肺癌标志物筛查和癌症风险评估

Textmasterformate durch Klicken bearbeiten,Zweite Ebene,Dritte Ebene,Vierte Ebene,Fnfte Ebene,Page,31,Klicken Sie, um das Titelformat zu bearbeiten,Textmasterformate durch Klicken bearbeiten,Zweite Ebene,Dritte Ebene,Vierte Ebene,Fnfte Ebene,Klicken Sie, um das Titelformat zu bearbeiten,Page,29,Textmasterformate durch Klicken bearbeiten,Zweite Ebene,Dritte Ebene,Vierte Ebene,Fnfte Ebene,Klicken Sie, um das Titelformat zu bearbeiten,*,肺癌标志物筛查与癌症风险评估,癌症面临的严峻形势,肿瘤标志物应用于癌症筛查和风险评估,早期识别高危人群,缩短癌症诊断周期,总结,概述,2011,年,CA,期刊全球肿瘤统计数据,全球男性,新发病例 死亡病例,肺和支气管癌,109.52,万,前列腺癌,90.35,万,结肠,/,直肠癌,66.36,万,胃癌,64.06,万,肝癌,52.24,万,食管癌,32.66,万,膀胱癌,29.73,万,肺和支气管癌,95.10,万,肝癌,47.83,万,胃癌,46.44,万,结肠,/,直肠癌,32.06,万,食管癌,27.61,万,前列腺癌,25.84,万,白血病,14.37,万,死亡,/,新发：肺癌,86.8%,前列腺癌,28.6%,要GDP，还是要命？-每分钟6个人确诊癌症*,截至,2012,年，中国,22.08%,的人患有癌症，,12.94%,的人死于癌症*,*2012,中国肿瘤登记年报,1/3,的癌症死亡是可以预防的,*,*2012,世界癌症日,面对癌症,我们能做什么,?,早期识别高危人群,需求,1,：,高风险人群,低风险人群,肿瘤标志物筛查的意义：对于癌症,高危,/,低危人群,的风险评估,表观健康人群,/,门诊患者,01,02,03,一管血检测肿瘤标志物,能否有助于癌症的风险评估,?,肿瘤标志物在,肺癌,风险评估中的实践应用,肺癌肿瘤标志物,ProGRP/NSE :,小细胞肺癌,CYFRA 21-1:,非小细胞肺癌,SCC:,肺鳞癌,CEA:,肺腺癌,肺癌,肺癌多联标志物筛查策略：灵敏度,80%,特异性,90%,多联肺癌标志物,，针对于高危人群（吸烟人群）及出现疑似肺癌症状（咳血，胸痛，肺部肿物）的患者进行肺癌筛查,非小细胞肺癌（,NSCLC,）：,CEA,SCC,Cyfra,小细胞肺癌（,SCLC,）：,ProGRP,NSE,CEA,灵敏度：,NSCLC 82,，,SCLC 80,特异性：,92,此筛查表现优于,PSA,在前列腺癌筛查中的表现,肺癌,双盲研究,:,来自于中国的肺癌多联标志物筛查结果令人振奋,未提供除肿瘤标志物结果以外的其他信息，运用肺癌肿瘤标志物检测组,（,ProGRP+SCC+CYFRA21-1+CEA,）,评估罹患肺癌的风险,N=155,表观健康人群,N=6,良性肺病,N,42,肺癌,N=107,（,NSCLC N,91,，,SCLC N=16,）,6/6,健康标本被评价为低危,32/42,良性疾病标本被评价为低危,96/107,恶性标本被评价为高危,数据来源：上海中山医院呼吸科,肺癌,CT筛查肺癌是否足够？,肺癌标志物检测组,检出,57%,CT漏检的肺癌患者,“,Role of progestrin releasing peptide (ProGRP), a serum based biomarker in early diagnosis of SCLC in cohort of high risk patient presenting with symptoms related to lung Caner,”,Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital Fudan University, Shanghai,2012 Asian Pacific Society of Respirology Congress Poster,(ProGRP+SCC+CYFRA21-1+CEA),肺癌 （,N=64),CT,阳性,50,14,CT,阴性,肺癌标志物检测组阳性,肺癌标志物检测组阴性,8,（,8/14=57%,）,6,敏感性,81.2%,(52/64),90.6%,（,58/64,）,78.1%,（,50/64,）,肺癌标志物检测组,CT,+,肺癌标志物检测组,CT,表：确诊为肺癌的,64,名病例：,CT筛查肺癌是否足够？,联合肺癌标志物检测组将,CT,的肺癌检出率从,78.1%,提高到,90.6%,（,ProGRP+SCC+CEA+CYFRA21-1),“,Role of progestrin releasing peptide (ProGRP), a serum based biomarker in early diagnosis of SCLC in cohort of high risk patient presenting with symptoms related to lung Caner,”,Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital Fudan University, Shanghai,2012 Asian Pacific Society of Respirology Congress Poster,肿瘤标志物应用于肺癌组织学诊断流程图,N,761,例肿瘤患者,Molina R, Auge JM, Bosch X, et al.,Tumor Biol,2009,30:121-9,.,NSCLC,：,SP:97.2%,SN:76.7%,PPV:98.6%,SCLC,：,SP:99.6%,SN:79.5%,PPV:98.6%,肿瘤标志物在不同病理类型中的表现,Molina R, Auge JM, Bosch X, et al.,Tumor Biol,2009,30:121-9,.,Percent of untreated lung cancer patients with serum tumor marker levels greater than the cutoff, categorized according to histology and tumor extension,ADK: Adenocarcinoma,LCLC: Large cell lung cancer,ProGRP,应用于小细胞肺癌诊断最灵敏,CYFRA21-1,是针对非小细胞肺癌最敏感的标志物,Clinical conditions,N,Plasma proGRP,平均值,(pg/mL),健康,49,42.5,良性疾病,23,40.1,肺癌,SCLC,37,1367.5,NSCLC,116,56.3,鳞癌,59,38.7,腺癌,40,59.2,未分型NSCLC,12,35.2,大细胞癌,5,290.9,继发转移性癌,2,34.3,关键性肺癌肿瘤标志物（ProGRP）表现卓越,J Korean Med Sci 2011; 26: 625-630,ProGRP,是小细胞肺癌的一个非常可靠的指标,具有很好的灵敏度,和特异性非常有助于组织分型。,当单独使用时,要远优于NSE,NSE对于筛查而言,缺少灵敏度和特异性。,高浓度的NSE也只是怀,疑有小细胞肺癌,缺少特异性,很多文献建议,使用NSE在诊断SCLC,的时候要结合ProGRP。,溶血标本中NSE会产生检测值假性升高，,ProGRP不受溶血影响,美国国家临床生化协会,肺癌肿瘤标志物-指南观点,男性, 69岁, 已戒烟。因X线发现肺部单个肿块入院,所有肿瘤标志物结果正常，提示非癌性肿块可能性大。,*75%肺癌肿瘤标志物异常，但15%-25%的肺癌患者的肿瘤标志物可能正常（取决于分期和病理类型）,最终诊断,:,肉芽肿,肌酐 0.9,mg/dl,GGT,23,U/L,AST 1,7,U/L,ALT 1,5,U/L,CEA,1.5,ng/ml,CYFRA,0.8,ng/ml,SCC0.,6,ng/ml,NSE,11,ng/ml,ProGRP 12 pg/ml,CA 1251,9,U/ml,CA 15.3,6,U/ml,CA 19.9,15,U/ml,CEA, 5 ng/mL,CYFRA, 3,3 ng/mL,SCC, 2,5ng/mL,CA 125, 40U/mL,CA 15.3, 35U/mL,CA 19.9, 37U/mL,TAG, 6U/mL,NSE, 25ng/mL,ProGRP, 50 pg/mL,病例1-肿瘤标志物帮助危险分层,男性, 65岁, 已戒烟。因呼吸短促入院。既往有COPD,糖尿病，高血压病史,ProGRP和NSE升高尤为明显，高度提示SCLC。,最终诊断,:,SCLC,肌酐 1.5,mg/dl,GGT,35,U/L,AST,56,U/L,ALT,29,U/L,CEA,5,ng/ml,CYFRA,6.8,ng/ml,SCC0.,4,ng/ml,NSE,370,ng/ml,ProGRP 1093 pg/ml,CA 1251,9,U/ml,CA 15.3,77,U/ml,CA 19.9,10,U/ml,CEA, 5 ng/mL,CYFRA, 3,3 ng/mL,SCC, 2,5ng/mL,CA 125, 40U/mL,CA 15.3, 35U/mL,CA 19.9, 37U/mL,TAG, 6U/mL,NSE, 25ng/mL,ProGRP,2mm,可被标志物,检出,肺癌启动,肺癌导致死亡,大约,10,年,潜伏期,大约,2,年,临床期,诊断,关键点,可实现有效筛查,诊断路径及延迟诊断,Ref: F. Olesen, British Journal of Cancer (2009) 101, S5 S8,从首次症状出现到确诊：需要,30 -120,天,当前诊断流程时间较长,Biopsy,Physical Exam,X-Ray,CT SCAN,Bronchoscopy,Risk Assessment,The most important risk factor is tobacco use,X-ray is the most universal approach,Detect location of a tumor,Visualizing the inside of airway for tumors,Gold Standard,To test lung function,14 60,天,Ref: Tumor Markers in Lung Cancer: Theory and Practice by Dr. Rafael Molina,血清学危险评估能够帮助缩短确诊时间,Biopsy,Physical Exam,X-Ray,LAB TEST,Bronchoscopy,CT Scan,Risk Assessment, 5,天,Patient,Oncologist,Day 1,Ref: Tumor Markers in Lung Cancer: Theory and Practice by Dr. Rafael Molina,对于,40%,的具有症状的非癌症患者的诊断给予支持,对于,5%-10%,的误判给予纠正,Creatinin 0,9 mg/dl,ALAT 21 U/L,GGT 21 U/L,LDH907 U/L,CEA31.9 ng/ml,CYFRA 11.9 ng/ml,SCC 0.5 ng/ml,CA 125 63 U/ml,CA 15.3 26 U/ml,CA 19.9 37 U/ml,TAG1,2 ng/ml,NSE 169 ng/ml,ProGRP 1835 pg/ml,最终诊断：小细胞肺癌,肺部,X,线支持为支气管肺炎，实验室根据肿瘤标志物检测,结果建议进行,PET,扫描排除,SCLC,的可能性,肺癌肿瘤标志物增加临床医生准确诊断的信心,结论,在基层医院，,应用肿瘤标志物谱,（,ProGRP+SCC+CYFRA211+CEA,）,可以提高肺癌早期诊断率,在综合医院，,联合肿瘤标志物谱和,CT,检查，可以提高肺癌早期诊断率,临床肿瘤标志物的检测具有一定成本效果,29,总结,运用肿瘤标志物评估癌症风险，早期识别高危人群，缩短诊断周期,合理优化的使用肿瘤标志物，最大程度发挥肿瘤标志物的临床价值,不断涌现的新型肿瘤标志物拓展了标志物的临床实践价值,