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简介：Objective:Toevaluatetherelationbetweenargyrophilicnucleolarorganizerregion(AgNOR)-associatedproteinsandclinicopathologicalparametersandsurvivalinnon-small-celllungcancer(NSCLC).Methods:Atotalof207surgicalspecimensdiagnosedasNSCLCwereincludedinthisstudy.Double-stainingprocedureswereperformedusingantigenKi-67(cloneMIB-1)andsilvernitratebyimmunohistochemicalandAgNOR-stainingmethods.Results:TheAgNORareainMIB-1-positivecellsofNSCLCisrelatedtoclinicopathologicalparametersundertheTNM(tumor,node,andmetastasis)system.ThesurvivalofpatientswithsmallAgNORareainMIB-1-positivecellsisbetterthanthatofpatientswithlargeAgNORarea.Molecular,biological(AgNORareainMIB-1-positivecells),andclinicopathological(greatesttumordimension,metastasestoregionallymphnodes,histology,anddifferentiation)parametersareindependentprognosticfactorsofNSCLC.Conclusion:TheAgNORareainMIB-1-positivecellsisrelatedtoclinicopathologicalparametersandsurvivalinNSCLC.

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简介：Duringthelastdecade,wehaveseentremendousprogressinthetherapyoflungcancer.DiscoveryofactionablemutationsinEGFRandtranslocationsinALKandROS1haveidentifiedsubsetsofpatientswithexcellenttumorresponsetooraltargetedagentswithmanageablesideeffects.Inthisreview,wehighlighttreatmentoptionsincludingcorrespondingclinicaltrialsforoncogenicalterationsaffectingthereceptortyrosinekinasesMET,FGFR,NTRK,RET,HER2,HER3,andHER4aswellascomponentsoftheRAS-RAF-MEKsignalingpathway.

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简介：Objective:Non-smallcelllungcancer(NSCLC)patientswithepidermalgrowthfactorreceptor(EGFR)-activatingmutationshavehigherresponserateandmoreprolongedsurvivalfollowingtreatmentwithsingle-agentEGFRtyrosinekinaseinhibitor(EGFR-TKI)comparedwithpatientswithwild-typeEGFR.However,allpatientstreatedwithreversibleinhibitorsdevelopacquiredresistanceovertime.Themechanismsofresistancearecomplicated.ThelackofestablishedtherapeuticoptionsforpatientsafterafailedEGFR-TKItreatmentposesagreatchallengetophysiciansinmanagingthisgroupoflungcancerpatients.ThisstudyevaluatestheinfluenceofEGFR-TKIretreatmentfollowingchemotherapyafterfailureofinitialEGFR-TKIwithinatleast6monthsonNSCLCpatients.Methods:Thedataof27patientswhoexperiencedtreatmentfailurefromtheirinitialuseofEGFR-TKIwithinatleast6monthswereanalyzed.Afterchemotherapy,thepatientswereretreatedwithEGFR-TKI(gefitinib250mgqdorerlotinib150mgqd),andthetumorprogressionwasobserved.Thepatientswereassessedforadverseeventsandresponsetotherapy.TargetedtumorlesionswereassessedwithCTscan.Results:Ofthe27patientswhoreceivedEGFR-TKIretreatment,1(3.7%)patientwasobservedincompleteresponse(CR),8(29.6%)patientsinpartialresponse(PR),14(51.9%)patientsinstabledisease(SD),and4(14.8%)patientsinprogressivedisease(PD).Thediseasecontrolrate(DCR)was85.2%(95%CI:62%-94%).Themedianprogression-freesurvival(mPFS)was6months(95%CI:1-29).Ofthe13patientswhoreceivedthesameEGFR-TKI,1patientinCR,3patientsinPR,8patientsinSD,and2patientsinPDwereobserved.TheDCRwas84.6%,andthemPFSwas5months.Ofthe14patientswhoreceivedanotherEGFR-TKI,nopatientinCR,6patientsinPR,6patientsinSD,and2patientsinPDwereobserved.TheDCRwas85.7%,andthemPFSwas9.5months.SignificantdifferencewasfoundbetweenthetwogroupsinPFSbutnotinresponserateorDCR.Conclusion:RetreatmentofEGFR-TKIscanbeconsideredano

简介：Objective:ActivatingKRASmutationsarethemostcommondriversinthedevelopmentofnon-smallcelllungcancer(NSCLC).However,unsuccessoftreatmentbydirectinhibitionofKRAShasbeenproven.DeregulationofPI3KsignalingplaysanimportantroleintumorigenesisanddrugresistanceinNSCLC.TheactivityofPI3Kα-selectiveinhibitionagainstKRAS-mutatedNSCLCremainslargelyunknown.Methods:CellproliferationwasdetectedbysulforhodamineBassay.Cellcycledistributionandapoptosisweremeasuredbyflowcytometry.CellsignalingwasassessedbyWesternblotandimmunohistochemistry.RNAinterferencewasusedtodown-regulatetheexpressionofcyclinD1.HumanNSCLCxenograftswereemployedtodetecttherapeuticefficacyinvivo.Results:CYH33possessedvariableactivityagainstapanelofKRAS-mutatedNSCLCcelllines.AlthoughCYH33blockedAKTphosphorylationinalltestedcells,RbphosphorylationdecreasedinCYH33-sensitive,butnotinCYH33-resistantcells,whichwasconsistentwithG1phasearrestinsensitivecells.CombinedtreatmentwiththeCDK4/6inhibitor,PD0332991,andCYH33displayedsynergisticactivityagainsttheproliferationofbothCYH33-sensitiveandCYH33-resistantcells,whichwasaccompaniedbyenhancedG1-phasearrest.Moreover,down-regulationofcyclinD1sensitizedNSCLCcellstoCYH33.Reciprocally,CYH33abrogatedthePD0332991-inducedup-regulationofcyclinD1andphosphorylationofAKTinA549cells.Co-treatmentwiththesetwodrugsdemonstratedsynergisticactivityagainstA549andH23xenografts,withenhancedinhibitionofRbphosphorylation.Conclusions:SimultaneousinhibitionofPI3KαandCDK4/6displayedsynergisticactivityagainstKRAS-mutatedNSCLC.ThesedataprovideamechanisticrationaleforthecombinationofaPI3KαinhibitorandaCDK4/6inhibitorforthetreatmentofKRASmutatedNSCLC.

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：Non-smallcelllungcancer(NSCLC)ranksastheleadingcauseofcancer-relateddeathintheworld.Brainmetastasis(BM)isacommoncomplicationofNSCLC,with25%–40%ofpatientsdevelopingBMduringthecourseofthedisease.Asignificantstrategyoflocaldiseasecontrolinthecentralnervoussystemisradiationtherapy.Withthedevelopmentofprecisionmedicine,theconceptoftreatinglungcancerBMhasgraduallychanged.Inthiscase,weperformedasurgicalproceduretoobtainenoughtumortissueforthedetectionofthetargetgeneandotherrelatedexperimentsafterthepatientwasinformed.Finally,wefoundthatthepatienthadbothhepatocytegrowthfactorreceptor(MET)geneamplificationandkinesinlightchain1-anaplasticlymphomakinasefusion(KLC1-ALK)throughnext-generationsequencingandshowedsensitivitytothetargetedtherapyofcrizotinib.Thepatientexhibitedgoodresponse.Ourcasewassuccessfulandunderwenttargetedtherapywiththeguidanceofprecisediagnosis.

简介：客观：为了探索病理和临床的反应率的变化，为非小的房间肺癌症与MVP政体由neoadjuvant化疗对待。方法：这是在有阶段I-IIIa的病人的使随机化的研究。在他们之中，46个病人在neoadjuvant注册了1鈥对待的化疗吗？功课MVP政体。MMC被给6mg/M2由静脉内(I.V)day1上的注入，VDS2.5鈥吗？day1,8或day15上的mg/M2I.V，day1上的DDP90mg/M2I.V。治疗每28天被再循环。评估与的临床的RR标准。所有外科的样品与病理被分类。结果：在2功课化疗的全面反应率在1堂功课比那好(P<0.01)。有病理等级的病人的数字我在2功课化疗的鈥揑I比那高嗨1堂功课(P<0.01)。但是RR不能完全翻译了成病理等级我鈥揑I。病理等级我鈥揑I仔细与肿瘤参与(T)被联系(P<0.01)然而并非与地区性的淋巴节点转移(N)密切相关。和PCR使用RR判定化疗反应是合理的。NR病人不能作为化疗失败是问候。不服务毒性和外科的死亡被观察。结论：MVP政体是为I-IIIaNSCLC的有效neoadjuvant治疗政体。

简介：Objective:Survivalbenefitofadjuvantchemotherapy(AC)ofpatientswithintrapulmonarylymphnode(IPLN)metastasis(level12-14)needsinvestigation.WeevaluatedtheimpactofAConpatientswhosemetastaticnodeswerelimitedtointrapulmonarylevelsaftersystematicdissectionofN1nodes.Methods:First,155consectivecasesoflungcancerconfirmedaspathologicN1werecollectedandevaluated.PatientsreceivedsystematicdissectionofN2andN1nodes.ForpatientswithIPLNmetastasis,survivaloutcomeswerecomparedbetweenthosereceivingACandthosenotreceivingAC.Results:Inthisgroup,112cases(72.3%)hadIPLNmetastasisand55cases(35.5%)hadN1involvementlimitedtolevel13-14withoutfurtherdiseasespreadtohigherlevels.PatientswithIPLNinvolvementhadabetterprognosisthanthatofpatientswithhilar-interlobarinvolvement.FortheintrapulmonaryN1group(level12-14-positive,level10-11-negativeorunknown,n=112),nosurvivalbenefitwasfoundbetweentheACgroupandnonACgroup[5-yearoverallsurvival(OS):54.6±1.6vs.50.4±2.4months,P=0.177].However,76of112casesforwhomharvestingoflevel-10andlevel-11nodeswasdonedidnotshowcancerinvolvementinpathologyreports(level12-14-positive,level10-11bothnegative),oncologicoutcomewasbetterforpatientsreceivingACthanthosenotreceivingACinthissubgroup(5-yearOS:57.3±1.5vs.47.1±3.2months,P=0.002).Conclusions:OncologicoutcomemaybeimprovedbyACforpatientswithinvolvementofN1nodeslimitedtointrapulmonarylevelsaftercompleteexaminationofN1nodes.

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.

简介：Objective:Apreviousstudydemonstratedthatnon-anthracycline-containingdocetaxelpluscyclophosphamide(TC)regimenwasinferiortodocetaxel,anthracyclineandcyclophosphamide(TAC)inneoadjuvanttreatmentoftriple-negativebreastcancer(TNBC)andhumanepidermalgrowthfactorreceptor-2-(HER2)-positivebreastcancerinashort-termfollow-up.Herein,long-termfollow-upsurvivaloutcomeshavebeeninvestigated.Methods:TNBCorHER2-positivepatientswererandomizedtoreceive6cyclesofTCorTACneoadjuvanttreatment.Theprimaryendpointwaspathologicalcompleteremission(pCR).Secondaryendpointsincludedclinicalresponserate,event-freesurvival(EFS),andoverallsurvival(OS).Results:Acohortof96patientsconsistedof45inTCand51inTACarm.Withamedianfollow-upperiodof53(range,8–76)months,thepatientsachievingpCRpostneoadjuvantchemotherapyexhibitedsuperiorEFSandOSthanpatientswithoutpCR(P<0.05).TACtreatmentresultedinconsistentlybetterEFSthanTCtreatment:theestimated5-yearEFSwas66.1%vs.29.8%(P=0.002).Moreover,theestimated5-yearOSwasalsoinfavorofTAC:88.4%vs.51.6%(P<0.001).Multivariableanalysisdemonstratedthatthetreatmentregimenwasanindependentprognosticfactor,andpatientstreatedwithTAChadasuperiorEFS[hazardratio(HR),0.48;95%confidenceinterval(95%CI),0.26–0.90;P=0.021]andOS(HR,0.20;95%CI,0.08–0.60;P=0.003).Conclusions:Theupdatedlong-termfollow-updatademonstratedasustainedbenefitinEFSandOSfromanthracycline-containingTACtreatment,indicatingthatanthracyclineisanessentialandeffectivedruginthisclinicaltrial.