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NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines®)GastricCancerNCCNGuidelinesforPatients®availableat/patientsVersion2.2022,01/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:49:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.er*JafferA.Ajani,MD/Chair†¤TheUniversityofTexasDavidJ.Bentrem,MD,MS¶JosephChao,MD†CityofHope*DavidCooke,MD¶enterCarlosCorvera,MD§DillerFamily*PrajnanDas,MD,MS,MPH§TheUniversityofTexasPeterC.Enzinger,MD†Dana-Farber/BrighamandWomen’senter*ThomasEnzler,MD,PhD†‡RogelCancerCenterPaulFanta,MD‡†enterFarhoodFarjah,MD¶HansGerdes,MD¤ÞenterMichaelGibson,MD,PhD†‡ÞVanderbilt-IngramCancerCenterStevenHochwald,MD¶enter*WayneL.Hofstetter,MD¶TheUniversityofTexas*DavidH.Ilson,MD,PhD†ÞenterRajeshN.Keswani,MD¤ÞSunnieKim,MD†UniversityofColoradoenter*LawrenceR.Kleinberg,MD§*SamuelKlempner,MD†enterJillLacy,MD,†YaleCancerCenter/SmilowCancerHospitalQuanP.Ly,MD¶enter*KristinaA.Matkowskyj,MD,PhD≠UniversityofWisconsinMichaelMcNamara,MD†CaseComprehensiveCancernMaryF.Mulcahy,MD‡†DarrylOutlaw,MD†HaeseongPark,MD,MPH†ÞSitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineKyleA.Perry,MD¶nd*JosePimiento,MD¶MoffittCancerCenter*GeorgeA.Poultsides,MD,MS¶ScottReznik,MD¶erRobertE.Roses,MD¶AbramsonCancerCenterattheVivianE.Strong,MD¶enterStaceySu,MD¶FoxChaseCancerCenter*HanlinL.Wang,MD,PhD≠enterGeorgiaWiesner,MD/Liaison∆Vanderbilt-IngramCancerCenter*ChristopherG.Willett,MD§DannyYakoub,MD,PhD¶St.JudeChildren'sResearchHospital/TheUniversityofTennesseeHealthScienceCenterHarryYoon,MD†cMillianMSPhDesPanelDisclosures‡Hematology/Hematology§Radiotherapy/Radiationoncology¶Surgery/Surgicaloncology*DiscussionWritingCommitteeMemberPrintedbyMinTangon3/14/20227:49:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.erdexFindanNCCNMemberInstitution:/home/member-institutions.dNCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.SummaryoftheGuidelinesUpdatesWorkupandAdditionalEvaluation(GAST-1)ConclusionsofMultidisciplinaryReview,PrimaryTreatment(GAST-2)ResponseAssessment,AdditionalManagement(GAST-3)SurgicalOutcomes/ClinicalPathologicFindingsforPatientsWhoHaveNotReceivedPreoperativeTherapy(GAST-4)SurgicalOutcomes/ClinicalPathologicFindingsforPatientsWhoHaveReceivedPreoperativeTherapy(GAST-5)Post-TreatmentAssessment/AdditionalManagement(GAST-6)Follow-up/Surveillance(GAST-7)Recurrence(GAST-8)PalliativeManagement(GAST-9)PrinciplesofEndoscopicStagingandTherapy(GAST-A)PrinciplesofPathologicReviewandBiomarkerTesting(GAST-B)PrinciplesofSurgery(GAST-C)PrinciplesofGeneticRiskAssessmentforGastricCancer(GAST-D)PrinciplesofMultidisciplinaryTeamApproachforEsophagogastricCancers(GAST-E)PrinciplesofSystemicTherapy(GAST-F)PrinciplesofRadiationTherapy(GAST-G)PrinciplesofSurveillance(GAST-H)PrinciplesofSurvivorship(GAST-I)PrinciplesofPalliativeCare/BestSupportiveCare(GAST-J)Staging(ST-1)TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNationalComprehensiveCancerNetworkAllrightsreservedTheNCCNGuidelinesandtheillustrationshereinmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.©2022.Version2.2022,01/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:49:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.erdexUpdatesinVersion2.2022oftheNCCNGuidelinesforGastricCancerfromVersion1.2022include:MS-1•TheDiscussionhasbeenupdatedtoreflectthechangesinthealgorithm.UpdatesinVersion1.2022oftheNCCNGuidelinesforGastricCancerfromVersion5.2021include:GAST-1GAST-BPrinciplesofPathologicReviewandBiomarkerTesting•Workup(continued)p9thBulletrevised:UniversaltestingforMSIbyPCR/MMRPCR/next-GAST-B3of6newlydiagnosedpatientsgenerationsequencing(NGS)orMMRbyIHCisrecommendedinall•AssessmentofOverexpressionorAmplificationofHER2newlydiagnosedpatientsCancerp11thBulletrevised:Ifsufficienttissueisavailableaftertheabovetestinghasbeencompleted,NGSmaybeconsideredpNewbulletadded:Ifanemiaissuspected,SeeNCCNGuidelinesforHematopoieticGrowthFactors•ClinicalStage;Locoregional(cM0)pathway;AdditionalEvaluation:"Considerlaparoscopywithcytology(category2B)"wasrecommendedforallpatientsinthispathway.ThisrecommendationwaschangedaspRevised:"...atraditionalbiopsy.p11thBulletrevised:Ifsufficienttissueisavailableaftertheabovetestinghasbeencompleted,NGSmaybeconsideredpNewbulletadded:Ifanemiaissuspected,SeeNCCNGuidelinesforHematopoieticGrowthFactors•ClinicalStage;Locoregional(cM0)pathway;AdditionalEvaluation:"Considerlaparoscopywithcytology(category2B)"wasrecommendedforallpatientsinthispathway.Thisrecommendationwaschangedasfollows:pMedicallyfit,potentiallyresectable:Changedfollows:pMedicallyfit,potentiallyresectable:Changedto,Recommendlaparoscopywithcytology.pMedicallyfit,surgicallyunresectable:Considerlaparoscopywithcytologychangedfromcategory2Btocategory2ApNon-surgicalcandidate:Changedto,PalliativeManagement(seeGAST-9)•MicrosatelliteInstability(MSI)orMismatchRepair(MMR)TestingpRevised:"UniversaltestingforMSIbypolymerasechainreaction(PCR),NGS,orMMR...inaccordancewithCAPDNAMismatchRepairBiomarkerReportingGuidelines.MMRorMSITestingshouldbeperformedonlyinCLIA-approvedlaboratories."•Footnoteh:"PCR/NGSforMSIandIHCforMMRproteins..."GAST-2•Locoregionaldisease(cM0)pathway;Medically•Locoregionaldisease(cM0)pathway;Medicallyfit,potentiallyresectable;cT2orhigher,AnyN;cT2orhigher,AnyN;PrimaryTreatment:Revised,Perioperativechemotherapy(category1)(preferred)(AlsoforGAST-3)GAST-9•Unresectablelocallyadvanced,Locallyrecurrentormetastaticdisease;ThirdcolumnrevisedpPerformHER2,PD-L1,MSIbyPCR/MMRandmicrosatellitebyIHCtesting(ifnotdonepreviously)ifmetastaticadenocarcinomacancerisdocumentedorsuspectedpBulletrevised:Ifsufficienttissueisavailableaftertheabovetestinghasbeencompleted,NGSmaybeconsideredviaavalidatedassaypAtpresent,threeseveraltargetedtherapeuticagents,trastuzumab,ramucirumab,andpembrolizumab/nivolumab,andentrectinib/larotrectinibhavebeenapprovedbytheFDAforuseingastriccancer.TrastuzumabisbasedontestingforHER2positivityoverexpression.Pembrolizumab/nivolumabisarebasedontestingforMSIbyPCR/MMRPCRor(AlsoforGAST-3)GAST-9•Unresectablelocallyadvanced,Locallyrecurrentormetastaticdisease;ThirdcolumnrevisedpPerformHER2,PD-L1,MSIbyPCR/MMRandmicrosatellitebyIHCtesting(ifnotdonepreviously)ifmetastaticadenocarcinomacancerisdocumentedorsuspectedpBulletrevised:Ifsufficienttissueisavailableaftertheabovetestinghasbeencompleted,NGSmaybeconsideredviaavalidatedassayhasseveralinherentlimitationsandthuswheneverpossible,TheuseGAST-BPrinciplesofPathologicReviewandBiomarkerTestingofgold-standardassays(IHC/FISH/targetedPCR)shouldbeperformedGAST-B1of6consideredfirstandifsufficienttissueisavailable,followedbyMMRchangedtoPCR/NGSorMMRthroughoutthetable.•PathologicReviewTable;Analysis/Interpretation/Reportingcolumn:PCR/additionalMMRchangedtoPCR/NGSorMMRthroughoutthetable.UPDATESVersion2.2022,01/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.•8thBulletrevised:Perioperativechemotherapyorpostoperativechemotherapypluschemoradiation4isthepreferredapproachforlocalizedgastriccancer.Perioperativetherapyisacategory1recommendationforlocalizedgastriccancer•8thBulletrevised:Perioperativechemotherapyorpostoperativechemotherapypluschemoradiation4isthepreferredapproachforlocalizedgastriccancer.Perioperativetherapyisacategory1recommendationforlocalizedgastriccancer.PostoperativechemotherapypluschemoradiationisanalternativeoptionforpatientswhoreceivedlessthanaD2lymphnodedissection.micTherapyforUnresectableLocallyAdvancedetastaticDiseaseFirstLineTherapyUsefulinCertainCircumstances;HER2erexpressionnegativeRevisedFluoropyrimidinefluorouracilorcapecitabineoxaliplatinandnivolumabPD-L1CPS1-4<5)goryB•Footnotekrevised:ForpatientsthathaveprogressedwhosecancerisprogressingonorfollowingpriortreatmentthatdidnotincludevenosatisfactoryalternativetreatmentoptionsPrioruseofimmuno-erdex 6uPrinciplesof 6uPrinciplesofPathologicReviewandBiomarkerTesting•LiquidBiopsy:Revised,"...Liquidbiopsyisbeingusedmorefrequentlyinpatientswithadvanceddisease,particularlythosewhoareunabletohaveaclinicalbiopsyfordiseasesurveillanceandmanagement...Therefore,forpatientswhohavemetastaticoradvancedgastriccancerandarewhomaybeunabletoundergoatraditionalbiopsy,orfordiseaseprogressionmonitoring,testingusingavalidatedNGS-basedcomprehensivegenomicprofilingassay..."GAST-F5of16•PerioperativeChemotherapy;PreferredRegimenspFluoropyrimidineandoxaliplatin:Revised,(34cyclespreoperativeand34cyclespostoperative)GAST-F7of16•PostoperativeChemoradiation:DosingforFluorouracilandCapecitabinewererevisedtoincludethefollowingstatement,Forcyclesafterchemoradiation,beginchemotherapy1monthafterchemoradiation.GAST-F10of16revisedTwodrugcytotoxicregimensrevisedTwodrugcytotoxicregimensarepreferredforithadvanceddiseasebecauseoflowerithadvanceddiseasebecauseoflowertoxicityThreerugcytotoxicregimensshouldbereservedformedicallyfitpatientswithgoodPSandaccesstofrequenttoxicityrugcytotoxicregimensshouldbereservedformedicallyfitpatientswithgoodPSandaccesstofrequenttoxicityevaluation.TheuseofthreecytotoxicdrugsTheuseofthreecytotoxicdrugsinaregimenshouldbereservedformedicallyfitpatientswithexcellentPSandeasyaccesstofrequenttoxicityevaluations.GAST-F14of16throughGAST-F16of16toxicityevaluations.•Thereferencepageswereupdatedtoreflectthechangesinthealgorithm.GAST-GPrinciplesofRadiationGAST-G1of5•SimulationandTreatmentPlanning;Firstbulletrevised:CTsimulationandconformaltreatmentplanningshouldbeusedwitheither3Dconformalradiation(3D-CRT)ensity-modulatedradiationtherapy(IMRT).maybeusedinclinicalsettingswherereductionindosetoorgansatrisk(eg,heart,lungs,liver,kidneys,smallbowel)isrequired,whichcannotbeachievedby3-Dtechniques.GAST-G3of5•NormalTissueToleranceDose-Limits:Thissectionwasextensivelyrevised•RTDosingrevised:45–50.4Gy(1.8Gy/day)(total25–28fractions)GAST-G5of5•Referenceswereupdated.oncologytherapyoncologytherapyinthesepatientswillmakethemineligiblefordostarlimab-gxly.Version2.2022,01/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.allyindicatedCBCandcomprehensivechemistryprofileEndoscopicultrasoundEUSifearly-stageeasesuspectedorifearlyversuslocallyanceddiseaseneedstobedeterminedredEndoscopicresectionERisessentialfortheaccuratestagingofearlystagecancers(T1aorallyindicatedCBCandcomprehensivechemistryprofileEndoscopicultrasoundEUSifearly-stageeasesuspectedorifearlyversuslocallyanceddiseaseneedstobedeterminedredEndoscopicresectionERisessentialfortheaccuratestagingofearlystagecancers(T1aorT1b).cEarly-stagecancerscanbestbediagnosedbyER.•Biopsyofmetastaticdiseaseasclinicallyindicated•UniversaltestingforMSIbyPCR/next-generationsequencing(NGS)orMMRbyIHCisrecommendedinallnewlydiagnosedpatientsdHERandPDL1testingifmetastaticcarcinomaisdocumentedecteddemaybeconsidereddAssessSiewertcategoryfutritionalassessmentandcounselingSmokingcessationadvice,counseling,andyasindicatedgeenforfamilyhistoryhIfanemiaissuspectedSeeNCCNGuidelinesforHematopoieticGrowthFactorsry SeeGAST-2iewpreferredmerdexWORKUP•H&P•UpperGIendoscopyandbiopsya•Chest/abdomen/pelvicCTwithoralandIVcontrastthigh)ifnoevidenceofM1diseasebandifthigh)ifnoevidenceofM1diseasebandifCLINICALSTAGEiADDITIONALEVALUATIONorcT1aMedicallyfitjNon-surgicalcandidatekjicallyfjicallyfjRecommendlaparoscopycytologylcytologylrlaparoscopycytologylcytologylcandidatekcandidatekStageIVSTANote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.GAST-1Version2.2022,01/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:49:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.erdexFOOTNOTESFORGAST-1aSeePrinciplesofEndoscopicStagingandTherapy(GAST-A).bMaynotbeappropriateforT1.cERmayalsobetherapeuticforearly-stagedisease/lesions.dSeePrinciplesofPathologicReviewandBiomarkerTesting(GAST-B).eTumorEpstein-Barrvirusstatusisemergingasapotentialbiomarkerforpersonalizedtreatmentstrategiesforgastriccancer,butisnotcurrentlyrecommendedforclinicalcare.fSeePrinciplesofSurgery(GAST-C).gSeeNCCNGuidelinesforSmokingCessation.hSeePrinciplesofGeneticRiskAssessmentforGastricCancer(GAST-D).AlsoseeNCCNGuidelinesforColorectalCancerScreeningandNCCNGuidelinesforGenetic/FamilialHigh-RiskAssessment:Breast,OvarianandPancreatic.iSeeStaging(ST-1)fortumorclassification.jMedicallyabletotoleratemajorsurgery.kMedicallyunabletotoleratemajorsurgeryormedicallyfitpatientswhodeclinesurgery.lLaparoscopywithcytologyisperformedtoevaluateforperitonealspreadwhenconsideringchemoradiationorsurgery.Laparoscopywithcytologyisnotindicatedifapalliativeresectionisplanned.LaparoscopywithcytologyisindicatedforclinicalstageT1borhigher.mSeePrinciplesofMultidisciplinaryTeamApproach(GAST-E).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.GAST-1AVersion2.2022,01/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:49:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.erdexCONCLUSIONSOFMULTIDISCIPLINARYFINALSTAGEiNon-surgicalNon-surgicalMedicallyfitf,jcTisorcT1acandidatektfjcTorhigher,AnyNeecMMedicallyfitcallydidatefkPRIMARYTREATMENTffjydfnydfnPerioperativechemotherapyo(category1)moradiationopyBtionopcctherapyoeGASTllancelOutcomesorPatientsWhoaveNotReceivedeoperativeTherapysessessmentAssessment/AdditionalMetastaticdisease(cM1)aSeePrinciplesofEndoscopicStagingandTherapy(GAST-A).dSeePrinciplesofPathologicReviewandBiomarkerTesting(GAST-B).fSeePrinciplesofSurgery(GAST-C).iSeeStaging(ST-1)fortumorclassification.jMedicallyabletotoleratemajorsurgery.eGASTkMedicallyunabletotoleratemajorsurgeryormedicallyfiteGASTnSurgeryasprimarytherapyisappropriatefor≥T1bcanceroractivelybleedingcancer,orwhenpostoperativetherapyispreferred.oSeePrinciplesofSystemicTherapy(GAST-F).pSeePrinciplesofRadiationTherapy(GAST-G).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.GAST-2Version2.2022,01/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:49:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.erdexPRIMARYTREATMENTFORMEDICALLYFITPATIENTSRESPONSEASSESSMENTOUTCOMEADDITIONALMANAGEMENTchemotherapy(category1)orationoationopyB•Chest/abdomen/pelvicCTscanwithcontrast•FDG-PET/CTscanasclinicallyindicatedSurgeryd,f,n(preferred)orPalliativeManagement(seeGAST-9)lOutcomesforPatientsWhoHaveceivedPreoperativeeGASTorMetastaticdiseasePalliativeManagement(seeGAST-9)dSeePrinciplesofPathologicReviewandBiomarkerTesting(GAST-B).fSeePrinciplesofSurgery(GAST-C).nSurgeryasprimarytherapyisappropriatefor≥T1bcanceroractivelybleedingcancer,orwhenpostoperativetherapyispreferred.oSeePrinciplesofSystemicTherapy(GAST-F).pSeePrinciplesofRadiationTherapy(GAST-G).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.GAST-3Version2.2022,01/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:49:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.erdexSURGICALOUTCOMES/CLINICALPATHOLOGICFINDINGSTUMORCLASSIFICATIONiPOSTOPERATIVEMANAGEMENTanceanceveChemotherapyorationancerimidinefluorouracilorcapecitabineorimidinefluorouracilorcapecitabineorthenfluoropyrimidine-basedchemoradiation,o,p,rthenfluoropyrimidine(fluorouracilorcapecitabine)o,rfortedpatientssrimidinefluorouracilthenfluoropyrimidine(fluorouracilorcapecitabine)o,rfortedpatientssrimidinefluorouracilorcapecitabineorthenfluoropyrimidine-basedchemoradiation,o,p,rthenfluoropyrimidine(fluorouracilorcapecitabine)o,rthenfluoropyrimidine(fluorouracilorcapecitabine)o,riflessthanaDdissectioncategory)mphnodedissectionfocategoryChemoradiationo,p(fluoropyrimidine-based)Chemoradiationo,p(fluoropyrimidine-based)Management(seeGAST-9)fSeePrinciplesofSurgery(GAS

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