Screening for lung cancer in high-risk groups: current status of low-dose spiral CT scanning and sputum markers

Lung cancer is the number one cause of death from cancer in the United States. Currently, there is no official recommendation to screen for lung cancer even in high-risk populations. Accordingly, we wait for patients to present with symptoms. Only 15-20% of patients are stage I lung cancer at diagnosis. Past screening trials with chest roentgenogram and sputum cytology did not show a reduction of lung cancer mortality in the screened population. Since the completion of those trials in the early 1980s we have learned that the chest X ray is not sensitive at detecting lesions <2 cm in size, and patients with chronic obstructive pulmonary disease (COPD) have a 4- to 6-fold increased risk of lung cancer independent of their smoking history. Recent trials with spiral computed tomography (CT) scan screening have detected 80-85% of lung cancers while they are stage I. The problems related to spiral CT screening are the cost and the frequent detection of benign lesions. Algorithms are being developed to try and prevent unnecessary biopsies and/or surgery. Sputum cytology is currently the only clinically approved sputum test for detecting lung cancer. However, in patients with moderate dysplasia of cytology, the LIFE autofluorescence bronchoscopy system may yield an increased sensitivity of detecting precancerous or cancerous lesions. More studies are needed before the LIFE system can be adopted as a standard clinical tool. Currently, investigators are evaluating the sputum for early lung cancer detection markers. The marker that is the most developed is the monoclonal antibody to the heterogeneous nuclear ribonucleoprotein A2/B1 on the sputum epithelial cell surface. Encouraging preliminary results have been reported and trials are ongoing. The future looks bright for the field of lung cancer screening.     

Results of 10-year mobile low-dose computed tomography screenings for lung cancer in Shimane,Japan

BackgroundSome randomized controlled trials have evaluated the effects of low-dose computed tomography (CT) screening on lung cancer mortality in heavy smokers. Based on the results of those trials, our CT screening program recommended screening for people aged ≥40 years with a history of smoking. This retrospective study aimed to verify the validity of our CT screening program and elucidate the current state of CT screening program.MethodsWe retrospectively examined lung cancer detection in 25,189 participants who underwent chest CT screening by a mobile low-dose CT screening unit in the 10-year period from April 2009 to March 2019. Participants were recruited at Japan Agricultural Cooperatives (JA) Shimane Kouseiren. Participants requested CT screening for lung cancer. CT images were read by two pulmonologists.ResultsLung cancer was identified in 82 of the 25,189 participants over 10 years, an overall lung cancer detection rate (percentage of lung cancers detected among all participants) of 0.33%. Lung cancer among never smokers accounted for 54.9% of the detected cases. The lung cancer detection rate was similar for smokers versus never smokers. The stage IA detection rate (percentage of stage IA lung cancers among all lung cancers detected) was 62%, while the stage Ⅳ detection rate was 10%.ConclusionsChest CT detected lung cancer in never smokers as well as current or former smokers. Our CT screening program was not effective for never smokers; thus, further study of the effectiveness of CT screening in never smokers is needed.     

Screening for lung cancer with low-dose spiral computed tomography

Studies suggest that screening with spiral computed tomography can detect lung cancers at a smaller size and earlier stage than chest radiography can. To evaluate low-radiation-dose spiral computed tomography and sputum cytology in screening for lung cancer, we enrolled 1,520 individuals aged 50 yr or older who had smoked 20 pack-years or more in a prospective cohort study. One year after baseline scanning, 2,244 uncalcified lung nodules were identified in 1,000 participants (66%). Twenty-five cases of lung cancer were diagnosed (22 prevalence, 3 incidence). Computed tomography alone detected 23 cases; sputum cytology alone detected 2 cases. Cell types were: squamous cell, 6; adenocarcinoma or bronchioalveolar, 15; large cell, 1; small cell, 3. Twenty-two patients underwent curative surgical resection. Seven benign nodules were resected. The mean size of the non-small cell cancers detected by computed tomography was 17 mm (median, 13 mm). The postsurgical stage was IA, 13; IB, 1; IIA, 5; IIB, 1; IIIA, 2; limited, 3. Twelve (57%) of the 21 non-small cell cancers detected by computed tomography were stage IA at diagnosis. Computed tomography can detect early-stage lung cancers. The rate of benign nodule detection is high.     

Lung cancer screening with CT

Lung cancer is the leading cause of cancer death in the United States. Non-small cell lung cancer accounts for 75% to 80% of all lung cancers. There is an impetus to find a screening test that can detect non-small cell lung cancer in its early preclinical stages, when surgical resection is most likely to reduce lung cancer mortality. Although earlier randomized controlled trials of lung cancer screening using chest radiography and sputum cytology failed to show reduced lung cancer mortality, CT is a much more sensitive test for detecting small lung nodules, and has generated considerable enthusiasm as a potential contemporary screening tool for lung cancer.     

Overview of observational studies of low-dose helical computed tomography screening for lung cancer

OBJECTIVE: Lung cancer is a substantial public health problem in Western countries. Evidence from previous controlled trials of chest radiography and sputum cytology does not support lung cancer screening, but computed tomography (CT) screening has recently emerged as a more sensitive screening tool. For the present article, the available observational studies of low-dose helical CT screening for lung cancer were reviewed. METHODOLOGY: An evidence-based review of all published observational studies of low-dose helical CT screening for lung cancer, identified by an extensive search of Medline, was conducted. RESULTS: Eight observational studies of CT screening for lung cancer were identified. Relative to chest radiography, low-dose helical CT is a sensitive screening tool and can detect a high proportion of small lung cancers at an early and resectable stage. The yield of sputum cytology in addition to CT screening appears to be relatively low. To date, 5-year lung cancer survival of all individuals participating in baseline screening has not been reported for any of the studies. CONCLUSIONS: Although these preliminary studies are very promising, it remains to be proven that the early detection and treatment of lung cancer will lead to a reduction in mortality. This issue will be addressed by randomized controlled trials. In the interim, the long-term follow up of these observational studies could provide further insights.     

纤维支气管镜活检病变组织标本和痰标本Survivin基因的检测对肺癌的诊断价值

目的明确纤维支气管镜(以下简称纤支镜)活检病变组织和痰标本中SurvivinmRNA的检测在肺癌诊断中的意义。方法应用逆转录聚合酶链反应(RT PCR)法检测41例肺癌手术标本癌组织、癌旁组织和9例良性肺疾病病变组织手术标本,80例肺癌和30例良性肺疾病纤支镜活检病变组织标本及所有(160例)患者痰标本SurvivinmRNA表达情况,并与病理组织学、刷检细胞学和痰细胞学检查结果比较。结果肺癌手术切除标本癌组织SurvivinmRNA的阳性率为70.7%(29/41),高于癌旁组织[17.1%(7/41)]和良性肺疾病组织(1/9),差异有统计学意义(χ2值分别为23.97和10.93,P均<0.05),而癌旁组织与肺良性疾病组织相比,差异无统计学意义(χ2=0.20,P>0.05);纤支镜活检肺癌组织标本SurvivinmRNA的阳性率为63.8%(51/80),高于良性肺疾病的13.3%(4/30,χ2值为22.18,P<0.05);肺癌患者癌组织SurvivinmRNA表达与否及表达水平与患者年龄、性别及肿瘤的病理分型、分级、部位及转移情况均无明显相关性(P均>0.05)。肺癌患者痰标本SurvivinmRNA的阳性率是59.5%(72/121),癌细胞的检出率是47.1%(57/121);痰Survivin mRNA检测联合痰细胞学检查诊断肺癌的敏感性为80.2%(97/121),高于单独痰细胞学及单独痰SurvivinmRNA检测的敏感性(P均<0.05)。手术标本、纤支镜活检标     

Screening for early lung cancer. Results of the Memorial Sloan-Kettering study in New York

The Memorial Sloan-Kettering lung cancer screening program was begun in 1974 to evaluate sputum cytology as a supplement to the annual chest x-ray examination for early detection and diagnosis. The 10,040 adult, male cigarette smokers who enrolled were randomly assigned to receive annual chest x-ray examinations only or a dual screen with annual chest x-ray examination and four monthly sputum cytology evaluation. Over 40 percent of the 288 who developed lung cancer were diagnosed in stage I, and their survival was 76 percent at five years; overall survival was 35 percent. Nearly one third of the lung cancers detected on first examination on the dual screen, and 14 percent of those on subsequent examinations were found by cytologic examination. The same number of cancers developed in the x-ray screen only group, and were diagnosed at a later date. Despite the delay, survival and mortality were the same, suggesting that the squamous carcinomas detected by cytologic examination alone are very slow growing and tend to remain localized until detectable by x-ray examination.     

Predictive value of image cytometry for diagnosis of lung cancer in heavy smokers.

The Research Institute for Diagnosis and Treatment of Early Lung Cancer (RIDTELC) Lung Study was initiated to determine whether lung cancer screening by automated sputum cytometry combined with conventional sputum cytology and auto-fluorescence in addition to white light bronchoscopy could enhance the detection rate of early lung cancer. The present study analyses the initial findings to evaluate the efficiency of automated sputum cytology in predicting the diagnosis of lung cancer. In this study, malignancy grade was used as a predictive parameter for lung cancer. In total, 2,480 heavy smokers (>30 pack-yrs), aged 50-74 yrs, with no previous cancer in the last 5 yrs, received chest radiology, conventional sputum cytology and sputum cytometry screening. In total, twenty-seven lung cancers were diagnosed, representing a prevalence of 1.1%, 25 of which provided sputum samples. Positive automated sputum cytology results were seen in 176 smokers (7.2%), 10 (0.4%) of whom had severe dysplasia or higher lesions (positive results) by conventional sputum cytology examination. Out of 25 tumour cases, 20 had suspicious results using automated sputum cytology, representing 80% sensitivity. One patient out of 24 with tumours had positive results on conventional sputum cytology, representing a sensitivity of 4.2%. For all stages of squamous cell lung cancer and later stage adenocarcinoma the sensitivity of automated sputum cytology was 100%. For adenocarcinoma stage I sensitivity was 25%. In conclusion, DNA analysis of sputum slides by automated sputum cytology may be a suitable tool for the detection of early lung cancer and the characterisation of a high-risk group with pre-invasive lesions for follow-up.     

Screening for lung cancer

The National Lung Screening Study has demonstrated that screening with low-dose spiral computed tomography results in fewer deaths from lung cancer compared with screening with chest radiography (CXR). Previous trials of screening with CXR and sputum cytology failed to exhibit fewer deaths compared with no screening intervention. Early computed tomography (CT) studies showed promise for CT to be a more sensitive test, yet were unable to demonstrate sufficient evidence of efficacy. This review examines the problem of early lung cancer detection, the issues presented by screening, and results of past and recent studies of lung cancer screening.     

Early lung cancer detection using spiral computed tomography and positron emission tomography

RATIONALE: Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. OBJECTIVE: To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: High-risk individuals underwent screening with annual spiral CTs. Follow-up CTs were done for noncalcified nodules of 5 mm or greater, and FDG-PET was done for nodules 10 mm or larger or smaller (> 7 mm), growing nodules. RESULTS: A total of 911 individuals completed a baseline CT study and 424 had at least one annual follow-up study. Of the former, 14% had noncalcified nodules of 5 mm or larger, and 3.6% had nodules of 10 mm or larger. Eleven non-small cell lung cancers (NSCLC) and one small cell lung cancer (SCLC) were diagnosed in the baseline study (prevalence rate, 1.32%), and two NSCLCs in the annual study (incidence rate, 0.47%). All NSCLCs (92% of prevalence cancers) were diagnosed in stage I (12 stage IA, 1 stage IB). FDG-PET was helpful for the correct diagnosis in 19 of 25 indeterminate nodules. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71%, respectively. However, the sensitivity and negative predictive value of the screening algorithm, which included a 3-month follow-up CT for nodules with a negative FDG-PET, was 100%. CONCLUSION: A protocol for early lung cancer detection using spiral CT and FDG-PET is useful and may minimize unnecessary invasive procedures for benign lesions.     

老年肺癌病人痰标本中p16基因异常甲基化的研究

目的分析老年肺癌病人痰标本中p16基因启动子区域异常高甲基化的改变情况,评价该指标作为肺癌辅助诊断分子标记物的价值。方法运用半巢式甲基化特异性聚合酶链反应技术,检测94例老年原发性肺癌病人痰标本和部分对应肿瘤组织,以及10例慢性肺炎病例痰标本中p16基因启动子区域的甲基化改变。结果74%的肺癌病人痰标本中检测到了p16基因异常高甲基化,与传统细胞学(46.8%)相比,痰标本中p16基因异常高甲基化对肿瘤的检出率(74.5%)灵敏度更高(P<0.01);痰细胞中p16甲基化检测和细胞学相结合,对肿瘤的检出率可达86.17%(81/94)。如果痰标本中p16基因启动子区域发生高甲基化,其对应的肿瘤组织中p16基因亦为高甲基化。10例慢性肺炎病人痰标本中仅3例检测出p16基因甲基化。结论痰标本中p16基因甲基化是临床肺癌辅助诊断的有效分子生物标记物之一。     

对肺结核可疑者采用症状查痰法提高患者发现率

目的探讨更全面的发现肺结核病例的检查诊断程序。方法在采用通用的胸透筛查法发现肺结核患者的基础上，采用症状查痰法，对有症状且≥3周者，直接做痰结核分枝杆菌检查，并拍摄X线胸片，对按胸透筛查法和症状查痰法发现的患者进行比较；对肺结核诊断程序改进后的结核病患者的发现情况进行分析。结果采用症状查痰法发现活动性肺结核新病例900例，比胸透筛查法多发现活动性肺结核患者73例，患者发现率提高8．8％(73／827)；发现涂阳肺结核病例262例，比胸透筛查法多发现活动性肺结核患者30例，患者发现率提高12．9％(30／232)；培养阳性肺结核病例360例，比胸透筛查法多发现患者63例，患者发现率提高21．2％(63／297)。症状查痰法发现新病例的细菌学检查阳性者的比例高于胸透筛查法，胸透筛查法发现新病例中，涂片阳性者占28．1％(232／827)，痰菌培养阳性者占35．9％(297／827)；而症状查痰法发现新病例中，涂片阳性者占29．1％(262／900)，痰菌培养阳性者占40．0％(360／900)。症状查痰法多检出的活动性肺结核患者73例中，涂阳和菌阳患者的比例均很高，分别为41．1％(30／73)和86．3％(63／73)，较胸透筛查法的检出涂阳比例(28．1％)和菌阳比例(35．9％)高。结论采用症状查痰法比胸透筛查法发现的活动性肺结核患者增加，特别是菌阳肺结核患者的发现率增加21．2％，使这些患者得到及时诊断，有利于结核病传染源的控制。     

The value of positron emission tomography in early detection of lung cancer in high‐risk population: a systematic review

Background: Early detection trials with chest radiography and sputum cytology were ineffective in decreasing lung cancer mortality. The advent of low‐dose spiral chest computed tomography (LDCT) provided clinicians with a new tool that could be with early diagnosis; however, this also raised significant concerns regarding the systematic use of LDCT with its high false‐positive rate for benign nodules. At this time, there is limited information about the true role of PET (positron emission tomography) for early detection of lung cancer. Methods: We used systematic methods, including Preferred Reporting Items for Systematic reviews and Meta‐Analyses statement, to identify relevant studies, assess study eligibility, evaluate study methodological quality, and summarize findings regarding diagnostic accuracy and outcome. Results: In total, only seven eligible studies were selected from 82 potentially relevant studies. The sensitivity of 18F‐FDG‐PET for the detection of T1 lung cancers ranged between 68% and 95%. The rate of detection tended to be lower for carcinoid tumors, adenocarcinoma and bronchoalveolar cell carcinomas. FDG‐PET using SUV (standardized uptake value) level can predict the outcome of the screening detected lung cancer. A combination of FDG‐PET and LDCT may improve screening for lung cancer in high‐risk patients. Conclusions: PET or PET/CT may be used as a useful tool for early detection of lung cancer in high‐risk population based on the existing information. However, there is still limited information with regards to evidence of survival benefits from PET screening in high‐risk patients. Please cite this paper as: Chang C‐Y, Chang S‐J, Chang S‐C and Yuan M‐K. The value of positron emission tomography in early detection of lung cancer in high‐risk population: a systematic review. Clin Respir J 2013; 7: 1–6.     

A case of active pulmonary tuberculosis in the right lower lung field detected by CT]

Many studies have indicated the pitfalls in detecting abnormalities on chest radiography, although radiography of the chest has been used for the screening of peripheral lung cancer. Recently, mass screening with a spiral computed tomography scanner has been performed for the detection of small peripheral lung cancers, and it has been clarified that spiral CT was superior to chest radiography in the screening and detection of peripheral lung cancer. However, there have been only a few reports on pulmonary tuberculosis that was detected by chest CT. We report a case of active pulmonary tuberculosis detected by chest CT, and invisible on plain chest radiography. 39 year old female consulted our hospital, because chest radiography at mass screening for lung cancer showed an abnormal shadow in the left upper lung field. Chest CT revealed a high density nodule with calcification compatible with old tuberculosis. However, there was another 20 mm x 10 mm sized nodule in right S9b that was invisible on plain chest radiography. The nodule had a clear margin with satellite lesion that characterize active pulmonary tuberculosis. Bronchial lavage was performed by bronchofiberscopy, and Mycobacterium tuberculosis was isolated from lavage fluid. The nodular shadow disappeared after the treatment with isoniazid and rifampicin for 9 months.     

Update on screening for lung cancer

Prognosis of lung cancer is markedly improved when cancers are resected in early stages (particularly in stage I). Previous investigations failed to show benefit with use of chest radiographs or sputum cytologies to screen for lung cancer among high-risk populations. More recently, computed tomography (CT) has been used as a screening technique and appears to detect lung cancer at earlier stages (e.g., stage I) compared with usual clinical practice. However, whether screening CT reduces death from lung cancer has not been clarified. This review examines the problem presented by lung cancer, the issues presented by screening, and the results of past and recent studies of lung cancer screening.     

肺癌患者肺组织和痰标本p53基因突变检测及其临床意义

目的　探讨肺癌患者支气管肺活检组织和痰标本中p5 3基因突变检测在肺癌诊断中意义。方法　应用聚合酶链反应 (PCR) 单链多肽性 (SSCP) 银染法检测 12 0例肺癌和 40例良性肺疾病支气管肺活检组织和痰标本p5 3基因第 5～ 8外显子突变情况。结果　 60例肺癌患者癌组织、癌旁组织和对侧支气管组织p5 3基因突变检出率分别为 60 % (3 6/ 60 )、17% (10 / 60 )和 5 % (3 / 60 ) ,三组间比较差异有显著性 (P <0 .0 0 5 )。 2 0例良性肺疾病支气管肺组织p5 3基因突变检出率为 5 %。故活检组织p5 3基因突变检出肺癌的敏感性为 60 % ,特异性为 95 % ;另外 60例肺癌痰标本p5 3基因突变检出的敏感性为 43 % (2 6/ 60 ) ,特异性为 10 0 %。肺癌痰标本p5 3基因突变联合细胞学检测使肺癌的诊断率从单纯细胞学的 48% (2 9/ 60 )提高到 68% (41/ 60 )。结论　痰标本p5 3基因检测联合细胞学检查可提高肺癌的诊断率     

Report of a lung cancer survey in Hunan realgar miners

A mass survey and follow-up examinations to screen lung cancer victims at hunan realgar mine have been carried out over three years. The checking methods include physical examinations sputum cytological screening and chest radiography. The incidence of lung cancer in those with moderate or severe broncho-epithelial hyperplasia found in sputum counts for 10.8%, which is much higher than that of the other cases, counting for 1.4% (P less than 0.05). Most of the victims belong to AJCC stage 1. When the check-up was done annually, nineteen cases of lung cancer were detected by chest radiography alone as compared with 11 cases by sputum cytological examination. In those X-ray positive cases three of them were failed to be detected in initial X-ray investigation.     

64排螺旋 CT 低剂量在高危人群早期肺癌筛查和诊断中的应用价值

目的：探讨64排螺旋 CT 低剂量在高危人群早期肺癌筛查和诊断中的应用价值。方法以本院2013年1月至2015年12月期间我院体检中心体检的1036例高危人群作为研究对象,分别采用 X 光机和 CT 机进行早期肺部癌症筛查。获得 DR 胸片和 CT 影像后由2位医师采用双盲法对影像进行观察并作出诊断。记录肺部结节数量、大小和最终诊断结果。结果采用 CT 扫描出肺部结节病灶共169例,检出率为16.31%;而采用 DR 胸片共检出76例,检出率为7.34%。2种方法在肺部结节检出率之间的差异有统计学意义(χ2=40.0360,P <0.05),CT 扫描检出率优于 DR 胸片检出率。2种方法在检出肺部不同大小结节数之间的差异有统计学意义(χ2=9.6688,P <0.05)。2种方法在>10 mm 结节检出率之间的差异有统计学意义(χ2=4.6677,P <0.05)。在1036例样本中,CT扫描确诊肺癌20例(1.93%),DR 胸片确诊肺癌6例(0.58%)。2种方法在肺癌筛查确诊率之间的差异有统计学意义(χ2=6.5826,P <0.05),CT 扫描检出肺癌率要优于 DR 胸片检查。结论针对肺癌高危人群的早期筛查工作,64排螺旋 CT 低剂量扫描对筛查肺部结节和确诊疾病并及时制定临床救治方案具有指导意义,适于推广与应用。     

Detection of extrapulmonary lesions with integrated PET/CT in the staging of lung cancer.

The aim of the present study was to assess retrospectively the additional value of positron emission tomography (PET)/computed tomography (CT) in the detection of unexpected extrapulmonary lesions in the staging of patients with a malignant pulmonary lesion in comparison with CT and PET used alone. A total of 217 patients with a pathologically proven lung tumour underwent PET/CT. CT, PET and PET/CT were evaluated in the detection of extrapulmonary lesions. These abnormalities were compared with the final diagnosis obtained from the medical records and statistical analysis was carried out. In total, 108 lesions were clinically detected. PET/CT showed a sensitivity, specificity, positive and negative predictive values and accuracy of 100, 81, 71, 100 and 87%, respectively, for the detection of extrapulmonary lesions and 92, 98, 89, 98 and 97%, respectively, for the detection of malignant extrapulmonary lesions. PET/CT was significantly better than CT and PET used alone. Conventional staging work-up has a poor sensitivity in detecting second primary cancers or unexpected metastases. The detection of malignant extrapulmonary lesions is necessary for correct tumour staging. By combining both metabolic and anatomical information, positron emission tomography/computed tomography is able to depict more unexpected extrapulmonary lesions than computed tomography and positron emission tomography used alone, and positron emission tomography/computed tomography provides more additional information of malignancy or benignancy of lesions detected with one of the two imaging modalities alone.     

A 10 year follow-up of semi-annual screening for early detection of lung cancer in the Erfurt County, GDR

A prospective and controlled study for early detection of lung cancer in the county of Erfurt with a follow-up of 10 years is presented. A collective of 41,532 males born between 1907 and 1932 was screened by chest fluorography at 6 month intervals and compared with a control group consisting of 102,348 males of the same age, who were screened at intervals of about 18 months. No significant reduction of overall mortality and of lung cancer mortality was achieved. Semi-annual screening brought about a higher detection rate (9%/6.5%), an increase in the resection rate (28%/19%) and higher 5 and 10 year survival rates (52%; 27%/39%; 19%) of resected patients than screening in 18 month intervals. Among those patients who refused resection or were surgically untreatable, the difference in survival rates between the two investigation groups lasted only up to the 12 months barrier. This is regarded as the effect of the lead-time bias. Fluorographic screening is effective only in patients with peripheral cancers. Patients resected for central lung cancers did not show differences in the survival rates. In both investigation groups considered together surgical therapy was possible mainly in those patients who had been detected by screening (resection rate: 48%; 5 yr survival rate: 26.9%). The resection rate of all the others amounted to 9%, the 5 yr survival rate to 1.4%. Therefore we consider fluorography to time as the only chance for lung cancer control of high risk groups in spite of the absence of reduction of lung cancer mortality.