肺癌中山大学.ppt

,肺癌,中山大学附属第一医院呼吸内科周燕斌,流行病学epidemiology,美国癌症死亡率(1992-2019),0,10,20,30,40,50,60,70,80,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,Riesetal2019,美国肺癌发病率和死亡率(1973-2019),10,50,100,Incidence-males,Mortality-males,Incidence-females,Mortality-females,Rateper100,000people(logscale),1974,76,78,80,82,84,86,88,90,92,94,96,Yearofdiagnosis/death,Riesetal2019,肺癌发生率：病理类型、性别、种族(1973-2019),60,10,1,94-6,85-7,1973-5,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,94-6,85-7,73-5,Rateper100,000people(logscale),94-6,85-7,73-5,94-6,85-7,73-5,Wingoetal2019,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:22.04,肺癌的流行病学特点,解剖和病理AnatomyandPathology,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,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0.20-0.25,症状和诊断SymptomsandDiagnosis,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,肺癌的症状学,外侵和转移症状上腔静脉综合征HornersSyndromePancoastsSyndrome肺癌伴随症状:肺性骨关节病类癌综合征男性乳房发育,肺癌的主要症状和体征,0,20,40,60,80,100,咯血,纳差,疼痛,咳嗽,呼吸困难,患者(%),Hollenetal2019,Transthoracicneedleaspiration(TTNA)ofanon-smallcellPancoasttumor,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,非小细胞肺癌的诊断,Physicalexamination,Detectsigns,Visualizeandsamplemediasturiallymphnodes,Detectposition,size,numberoftumors,Detectchestwallinvasionmediastinallymphodenopathydistantmetastases,Lymphnodestaging,Detectchangesinhormoneproduction,andhematologicalmanifestationsoflungcancer,Preciselocationoftumorobtainbiopsy,ChestX-ray,CTscan,PETscan,Laboratoryanalysis,Bronchoscopy,Mediastinoscopy,FNA,Cytology,NCCNGuidelines2000,诊断（Diagnosis）1、CXR，CT，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。BBTSGuidelinesThorax2019,5689-108,非小细胞肺癌X线胸片,非小细胞肺癌CT扫描,纵隔镜检查,分期和预后stagingandprognostication,Mountain2019,非小细胞肺癌分期,DiseaseEarlyLocalizedAdvanced,Stage0IAIBIIAIIBIIIAIIIBIV,TNMTISN0M0(carcinomainsitu)T1N0M0T2N0M0T1N1M0T2N1M0T3N0M0T3N1M0T1-3N2M0T4,AnyN,M0AnyT,N3,M0AnyT,AnyN,M1,非小细胞肺癌分期,Stage0,StageIA,StageIIB,StageIIIB,StageIV,Lymphnodes,Mainbronchus,Contralaterallymphnode,Metastasistodistantorgans,Invasionofchestwall,非小细胞肺癌：临床分期与预后,1year,3years,5years,0,10,20,30,40,50,60,70,80,90,100,IA,IB,IIA,T2N1M0,IV,IIB,IIIA,IIIB,Clinicalstageatpresentation,Survival(%),Mountain2019,T3N0M0,T3N1M0,T1-3N2M0,T4,N3,Probabilityofsurvivalaccordingtoclinicalstage,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,Harpole2019,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,Albainetal1991,治疗Treatment,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,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,PDQGuidelines,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),PDQGuidelines,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,PDQGuidelines,I期非小细胞肺癌:手术,Locoregionalrecurrencerate(perperson-year),Locoregionalrecurrencerate(%ofpatients),0,10,20,30,40,50,Segmen-tectomy(n=68),Lobectomy(n=105),00.0,0.01,0.02,0.03,0.04,0.05,0.06,0.07,0.08,0.09,0.10,Limitedresection(n=122),Lobectomy(n=125),p=0.008,WarrenandFaber1994,GinsbergandRubinstein2019,p65Gray,60Gray,Radiationdose,Disease-freesurvival(%),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）,PDQGuidelines,III期非小细胞肺癌:手术联合其他治疗,StudyPassetal1992Rothetal1994Roselletal1994,RegimensSurgerypluschemotherapy(n=13)Surgeryplusradiotherapy(n=14)Surgerypluschemotherapy(n=28)Surgeryalone(n=32)Surgeryplusradiotherapypluschemotherapy(n=30)Surgeryplusradiotherapy(n=30),Mediansurvival(months)28.715.66411268,pvalue0.0950.0080.001,I-IIIB期非小细胞肺癌:CHART,0,10,20,30,40,50,60,70,1-year,2-year,Survival(%patients),Saundersetal2019,p=0.004,III期非小细胞肺癌:联合放、化疗,NSCLCCollaborativeGroup2019,IV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）,PDQGuidelines,IV期非小细胞肺癌:联合化疗,0,5,10,15,20,25,30,35,PVp,PVpm,PVe,PVeMi,FOMi/CAP,Responserate(%),p0.001acrosstreatments,0,1,2,3,4,5,6,7,8,9,10,PVp,PVpm,PVe,PVeMi,FOMi/CAP,Mediansurvival(months),p=0.61acrosstreatments,Weicketal1991,IV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,Jassem2019,晚期非小细胞肺癌的联合化疗:近年的随机试验(1),StudyLeChevalieretal1994Bonomietal2019Crinoetal2019Belanietal2019Cardenaletal2019,RegimensVindesine/cisplatinVinorelbine/cisplatinEtoposide/cisplatinPaclitaxel(135)/cisplatinPaclitaxel(250)/cisplatin/G-CSFMitomycin/ifosfamide/cisplatinGemcitabine/cisplatinEtoposide/cisplatinPaclitaxel/cisplatinEtoposide/cisplatinGemcitabine/cisplatin,Mediansurvival(months)7.69.5*7.69.5*9.9*9.68.68.27.77.28.7,1-yearsurvival(%)2837323739343337322632,Tumorresponse(%)1930*12*27*32*2638*1423*21.940.6*,*p0.05,Gandaraetal2019,晚期非小细胞肺癌的联合化疗:近年的随机试验(2),StudyKellyetal2019Schilleretal2000,RegimensVinorelbine(25)/cisplatin(100)Paclitaxel(225)/carboplatin(AUC6)Paclitaxel(135)/cisplatin(75)Gemcitabine(1000)/cisplatin(100)Docetaxel(75)/cisplatin(75)Paclitaxel(225)/carboplatin(AUC6),Mediansurvival(months)887.88.17.48.2,Tumorresponse(%)272721.321.017.315.3,Schilleretal2000,Kellyetal2019,非小细胞肺癌化疗后复发,手术(部分伴局限脑转移灶)姑息放疗姑息化疗内镜下激光治疗或组织内放疗,PDQGuidelines,顺铂耐药,Significantprobleminmanysolidtumors,includingNSCLCMultifactorial:reducedtransportintocellsdeactivationbyintracellularthiolsincreasedDNArepairincreasedDNAdamagetolerance,Perez2019,展望未来Futuredevelopments,非小细胞肺癌:未来发展,目前的治疗方案疗效欠佳预防早期诊断提高治疗疗效,PDQGuidelines,预防,教育避免环境致癌物，如吸烟化学预防?vitaminA异维甲酸,早期诊断,阻塞性肺部疾病遗传危险因素痰脱落细胞学分子肿瘤标记物CT扫描PET,Edell2019,治疗,NSCLC,Novelbiologica