简介：Objective:Toassesstheresponserateofpatientswithrectaladenocarcinomatoneoadjuvanttherapyandtoidentifythepredictorsofhistologicalregressionafterneoadjuvantradiotherapy(RT)orconcurrentchemoradiotherapy(CCRT).Methods:Thisstudyrecruited64patients.Thepatientshadresectablecancerofthelowerandthemiddlerectum(T3/T4and/orN+)withoutdistantmetastasisandreceivedneoadjuvantRTorCCRTfollowedbyradicalsurgerywithtotalmesorectalexcision(TME)betweenJanuary2006andDecember2011.Thepatientswereclassifiedintonon-response(NR),partialresponse(PR),andpathologiccompleteresponse(pCR)basedontheDworaktumorregressiongradingsystem.Results:Themedianageofpatientswas57years(rangingfrom22to85).Atotalof24patientsweretreatedwithneoadjuvantCCRT,whereas40patientsweretreatedwithRTalone.Abdominoperinealresection(APR)wasperformedon29patients(45%).AnteriorresectionwithTMEwasperformedon34patients(53%).Onepatienthadlocalresection.Histologically,12(19%),24(73%),and28(44%)patientsexhibitedpCR,PR,andNR,respectively.Univariateanalysisrevealedthatthepredictorsoftumorregressionwereasfollows:theabsenceoflymphnodeinvolvementfrominitialimaging(cN0)(P=0.021);normalinitialcarcinoembryonicantigen(CEA)level(P=0.01);hemoglobinlevel≥12g/dl(P=0.009);CCRT(P=0.021);andtumordownstaginginimaging(P=0.001).MultivariateanalysisshowedthatthemainpredictorsofpCRwereCTcombinedwithneoadjuvantRT,cN0stage,andtumorregressiononimaging.Conclusions:IdentifyingthepredictorsofpCRfollowingneoadjuvanttherapyaidstheselectionofresponsivepatientsfornonaggressivesurgicaltreatmentandpossiblesurveillance.

简介：Purpose:Anumberofdifferentclinicalcharacteristicshavebeenreportedtosinglycorrelatewiththerapeuticactivityofepidermalgrowthfactorreceptor(EGFR)tyrosinekinaseinhibitors(TKIs)inadvancednon-small-celllungcancer(NSCLC).Thisstudyaimedtoidentifypredictivefactorsassociatedwithprognosticbenefitsofgefitinib.Patientsandmethods:EGFRgenetypingin33advancedNSCLCpatientsreceivedgefitinib(250mg/day)wereanalyzedwithmutant-enrichedPCRassay.Gefitinibresponsewasevaluatedwithpotentialpredictivefactorsretrospectively.Results:Theoverallobjectiveresponserate(ORR)andmedianprogression-freesurvival(PFS)inthe33patientstreatedbygefitinibwere45.5%and3.0(2.0-4.0)months.TheORRandmedianPFSinEGFRgenemutationpatientsweresignificantlyhigher/longerthanthoseinEGFRgenewild-typepatients(P<0.01).Similarly,theORRandmedianPFSinnon-smokerpatientsweresignificantlyhigher/longerthanthoseinsmokerpatients(P<0.05,P<0.01,respectively).However,nodifferenceforORRandmedianPFSoccurredbetweenmaleandfemalepatients.LogisticmultivariateanalysisshowedthatonlyEGFRmutatedgenewassignificantlyassociatedwiththeORR(P<0.01).BothEGFRmutatedgeneandnon-smokerwerethemajorfactorsthatcontributedtoPFS(P<0.05).Conclusions:EGFRmutatedgeneandnon-smokerstatusarepotentialpredictorsforgefitinibresponseinNSCLCpatients.

简介：Objective:Theepidermalgrowthfactorreceptor(EGFR)inhibitorsmonoclonalantibodies(MoAbs)havealreadyshownthetherapeuticeffectivenessinpatientswithmetastaticcolorectalcancer(mCRC).Butmanypatientsresisttothetreatment.Theaimofthismeta-analysiswastoassessEGFRgenecopynumber(GCN)asacandidatepredictivebiomarkerforresistancetoanti-EGFRMoAbsinmCRCtreatment.Methods:SystematiccomputerizedsearchesofthePubMed,EMBaseandCochraneLibrarywereperformed.Theprimaryendpointwasobjectiveresponserate(ORR).Thesecondendpointsincludedprogression-freesurvival(PFS),andoverallsurvival(OS).Thepooledoddratio(OR)andpooledsensitivity,specificity,andsummaryreceiveroperatorcharacteristic(SROC)forORRwereestimated.Thepooledhazardratios(HR)forPFSandOSwerealsocalculated.Results:Fourteenstudieswith1,021patientswereincluded.IncreasedEGFRGCNwasassociatedwithincreasedORR(OR=6.905;95%CI:4.489-10.620).Itwasalsofoundinwild-typeKRASmCRCpatients,withthepooledORof8.133(95%CI:4.316-15.326).GCNhasmediumvalueforpredictingORR,withthepooledsensitivityof0.79(95%CI:0.73-0.84),thepooledspecificityof0.59(95%CI:0.55-0.62).InwildtypeKRASmCRCpatients,thesensitivityandthespecificitywere0.80(95%CI:0.70-0.87)and0.60(95%CI:0.53-0.66),respectively.IncreasedEGFRGCNwasassociatedwithincreasedPFS(HR=0.557;95%CI:0.382-0.732)andOS(HR=0.579;95%CI:0.422-0.737).Conclusions:Thismeta-analysissuggeststhatEGFRGCNrepresentsapredictivebiomarkerfortumorresponseinmCRCpatientstreatedwithMoAbsregardlessofKRASmutation.mCRCpatientswithincreasedEGFRGCNaremorelikelytohaveabetterresponse,PFS,andOSwhentreatedwithcetuximaborpanitumumab.

简介：Blockadeofimmunecheckpointshasrecentlyemergedasanoveltherapeuticstrategyinvarioustumors.Inparticular,monoclonalantibodiestargetingprogrammedcelldeath1(PD-1)oritsligand(PD-L1)havebeenmoststudiedinlungcancer,andPD-1inhibitorsarenowestablishedagentsinthemanagementofnon-smallcelllungcancer(NSCLC).ThereportsonhighprofileclinicaltrialshaveshowntheassociationofPD-L1expressionbyimmunohistochemistry(IHC)withhigheroverallresponseratestothePD-1/PD-L1axisblockadesuggestingthatPD-L1expressionmayserveasapredictivemarker.Unfortunately,however,eachPD-1orPD-L1inhibitoriscoupledwithaspecificPD-L1antibody,IHCprotocolandscoringsystemforthebiomarkerassessment,makingthehead-to-headcomparisonofthestudiesdifficult.Similarly,multipleclinicalseriesthatcorrelatedPD-L1expressionwithclinicopathologicand/ormolecularvariablesand/orsurvivalhavereportedconflictingresults.Thediscrepancycouldbeexplainedbythedifferencesinethnicityand/orhistologictypesincludedinthestudies,butitappearstobeattributedinparttothedifferencesinPD-L1IHCmethods.Thus,orchestratedeffortstostandardizethePD-L1IHCarewarrantedtoestablishtheIHCasapredictiveand/orprognosticbiomarkerinNSCLC.

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简介：Objective:Ameta-analysiswasperformedtoaugmenttheinsufficientdataontheimpactofmutativeEGFRdownstreamphosphatidylinositol-3-kinase(PI3K)andmitogen-activatedproteinkinase(MAPK)pathwaysontheclinicalefficiencyofepidermalgrowthfactorreceptortyrosinekinaseinhibitor(EGFR-TKI)treatmentofnon-smallcelllungcancer(NSCLC)patients.Methods:NetworkdatabaseswereexploredinApril,2015.PapersthatinvestigatedtheclinicaloutcomesofNSCLCpatientstreatedwithEGFR-TKIsaccordingtothestatusofK-rasand/orPIK3CAgenemutationwereincluded.Aquantitativemeta-analysiswasconductedusingstandardstatisticalmethods.Oddsratios(ORs)forobjectiveresponserate(ORR)andhazardratios(HRs)forprogression-freesurvival(PFS)andoverallsurvival(OS)werecalculated.Results:MutationinK-rassignificantlypredictedpoorORR[OR=0.22;95%confidenceinterval(CI),0.13-0.35],shorterPFS(HR=1.56;95%CI,1.27-1.92),andshorterOS(HR=1.59;95%CI,1.33-1.91)inNSCLCpatientstreatedwithEGFR-TKIs.MutantPIK3CAsignificantlypredictedshorterOS(HR=1.83;95%CI,1.05-3.20),showedpoorORR(OR=0.70;95%CI,0.22-2.18),andshorterPFS(HR=1.79;95%CI,0.91-3.53)inNSCLCpatientstreatedwithEGFR-TKIs.Conclusion:K-rasmutationadverselyaffectedtheclinicalresponseandsurvivalofNSCLCpatientstreatedwithEGFRTKIs.PIK3CAmutationshowedsimilartrends.InadditiontoEGFR,addingK-rasandPIK3CAasroutinegenebiomarkersinclinicalgeneticanalysisisvaluabletooptimizetheeffectivenessofEGFR-TKIregimensandidentifyoptimalpatientswhowillbenefitfromEGFR-TKItreatment.