（参考课件）结直肠癌.ppt

Challengesbehindprovingefcacyofadjuvantchemotherapyafterpreoperativechemoradiationforrectalcancer,LancetOncol2017;18:e35463CarlosCarvalho-ChampalimaudCancerCentre,Lisbon,PortugalRobGlynne-Jones-MountVernonCentreforCancerTreatment,MountVernonHospital,Northwood,UK唐睿2017-10,Introduction,Methods,3,Background,1,2,Findings,4,Conclusion,Background,1、coloncancer（high-riskstageIIorstageIII）adjuvantchemotherapy：fuoropyrimidinemonotherapyreducestheriskofrecurrenceanddeathbyapproximately2030%.Additionalimprovementswhenoxaliplatinwasaddedtothechemoradiationregimen；2、rectalcancerpatientswereexcludedfromthesestudiesbecauseofpotentialtoxicityandtheconfoundingimpactofradiotherapyandchemoradiation.3、clinicalguidelinesofferinconsistentrecommendationsforthemanagementofrectalcancerpatients；4、wesuggestthatnotroutinelyusedthepostoperativeadjuvantchemotherapyforpatientswithrectalcancertreatedwithpreoperativechemoradiation.Anddiscussingsourcesofbiasandofferpotentialreasons,aswellasproposearecommendedschemaforarandomisedphase3trial,Introduction,InthisReview,weanalysetheavailabledatafromrectalcancertrials.Noneofthesetrialsrobustlysupporttheroutineuseofpostoperativeadjuvantchemotherapyforpatientswithrectalcancertreatedwithpreoperativechemoradiation.,Methods,Searchstrategyandselectioncriteria,Findings,1、ACochranemeta-analysisof21trials(publishedupto2011)：signifcantbeneftindisease-freesurvivalandoverallsurvivalforpatientswhoreceivedpostoperativefuoropyrimidine-basedchemotherapy；Shortcoming：widespreaduseoftotalmesorectalexcision；postoperativeradiotherapyorchemoradiationwithoutseparateanalyses；advancedageandcomorbidities,1、Threeotherrandomisedphase3trials15-17,Noneofthemshowedasignifcantoverallsurvivalbeneftoverobservationaloneforpatientswithrectalcancer;AssameasTheFrenchGERCORR98Intergrouptrial(irinotecanfuorouracilplusleucovorininpatientswithresectedstageIIIIIrectalcancer.),Therandomisedphase2ADOREtrial20showedanimprovementinthe3-yeardisease-freesurvivalforpatientswithrectalcancerof72%versus63%infavouroftheFOLFOX(leucovorin,fuorouracil,andirinotecan)group.anoutlier:alowerreporteddisease-freesurvivalSt:withoutthetimingofadjuvantchemotherapyaftersurgeryage、TNM、EMVI、R0、conventionalcircumferentialresectionmargin、localrecurrencesrecordedasdisease-freesurvivalevents,Inthephase3randomisedGermanCAO/ARO/AIO-04trial19：oxaliplatinwasaddedtobothfuorouracil-basedpreoperativeandpostoperativechemotherapyandcomparedwithacontrolgroupoffuorouracil-basedpreoperativeandpostoperativechemotherapEnding：3-yeardisease-freesurvivalimprovedby47%intheoxaliplatingroupShorting：didnotdistinguishwhetherthissmallbeneftderivesfromthepreoperativechemoradiationorfromthepostoperativeoxaliplatin,orfromboth,andwhetherthisbeneftwilleventuallycontributetoanimprovementinoverallsurvival.,(NCCN)guidelinesstillrecommendpostoperativechemotherapyforallhistopathologicalstagesfollowingpreoperativechemoradiation；USAandCanadaoncologists:preoperativechemoradiationstageIIIrectalcancers,butnoconsensusforstageII;TheEuropean:recommendadjuvantchemotherapyhigh-riskrectalcancerpatientswithshort-coursepreoperativeradiotherapyorchemoradiation,(lackenoughscientifcevidencerobustinrectalcancer),next,Offerexplanationswhyresearchershavenotshownadjuvanthemotherapytobeefectiveafterpreoperativeradiotherapyorchemoradiationinrectalcancerbycontrastwithcoloncancer,Reasons,EfectofdiferentmolecularsubtypesonoutcomesEfectsofinaccuratebaselinestagingChemoradiationdownstagingandhistopathologyInclusionofverylow-riskpatientsInclusionofveryhigh-riskpatientsNoassessmentofqualityofrectalsurgeryEfectofsuboptimalchemotherapyontreatmentLongintervalbeforestartingadjuvantchemotherapyEfectofpoorcomplianceontreatmentTumourbiologymodifcationfromchemoradiationOtherpotentialbiases,ColonandrectalcancerhavesimilarnumbersofKRASmutations.andmostsharecommongenomicproflesdierentbiologicalandclinicaltumoursubtypesdierentprognosticproflesandsensitivitiestochemotherapeuticandbiologicalagents.Distalcancers-moreassociatedwithWNT,MYC,andSCRactivation-chemoresistance.,1、Inmosttrialstumorstagingreliesondigitalrectalexamination,CTscans,ndorectalultrasoundexaminations.(直肠超声)2、Intrialsthatrandomisedpostoperativelyusingsurgicalpathologyfndings,1、preoperativechemoradiation-pathologicalcompleteresponseordownstagedtoypT1/T2N0.2、theintervalbetweenpreoperativeradiotherapyandsurgerycouldaectthecompletenessoftheresponseandthepathologicalstaging.3、responsetochemoradiation,1、ClinicalstudiesinrectalcancerexpressingthestemcellmarkerCD133afteruorouracil-basedpreoperativechemoradiation.2、TheseupregulatedCD133-positivecancercellscorrelatewithanincreasedriskofdistantrecurrence,anddecreasedsurvival.3、patientswithCD133-positivecellsshowedresistancetofuorouracil-basedchemotherapy；,1、Age2、chemoradiationincreasedincidenceofnon-cancerdeathsinthechemoradiation3、Aspirinuse,Conclusion,Thedatafromtheadjuvantrectalcancertrialsdonotsupporttheuseofpostoperativeadjuvantchemotherapyforpatientswithrectalcancertreatedwithpreoperativechemoradiation.explain,imagine,18002400patientswithappropriatestratifcation,modernerasurgery,andselectioncriteriaisneed