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肺癌中山大学附属第一医院呼吸内科周燕斌1流行病学epidemiology2美国癌症死亡率(1992-1996)01020304050607080直肠癌胰腺癌肺癌前列腺癌乳腺癌卵巢癌男女死亡率100,000人/每年Riesetal19993美国肺癌发病率和死亡率(1973-1996)1050100Incidence-malesMortality-malesIncidence-femalesMortality-femalesRateper100,000people(logscale)19747678808284868890929496Yearofdiagnosis/deathRiesetal19994肺癌发生率：病理类型、性别、种族(1973-1996)6010194-685-71973-5男性黑人男性白人女性黑人女性白人Yearofdiagnosis鳞癌腺癌大细胞癌小细胞癌94-685-773-5Rateper100,000people(logscale)94-685-773-594-685-773-5Wingoetal19995肺癌的流行病学特点–90-92年肺癌占恶性肿瘤死因第1位的省市:上海:43.53/10万天津:38.86辽宁:32.07黑龙江:29.06吉林:28.06云南:23.07北京:22.25内蒙古:22.046肺癌的流行病学特点全国上海广东051015202530354045全国上海广东72--7490--927解剖和病理AnatomyandPathology891011肺癌的分类学按部位分:–中央型–周围型按生物学分:–小细胞肺癌:(15-20%)–非小细胞肺癌:(80-85%)鳞癌腺癌大细胞癌腺鳞癌其它12肺癌病理类型鳞癌0.30-0.35腺癌0.35-0.40大细胞癌0.10小细胞癌0.20-0.2513症状和诊断SymptomsandDiagnosis14肺癌的症状学发生发展表现–肺癌形成无症状–累及小支气管咳嗽–累及粘膜微血管血痰–侵及胸膜胸壁胸闷胸痛–阻塞支气管气促发热–胸膜播散胸水非特异性症状:食欲不振体重下降15肺癌的症状学外侵和转移症状–上腔静脉综合征–Horner’sSyndrome–Pancoast’sSyndrome肺癌伴随症状:–肺性骨关节病–类癌综合征–男性乳房发育16肺癌的主要症状和体征020406080100咯血纳差疼痛咳嗽呼吸困难患者(%)Hollenetal1999171819Transthoracicneedleaspiration(TTNA)ofanon-smallcellPancoasttumor202122肺癌的诊断学几个需要遵循的原则–警惕经治未愈的呼吸道症状–注意少见的肺外表现–从常规到复杂从无创到有创–重视获取病理学诊断细胞学,组织学23非小细胞肺癌的诊断PhysicalexaminationDetectsignsVisualizeandsamplemediasturiallymphnodesDetectposition,size,numberoftumorsDetectchestwallinvasionmediastinallymphodenopathydistantmetastasesLymphnodestagingDetectchangesinhormoneproduction,andhematologicalmanifestationsoflungcancerPreciselocationoftumorobtainbiopsyChestX-rayCTscanPETscanLaboratoryanalysisBronchoscopyMediastinoscopyFNACytologyNCCNGuidelines200024诊断（Diagnosis）1、CXR，CT，包括胸部、肝和肾上腺B2、对肺周围型病变经皮肺穿刺是合适的，但非强制性，特别是既往胸片检查无病变者。B3、CT提示纵隔淋巴结1cm（短径）应行纵隔镜检，前纵隔切开活检或穿刺。BBTSGuidelinesThorax2001,5689-10825非小细胞肺癌X线胸片26非小细胞肺癌CT扫描2728纵隔镜检查29分期和预后stagingandprognostication303132Mountain1997非小细胞肺癌分期DiseaseEarlyLocalizedAdvancedStage0IAIBIIAIIBIIIAIIIBIVTNMTISN0M0(carcinomainsitu)T1N0M0T2N0M0T1N1M0T2N1M0T3N0M0T3N1M0T1-3N2M0T4,AnyN,M0AnyT,N3,M0AnyT,AnyN,M133非小细胞肺癌分期Stage0StageIAStageIIBStageIIIBStageIVLymphnodesMainbronchusContralaterallymphnodeMetastasistodistantorgansInvasionofchestwall34非小细胞肺癌：临床分期与预后1year3years5years0102030405060708090100IAIBIIAT2N1M0IVIIBIIIAIIIBClinicalstageatpresentationSurvival(%)Mountain1997T3N0M0T3N1M0T1-3N2M0T4N335Probabilityofsurvivalaccordingtoclinicalstage36非小细胞肺癌:其他影响预后因素可手术(0-IIIA期)肺部症状肿瘤的最大径erbB-2,p53过表达血管侵犯肿瘤血管形成Harpole199537非小细胞肺癌:其他影响预后因素不可手术(IIIB-IV期)PS评分年龄和性别体重下降转移灶LDH,AKP（碱性磷酸酶）,血钙，血红蛋白含铂化疗方案Albainetal199138治疗Treatment39肺癌治疗思维决策先进行肺癌的生物学分类–小细胞肺癌–非小细胞肺癌再根据资料作肺癌的分期决定肺癌的治疗方案治疗结束安排随防计划40非小细胞肺癌：治疗概况肿瘤局限手术肿瘤范围较大化疗,放疗(手术)晚期肿瘤化疗PDQGuidelines41非小细胞肺癌的治疗：0期肺叶，肺段切除术，或楔形切除术根治性化疗（有手术禁忌者）内镜下光动力学治疗(疗效待评估)PDQGuidelines42非小细胞肺癌的治疗：I期和II期肺叶切除术或肺切除术根治性化疗（有手术禁忌者）辅助化疗辅助放疗新辅助化疗PDQGuidelines43I期非小细胞肺癌:手术Locoregionalrecurrencerate(perperson-year)Locoregionalrecurrencerate(%ofpatients)01020304050Segmen-tectomy(n=68)Lobectomy(n=105)00.00.010.020.030.040.050.060.070.080.090.10Limitedresection(n=122)Lobectomy(n=125)p=0.008WarrenandFaber1994GinsbergandRubinstein1995p0.0544I期和II期非小细胞肺癌:放疗Dosoretzetal199201020304050607080Overall65Gray60GrayT1T2T3RadiationdoseDisease-freesurvival(%)45非小细胞肺癌的治疗：III期单纯手术治疗(部分IIIA期患者)术后放疗化疗+放疗单纯放疗单纯化疗(IIIB期伴恶性胸腔积液）PDQGuidelines46III期非小细胞肺癌:手术联合其他治疗StudyPassetal1992Rothetal1994Roselletal1994RegimensSurgerypluschemotherapy(n=13)Surgeryplusradiotherapy(n=14)Surgerypluschemotherapy(n=28)Surgeryalone(n=32)Surgeryplusradiotherapypluschemotherapy(n=30)Surgeryplusradiotherapy(n=30)Mediansurvival(months)28.715.66411268pvalue0.0950.0080.00147I-IIIB期非小细胞肺癌:CHART0102030405060701-year2-yearConventionalradiotherapy(n=225)CHART(n=338)Survival(%patients)Saundersetal1997p=0.00448III期非小细胞肺癌:联合放、化疗NSCLCCollaborativeGroup19950.00.51.01.52.0RadiotherapypluschemotherapybetterRadiotherapy(control)betterBuenosAiresBrusselsFLCSG2EssenSLCSGCEBI138WSLCRG/FIPerugiaCALGB8433EORTC08842SWOG8300aSWOG8300bSubtotalp=0.00549IV期非小细胞肺癌的治疗化疗（含铂方案）,有生存获益新一代化疗药物外放射治疗(姑息治疗)内镜下激光治疗或近距离化疗（解除气道阻塞）PDQGuidelines50IV期非小细胞肺癌:联合化疗05101520253035PVpPVpmPVePVeMiFOMi/CAPResponserate(%)p0.001acrosstreatments012345678910PVpPVpmPVePVeMiFOMi/CAPMediansurvival(months)p=0.61acrosstreatmentsWeicketal199151IV期非小细胞肺癌:新一代化疗药物Paclitaxel,vinorelbine,docetaxelGemcitabine,topotecan,irinotecan单药疗效优于顺铂联合化疗：在研Jassem199952晚期非小细胞肺癌的联合化疗:近年的随机试验(1)StudyLeChevalieretal1994Bonomietal1996Crinoetal1998Belanietal1998Cardenaletal1999RegimensVindesine/cisplatinVinorelbine/cisplatinEtoposide/cisplatinPaclitaxel(135)/cisplatinPaclitaxel(250)/cisplatin/G-CSFMitomycin/ifosfamide/cisplatinGemcitabine/cisplatinEtoposide/cisplatinPaclitaxel/cisplatinEtoposide/cisplatinGemcitabine/cisplatinMediansurvival(months)7.69.5*7.69.5*9.9*9.68.68.27.77.28.71-yearsurvival(%)2837323739343337322632Tumorresponse(%)1930*12*27*32*2638*1423*21.940.6**p0.05Gandaraetal199953晚期非小细胞肺癌的联合化疗:近年的随机试验(2)StudyKellyetal1999Schilleretal2000RegimensVinorelbine(25)/cisplatin(100)Paclitaxel(225)/carboplatin(AUC6)Paclitaxel(135)/cisplatin