPAofThistemplatecanalsobeusedforampullarytumors.ancisIRChariSTetalPancreaticductaladenocarcinomaradiologyreportingtemplateconsensusstatementoftheSocietyofAbdominalRadiologyandtheAmericanPancreaticAssociationRadiology260.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2022,03/09/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:27:24AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRights