肺癌的ppt课件.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 (1992-1996),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,Ries et al 1999,美国肺癌发病率和死亡率 (1973-1996),10,50,100,Incidence - males,Mortality - males,Incidence - females,Mortality - females,Rate per 100,000 people(log scale),1974,76,78,80,82,84,86,88,90,92,94,96,Year of diagnosis/death,Ries et al 1999,肺癌发生率：病理类型、性别、种族 (1973-1996),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,Year of diagnosis,鳞癌,腺癌,大细胞癌,小细胞癌,94-6,85-7,73-5,Rate per 100,000people (log scale),94-6,85-7,73-5,94-6,85-7,73-5,Wingo et al 1999,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Anatomy and Pathology,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Symptoms and Diagnosis,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Horners SyndromePancoasts Syndrome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(%),Hollen et al 1999,Transthoracic needle aspiration (TTNA) of a non-small cell Pancoast tumor,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,Physical examination,Detect signs,Visualize and sample mediasturial lymph nodes,Detect position, size, number of tumors,Detect chest wall invasion mediastinal lymphodenopathy distant metastases,Lymph node staging,Detect changes in hormone production, and hematological manifestations of lung cancer,Precise location of tumor obtain biopsy,Chest X-ray,CT scan,PET scan,Laboratory analysis,Bronchoscopy,Mediastinoscopy,FNA,Cytology,NCCN Guidelines 2000,诊断（Diagnosis） 1、CXR，CT， B 2、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。 B 3、CT提示纵隔淋巴结1 cm（短径）应行纵隔 镜检，前纵隔切开活检或穿刺。 B BTS Guidelines Thorax 2001,56 89-108,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staging and prognostication,Mountain 1997,非小细胞肺癌分期,DiseaseEarlyLocalizedAdvanced,Stage0IAIBIIAIIBIIIAIIIBIV,TNMTIS N0 M0 (carcinoma in situ)T1 N0 M0T2 N0 M0T1 N1 M0T2 N1 M0T3 N0 M0T3 N1 M0T1-3 N2 M0T4, Any N, M0Any T, N3, M0Any T, Any N, M1,非小细胞肺癌分期,Stage 0,Stage IA,Stage IIB,Stage IIIB,Stage IV,Lymph nodes,Main bronchus,Contralateral lymph node,Metastasis to distant organs,Invasion of chest wall,非小细胞肺癌：临床分期与预后,1 year,3 years,5 years,0,10,20,30,40,50,60,70,80,90,100,IA,IB,IIA,T2N1M0,IV,IIB,IIIA,IIIB,Clinical stage at presentation,Survival (%),Mountain 1997,T3N0M0,T3N1M0,T1-3N2M0,T4,N3,Probability of survival according to clinical stage,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,Harpole 1995,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,Albain et al 1991,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,PDQ Guidelines,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),PDQ Guidelines,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,PDQ Guidelines,I期非小细胞肺癌: 手术,Locoregionalrecurrencerate(per person-year),Locoregionalrecurrencerate(% of patients),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,Warren and Faber 1994,Ginsberg and Rubinstein1995,p0.05,I期和 II期非小细胞肺癌:放疗,Dosoretz et al 1992,0,10,20,30,40,50,60,70,80,Overall,65 Gray,60 Gray,Radiation dose,Disease-free survival (%),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）,PDQ Guidelines,III期非小细胞肺癌: 手术联合其他治疗,StudyPass et al 1992Roth et al 1994Rosell et al 1994,RegimensSurgery plus chemotherapy (n=13)Surgery plus radiotherapy (n=14)Surgery plus chemotherapy (n=28)Surgery alone (n=32)Surgery plus radiotherapy plus chemotherapy (n=30)Surgery plus radiotherapy (n=30),Median survival (months)28.715.66411268,p value 0.0950.0080.001,I-IIIB期非小细胞肺癌: CHART,0,10,20,30,40,50,60,70,1-year,2-year,Survival(% patients),Saunders et al 1997,p=0.004,III期非小细胞肺癌:联合放、化疗,NSCLC Collaborative Group 1995,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）,PDQ Guidelines,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 (%),p0.001 across treatments,0,1,2,3,4,5,6,7,8,9,10,PVp,PVpm,PVe,PVeMi,FOMi/CAP,Mediansurvival(months),p=0.61 across treatments,Weick et al 1991,IV期非小细胞肺癌:新一代化疗药物,Paclitaxel, vinorelbine, docetaxel Gemcitabine, topotecan, irinotecan单药疗效优于顺铂联合化疗：在研,Jassem 1999,晚期非小细胞肺癌的联合化疗: 近年的随机试验(1),StudyLe Chevalier et al 1994Bonomi et al 1996Crino et al 1998Belani et al 1998 Cardenal et al 1999,RegimensVindesine/cisplatinVinorelbine/cisplatinEtoposide/cisplatinPaclitaxel (135)/cisplatinPaclitaxel (250)/cisplatin/G-CSFMitomycin/ifosfamide/cisplatinGemcitabine/cisplatinEtoposide/cisplatinPaclitaxel/cisplatinEtoposide/cisplatinGemcitabine/cisplatin,Median survival (months)7.69.5*7.69.5*9.9*9.68.68.27.77.28.7,1-year survival (%) 2837323739343337322632,Tumor response (%)1930*12*27*32*2638*1423*21.940.6*,*p0.05,Gandara et al 1999,晚期非小细胞肺癌的联合化疗: 近年的随机试验(2),StudyKelly et al 1999Schiller et al 2000,RegimensVinorelbine (25)/cisplatin (100)Paclitaxel (225)/carboplatin (AUC6)Paclitaxel (135)/cisplatin (75)Gemcitabine (1000)/cisplatin (100)Docetaxel (75)/cisplatin (75)Paclitaxel (225)/carboplatin (AUC6),Median survival (months)887.88.17.48.2,Tumor response (%)272721.321.017.315.3,Schiller et al 2000,Kelly et al 1999,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,PDQ Guidelines,顺铂耐药,Significant problem in many solid tumors, including NSCLCMultifactorial:reduced transport into cellsdeactivation by intracellular thiolsincreased DNA repairincreased DNA damage tolerance,Perez 1997,展望未来Future developments,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,PDQ Guidelines,预防,教育避免环境致癌物，如吸烟化学预防?vitamin A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,Edell 1997,治疗,NSCLC,Novel biological targets,Immunology:- interleukins- interferons- vaccines,Newchemotherapydrugs,Gene therapy:- interleukins- K-ras,新的化疗方法,拓扑异构酶抑制剂 新的抗叶酸剂,新的生物学治疗方法,表皮生长因子酪氨酸激酶抑制剂 (EGF-TKIs) 抗血管治疗金属蛋白酶抑制剂,克服顺铂耐药,Chemopotentiators 多聚铂酸盐类不同的 DNA 结合方式克服巯基失活,免疫治疗和基因治疗,免疫调节剂 干扰素, 白介素疫苗被动免疫主动免疫基因治疗?癌基因，如 K-ras免疫调节剂，如 白介素,