肺癌洪小南课件

肺癌的治疗肺癌的治疗 LUNG CANCERLUNG CANCER Worldwide incidence*Worldwide incidence* *Incidence per 100,000 population. Male54.8 Female8.1 Male75.9 Female10.3 Male39.3 Female11.2 Male47.6 Female16.1 Male34.7 Female13.4 Male12.9 Female2.6 Male29.1 Female 7.7 Male69.6 Female32.9 Male19.3 Female7.9 Male55.1 Female7.6 Eastern Eastern EuropeEurope JapanJapan AustraliaAustralia New ZealandNew Zealand ChinaChina Northern Northern AfricaAfrica Southern Southern AfricaAfrica Central Central AmericaAmerica WesternWestern Europe Europe NorthNorth AmericaAmerica Temperate Temperate South AmericaSouth America LUNG CANCERLUNG CANCER 5-year survival rates5-year survival rates 7% 12% 21% 13% 8% 8% 10% 14% 14% Eastern Eastern EuropeEurope JapanJapan AustraliaAustralia New ZealandNew Zealand ChinaChina Middle East/Middle East/ Northern AfricaNorthern Africa Sub-Saharan Sub-Saharan AfricaAfrica Latin America/Latin America/ CaribbeanCaribbean NorthwesternNorthwestern Europe Europe USAUSA LUNG CANCERLUNG CANCER Risk factorssmokingRisk factorssmoking Smoking causes:Smoking causes: l80% of lung cancer deaths in men l75% of lung cancer deaths in women l17% of lung cancer cases in nonsmokers l28% of all cancer deaths 35-year old male who smokes 35-year old male who smokes 25 cigarettes per day:25 cigarettes per day: l13% risk of dying from lung cancer before age 75 l10% risk of dying from coronary disease l28% risk of dying from smoking-related disease LUNG CANCERLUNG CANCER Impact of smoking on riskImpact of smoking on risk CigarettesCigarettes smoked/daysmoked/day Risk of developingRisk of developing lung cancer*lung cancer* Risk after Risk after 16 years16 years of smoking cessation*of smoking cessation* 1-2010.3-fold1.6-fold 2021.2-fold4.0-fold *Data in women; risk compared to nonsmokers. LUNG CANCERLUNG CANCER Lung cancer controlLung cancer control lHealth policy Smoke-free environments Restricted advertising Educational curriculum lEconomic incentives Cigarette tax Health insurance discount for nonsmokers lMedia coverage/advocacy lSocietal stigma associated with smoking LUNG CANCERLUNG CANCER Risk factors other than smokingRisk factors other than smoking lAsbestos lRadon (from mining or indoor exposure) lOther “occupational carcinogens” lDiet (vitamins A, C, E, -carotene deficiencies) lGenetic/familial factors LUNG CANCERLUNG CANCER Genetic abnormalitiesGenetic abnormalities *In cancer cell lines. Genetic abnormalityGenetic abnormalityNSCLCNSCLCSCLCSCLC Chromosome 3pXX deletions p53 gene mutation X*X Rb gene abnormalitiesX X* myc oncogene family X*X K-ras oncogeneX mutation LUNG CANCERLUNG CANCER DiagnosisDiagnosis Diagnosis of suspected lung cancer Chest X-ray film CT scan Peripheral tumorCentral tumor OptionsOptions Sputum cytology Bronchoscopy Percutaneous fine-needle aspiration Thoracoscopy OptionsOptions Percutaneous fine-needle aspiration Bronchoscopy Video-assisted thoracoscopy LUNG CANCERLUNG CANCER RadiographyRadiography LUNG CANCERLUNG CANCER BronchoscopyBronchoscopy LUNG CANCERLUNG CANCER CT ScanCT Scan LUNG CANCERLUNG CANCER MRIMRI LUNG CANCERLUNG CANCER Bone scintigraphyBone scintigraphy P E TP E T l全称：正电子发射计算机体层摄影（positron emission computed tomography, PET) l代谢示踪剂：18F-DG，葡萄糖类似物 l诊断原理：肿瘤及其转移灶摄取18F-DG异常增加 l临床应用：肿瘤良恶性的鉴别 肿瘤恶性程度的评价和分期 治疗效果的监测 与坏死和疤痕组织的鉴别 PETPET CT-PETCT-PET 非小细胞肺癌的化疗非小细胞肺癌的化疗 NON-SMALL CELL LUNG CANCERNON-SMALL CELL LUNG CANCER Incidence of major histologic types*Incidence of major histologic types* * Numbers do not sum to 100% because of differences in diagnostic criteria. 18%18% 40%40% Squamous Squamous cellcell carcinomacarcinoma Small-cellSmall-cell carcinomacarcinoma 30%30% AdenocarcinomaAdenocarcinoma 15%15% OtherOther NON-SMALL CELL LUNG CANCER NON-SMALL CELL LUNG CANCER Histologic typesHistologic types Adapted from Rosenow and Carr. Smoker (%)Smoker (%)Nonsmoker (%)Nonsmoker (%)Smoker (%)Smoker (%)Nonsmoker (%)Nonsmoker (%) MaleMale Female Female 3838 2121 1717 2323 Squamous Cell Adenocarcinoma Large Cell Small Cell Bronchoalveolar 1 1 1010 5656 2323 6 6 5 5 2222 3535 1313 2727 3 3 9 9 6868 1010 2 2 1111 Smokers vs nonsmokersSmokers vs nonsmokers NON-SMALL CELL LUNG CANCERNON-SMALL CELL LUNG CANCER Signs and symptoms at diagnosisSigns and symptoms at diagnosis 7575 4040 4040 3535 2525 5050 4040 3030 2525 1515 1515 4040 3535 3535 1515 1515 Cough Dyspnea Chest Pain Hemoptysis Pneumonitis Weight Loss Generalized Weakness Anorexia Fever Anemia Frequency (%) 31%31% Stage IIIStage III 38%38% Stage IVStage IV 24%24% Stage IStage I 7%7% Stage IIStage II NON-SMALL CELL LUNG CANCERNON-SMALL CELL LUNG CANCER Stages at presentationStages at presentation NON-SMALL CELL LUNG CANCERNON-SMALL CELL LUNG CANCER Prognostic factorsPrognostic factors Early-stage disease (I, II, resectable Stage III)Early-stage disease (I, II, resectable Stage III) lTumor size lPresence/absence of lymph node metastasis lHistologic subtype Advanced-stage disease (unresectable Stage III and IV)Advanced-stage disease (unresectable Stage III and IV) lPretreatment stage lPerformance status lWeight loss lGender lSerum lactate dehydrogenase lMetastatic site YearsYears NON-SMALL CELL LUNG CANCER NON-SMALL CELL LUNG CANCER Survival by stageSurvival by stage NON-SMALL CELL LUNG CANCERNON-SMALL CELL LUNG CANCER 非小细胞肺癌治疗的选择： 1.、期首选手术。 期术后不进行放疗，其中T1N0有高危复发因素（细胞分化差、脉 管有癌栓）可化疗。T2N0术后应辅助化疗。 T1-2N1切缘阴性，有不良因素（不恰当的纵隔淋巴结切除，肿瘤累 及淋巴结包膜外，肺门淋巴结多个阳性，切缘离肿瘤边缘近）术 后化疗+/-放疗。 2.III期术后单纯化疗或放化疗。 III期新辅助治疗，序贯放化疗或同步放化疗 T4N0-1同侧肺叶内卫星结节术后要辅助化疗。 3.一般情况好的予期予化疗。放疗可作为脑转移。骨转移。原发灶 的姑息性治疗。 NON-SMALL CELL LUNG CANCERNON-SMALL CELL LUNG CANCER 期非小细胞肺癌的综合治疗 期病变是局部晚期病变。 病变累及纵隔和/或锁骨上淋巴结和/或侵犯纵隔内主要脏 器 占非小细胞肺癌的3144，A、B各一半 期五年生存率1523。B五年生存率67% 化疗是期NSCLC的主要治疗手段，与放疗和/或手术综 合治疗是目前标准治疗。 NON-SMALL CELL LUNG CANCERNON-SMALL CELL LUNG CANCER 1、 综合治疗可改善预后，增加有效率，延长生存期。同时也增加 不良反应。 2、 放化疗同步治疗疗效优于序贯治疗，增加缓解率，略延长生存 ，但毒性增加，特别是放射性食管炎和贫血。 3、 序贯化放疗中化疗可用常规剂量，毒副反应可耐受。化放疗同 步治疗时化疗药应减量，例如NVB、15mg/m2/周，健择300mg/m2/ 周。 4、 治疗时间的安排：序贯治疗：常规剂量化疗2疗程休2周后放疗 。同步化放疗通常在同一天开始两种治疗。 5、 同步化放疗中的化疗通常含铂的两药联合方案。放疗以每天1次 的常规分割为宜。 NON-SMALL CELL LUNG CANCERNON-SMALL CELL LUNG CANCER 肺上钩瘤（Pancoasts tumor）是特殊类型的期病变， 占全部肺癌的24。病变位于肺炎，大多数是鳞 癌。常有颈8、胸1神经，第1、2肋骨破坏，但属邻近 侵犯，与血道播散的骨转移、神经侵犯不同，标准治 疗是术前新辅助放疗或新辅助放化疗。目前更倾向同 时放化疗。术后五年生存率2030，肿瘤能完全 切除者五年生存率可达40。 期非小细胞肺癌的化疗 期非小细胞肺癌的预后与一般状况密切相关。PS2， 36月内体重下降5% , 经化疗可缓解症状，延长生 存。一般情况差者应予对症支持治疗。积极强烈的化 疗增加毒性，不改善生存。 SCLCSCLC l占所有肺癌的15%-20%。 l光镜：细胞体积小，胞浆少，核大，核分裂多。 l电镜：有神经内分泌颗粒。 l临床：生物学行为恶劣，生长迅速，早期远处转移。 诊断时LD30%-40% ED60%-70% SMALL CELL LUNG CANCERSMALL CELL LUNG CANCER Incidence of histologic typesIncidence of histologic types Mixed small cell/Mixed small cell/ large cell carcinomalarge cell carcinoma 4-6%4-6% Combined small Combined small cell carcinomacell carcinoma 90%90% SMALL CELL LUNG CANCERSMALL CELL LUNG CANCER SymptomsSymptoms Primary tumorPrimary tumor lCough lDyspnea lWheezing lHemoptysis lChest pain lPostobstructive pneumonitis Regional metastasesRegional metastases lSuperior vena cava syndrome lHoarseness lDysphagia Distant metastasesDistant metastases lBone pain lCNS symptoms (headache, double vision) . SMALL CELL LUNG CANCERSMALL CELL LUNG CANCER Differentiating signs from NSCLCDifferentiating signs from NSCLC More common in SCLCMore common in SCLC lHilar and mediastinal adenopathy lAtelectasis lPneumonitis Less common in SCLCLess common in SCLC lPeripheral location lPleural effusion lChest wall invovement SMALL CELL LUNG CANCERSMALL CELL LUNG CANCER StagingStaging Limited diseaseLimited disease lDisease confined to one hemithorax and regional lymph nodes: hilar, ipsilateral, and contralateral mediastinal; supraclavicular (controversial) lIpsilateral pleural effusion (contoversial) Extensive diseaseExtensive disease lAny disease beyond limited disease sites SMALL CELL LUNG CANCERSMALL CELL LUNG CANCER Stage and extrathoracic disease sites Stage and extrathoracic disease sites at presentationat presentation Percentage with FindingPercentage with Finding Final stage Limited30%-40% Extensive60%-70% Bone19%-38% Liver17%-34% Bone marrow17%-23% Brain0%-14% Lymph nodes7%-25% Soft tissue3%-11% SMALL CELL LUNG CANCERSMALL CELL LUNG CANCER Evaluation of disease extentEvaluation of disease extent Minimum EvaluationMinimum Evaluation lHistory and physical examination lChest radiograph CT lLiver function tests and examination liver scan lBone pain and alkaline phosphatase bone scan lNeurologic history and examination brain CT lPlatelet count or leukoerythroblastic peripheral blood smear SMALL CELL LUNG CANCERSMALL CELL LUNG CANCER Evaluation of disease extent (contd)Evaluation of disease extent (contd) Evaluation for Stage Dependent TherapyEvaluation for Stage Dependent Therapy lHistory and physical examination lChest radiograph CT fiberoptic bronchoscopy lLiver function tests and liver scan liver biopsy lBone scan lBone marrow aspiration l Brain CT Evaluation for Surgical Resection (in addition to above)Evaluation for Surgical Resection (in addition to above) lFiberoptic bronchoscopy lChest CT and mediastinoscopy SMALL CELL LUNG CANCERSMALL CELL LUNG CANCER Prognostic factorsPrognostic factors lStage lPerformance status lGender lAge lHistological subclassification lBone marrow metastases lLiver metastases lCNS involvement lBlood biochemistry, especially lactate dehydrogenase SMALL CELL LUNG CANCERSMALL CELL LUNG CANCER Survival by stageSurvival by stage Median Survival Median Survival Median Survival Median Survival 5-Year Survival5-Year Survival Untreated PatientsUntreated PatientsTreated PatientsTreated Patients(%)(%) (wk)(wk)(mo)(mo) Limited disease1214-2010%-20% Extensive disease 58-123%-5% l常见转移部位： l骨 19%-38% 肝脏 17%-34% l骨髓 17%-23% 脑0-14% l淋巴结7%-25% 软组织3-11% l胰腺，肾上腺，肾脏 l内分泌器官转移倾向：甲状腺8%，垂体15%，睾丸 7%，甲旁腺1% l中枢神经系统：脑，硬膜外，脑脊膜腔，尸检多处转 移：73% 有效单药有效单药 ADM 30% CTX 39-40 % HN2 40-44 % MTX 30 % HMM 30 % Vp-16 37-45 % VCR 35-42 % CBP 50 % VM-26 19-65 % IFO 24-71 % VDS 25-32 % DDP 16 % Taxol 34-41 % Docetaxel 28 % CPT-11复治 47 % Topotecan 39 %,复治 25 % Gem 26 % 联合化疗联合化疗 疗效：三药优于二药优于单药， 超过四药增加毒性。 RR CR MS 2YS LD80-90%50-60%12-20M15-40% ED60-80%15-20