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¤TenterMichaelGibson,MD,PhD??TVanderbilt-IngramCancerCenterStevenHochwald,MD?enter*WayneL.Hofstetter,MD?TheUniversityofTexas*DavidH.Ilson,MD,PhD?TenterRajeshN.Keswani,MD¤TSunnieKim,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?TSitemanCancerCenteratBarnes-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