小细胞肺癌诊疗治疗进展专家讲座

SmallCellLungCancer(SCLC):

Diagnosis,TreatmentandNaturalHistoryGaryL.WeinsteinM.D.小细胞肺癌诊疗治疗进展第1页SCLCLungcancerepidemiologySCLCPathologyTumormarkersGeneticsClinicalcourseStagingTreatment小细胞肺癌诊疗治疗进展第2页小细胞肺癌诊疗治疗进展第3页小细胞肺癌诊疗治疗进展第4页小细胞肺癌诊疗治疗进展第5页小细胞肺癌诊疗治疗进展第6页小细胞肺癌诊疗治疗进展第7页小细胞肺癌诊疗治疗进展第8页小细胞肺癌诊疗治疗进展第9页小细胞肺癌诊疗治疗进展第10页小细胞肺癌诊疗治疗进展第11页小细胞肺癌诊疗治疗进展第12页小细胞肺癌诊疗治疗进展第13页小细胞肺癌诊疗治疗进展第14页小细胞肺癌诊疗治疗进展第15页小细胞肺癌诊疗治疗进展第16页小细胞肺癌诊疗治疗进展第17页小细胞肺癌诊疗治疗进展第18页小细胞肺癌诊疗治疗进展第19页小细胞肺癌诊疗治疗进展第20页小细胞肺癌诊疗治疗进展第21页小细胞肺癌诊疗治疗进展第22页小细胞肺癌诊疗治疗进展第23页小细胞肺癌诊疗治疗进展第24页小细胞肺癌诊疗治疗进展第25页小细胞肺癌诊疗治疗进展第26页小细胞肺癌诊疗治疗进展第27页SCLC,factoids15–25%ofalllungcancersAlmostexclusivelyinsmokersDistinguishedfromNSCLCby:RapiddoublingtimeHighgrowthfractionEarlydevelopmentofwide-spreadmets小细胞肺癌诊疗治疗进展第28页SCLC,factoids(cont’d)Consideredhighlyresponsiveto“chemsandbeams”BUT…usuallyrelapseswithin2yearsdespitetreatmentOverall,only3–8%ofallpatientssurvivemorethan5yearsMostcommonmalignancyassociatedwithNeurologicparaneoplasticsyndromes小细胞肺癌诊疗治疗进展第29页SCLC,pathologyMostrecent(1999)WHOclassificationClassicalsmallcellcarcinomaLargecellneuroendocrinecancerCombinedsmallcellcarcinomawithsomeNSCLCCellsareapprox.2X’sthesizeofnormallymphocytes小细胞肺癌诊疗治疗进展第30页SCLC,pathology

小细胞肺癌诊疗治疗进展第31页SCLC,pathology

小细胞肺癌诊疗治疗进展第32页SCLC,clinicalpresentationTypicallyarisecentrallyMostcommonpresentationisalargehilarmasswithbulkymediastinalLANCommonsymptomscough,SOB,wtlossApprox.70%withovertmetsatpresentationCommonlyspreadtoliver,adrenals,boneandbrainCanpresentwithparaneoplasticsyndome小细胞肺癌诊疗治疗进展第33页SCLC,tumormarkers3maingroups:Neural,Epithelial,NeuroendocrineEpithelial:virtuallyallSCLCsareimmunoreactiveforKeratinandEpithelialMembraneAntigen1ormoremarkersofNeural/Neuroendocrinedifferentiationfoundinapprox.75%ofSCLCs小细胞肺癌诊疗治疗进展第34页SCLC,tumormarkersLeadstoexpressionofdopadecarboxylase,calcitonin,neuron-specificenolase,chromograninA,CD-56(aneuralcelladhesionmolecule)gastrinreleasingpeptideandinsulin-likegrowthhormoneOccasionallypatientsproduceantibodiesthatcross-reactwithboththeSCLCcellsandtheCNScerebellardegenerationsyndromesSCLCcellscanproduceanumberofpolypeptidehormonesincludingACTHandVasopressin

小细胞肺癌诊疗治疗进展第35页NeurologicParaneoplasticSyndromes

小细胞肺癌诊疗治疗进展第36页Lungcancer,ParaneoplasticSyndromes

小细胞肺癌诊疗治疗进展第37页SCLC,geneticsDevelopmentoflungcancersoccurthroughstimulationofproliferationandmutagenesis,occurringoverYEARSandresultingfromexposuretotobaccoandothercarcinogens小细胞肺癌诊疗治疗进展第38页SCLC,geneticsThemostcommongeneticsofSCLCare:P53mutationispresentin75-90%Lossofheterozygosityofc-somes9pand10qinthemajorityDeletionof3pinactivationofasmanyas3tumorsuppressorgenesLossoftheretinoblastomagenefunctionisnearlyubiquitousActivationoftelomeraseinapprox.90%(allowscellstodivideforever)小细胞肺癌诊疗治疗进展第39页小细胞肺癌诊疗治疗进展第40页小细胞肺癌诊疗治疗进展第41页小细胞肺癌诊疗治疗进展第42页小细胞肺癌诊疗治疗进展第43页小细胞肺癌诊疗治疗进展第44页小细胞肺癌诊疗治疗进