內(nèi)科學(xué)教學(xué)課件：17 支氣管肺癌-Lung Cancer

LungCancerLungCancerEpidemiology:EstimatedNewCancerCases,UnitedStates,2011Prostate 240,800

Lung&bronchus

115,060Colonandrectum 71,850Urinarysystem 90,750Non-Hodgkin’sLymph 36,060

Leukemia 25,320Pancreas 22,050Stomach 13,120Liverandintrahepatic 19,260

Esophagus 13,450UnspecifiedPrimarysites 15,220Breast 230,480Lung&bronchus 106,070Colonandrectum 69,360

Urinarysystem 42,150Non-Hodgkin’slymph30,300Pancreas 21,980Stomach 8,400Leukemia 19,280Liverandintrahepatic 6,930Esophagus 3,530UnspecifiedPrimarysites 15,280Deaths85600(LungCanver)7134033720(Prostate)(Breast)39520

MaleCancer

FemaleCancer中國肺癌流行病學(xué)回顧26.9%38.4%30.5%2000-2005年肺癌患者數(shù)Yangetal,2005患者數(shù)RiskFactors

SmokingCigarettesmokingStrongevidenceofcausalrelationshipResponsiblefor>80%ofcasesRelativeriskofdyingfromlungcancer:15-20xhighercomparedtonon-smokersPassivesmokingResponsiblefor

25%ofcasesinnon-smokersSmokingConsequences—

LungCancerCigarettesmokingistheleadingcauseoflungcanceramongwomen.Lungcancermortalityrateshaveskyrocketed600%since1950.Theriskforlungcancerincreaseswithamount,duration,andintensityofsmoking.MortalityandCigaretteSmoking051015202531+NoneAllSM<1011-192021-30No.ofcigarettessmokeddailyRelationshiptoSmokingGlobalCigarette

ConsumptionMarlboroManMaleCancer

RiskFactors

Others

AsbestosRadonRadiationChronicinflammationGeneticpredispositionEtiologyTobacco (%)active 85-87passive 3-5Radon 3-5Industrialpollution 0-5Other 0-9ClinicalPresentation

PrimaryTumor?Cough?Hemoptysis?Wheezes?Dyspnea?Post-obstructivepneumonia?Weightloss?AnorexiaClinicalPresentation

LocalInvasion?Pleuriticchestpain?Hoarseness?Superiorvenacavasyndrome?Horner’ssyndrome?Dysphagia?CardiacinvolvementClinicalPresentation

DistantMetastases?LymphnodesBrainBonesLiverLung/pleuraAdrenalglandClinicalPresentation

ParaneoplasticSyndromes

NonSmallCellLungCancerhypercalcemiaskeletal-connectivetissuesyndromesSmallCellLungCancerinappropriatesecretionofADHectopiaACTHsecretionneurologic/myopathicsyndromesDiagnosisHistoryandPhysicalexamDiagnostictestsChestx-rayBiopsy(bronchoscopy,needlebiopsy,surgery)StagingtestsCTchest/abdomenBonescanBonemarrowaspirationPETscanLungCancerSquamousCellSolitaryPulmonaryNoduleCTScan–TypicalAdenocarcinomaT1N0M0LungCancerNonSmallCellLungCancer(NSCLC)–80%SquamousAdenocarcinomaLargeCellBronchoalveolarSmallCellLungCancer(SCLC)–15%BronchialCarcinoid–3%Other–2%SquamouscellcarcinomaadenocarcinomaBronchiolo-alveolarcarcinomaSmallcellcarcinoma

T=tumorsize

(T1<3cm,T2>3cm+atelectasis),tumorsite(T3extensiontopleura,chestwall,pericardiumortotalatelectasis),localinvolvement

(T4invasionofmediastinumorpleuraleffusion);

N=lymphnodespread

N1bronchopulmonary,N2(ipsilateralmediastinal)andN3(contralateralorsupraclavicular);

M=absence(M0)orpresence(M1)of

metastases新舊分期系統(tǒng)對比TNM分期系統(tǒng)第6版第7版0期TisN0M0I期AT1N0M0BT2N0M0T2aN0M0II期AT1N1M0T2bN0M0,T1N1M0,T2aN1M0BT2N1M0,T3N0M0T2bN1M0，T3N0M0III期AT3N1M0,T1N2MO,T2N2M0T3N2M0T3N1M0,T1N2MO,T2N2M0T3N2M0，T4N0M0,T4N1M0BanyT，N3,M0;T4,anyN,M0anyT，N3,M0;T4,N2,M0IV期anyT,anyN,M1STAGEISTAGEIISTAGEIIIASTAGEIIIBAlsowithmalignantPleuraleffusionDifferentialDiagnosis一、Tuberculosis

Tuberculoma

Tuberculosisofhilarlymphnode

Acutemiliarytuberculosis二、Pneumonia三、Lungabscess四、Differentialdiagnosisofpleuraleffusion

NSCLC:TreatmentSurgeryMediastinoscopyVideo-assistedThoracoscopy(VAT)Thoracotomy:Lobectomy.PneumonectomyRadiationExternalBeamBrachytherapyNSCLC:TreatmentChemotherapyStandardCisplatin,CarboplatinNeweragents:Gemcitabine,Paclitaxel,Docetaxel,Vinorelbine,IrinotecanusedaloneandincombinationNSCLC系統(tǒng)化治療發(fā)展史的主要里程碑

FDA批準(zhǔn)的藥物1995GemcitabineVinorelbinePaclitaxelDocetaxel19941st-lineunresectableadvancedNSCLC19981st-linelocallyadvancedormetastaticNSCLC19981st-lineforunresectableNSCLC1999(2nd-line)2002(1st-line)LocallyadvancedormetastaticNSCLC200020052010ErlotinibGefitinib20032nd-linelocallyadvancedormetastaticNSCLC2004(2nd-line)2010(maintenance)2013(1st-line)LocallyadvancedormetastaticNSCLCPemetrexedCrizotinibBevacizumab2004(2nd-line)2008(1st-line)2009(maintenance)nonsquamousNSCLC20061st-lineunresectable,locallyadvanced,recurrentormetastaticnonsquamousNSCLC2011LocallyadvancedormetastaticALK+NSCLCAbraxane20121st-lineforlocallyadvancedormetastaticNSCLCChemotherapyTargetedtherapyAfatinib20131st-lineformetastaticNSCLCCeritinib20142nd-linemetastaticALK+NSCLCECOG1594研究IV期NSCLC生存曲線0510152025300.20.40.60.81.0Cis/PaclitaxelCis/GemcitabineCis/DocetaxelCarbo/Paclitaxel月靶點(diǎn)類型代表藥物EGFR1.TKI單靶點(diǎn)可逆：吉非替尼、厄洛替尼單靶點(diǎn)不可逆：EKB-569、CL-387多靶點(diǎn)不可逆：HKI-272、卡奈替尼、PF-00299804、BIBW29922.MAB西妥昔單抗VEGF1.MAB貝伐單抗2.RTKI索拉非尼、凡德他尼、舒尼替尼、Cediranib3.TRAPAVE0005抗血管生成1.Endostatin恩度2.VDAASA404IGF-1RMABFigitumumabmTOR抑制劑西羅莫司、依維莫司MET抑制劑MetMAb,ARQ197EML4-ALK抑制劑Crizotinib免疫調(diào)節(jié)劑Ipilimumab蛋白酶體抑制劑硼替佐米HDAC抑制劑VorinostatPallisAG,etal.EJC2009;45:2473-2487.

TargetTherapyforAdvancedNSCLCNEJ002：更新PFS和OS10.8月5.4月易瑞沙(n=98)卡鉑/紫杉醇(n=101)中位PFS(月)10.85.4HR(95%CI)0.322(0.236-0.438)1年P(guān)FS43.8%4.2%易瑞沙(n=69)卡鉑/紫杉醇(n=69)中位OS(月)27.726.6HR(95%CI)0.887(0.634-1.241)1年生存率85.0%86.8%2年生存率57.9%53.7%26.6月27.7月免疫靶向治療PD-1通路為靶點(diǎn)的抑制劑Nivolumab(anti-PD-1)Lambrolizumab(MK-3475,anti-PD-1)MDPL3280A(anti-PD-L1)BMS-936559(anti-PD-L1)Pidilizumab(anti-PD-1)Nivolumab與多西他賽二線治療IIIb/IV期鱗狀NSCLC

最低生存隨訪:18個(gè)月K.Reckamp,etal.2015WCLCOral02.01.NSCLC:TreatmentbyStageStageIandII

-

Surgeryasprimarytreatment

StageIII-

MultimodalityTherapy

IIIA–Neoadjuvanttherapy(chemo/radiation)followedbysurgery+/-additionaltherapyIIIB-CombinationchemotherapyandradiationtherapyStageIV-

Palliativechemotherapyand/orradiationNSCLC:TreatmentOutcomesStageIIIIIIaIIIbIV5YearSurvival

38-67% 24-37% 9-13% 5%< 1%SmallCellLungCancer(SCLC)MostaggressivelungcancerResponsivetochemotherapyandradiationbutrecurrencerateishigheveninearlystageSCLC:StagingLimitedDisease-Diseaseconfinedtoonesideofthechestandtheregionallymphnodesencompassedinoneradiatio