低剂量螺旋CT早期肺癌筛查—肺结节的检出及其相关研究
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摘要
第一部分LDCT检出肺结节和其他病变的分析
目的分析LDCT检出的非钙化肺结节和肺癌及其相关流行病学因素,并分析同时检出的其他病变。
材料与方法1653例符合入组条件的受检者纳入本研究。每例受检者均行LDCT平扫。以65岁为界分为中年组(40-64岁)和老年组(65-79岁)。其中1550例有烟草接触史记录者分为吸烟组(吸烟者和少量吸烟者)和非吸烟组(二手烟暴露组和无二手烟暴露组)。对检出的肺结节和其他病变依照I-ELCAP方案分类,基线筛查受检者至少检出1个直径≥5mmm的实性或部分实性结节或直径≥8mm的非实性结节者结果为阳性,仅检出直径<5mmm的实性或部分实性结节或直径<8mm的非实性结节者结果为半阳性,未检出结节者结果为阴性。对结果进行统计学分析。肺癌分期按照IASLC修订的第7版分期系统。
结果基线筛查1653例受检者中,男1293例,女360例,中位年龄48岁(40-79岁)。中年组1511例,老年组142例。吸烟组824例(男803例,女21例),非吸烟组726例(男429例,女297例),性别间吸烟人数差异有统计学意义(P<0.0001)。非吸烟组二手烟暴露率较高(70.5%),但性别间差异无统计学意义(P=0.452)。基线筛查中244例(14.8%)结果为阳性,717例(43.4%)结果为半阳性,692例(41.8%)结果为阴性。老年组结果为阳性者高于中年组(30.3% vs 13.3%,P<0.0001)。基线筛查共检出阳性结节337个(14.6%),其中部分实性结节的恶性比率最高(12.5%)。190例行CT复诊。与基线筛查比较,复诊398个结节无变化,其中6个阳性结节可疑或高度可疑恶性；22个结节缩小或消失；2个结节再次筛查增大(中分化腺癌和细支气管肺泡癌各1例)；新出现9个结节,其中8个考虑良性,1个良恶性不能确定。基线与复诊CT共检出经病理证实的肺癌14例,包括腺癌10例,BAC3例,类癌1例。其中ⅠA期7例,ⅠB期5例,ⅢA期2例。检出冠状动脉钙化242例(14.6%),男性、老年组、吸烟者和糖尿病是其独立预测因子。检出肺气肿58例(3.5%),以男性、老年组和吸烟者居多。1321例次有辐射剂量记录的受检者中位ED为0.89mSv。
结论受检者吸烟现状和二手烟暴露率与我国整体调查趋势一致。阳性组部分实性肺结节的恶性比率相对较高,应予以密切关注。检出的肺癌绝大多数为早期腺癌,且以女性居多。LDCT可明显降低受检者的辐射剂量,在进行肺癌筛查的同时,尚可行冠状动脉钙化和肺气肿筛查。
第二部分计算机辅助检测系统对肺结节的应用研究
目的评价CAD系统检出LDCT筛查者非钙化肺结节的能力及应用价值。材料与方法100例受检者的胸部LDCT图像纳入本研究。采用(1)方法A：CAD肺结节分析软件；(2)方法B：横断面1.25mm层厚图像结合MIP成像(层厚10mm)；(3)方法C：方法A+方法B。方法B和C由低年资和中年资影像诊断科医师各1名独立完成。以2名高年资影像诊断科医师检出的非钙化肺结节的一致意见为真结节参照标准。记录检出肺结节的大小、位置和密度,并对上述方法的结果行统计学分析。
结果两位高年资医师确定了269个真结节。CAD系统、低年资医师应用方法B、低年资医师应用方法C、中年资医师应用方法B和中年资医师应用方法C检出的真结节数、敏感性和假阴性分别为181个(67.3%,32.7%)、110个(40.9%,59.1%)、206个(76.6%,23.4%)、215个(79.9%,20.1%)和256个(95.2%,4.8%)。低年资和中年资医师应用方法C的敏感性均高于应用方法B且差异有统计学意义(P<0.0001)。低年资医师应用方法C的敏感性与中年资医师应用方法B接近且差异无统计学意义(P=0.422)。两位医师应用方法C与参照标准的一致性均达到极高(Kappa=0.806和0.953)。应用方法C两位医师之间的一致性达到极高(Kappa=O.835)。造成CAD假阴性的常见原因为结节较小(<4mm)、密度较低(磨玻璃密度)和分割算法(与血管、胸膜相连或邻近)；CAD系统对非实性结节的漏检率达到89.5%。
结论CAD系统在提高肺结节检出方面对影像诊断科医师有所帮助,一定程度上弥补了低年资医师工作经验的不足。但由于CAD系统相对较高的假阴性,特别是对非实性肺结节的漏检率过高,在实际工作中尚不能独立应用。
Objective To analyze the non-calcified pulmonary nodules and lung cancers by low-dose computed tomography (LDCT) screening and the relevant epidemiological factors, as well as the other lesions identified simultaneously.
Materials and methods We performed LDCT screening without contrast medium for lung cancer on 1,653 eligible participants. They were divided into two age groups:the middle-aged group (between 40 and 64) and the elderly group (between 65 and 79). One thousand five hundred and fifty subjects who had information of smoking or tobacco exposure recorded were divided into ever smokers (smokers or light smokers) and non-smokers (with or without secondhand smoking exposure). The classification for pulmonary nodules and other chest lesions identified by LDCT conformed to the I-ELCAP protocol. At baseline screening, the result was positive when at least one solid or part-solid nodule 5mm or more in diameter or at least one nonsolid nodule 8mm or more in diameter was identified. The result was semi-positive when all of non-calcified nodules identified were too small to imply a positive result. If none of non-calcified nodule was identified the result was negative. Statistical significance was analyzed. The seventh edition of lung cancer staging revised by the IASLC was adopted.
Results At baseline screening,1,653 subjects who met the inclusion criteria were recruited (1,293 men and 360 women). Median age was 48 years (range:40 to 79 years). Of these subjects,1,511 were in the middle-aged group and 142 in the elderly group, including 824 ever smokers (803 men,21 women) and 726 non-smokers (429 men,297 women). The difference of population between ever smokers and non-smokers among different gender was statistically significant (P<0.0001). The secondhand smoke exposure rate of non-smokers was high (70.5%) whereas the difference between different gender was not statistically significant (P=0.452). At baseline screening, the results of 244 subjects (14.8%) were positive,717 subjects (43.4%) were semi-positive, and 692 subjects (41.8%) were negative. The positive result rate was higher in the elderly group than in the middle-aged group (30.3% versus 13.3%, P<0.0001). Three hundred and thirty seven positive nodules were identified at baseline screening, in which the malignant rate of part-solid nodules was highest (12.5%). Follow-up CT scans were performed in 190 subjects. Compared with baseline screening,398 nodules had no changes, including 6 positive nodules that maybe malignancies,22 nodules shrank or disappeared,2 nodules increased (1 adenocarcinoma and 1 bronchioalveolar carcinoma, respectively), and 9 nodules newly emerged at follow-up CT. Of the new nodules,8 were considered benign, and 1 undetermined. Fourteen cases of lung cancer confirmed pathologically were identified at baseline and follow-up CT. Of them, the pathological types included adenocarcinoma (10 cases), BAC (3 cases) and carcinoid (1 case). Based on the seventh edition of the TNM stage,7 cases were in stage I A,5 cases in I B, and 2 cases inⅢA. Positive coronary artery calcification (CAC) were observed in 242 subjects (14.6%), and male, the elderly group, smokers or diabetes were the independent predictors. Emphysema was screened in 58 cases (3.5%), and male, the elderly group and smokers were in the majority. Finally, the median effective dose of 1321 subjects who had recorded radiation dose was 0.89mSv.
Conclusion The smoking situation and secondhand smoke exposure rate in our study are consistent with the overall survey trend in China. The malignant rate of positive part-solid pulmonary nodules was highest that should be followed up closely. Early lung adenocarcinoma was the most common pathological type in identified lung cancer and female patients were in the majority. The radiation dose was reduced markedly by LDCT and the CAC and emphysema can be screened simultaneously.
Objective To evaluate the detectability and application of computer-aided detection (CAD) system for non-calcified pulmonary nodules in low-dose computed tomography (LDCT) screening.
Materials and methods One hundred subjects who underwent LDCT screening were adopted to evaluate. Three analysis methods were designed. Method A:CAD pulmonary nodules detection system; Method B:axial images of 1.25mm thickness with MIP imaging (10mm thickness); Method C:combining A and B. Method B and C were applied independently by one resident and one junior radiologist. The reference standard of true non-calcified nodules was determined in consensus by another two senior radiologists. Nodules'size, location and consistency were recorded. The matching chi-square test and Kappa test were used.
Results There were 269 true nodules determined by two senior radiologists. The number of true nodules, sensitivity and false negatives of CAD, method B and C by resident, method B and C by junior radiologist were 181 (67.3%,32.7%),110 (40.9%,59.1%), 206 (76.6%,23.4%),215 (79.9%,20.1%),256 (95.2%,4.8%), respectively. The sensitivity of method C was higher than that of method B by both resident and junior radiologist, and the difference was statistically significant (P<0.0001). The sensitivity of method C by resident was close to that of method B by junior radiologist, and the difference was not statistically significant (P=0.422). The agreement for method C and the reference standard was excellent (Kappa=0.806 by resident, and 0.953 by junior radiologist). There also was an excellent inter-observer agreement (Kappa=0.&35). Missing true nodules by CAD in our study was predominantly due to small size (<4mm), lower attenuation (ground-glass opacity) and the segmentation algorithm (connected or adjacent to blood vessels or pleura). The missing rate of nonsolid nodules by CAD was 89.5%.
Conclusion CAD can improve radiologists'performance in detecting pulmonary nodules, particularly for residents or junior radiologists who have limited experience. However, the high false negatives of CAD limit its application as a stand-alone technique, especially to nonsolid pulmonary nodules which are more missed.
目的分析LDCT检出的非钙化肺结节和肺癌及其相关流行病学因素,并分析同时检出的其他病变。
材料与方法1653例符合入组条件的受检者纳入本研究。每例受检者均行LDCT平扫。以65岁为界分为中年组(40-64岁)和老年组(65-79岁)。其中1550例有烟草接触史记录者分为吸烟组(吸烟者和少量吸烟者)和非吸烟组(二手烟暴露组和无二手烟暴露组)。对检出的肺结节和其他病变依照I-ELCAP方案分类,基线筛查受检者至少检出1个直径≥5mmm的实性或部分实性结节或直径≥8mm的非实性结节者结果为阳性,仅检出直径<5mmm的实性或部分实性结节或直径<8mm的非实性结节者结果为半阳性,未检出结节者结果为阴性。对结果进行统计学分析。肺癌分期按照IASLC修订的第7版分期系统。
结果基线筛查1653例受检者中,男1293例,女360例,中位年龄48岁(40-79岁)。中年组1511例,老年组142例。吸烟组824例(男803例,女21例),非吸烟组726例(男429例,女297例),性别间吸烟人数差异有统计学意义(P<0.0001)。非吸烟组二手烟暴露率较高(70.5%),但性别间差异无统计学意义(P=0.452)。基线筛查中244例(14.8%)结果为阳性,717例(43.4%)结果为半阳性,692例(41.8%)结果为阴性。老年组结果为阳性者高于中年组(30.3% vs 13.3%,P<0.0001)。基线筛查共检出阳性结节337个(14.6%),其中部分实性结节的恶性比率最高(12.5%)。190例行CT复诊。与基线筛查比较,复诊398个结节无变化,其中6个阳性结节可疑或高度可疑恶性；22个结节缩小或消失；2个结节再次筛查增大(中分化腺癌和细支气管肺泡癌各1例)；新出现9个结节,其中8个考虑良性,1个良恶性不能确定。基线与复诊CT共检出经病理证实的肺癌14例,包括腺癌10例,BAC3例,类癌1例。其中ⅠA期7例,ⅠB期5例,ⅢA期2例。检出冠状动脉钙化242例(14.6%),男性、老年组、吸烟者和糖尿病是其独立预测因子。检出肺气肿58例(3.5%),以男性、老年组和吸烟者居多。1321例次有辐射剂量记录的受检者中位ED为0.89mSv。
结论受检者吸烟现状和二手烟暴露率与我国整体调查趋势一致。阳性组部分实性肺结节的恶性比率相对较高,应予以密切关注。检出的肺癌绝大多数为早期腺癌,且以女性居多。LDCT可明显降低受检者的辐射剂量,在进行肺癌筛查的同时,尚可行冠状动脉钙化和肺气肿筛查。
第二部分计算机辅助检测系统对肺结节的应用研究
目的评价CAD系统检出LDCT筛查者非钙化肺结节的能力及应用价值。材料与方法100例受检者的胸部LDCT图像纳入本研究。采用(1)方法A：CAD肺结节分析软件；(2)方法B：横断面1.25mm层厚图像结合MIP成像(层厚10mm)；(3)方法C：方法A+方法B。方法B和C由低年资和中年资影像诊断科医师各1名独立完成。以2名高年资影像诊断科医师检出的非钙化肺结节的一致意见为真结节参照标准。记录检出肺结节的大小、位置和密度,并对上述方法的结果行统计学分析。
结果两位高年资医师确定了269个真结节。CAD系统、低年资医师应用方法B、低年资医师应用方法C、中年资医师应用方法B和中年资医师应用方法C检出的真结节数、敏感性和假阴性分别为181个(67.3%,32.7%)、110个(40.9%,59.1%)、206个(76.6%,23.4%)、215个(79.9%,20.1%)和256个(95.2%,4.8%)。低年资和中年资医师应用方法C的敏感性均高于应用方法B且差异有统计学意义(P<0.0001)。低年资医师应用方法C的敏感性与中年资医师应用方法B接近且差异无统计学意义(P=0.422)。两位医师应用方法C与参照标准的一致性均达到极高(Kappa=0.806和0.953)。应用方法C两位医师之间的一致性达到极高(Kappa=O.835)。造成CAD假阴性的常见原因为结节较小(<4mm)、密度较低(磨玻璃密度)和分割算法(与血管、胸膜相连或邻近)；CAD系统对非实性结节的漏检率达到89.5%。
结论CAD系统在提高肺结节检出方面对影像诊断科医师有所帮助,一定程度上弥补了低年资医师工作经验的不足。但由于CAD系统相对较高的假阴性,特别是对非实性肺结节的漏检率过高,在实际工作中尚不能独立应用。
Objective To analyze the non-calcified pulmonary nodules and lung cancers by low-dose computed tomography (LDCT) screening and the relevant epidemiological factors, as well as the other lesions identified simultaneously.
Materials and methods We performed LDCT screening without contrast medium for lung cancer on 1,653 eligible participants. They were divided into two age groups:the middle-aged group (between 40 and 64) and the elderly group (between 65 and 79). One thousand five hundred and fifty subjects who had information of smoking or tobacco exposure recorded were divided into ever smokers (smokers or light smokers) and non-smokers (with or without secondhand smoking exposure). The classification for pulmonary nodules and other chest lesions identified by LDCT conformed to the I-ELCAP protocol. At baseline screening, the result was positive when at least one solid or part-solid nodule 5mm or more in diameter or at least one nonsolid nodule 8mm or more in diameter was identified. The result was semi-positive when all of non-calcified nodules identified were too small to imply a positive result. If none of non-calcified nodule was identified the result was negative. Statistical significance was analyzed. The seventh edition of lung cancer staging revised by the IASLC was adopted.
Results At baseline screening,1,653 subjects who met the inclusion criteria were recruited (1,293 men and 360 women). Median age was 48 years (range:40 to 79 years). Of these subjects,1,511 were in the middle-aged group and 142 in the elderly group, including 824 ever smokers (803 men,21 women) and 726 non-smokers (429 men,297 women). The difference of population between ever smokers and non-smokers among different gender was statistically significant (P<0.0001). The secondhand smoke exposure rate of non-smokers was high (70.5%) whereas the difference between different gender was not statistically significant (P=0.452). At baseline screening, the results of 244 subjects (14.8%) were positive,717 subjects (43.4%) were semi-positive, and 692 subjects (41.8%) were negative. The positive result rate was higher in the elderly group than in the middle-aged group (30.3% versus 13.3%, P<0.0001). Three hundred and thirty seven positive nodules were identified at baseline screening, in which the malignant rate of part-solid nodules was highest (12.5%). Follow-up CT scans were performed in 190 subjects. Compared with baseline screening,398 nodules had no changes, including 6 positive nodules that maybe malignancies,22 nodules shrank or disappeared,2 nodules increased (1 adenocarcinoma and 1 bronchioalveolar carcinoma, respectively), and 9 nodules newly emerged at follow-up CT. Of the new nodules,8 were considered benign, and 1 undetermined. Fourteen cases of lung cancer confirmed pathologically were identified at baseline and follow-up CT. Of them, the pathological types included adenocarcinoma (10 cases), BAC (3 cases) and carcinoid (1 case). Based on the seventh edition of the TNM stage,7 cases were in stage I A,5 cases in I B, and 2 cases inⅢA. Positive coronary artery calcification (CAC) were observed in 242 subjects (14.6%), and male, the elderly group, smokers or diabetes were the independent predictors. Emphysema was screened in 58 cases (3.5%), and male, the elderly group and smokers were in the majority. Finally, the median effective dose of 1321 subjects who had recorded radiation dose was 0.89mSv.
Conclusion The smoking situation and secondhand smoke exposure rate in our study are consistent with the overall survey trend in China. The malignant rate of positive part-solid pulmonary nodules was highest that should be followed up closely. Early lung adenocarcinoma was the most common pathological type in identified lung cancer and female patients were in the majority. The radiation dose was reduced markedly by LDCT and the CAC and emphysema can be screened simultaneously.
Objective To evaluate the detectability and application of computer-aided detection (CAD) system for non-calcified pulmonary nodules in low-dose computed tomography (LDCT) screening.
Materials and methods One hundred subjects who underwent LDCT screening were adopted to evaluate. Three analysis methods were designed. Method A:CAD pulmonary nodules detection system; Method B:axial images of 1.25mm thickness with MIP imaging (10mm thickness); Method C:combining A and B. Method B and C were applied independently by one resident and one junior radiologist. The reference standard of true non-calcified nodules was determined in consensus by another two senior radiologists. Nodules'size, location and consistency were recorded. The matching chi-square test and Kappa test were used.
Results There were 269 true nodules determined by two senior radiologists. The number of true nodules, sensitivity and false negatives of CAD, method B and C by resident, method B and C by junior radiologist were 181 (67.3%,32.7%),110 (40.9%,59.1%), 206 (76.6%,23.4%),215 (79.9%,20.1%),256 (95.2%,4.8%), respectively. The sensitivity of method C was higher than that of method B by both resident and junior radiologist, and the difference was statistically significant (P<0.0001). The sensitivity of method C by resident was close to that of method B by junior radiologist, and the difference was not statistically significant (P=0.422). The agreement for method C and the reference standard was excellent (Kappa=0.806 by resident, and 0.953 by junior radiologist). There also was an excellent inter-observer agreement (Kappa=0.&35). Missing true nodules by CAD in our study was predominantly due to small size (<4mm), lower attenuation (ground-glass opacity) and the segmentation algorithm (connected or adjacent to blood vessels or pleura). The missing rate of nonsolid nodules by CAD was 89.5%.
Conclusion CAD can improve radiologists'performance in detecting pulmonary nodules, particularly for residents or junior radiologists who have limited experience. However, the high false negatives of CAD limit its application as a stand-alone technique, especially to nonsolid pulmonary nodules which are more missed.
引文
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[22]Rubin GD, Lyo JK, Paik DS, et al. Pulmonary nodules on multi-detector row CT scans: performance comparison of radiologists and computer-aided detection. Radiology.2005; 234(1):274-283.
[23]Leader JK, Warfel TE, Fuhrman CR, et al. Pulmonary nodule detection with low-dose CT of the lung:agreement among radiologists. AJR Am J Roentgenol.2005; 185 (10): 973-978.
[24]Henschke CI, Yankelevitz DF, Mirtcheva R, et al. CT screening for lung cancer: frequency and significance of part-solid and nonsolid nodules. AJR Am J Roentgenol.2002; 178(5):1053-1057.
[25]Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society:glossary of terms for thoracic imaging. Radiology.2008; 246 (3):697-722.
[26]International Early Lung Cancer Action Program. International Early Lung Cancer Action Program:Enrollment and Screening Protocol. New York, NY:International Early Lung Cancer Action Program; 2010. Available: www.ielcap.org/professionals/protocols.html (accessed 2010 Oct.15).
[27]Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol.2007; 2 (8):706-714.
[28]Shemesh J, Henschke CI, Farooqi A, et al. Frequency of coronary artery calcification on low-dose computed tomography screening for lung cancer. Clin Imaging.2006; 30 (3): 181-185.
[29]Lee CH, Goo JM, Lee HJ, et al. Radiation dose modulation techniques in the multidetector CT era:from basics to practice. RadioGraphics.2008; 28 (5):1451-1459.
[30]MacMahon H, Austin,JH, Gamsu G, et al. Guidelines for management of small pulmonary nodules detected on CT scans:a statement from the Fleischner Society. Radiology.2005; 237 (2):395-400.
[31]Swensen SJ, Jett JR, Hartman T, et al. Screening for lung cancer with CT:Mayo Clinic experience. Radiology.2003; 226 (3):756-761.
[32]Centers for Disease Control and Prevention (CDC). Cigarette smoking among adults-United States,2006. MMWR Morb Mortal Wkly Rep.2007; 56 (44):1157-1161.
[33]Gohagan J, Marcus P, Fagerstrom R, et al. Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph:the lung screening study of the national cancer institute. Chest.2004; 126 (1):114-121.
[34]聂永康,蔡祖龙,赵绍宏.低剂量螺旋CT筛选检查早期肺癌的初步研究.中华放射学杂志.2002；36(3)：230-234.
[35]王颖,柳学国,张秀兰.低剂量多层螺旋CT普查早期肺癌的探讨.影像诊断与介入放射学.2006；15(5)：238-240.
[36]黄明刚,王青,齐敏,等.低剂量螺旋CT筛查肺癌的诊断效能及价值.实用放射学杂志.2008；24(8)：1030-1039.
[37]Raggi P, Gongora MC, Gopal A, et al. Coronary artery calcium to predict all-cause mortality in elderly men and women. J Am Coll Cardiol.2008; 52 (1):17-23.
[38]白玫,郑钧正.多排(层)螺旋CT的辐射剂量表达及其影响因素探讨.辐射防护.2008；28(1)：1-12.
[39]刘彬,白玫,费晓璐,等.CT剂量表征量的选择.中国医疗设备.2008；23(3)：54-56.
[40]吴晓华,马大庆,张忠嘉,等.多层螺旋CT胸部低剂量扫描发现肺结节的临床研究.中华放射学杂志.2004；38(7)：767-770.
[41]Brown MS, Goldin JG, Suh RD, et al. Lung micronodules:automated method for detection at thin-section CT--initial experience. Radiology.2003; 226 (1):256-262.
[42]Goo JM, Lee JW, Lee HJ, et al. Automated lung nodule detection at low-dose CT: preliminary experience. Korean J Radiol.2003; 4 (4):211-216.
[43]彭芸,马大庆,李剑颖,等.64层螺旋CT自动管电流调节技术在婴幼儿胸部低剂量CT扫描中应用的可行性研究.中华放射学杂志.2008；42(10)：1045-1049.
[44]Gruden JF, Ouanounou S, Tigges S, et al. Incremental benefit of maximum-intensity-projection images on observer detection of small pulmonary nodules revealed by multidetector CT. AJR Am J Roentgenol.2002; 179 (1):149-157.
[45]Yuan R, Vos PM, Cooperberg PL. et al. Computer-aided detection in screening CT for pulmonary nodules. AJR Am J Roentgenol.2006; 186 (5):1280-1287.
[46]Bae KT, Kim JS, Na YH, et al. Pulmonary nodules:automated detection on CT images with morphologic matching algorithm--preliminary results. Radiology.2005; 236 (1): 286-293.
[47]Beigelman-Aubry C, Raffy P, Yang W, et al. Computer-aided detection of solid lung nodules on follow-up MDCT screening:evaluation of detection, tracking, and reading time. AJR Am J Roentgenol.2007; 189 (4):948-955.
[48]Das M, Miihlenbruch G, Heinen S, et al. Performance evaluation of a computer-aided detection algorithm for solid pulmonary nodules in low-dose and standard-dose MDCT chest examinations and its influence on radiologists. Br J Radiol.2008; 81 (971):841-847.
[49]Sahiner B, Chan HP, Hadjiiski LM, et al. Effect of CAD on radiologists'detection of lung nodules on thoracic CT scans:analysis of an observer performance study by nodule size. Acad Radiol.2009; 16 (12):1518-1530.
[50]Goo JM. A Computer-Aided Diagnosis for Evaluating Lung Nodules on Chest CT:the Current Status and Perspective. Korean J Radiol.2011; 12 (2):145-155.
[51]Yanagawa M, Honda O, Yoshida S, et al. Commercially available computer-aided detection system for pulmonary nodules on thin-section images using 64 detectors-row CT: preliminary study of 48 cases. Acad Radiol.2009; 16 (8):924-933.
[1]American Cancer Society. Global cancer facts and figures 2007. Atlanta (GA):American Cancer Society,2007.14.
[2]中华人民共和国卫生部.《2010中国卫生统计年鉴》.北京：中华人民共和国卫生部,2010Available: http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/ptjnj/year2010/index2010.ht ml (accessed 2011 Mar.12).
[3]American Cancer Society. Cancer facts and figures 2010. Atlanta (GA):American Cancer Society,2010.4,15.
[4]Aberle DR, Brown K. Lung Cancer Screening with CT. Clin Chest Med.2008,29 (1): 1-14.
[5]Boiselle PM and White CS ed. Lung cancer screening:past, present, and future. New Techniques in Thoracic Imaging. New York:Marcel Dekker, Inc.2002.1-23.
[6]International Early Lung Cancer Action Program Investigators, Henschke CI, Yip R, Miettinen OS. Women's susceptibility to tobacco carcinogens and survival after diagnosis of lung cancer. JAMA.2006,296 (2):180-184.
[7]Ebbert JO, Yang P, Vachon CM, et al. Lung cancer risk reduction after smoking cessation:observations from a prospective cohort of women. J Clin Oncol.2003,21 (5): 921-926.
[8]Smith RA, Glynn TJ. Epidemiology of lung cancer. Radiol Clin North Am.2000,38 (3): 453-470.
[9]Mountain CF. Revisions in the international system for staging lung cancer. Chest.1997, 111 (6):1710-1717.
[10]Ravenel JG, Costello P, Silvestri GA. Screening for lung cancer. AJR Am J Roentgenol. 2008,190 (3):755-761.
[11]Miser WF. Cancer screening in the primary care setting:the role of the primary care physician in screening for breast, cervical, colorectal, lung, ovarian, and prostate cancers. Prim Care.2007,34 (1):137-167.
[12]Henschke CI, Shaham D, Yankelevitz DF, et al. CT screening for lung pancer:past and ongoing Studies. Semin Thorac Cardiovasc Surg.2005,17 (2):99-106.
[13]National Lung Screening Trial Research Team. The National Lung Screening Trial: Overview and Study Design. Radiology.2011,258 (1):243-253.
[14]Gohagan J, Marcus P, Fagerstrom R, et al. Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph:the lung screening study of the national cancer institute. Chest.2004,126 (1):114-121.
[15]Ganti AK, Mulshine JL. Lung cancer screening. Oncologist.2006,11(5):481-487.
[16]Bach PB, Niewoehner DE, Black WC. Screening for lung cancer:the guidelines. Chest. 2003,123 (1 Suppl):83S-88S.
[17]Kitajima T, Nishii K, Ueoka H, et al. Recent improvement in lung cancer screening:a comparison of the results carried out in two different time periods. Acta Med. Okayama. 2006,60 (3):173-179.
[18]Rubin GD. Lyo JK, Paik DS, et al. Pulmonary nodules on multi-detector row CT scans: performance comparison of radiologists and computer-aided detection.Radiology.2005, 234 (1):274-283.
[19]Ko JP, Naidich DP. Lung nodule detection and characterization with multislice CT. Radiol Clin North Am.2003,41 (3):575-597.
[20]Leader JK, Warfel TE, Fuhrman CR, et al. Pulmonary nodule detection with low-dose CT of the lung:agreement among radiologists. AJR Am J Roentgenol. 2005,185 (10): 973-978.
[21]Henschke CI, Yankelevitz DF, Mirtcheva R, et al. CT screening for lung cancer: frequency and significance of part-solid and nonsolid nodules. AJR Am J Roentgenol.2002, 178 (5):1053-1057.
[22]Naidich DP, Marshall CH, Gribbin C, et al. Low-dose CT of the lungs:preliminary observations. Radiology.1990,175 (3):729-731.
[23]Lee JY, Chung MJ, Yi CA, et al. Ultra-low-dose MDCT of the chest:influence on automated lung nodule detection. Korean J Radiol.2008,9 (2):95-101.
[24]Sone S, Shodayu T, Li F, et al. Mass screening for lung cancer with mobile spiral computed tomography scanner. Lancet.1998,351 (9111):1242-1245.
[25]Henschke CI, McCauley DI, Yankelevitz DF, et al. Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet.1999,354 (9,173):99-105.
[26]International Early Lung Cancer Action Program Investigators, Henschke CI, Yankelevitz DF, Libby DM, et al. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med.2006,355 (17):1763-1771.
[27]International Early Lung Cancer Action Program. T-ELCAP Mission& History. New York, NY:I-ELCAP,2007. Available:http://www.ielcap.org/ielcap/about.html (accessed 2009 May.3).
[28]Van Iersel CA, de Koning HJ, Draisma G, et al. Risk-based selection from the general population in a screening trial:selection criteria, recruitment and power for the Dutch-Belgian randomised lung cancer multi-slice CT screening trial (NELSON). Int J Cancer.2006,120 (4):868-874.
[29]Xu DM, Gietema H, de Koning H, et al. Nodule management protocol of the NELSON randomised lung cancer screening trial. Lung Cancer.2006,54 (2):177-184.
[30]Henschke CI, Boffetta P, Gorlova O, et al. Assessment of lung-cancer mortality reduction from CT Screening. Lung Cancer.2010 Dec 17. [Epub ahead of print].
[31]Stanbrook MB, Flegel K. A pause for thought on lung cancer screening. CMAJ.2009, 180 (8):793.
[32]National Cancer Institute. Lung cancer trial results show mortality benefit with low-dose CT:Twenty percent fewer lung cancer deaths seen among those who were screened with low-dose spiral CT than with chest X-ray. Bethesda, MD:National Cancer Institute,2010. Available: www.cancer.gov/newscenter/pressreleases/NLSTresultsRelease(accessed 2010 Nov.09).
[2]中华人民共和国卫生部.《2010中国卫生统计年鉴》.北京：中华人民共和国卫生部：2010Available: http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/ptjnj/year2010/index2010.htm 1 (accessed 2011 Mar.12).
[3]American Cancer Society. Cancer facts and figures 2010. Atlanta (GA):American Cancer Society; 2010:4,15.
[4]Aberle DR, Brown K. Lung cancer screening with CT. Clin Chest Med.2008; 29 (1): 1-14.
[5]Smith RA, Glynn TJ. Epidemiology of lung cancer. Radiol Clin North Am.2000; 38 (3): 453-470.
[6]Samet JM, Avila-Tang E, Boffetta P, et al. Lung cancer in never smokers:clinical epidemiology and environmental risk factors. Clin Cancer Res.2009; 15 (18):5626-5645.
[7]Boiselle PM and White CS, ed. Lung cancer screening:past, present, and future. New Techniques in Thoracic Imaging. New York:Marcel Dekker, Inc.2002:1-23.
[8]International Early Lung Cancer Action Program Investigators, Henschke CI, Yip R, Miettinen OS. Women's susceptibility to tobacco carcinogens and survival after diagnosis of lung cancer. JAMA.2006; 296 (2):180-184.
[9]杨功焕,胡鞍钢主编.控烟与中国未来：中外专家中国烟草使用与烟草控制联合评估报告.北京：经济日报出版社.2011：109-116.
[10]Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997; 111 (6):1710-1717.
[11]Miser WF. Cancer screening in the primary care setting:the role of the primary care physician in screening for breast, cervical, colorectal, lung, ovarian, and prostate cancers. Prim Care.2007; 34 (1):137-167.
[12]National Lung Screening Trial Research Team, Aberle DR, Berg CD, Black WC, et al. The National Lung Screening Trial:overview and study design. Radiology.2011; 258 (1): 243-253.
[13]Ganti AK, Mulshine JL. Lung cancer screening. Oncologist.2006; 11(5):481-487.
[14]Bach PB, Niewoehner DE, Black WC. Screening for lung cancer:the guidelines. Chest. 2003; 123 (1 Suppl):83S-88S.
[15]Naidich DP, Marshall CH, Gribbin C, et al. Low-dose CT of the lungs:preliminary observations. Radiology.1990; 175 (3):729-731.
[16]Lee JY, Chung MJ, Yi CA, et al. Ultra-low-dose MDCT of the chest:influence on automated lung nodule detection. Korean J Radiol.2008; 9 (2):95-101.
[17]Sone S, Shodayu T, Li F, et al. Mass screening for lung cancer with mobile spiral computed tomography scanner. Lancet.1998; 351 (9111):1242-1245.
[18]Henschke CI, McCauley Dl, Yankelevitz DF, et al. Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet.1999; 354 (9173):99-105.
[19]lnternational Early Lung Cancer Action Program Investigators, Henschke CI, Yankelevitz DF, Libby DM, et al. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med.2006; 355 (17):1763-1771.
[20]Van Iersel CA, de Koning HJ, Draisma G. et al. Risk-based selection from the general population in a screening trial:selection criteria, recruitment and power for the Dutch-Belgian randomised lung cancer multi-slice CT screening trial (NELSON). Int J Cancer.2006; 120 (4):868-874.
[21]National Cancer Institute. Lung cancer trial results show mortality benefit with low-dose CT:Twenty percent fewer lung cancer deaths seen among those who were screened with low-dose spiral CT than with chest X-ray. Bethesda, MD:National Cancer Institute; 2010. Available: www.cancer.gov/newscenter/pressreleases/NLSTresultsRelease(accessed 2010 Nov.09).
[22]Rubin GD, Lyo JK, Paik DS, et al. Pulmonary nodules on multi-detector row CT scans: performance comparison of radiologists and computer-aided detection. Radiology.2005; 234(1):274-283.
[23]Leader JK, Warfel TE, Fuhrman CR, et al. Pulmonary nodule detection with low-dose CT of the lung:agreement among radiologists. AJR Am J Roentgenol.2005; 185 (10): 973-978.
[24]Henschke CI, Yankelevitz DF, Mirtcheva R, et al. CT screening for lung cancer: frequency and significance of part-solid and nonsolid nodules. AJR Am J Roentgenol.2002; 178(5):1053-1057.
[25]Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society:glossary of terms for thoracic imaging. Radiology.2008; 246 (3):697-722.
[26]International Early Lung Cancer Action Program. International Early Lung Cancer Action Program:Enrollment and Screening Protocol. New York, NY:International Early Lung Cancer Action Program; 2010. Available: www.ielcap.org/professionals/protocols.html (accessed 2010 Oct.15).
[27]Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol.2007; 2 (8):706-714.
[28]Shemesh J, Henschke CI, Farooqi A, et al. Frequency of coronary artery calcification on low-dose computed tomography screening for lung cancer. Clin Imaging.2006; 30 (3): 181-185.
[29]Lee CH, Goo JM, Lee HJ, et al. Radiation dose modulation techniques in the multidetector CT era:from basics to practice. RadioGraphics.2008; 28 (5):1451-1459.
[30]MacMahon H, Austin,JH, Gamsu G, et al. Guidelines for management of small pulmonary nodules detected on CT scans:a statement from the Fleischner Society. Radiology.2005; 237 (2):395-400.
[31]Swensen SJ, Jett JR, Hartman T, et al. Screening for lung cancer with CT:Mayo Clinic experience. Radiology.2003; 226 (3):756-761.
[32]Centers for Disease Control and Prevention (CDC). Cigarette smoking among adults-United States,2006. MMWR Morb Mortal Wkly Rep.2007; 56 (44):1157-1161.
[33]Gohagan J, Marcus P, Fagerstrom R, et al. Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph:the lung screening study of the national cancer institute. Chest.2004; 126 (1):114-121.
[34]聂永康,蔡祖龙,赵绍宏.低剂量螺旋CT筛选检查早期肺癌的初步研究.中华放射学杂志.2002；36(3)：230-234.
[35]王颖,柳学国,张秀兰.低剂量多层螺旋CT普查早期肺癌的探讨.影像诊断与介入放射学.2006；15(5)：238-240.
[36]黄明刚,王青,齐敏,等.低剂量螺旋CT筛查肺癌的诊断效能及价值.实用放射学杂志.2008；24(8)：1030-1039.
[37]Raggi P, Gongora MC, Gopal A, et al. Coronary artery calcium to predict all-cause mortality in elderly men and women. J Am Coll Cardiol.2008; 52 (1):17-23.
[38]白玫,郑钧正.多排(层)螺旋CT的辐射剂量表达及其影响因素探讨.辐射防护.2008；28(1)：1-12.
[39]刘彬,白玫,费晓璐,等.CT剂量表征量的选择.中国医疗设备.2008；23(3)：54-56.
[40]吴晓华,马大庆,张忠嘉,等.多层螺旋CT胸部低剂量扫描发现肺结节的临床研究.中华放射学杂志.2004；38(7)：767-770.
[41]Brown MS, Goldin JG, Suh RD, et al. Lung micronodules:automated method for detection at thin-section CT--initial experience. Radiology.2003; 226 (1):256-262.
[42]Goo JM, Lee JW, Lee HJ, et al. Automated lung nodule detection at low-dose CT: preliminary experience. Korean J Radiol.2003; 4 (4):211-216.
[43]彭芸,马大庆,李剑颖,等.64层螺旋CT自动管电流调节技术在婴幼儿胸部低剂量CT扫描中应用的可行性研究.中华放射学杂志.2008；42(10)：1045-1049.
[44]Gruden JF, Ouanounou S, Tigges S, et al. Incremental benefit of maximum-intensity-projection images on observer detection of small pulmonary nodules revealed by multidetector CT. AJR Am J Roentgenol.2002; 179 (1):149-157.
[45]Yuan R, Vos PM, Cooperberg PL. et al. Computer-aided detection in screening CT for pulmonary nodules. AJR Am J Roentgenol.2006; 186 (5):1280-1287.
[46]Bae KT, Kim JS, Na YH, et al. Pulmonary nodules:automated detection on CT images with morphologic matching algorithm--preliminary results. Radiology.2005; 236 (1): 286-293.
[47]Beigelman-Aubry C, Raffy P, Yang W, et al. Computer-aided detection of solid lung nodules on follow-up MDCT screening:evaluation of detection, tracking, and reading time. AJR Am J Roentgenol.2007; 189 (4):948-955.
[48]Das M, Miihlenbruch G, Heinen S, et al. Performance evaluation of a computer-aided detection algorithm for solid pulmonary nodules in low-dose and standard-dose MDCT chest examinations and its influence on radiologists. Br J Radiol.2008; 81 (971):841-847.
[49]Sahiner B, Chan HP, Hadjiiski LM, et al. Effect of CAD on radiologists'detection of lung nodules on thoracic CT scans:analysis of an observer performance study by nodule size. Acad Radiol.2009; 16 (12):1518-1530.
[50]Goo JM. A Computer-Aided Diagnosis for Evaluating Lung Nodules on Chest CT:the Current Status and Perspective. Korean J Radiol.2011; 12 (2):145-155.
[51]Yanagawa M, Honda O, Yoshida S, et al. Commercially available computer-aided detection system for pulmonary nodules on thin-section images using 64 detectors-row CT: preliminary study of 48 cases. Acad Radiol.2009; 16 (8):924-933.
[1]American Cancer Society. Global cancer facts and figures 2007. Atlanta (GA):American Cancer Society,2007.14.
[2]中华人民共和国卫生部.《2010中国卫生统计年鉴》.北京：中华人民共和国卫生部,2010Available: http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/ptjnj/year2010/index2010.ht ml (accessed 2011 Mar.12).
[3]American Cancer Society. Cancer facts and figures 2010. Atlanta (GA):American Cancer Society,2010.4,15.
[4]Aberle DR, Brown K. Lung Cancer Screening with CT. Clin Chest Med.2008,29 (1): 1-14.
[5]Boiselle PM and White CS ed. Lung cancer screening:past, present, and future. New Techniques in Thoracic Imaging. New York:Marcel Dekker, Inc.2002.1-23.
[6]International Early Lung Cancer Action Program Investigators, Henschke CI, Yip R, Miettinen OS. Women's susceptibility to tobacco carcinogens and survival after diagnosis of lung cancer. JAMA.2006,296 (2):180-184.
[7]Ebbert JO, Yang P, Vachon CM, et al. Lung cancer risk reduction after smoking cessation:observations from a prospective cohort of women. J Clin Oncol.2003,21 (5): 921-926.
[8]Smith RA, Glynn TJ. Epidemiology of lung cancer. Radiol Clin North Am.2000,38 (3): 453-470.
[9]Mountain CF. Revisions in the international system for staging lung cancer. Chest.1997, 111 (6):1710-1717.
[10]Ravenel JG, Costello P, Silvestri GA. Screening for lung cancer. AJR Am J Roentgenol. 2008,190 (3):755-761.
[11]Miser WF. Cancer screening in the primary care setting:the role of the primary care physician in screening for breast, cervical, colorectal, lung, ovarian, and prostate cancers. Prim Care.2007,34 (1):137-167.
[12]Henschke CI, Shaham D, Yankelevitz DF, et al. CT screening for lung pancer:past and ongoing Studies. Semin Thorac Cardiovasc Surg.2005,17 (2):99-106.
[13]National Lung Screening Trial Research Team. The National Lung Screening Trial: Overview and Study Design. Radiology.2011,258 (1):243-253.
[14]Gohagan J, Marcus P, Fagerstrom R, et al. Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph:the lung screening study of the national cancer institute. Chest.2004,126 (1):114-121.
[15]Ganti AK, Mulshine JL. Lung cancer screening. Oncologist.2006,11(5):481-487.
[16]Bach PB, Niewoehner DE, Black WC. Screening for lung cancer:the guidelines. Chest. 2003,123 (1 Suppl):83S-88S.
[17]Kitajima T, Nishii K, Ueoka H, et al. Recent improvement in lung cancer screening:a comparison of the results carried out in two different time periods. Acta Med. Okayama. 2006,60 (3):173-179.
[18]Rubin GD. Lyo JK, Paik DS, et al. Pulmonary nodules on multi-detector row CT scans: performance comparison of radiologists and computer-aided detection.Radiology.2005, 234 (1):274-283.
[19]Ko JP, Naidich DP. Lung nodule detection and characterization with multislice CT. Radiol Clin North Am.2003,41 (3):575-597.
[20]Leader JK, Warfel TE, Fuhrman CR, et al. Pulmonary nodule detection with low-dose CT of the lung:agreement among radiologists. AJR Am J Roentgenol. 2005,185 (10): 973-978.
[21]Henschke CI, Yankelevitz DF, Mirtcheva R, et al. CT screening for lung cancer: frequency and significance of part-solid and nonsolid nodules. AJR Am J Roentgenol.2002, 178 (5):1053-1057.
[22]Naidich DP, Marshall CH, Gribbin C, et al. Low-dose CT of the lungs:preliminary observations. Radiology.1990,175 (3):729-731.
[23]Lee JY, Chung MJ, Yi CA, et al. Ultra-low-dose MDCT of the chest:influence on automated lung nodule detection. Korean J Radiol.2008,9 (2):95-101.
[24]Sone S, Shodayu T, Li F, et al. Mass screening for lung cancer with mobile spiral computed tomography scanner. Lancet.1998,351 (9111):1242-1245.
[25]Henschke CI, McCauley DI, Yankelevitz DF, et al. Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet.1999,354 (9,173):99-105.
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