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1.  Lung cancer screening: from imaging to biomarker 
Biomarker Research  2013;1:4.
Despite several decades of intensive effort to improve the imaging techniques for lung cancer diagnosis and treatment, primary lung cancer is still the number one cause of cancer death in the United States and worldwide. The major causes of this high mortality rate are distant metastasis evident at diagnosis and ineffective treatment for locally advanced disease. Indeed, approximately forty percent of newly diagnosed lung cancer patients have distant metastasis. Currently, the only potential curative therapy is surgical resection of early stage lung cancer. Therefore, early detection of lung cancer could potentially increase the chance of cure by surgery and underlines the importance of screening and detection of lung cancer. In the past fifty years, screening of lung cancer by chest X-Ray (CXR), sputum cytology, computed tomography (CT), fluorescence endoscopy and low-dose spiral CT (LDCT) has not improved survival except for the recent report in 2010 by the National Lung Screening Trial (NLST), which showed a 20 percent mortality reduction in high risk participants screened with LDCT compared to those screened with CXRs. Furthermore, serum biomarkers for detection of lung cancer using free circulating DNA and RNA, exosomal microRNA, circulating tumor cells and various lung cancer specific antigens have been studied extensively and novel screening methods are being developed with encouraging results. The history of lung cancer screening trials using CXR, sputum cytology and LDCT, as well as results of trials involving various serum biomarkers, are reviewed herein.
PMCID: PMC3776246  PMID: 24252206
2.  Early detection for lung cancer. New tools for casefinding. 
Canadian Family Physician  2001;47:537-544.
OBJECTIVE: To review data from published population trials and clinical practice guidelines on screening for lung cancer to provide a recommendation for early detection of lung cancer. QUALITY OF EVIDENCE: Literature was searched via MEDLINE using the MeSH headings "lung neoplasm," "mass screening," "thoracic radiography," and "sputum." Only prospective randomized controlled trials with large numbers of subjects were selected. MAIN MESSAGE: Risk of lung cancer among long-term heavy smokers continues even years after stopping smoking. Risk is highest in smokers with chronic obstructive pulmonary disease. Canadian clinical practice guidelines currently recommend that sputum cytology examination and chest radiography (CXR) not be used for lung cancer screening. This guideline was deducted from four randomized population trials in the 1970s that have serious limitations and applies to asymptomatic adults only. A CXR and sputum cytology examination are indicated in symptomatic current and former smokers older than 45 years with a smoking history of 30 pack-years or more and airflow obstruction defined as a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of 70% or less and a FEV1 lower than 70%. Curative treatment is available for early lung cancer. Substantial advances in innovative technologies for early detection using low-dose spiral CT and newer sputum tests have been made in the last three decades. Additional studies are under way to evaluate these new technologies. CONCLUSION: Primary care physicians have an important role in identifying people at risk of developing lung cancer and in supporting research to evaluate new screening technology.
PMCID: PMC2018399  PMID: 11281087
3.  Early diagnosis of lung cancer 
F1000Prime Reports  2013;5:12.
A large randomized controlled trial, The National Lung Screening Study (NLST), has demonstrated that screening with low-dose spiral computed tomography saved lives from lung cancer when compared with screening with chest radiographs. This is the first test showing efficacy in screening for lung cancer as previous trials of chest radiographs and sputum cytology failed to result in fewer deaths with screening. This review will examine the problem of lung cancer, the issues presented by screening, and the results of computed tomography (CT) studies for lung cancer screening. Now that CT screening has been shown to be effective, implementation of screening becomes the next step.
PMCID: PMC3616602  PMID: 23585930
4.  Randomized controlled trials of the efficacy of lung cancer screening by sputum cytology revisited: a combined mortality analysis from the Johns Hopkins Lung Project and the Memorial Sloan-Kettering Lung Study 
Cancer  2009;115(21):5007-5017.
Two randomized controlled trials of lung cancer screening initiated in the 1970's, the Johns Hopkins Lung Project and the Memorial Sloan-Kettering Lung Study, compared one arm which received annual chest x-ray and four-monthly sputum cytology (dual-screen) to a second arm which received annual chest x-ray only. Previous publications from these trials reported similar lung cancer mortality between the two groups. However, these findings were based on incomplete follow-up, and each trial on its own was underpowered to detect a modest mortality benefit.
We estimated the efficacy of lung cancer screening with sputum cytology in an intention-to-screen analysis of lung cancer mortality, using combined data from these trials (n=20,426).
Over one-half of squamous cell lung cancers diagnosed in the dual-screen group were identified by cytology; these cancers tended to be more localized than squamous cancers diagnosed in the x-ray only arm. After nine years of follow-up, lung cancer mortality was slightly lower in the dual-screen than in the x-ray only arm (rate ratio (RR) 0.88, 95% confidence interval (CI) 0.74-1.05). Reductions were seen for squamous cell cancer deaths (RR 0.79, 95% CI 0.54-1.14) and in the heaviest smokers (RR 0.81, 95% CI 0.67-1.00). There were also fewer deaths from large cell carcinoma in the dual-screen group, though the reason for this is unclear.
These data are suggestive of a modest benefit of sputum cytology screening, though we cannot rule out chance as an explanation for these findings.
PMCID: PMC2767423  PMID: 19637354
lung cancer; screening; sputum cytology; chest x-ray
5.  Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in the post-National Lung Screening Trial era 
BMC Medicine  2013;11:168.
Lung cancer is the leading cause of cancer death worldwide in part due to our inability to identify which smokers are at highest risk and the lack of effective tools to detect the disease at its earliest and potentially curable stage. Recent results from the National Lung Screening Trial have shown that annual screening of high-risk smokers with low-dose helical computed tomography of the chest can reduce lung cancer mortality. However, molecular biomarkers are needed to identify which current and former smokers would benefit most from annual computed tomography scan screening in order to reduce the costs and morbidity associated with this procedure. Additionally, there is an urgent clinical need to develop biomarkers that can distinguish benign from malignant lesions found on computed tomography of the chest given its very high false positive rate. This review highlights recent genetic, transcriptomic and epigenomic biomarkers that are emerging as tools for the early detection of lung cancer both in the diagnostic and screening setting.
PMCID: PMC3717087  PMID: 23870182
Biomarker; Diagnostics; Early detection; Epigenetics; Genetics; Lung cancer; Screening; Transcriptomics
6.  An evaluation of screening for lung cancer in Niigata Prefecture, Japan: a population-based case–control study 
British Journal of Cancer  2001;85(9):1326-1331.
Although an annual screening programme for lung cancer has been carried out widely in Japan since 1987, there is insufficient evidence to confirm its efficacy in terms of reducing mortality. In order to evaluate the efficacy of the lung cancer screening which has been widely carried out in Japan since 1987, a case–control study was conducted in Niigata Prefecture, Japan. In the study area, chest X-ray examinations for all participants and sputum cytology for high-risk participants were offered annually. Case subjects, who had died from lung cancer (174), and control subjects matched by sex, year of birth, residence and smoking status (801), who had been alive at the time of diagnosis of the corresponding case, were selected from the National Health Insurance holders. Screening histories of the subjects were compared between cases and matched controls for the identical calendar period before the time of diagnosis of the cases. The odds ratio of death from lung cancer for those screened within 12 months vs those not screened was 0.401 (95% CI: 0.272–0.591) with adjustment by smoking index. Our results suggest that annual lung cancer screening might reduce mortality from lung cancer by approximately 60%. © 2001 Cancer Research Campaign
PMCID: PMC2375248  PMID: 11720469
lung cancer; screening; case–control study; efficacy
7.  "Risk homeostasis"or "teachable moment"? the interaction between smoking behavior and lung cancer screening in the Mayo Lung Project 
The chest X-ray lung cancer screening program of Mayo Lung Project (MLP) yielded mixed results of improved lung case survival but no improvement in lung cancer mortality. This paper analyzes the smoking patterns of study participants in order to examine possible behavioral ramifications of periodic lung cancer screening. Using a longitudinal difference-of-difference model, we compared the smoking behavior, in terms of current smoker status among all subjects and the intensity of smoking among those continuing smokers, between those who received periodic lung cancer screening and those who received usual-care. In both arms of this lung cancer screening trial, there was a sizable decline in cigarette smoking one year after participants received baseline prevalence screening. There was no significant difference in current smoker status between the intervention group receiving periodic X-ray screening and the control group receiving usual care. While we detect that the continuing smokers in the intervention group smoked more than their counterparts in the control group, the magnitude of the difference is not sufficient to explain a substantial difference in lung cancer incidence between the two groups. Our study shows that periodic lung screening in MLP did not decrease smoking behavior beyond the observed decline following the initial prevalence screening conducted at baseline for both the intervention and control groups. Our results also indicate, paradoxically, that participants assigned to the intervention group smoked more cigarettes per day on average than those in the control group. Lung cancer screening programs need additional cessation components to sustain the abstinence effect typically observed following initial lung screening.
PMCID: PMC3033237  PMID: 21255463
8.  Computed Tomography Screening for Lung Cancer: Has It Finally Arrived? Implications of the National Lung Screening Trial 
Journal of Clinical Oncology  2013;31(8):1002-1008.
The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The NLST randomized 53,454 older current or former heavy smokers to receive LDCT or chest radiography (CXR) for three annual screens. Participants were observed for a median of 6.5 years for outcomes. Vital status was available in more than 95% of participants. LDCT was positive in 24.2% of screens, compared with 6.9% of CXRs; more than 95% of all positive LDCT screens were not associated with lung cancer. LDCT detected more than twice the number of early-stage lung cancers and resulted in a stage shift from advanced to early-stage disease. Complications of LDCT screening were minimal. Lung cancer–specific mortality was reduced by 20% relative to CXR; all-cause mortality was reduced by 6.7%. The major harms of LDCT are radiation exposure, high false-positive rates, and the potential for overdiagnosis. This review discusses the risks and benefits of LDCT screening as well as an approach to LDCT implementation that incorporates systematic screening practice with smoking cessation programs and offers opportunities for better determination of appropriate risk cohorts for screening and for better diagnostic prediction of lung cancer in the setting of screen-detected nodules. The challenges of implementation are considered for screening programs, for primary care clinicians, and across socioeconomic strata. Considerations for future research to complement imaging-based screening to reduce the burden of lung cancer are discussed.
PMCID: PMC3589698  PMID: 23401434
9.  Sensitivity and specificity of lung cancer screening using chest low-dose computed tomography 
British Journal of Cancer  2008;98(10):1602-1607.
Lung cancer screening programmes using chest X-ray and sputum cytology are routinely performed in Japan; however, the efficacy is insufficient. Screening using low-dose computed tomography (CT) is a more effective approach and has the potential to detect the disease more accurately. A total of 7183 low-dose CT screening tests for 4689 participants and 36 085 chest X-ray screening tests for 13 381 participants were conducted between August 1998 and May 2002. Sensitivity and specificity of lung cancer screening were calculated by both the detection method and the incidence method by linkage of the screening database and the Cancer Registry database. The preclinical detectable phase was assumed to be 1 year. Sensitivity and specificity by the detection method were 88.9 and 92.6% for low-dose CT and 78.3 and 97.0% for chest X-ray, respectively. Sensitivity of low-dose CT by the incidence method was 79.5%, whereas that of chest X-ray was 86.5%. Lung cancer screening using low-dose CT resulted in higher sensitivity and lower specificity than traditional screening according to the detection method. However, sensitivity by the incidence method was not as high as this. These findings demonstrate the potential for overdiagnosis in CT screening-detected cases.
PMCID: PMC2391122  PMID: 18475292
sensitivity; specificity; lung cancer; screening
10.  Screening for lung cancer: a systematic review and meta-analysis of controlled trials 
Thorax  2003;58(9):784-789.
Background: Lung cancer is a substantial public health problem in western countries. Previous studies have examined different screening strategies for lung cancer but there have been no published systematic reviews.
Methods: A systematic review of controlled trials was conducted to determine whether screening for lung cancer using regular sputum examinations or chest radiography or computed tomography (CT) reduces lung cancer mortality. The primary outcome was lung cancer mortality; secondary outcomes were lung cancer survival and all cause mortality.
Results: One non-randomised controlled trial and six randomised controlled trials with a total of 245 610 subjects were included in the review. In all studies the control group received some type of screening. More frequent screening with chest radiography was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, 95% CI 1.00 to 1.23). A non-statistically significant trend to reduced mortality from lung cancer was observed when screening with chest radiography and sputum cytological examination was compared with chest radiography alone (RR 0.88, 95% CI 0.74 to 1.03). Several of the included studies had potential methodological weaknesses. Controlled studies of spiral CT scanning have not been reported.
Conclusions: The current evidence does not support screening for lung cancer with chest radiography or sputum cytological examination. Frequent chest radiography might be harmful. Further methodologically rigorous trials are required before any new screening methods are introduced into clinical practice.
PMCID: PMC1746815  PMID: 12947138
11.  Identification of lung cancer with high sensitivity and specificity by blood testing 
Respiratory Research  2010;11(1):18.
Lung cancer is a very frequent and lethal tumor with an identifiable risk population. Cytological analysis and chest X-ray failed to reduce mortality, and CT screenings are still controversially discussed. Recent studies provided first evidence for the potential usefulness of autoantigens as markers for lung cancer.
We used extended panels of arrayed antigens and determined autoantibody signatures of sera from patients with different kinds of lung cancer, different common non-tumor lung pathologies, and controls without any lung disease by a newly developed computer aided image analysis procedure. The resulting signatures were classified using linear kernel Support Vector Machines and 10-fold cross-validation.
The novel approach allowed for discriminating lung cancer patients from controls without any lung disease with a specificity of 97.0%, a sensitivity of 97.9%, and an accuracy of 97.6%. The classification of stage IA/IB tumors and controls yielded a specificity of 97.6%, a sensitivity of 75.9%, and an accuracy of 92.9%. The discrimination of lung cancer patients from patients with non-tumor lung pathologies reached an accuracy of 88.5%.
We were able to separate lung cancer patients from subjects without any lung disease with high accuracy. Furthermore, lung cancer patients could be seprated from patients with other non-tumor lung diseases. These results provide clear evidence that blood-based tests open new avenues for the early diagnosis of lung cancer.
PMCID: PMC2832627  PMID: 20146812
12.  Lung cancer screening update 
Lung cancer is the leading cause of cancer-related mortality globally and the American cancer society estimates approximately 226,160 new cases and 160,340 deaths from lung cancer in the USA in the year 2012. The majority of lung cancers are diagnosed in the later stages which impacts the overall survival. The 5-year survival rate for pathological st age IA lung cancer is 73% but drops to only 13% for stage IV. Thus, early detection through screening and prevention are the keys to reduce the global burden of lung cancer. This article discusses the current state of lung cancer screening, including the results of the National Lung Cancer Screening Trial, the consideration of implementing computed tomography screening, and a brief overview of the role of bronchoscopy in early detection and potential biomarkers that may aid in the early diagnosis of lung cancer.
PMCID: PMC3622360  PMID: 23599684
Early detection; lung cancer; screening
13.  A Cost-Utility Analysis of Lung Cancer Screening and the Additional Benefits of Incorporating Smoking Cessation Interventions 
PLoS ONE  2013;8(8):e71379.
A 2011 report from the National Lung Screening Trial indicates that three annual low-dose computed tomography (LDCT) screenings for lung cancer reduced lung cancer mortality by 20% compared to chest X-ray among older individuals at high risk for lung cancer. Discussion has shifted from clinical proof to financial feasibility. The goal of this study was to determine whether LDCT screening for lung cancer in a commercially-insured population (aged 50–64) at high risk for lung cancer is cost-effective and to quantify the additional benefits of incorporating smoking cessation interventions in a lung cancer screening program.
Methods and Findings
The current study builds upon a previous simulation model to estimate the cost-utility of annual, repeated LDCT screenings over 15 years in a high risk hypothetical cohort of 18 million adults between age 50 and 64 with 30+ pack-years of smoking history. In the base case, the lung cancer screening intervention cost $27.8 billion over 15 years and yielded 985,284 quality-adjusted life years (QALYs) gained for a cost-utility ratio of $28,240 per QALY gained. Adding smoking cessation to these annual screenings resulted in increases in both the costs and QALYs saved, reflected in cost-utility ratios ranging from $16,198 per QALY gained to $23,185 per QALY gained. Annual LDCT lung cancer screening in this high risk population remained cost-effective across all sensitivity analyses.
The findings of this study indicate that repeat annual lung cancer screening in a high risk cohort of adults aged 50–64 is highly cost-effective. Offering smoking cessation interventions with the annual screening program improved the cost-effectiveness of lung cancer screening between 20% and 45%. The cost-utility ratios estimated in this study were in line with other accepted cancer screening interventions and support inclusion of annual LDCT screening for lung cancer in a high risk population in clinical recommendations.
PMCID: PMC3737088  PMID: 23940744
14.  Lung Cancer Risk Prediction: Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial Models and Validation 
Identification of individuals at high risk for lung cancer should be of value to individuals, patients, clinicians, and researchers. Existing prediction models have only modest capabilities to classify persons at risk accurately.
Prospective data from 70 962 control subjects in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) were used in models for the general population (model 1) and for a subcohort of ever-smokers (N = 38 254) (model 2). Both models included age, socioeconomic status (education), body mass index, family history of lung cancer, chronic obstructive pulmonary disease, recent chest x-ray, smoking status (never, former, or current), pack-years smoked, and smoking duration. Model 2 also included smoking quit-time (time in years since ever-smokers permanently quit smoking). External validation was performed with 44 223 PLCO intervention arm participants who completed a supplemental questionnaire and were subsequently followed. Known available risk factors were included in logistic regression models. Bootstrap optimism-corrected estimates of predictive performance were calculated (internal validation). Nonlinear relationships for age, pack-years smoked, smoking duration, and quit-time were modeled using restricted cubic splines. All reported P values are two-sided.
During follow-up (median 9.2 years) of the control arm subjects, 1040 lung cancers occurred. During follow-up of the external validation sample (median 3.0 years), 213 lung cancers occurred. For models 1 and 2, bootstrap optimism-corrected receiver operator characteristic area under the curves were 0.857 and 0.805, and calibration slopes (model-predicted probabilities vs observed probabilities) were 0.987 and 0.979, respectively. In the external validation sample, models 1 and 2 had area under the curves of 0.841 and 0.784, respectively. These models had high discrimination in women, men, whites, and nonwhites.
The PLCO lung cancer risk models demonstrate high discrimination and calibration.
PMCID: PMC3131220  PMID: 21606442
15.  Sputum examination for early detection of lung cancer 
Journal of Clinical Pathology  2003;56(11):805-810.
Conventional sputum cytology can be used for the detection of lung cancer, but has shown a low yield in prospective screening trials. This review focuses on the technical aspects relevant to the outcome of DNA and image analysis in sputum. Published articles are discussed in the light of the technical background. Recent developments in DNA analysis and nuclear image analysis show a clear potential to improve or refine diagnosis beyond that achieved with conventional sputum cytology examination. The challenge for future studies in DNA and nuclear analysis of sputum is to ensure high levels of quality control and to confirm these initial encouraging results.
PMCID: PMC1770101  PMID: 14600122
Sputum samples; lung cancer; early diagnosis; cytology; molecular markers
16.  Results of Initial Low-Dose Computed Tomographic Screening for Lung Cancer 
The New England journal of medicine  2013;368(21):1980-1991.
Lung cancer is the largest contributor to mortality from cancer. The National Lung Screening Trial (NLST) showed that screening with low-dose helical computed tomography (CT) rather than with chest radiography reduced mortality from lung cancer. We describe the screening, diagnosis, and limited treatment results from the initial round of screening in the NLST to inform and improve lung-cancer– screening programs.
At 33 U.S. centers, from August 2002 through April 2004, we enrolled asymptomatic participants, 55 to 74 years of age, with a history of at least 30 pack-years of smoking. The participants were randomly assigned to undergo annual screening, with the use of either low-dose CT or chest radiography, for 3 years. Nodules or other suspicious findings were classified as positive results. This article reports findings from the initial screening examination.
A total of 53,439 eligible participants were randomly assigned to a study group (26,715 to low-dose CT and 26,724 to chest radiography); 26,309 participants (98.5%) and 26,035 (97.4%), respectively, underwent screening. A total of 7191 participants (27.3%) in the low-dose CT group and 2387 (9.2%) in the radiography group had a positive screening result; in the respective groups, 6369 participants (90.4%) and 2176 (92.7%) had at least one follow-up diagnostic procedure, including imaging in 5717 (81.1%) and 2010 (85.6%) and surgery in 297 (4.2%) and 121 (5.2%). Lung cancer was diagnosed in 292 participants (1.1%) in the low-dose CT group versus 190 (0.7%) in the radiography group (stage 1 in 158 vs. 70 participants and stage IIB to IV in 120 vs. 112). Sensitivity and specificity were 93.8% and 73.4% for low-dose CT and 73.5% and 91.3% for chest radiography, respectively.
The NLST initial screening results are consistent with the existing literature on screening by means of low-dose CT and chest radiography, suggesting that a reduction in mortality from lung cancer is achievable at U.S. screening centers that have staff experienced in chest CT. (Funded by the National Cancer Institute; NLST number, NCT00047385.)
PMCID: PMC3762603  PMID: 23697514
17.  Screening for lung cancer. 
The survival from bronchogenic carcinoma is highly dependent upon stage at the time of treatment. This is particularly true for squamous cell carcinoma, adenocarcinoma, and large cell carcinoma, but holds true for small cell carcinoma as well. The problem presented to the medical profession has been to find a practical means of detecting lung cancer while it is still at an early stage. Three studies in progress have indicated that a larger proportion of the patients may be found to have early stage lung cancer when screened with a combination of chest X-rays and sputum cytology. However, the detection of these early stage cases has not yet been translated into an improvement in the overall mortality rate from lung cancer.
PMCID: PMC2596037  PMID: 6278787
18.  Bronchial sleeve resection for early-stage squamous cell carcinoma 
A 75-year-old man complained of sputum and was referred to our department. His sputum cytology was class III. Chest X-ray and computed tomography showed no abnormalities, but bronchoscopy revealed an elevated lesion in the membranous portion of the left main bronchus, which was pathologically diagnosed as squamous cell carcinoma in situ. Since bronchoscopy revealed no other lesions in the visible parts of the airway, it was considered to be a solitary, early lung cancer, and sleeve resection of the left main bronchus was performed. The postoperative pathological diagnosis was squamous cell carcinoma in situ, pTisN0M0, stage 0. In recent years, an increasing number of studies have reported photodynamic therapy and brachytherapy for the treatment of early lung cancer. However, aggressive bronchoplastic surgery with emphasis on curability should be considered for lesions that are deemed resectable based on their number and extent of invasion.
PMCID: PMC3466150  PMID: 22510543
Early-stage lung cancer; Bronchial sleeve resection; Surgery
19.  Smoking Cessation and Lung Cancer: Oncology Nurses Can Make a Difference 
Seminars in oncology nursing  2008;24(1):16-26.
Provide an overview of the impact of smoking after a diagnosis of lung cancer, discuss the relationship between smoking cessation and improved outcomes during the lung cancer trajectory, present information about tobacco dependence evidence-based treatments, reimbursement for these treatments, and tobacco-related resources available for patients and health care professionals, and emphasize the important role of nurses.
Published articles, reports, websites, and research studies.
Tobacco use is associated with 30% of cancer deaths. Prevention of tobacco use and cessation are primary ways to prevent lung cancer. However, even after a diagnosis of lung cancer, smoking cessation is important in improving survival and quality of life. Although effective tobacco dependence treatments are available to help smokers quit smoking, persistent efforts over repeated contacts may be necessary to achieve long-term cessation.
Oncology nursing action is essential in the identification of and intervention with patients who struggle with tobacco dependence after diagnosis.
PMCID: PMC2249620  PMID: 18222148
smoking cessation interventions; tobacco dependence treatment and lung cancer
20.  Attitudes towards screening for lung cancer among smokers and their non‐smoking counterparts 
Thorax  2006;62(2):126-130.
There has been resurgence of interest in lung cancer screening using low‐dose computed tomography. The implications of directing a screening programme at smokers has been little explored.
A nationwide telephone survey was conducted. Demographics, certain clinical characteristics and attitudes about screening for lung cancer were ascertained. Responses of current, former and never smokers were compared.
2001 people from the US were interviewed. Smokers were significantly (p<0.05) more likely than never smokers to be male, non‐white, less educated, and to report poor health status or having had cancer, and less likely to be able to identify a usual source of healthcare. Compared with never smokers, current smokers were less likely to believe that early detection would result in a good chance of survival (p<0.05). Smokers were less likely to be willing to consider computed tomography screening for lung cancer (71.2% (current smokers) v 87.6% (never smokers) odds ratio (OR) 0.48; 95% confidence interval (CI) 0.32 to 0.71). More never smokers as opposed to current smokers believed that the risk of disease (88% v 56%) and the accuracy of the test (92% v 71%) were important determinants in deciding whether to be screened (p<0.05). Only half of the current smokers would opt for surgery for a screen‐diagnosed cancer.
The findings suggest that there may be substantial obstacles to the successful implementation of a mass‐screening programme for lung cancer that will target cigarette smokers.
PMCID: PMC2111262  PMID: 17101739
21.  Examining Whether Lung Screening Changes Risk Perceptions: NLST Participants at 1-year Follow-up 
Cancer  2012;119(7):1306-1313.
The National Lung Screening Trial (NLST) Research Team reported reduced lung cancer mortality among current and former smokers with a minimum 30-pack/year history, screened with spiral CT scans compared with chest x-ray. The objectives of this study are to examine, at one-year follow-up: 1) risk perceptions of lung cancer and smoking related diseases and behavior change determinants, 2) whether changes in risk perceptions differ by baseline screening result; and 3) whether changes in risk perceptions affect smoking behavior.
A 25-item risk perceptions sub-study questionnaire was administered to a subset of participants at 8 American College of Radiology Imaging Network (ACRIN)/NLST sites, prior to initial and one-year follow-up screens. Items assessed risk perceptions of lung cancer and smoking related diseases, cognitive and emotional determinants of behavior change, and knowledge of smoking risks.
Among 430 NLST participants (M age=61.0, 55.6% male, 91.9% white), half were current smokers at baseline. Overall, risk perceptions, and associated cognitive and emotional determinants of behavior change, did not change significantly from prescreen trial enrollment to 1 year follow-up and did not significantly differ by screening test result. Changes in risk perceptions were not associated with smoking status changes (9.7% quitting, 6.6% relapse) at one-year follow-up.
Lung screening did not change participants’ risk perceptions for lung cancer or smoking related disease. A negative screening test, the most common result of screening, did not appear to decrease risk perceptions nor provide false reassurance to smokers.
PMCID: PMC3604047  PMID: 23280348
Cancer; Lung Screening; Risk Perception; Smoking
22.  Baseline Characteristics of Participants in the Randomized National Lung Screening Trial 
The National Lung Screening Trial (NLST), a randomized study conducted at 33 US sites, is comparing lung cancer mortality among persons screened with reduced dose helical computerized tomography and among persons screened with chest radiograph. In this article, we present characteristics of the study population.
Eligible participants were aged 55–74 years and were current or former smokers with a cigarette smoking history of at least 30 pack-years. Randomization was stratified by site, sex, and age. To assess representativeness of the study population, demographic characteristics of individuals from the general population who met NLST age and smoking history inclusion criteria were obtained from the Tobacco Use Supplement of the US Census Bureau Current Population Surveys.
The NLST enrolled 53 456 persons, with 26 733 randomly assigned to chest radiograph screening and 26 723 to computerized tomography screening. Characteristics of the participants were as follows: 31 533 (59%) were men, 39 234 (73%) were younger than 65 years, 25 779 (48%) were current smokers, and 16 839 (32%) had a college or higher degree. Median cigarette exposure was 48 pack-years. Among Tobacco Use Supplement respondents who met NLST age and smoking history criteria, 59% were men, 65% were younger than 65 years, and 57% were current smokers. Median cigarette exposure among this group was 47 pack-years, and 14% had a college degree or higher.
The NLST cohort has a distribution of sex and pack-year history that is similar to the component of the general US population that meets the major NLST eligibility criteria; however, NLST participants are younger, better educated, and less likely to be current smokers.
PMCID: PMC2994863  PMID: 21119104
23.  Screening for occult lung cancer. 
A pilot screening program for the early detection of lung cancer was carried out in Saskatchewan in 1968 using chest roentgenography and cytologic examination of sputum samples. The yield from 23 000 men aged 40 years and over was only 10 cases. Nine of the men had advanced disease. One had occult lung cancer. A period of 31 months elapsed between the discovery of malignant cells in this patient's sputum and roentgenographic localization of the tumour. Following pneumonectomy he has survived with no discernible residual or metastatic tumour for 12 years. The morphologic changes in the resected lung provided a basis for discussing the preclinical phase of squamous cancer of the lung, the treatment of occult cancer and multicentric primary pulmonary tumours. The survey would have been more successful with a narrower target group and more frequent examination.
PMCID: PMC1875418  PMID: 6299495
24.  NLST ACRIN Biomarker Repository Originating from the Contemporary Screening for the Detection of Lung Cancer Trial (NLST, ACRIN 6654):Design, Intent, and Availability of Specimens for Validation of Lung Cancer Biomarkers 
Lung cancer continues to be a major public health problem, and more patients die from this disease than any other cancer. The vast majority of patients present with advanced stage disease when therapeutic options are limited and the overall 5 year survival rate remains approximately 15%. Screening with low dose helical computed tomography (CT)has been suggested for early detection, although the effect on mortality is currently under investigation. As part of the National Lung Cancer Screening Trial, a specimen biorepository including blood, sputum, and urine were collected serially for the primary purpose of validating early detection lung cancer biomarkers. In addition tumor samples have been obtained from patients diagnosed with lung cancer to be included in a tissue microarray. This commentary describes the rationale, composition, intent, and availability of specimen in the biorepository.
PMCID: PMC2963472  PMID: 20871260
25.  The Pittsburgh Lung Screening Study (PLuSS) 
Rationale: The role of computed tomography (CT) screening for lung cancer is controversial, currently under study, and not yet fully elucidated.
Objectives: To report findings from initial and 1-year repeat screening low-radiation-dose CT of the chest and 3-year outcomes for 50- to 79-year-old current and ex-smokers in the Pittsburgh Lung Screening Study (PLuSS).
Methods: Notified of findings on screening CT, subjects received diagnostic advice from both study and personal physicians. Tracking subjects for up to three years since initial screening, we obtained medical records to document diagnostic procedures, lung cancer diagnoses, and deaths.
Measurements and Main Results: 3,642 and 3,423 subjects had initial and repeat screening. A total of 1,477 (40.6% of 3,624) were told about noncalcified lung nodules on the initial screening and, before repeat screening, 821 (55.6% of 1,477, 22.5% of 3,642) obtained one or more subsequent diagnostic imaging studies (CT, positron emission tomography [PET], or PET-CT). Tracking identified 80 subjects with lung cancer, including 53 subjects with tumor seen at initial screening. In all, 36 subjects (1.0% of the 3,642 screened), referred for abnormalities on either the initial or repeat screening, had a major thoracic surgical procedure (thoracotomy, video-assisted thoracoscopic surgery [VATS], median sternotomy, or mediastinoscopy) leading to a noncancer final diagnosis. Out of 82 subjects with thoracotomy or VATS to exclude malignancy in a lung nodule, 28 (34.1%) received a noncancer final diagnosis. Forty of 69 (58%) subjects with non–small cell lung cancer had stage I disease at diagnosis.
Conclusions: Though leading to the discovery of early stage lung cancer, CT screening also led to many diagnostic follow-up procedures, including major thoracic surgical procedures with noncancer outcomes.
PMCID: PMC2720144  PMID: 18635890

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