Reduction In Lung Cancer-specific Mortality Research Articles

Cell-free DNA assay for malignancy classification of high-risk lung nodules

ObjectiveAlthough low-dose computed tomography has been proven effective to reduce lung cancer–specific mortality, a considerable proportion of surgically resected high-risk lung nodules were still confirmed pathologically benign. There is an unmet need of a novel method for malignancy classification in lung nodules. MethodsWe recruited 307 patients with high-risk lung nodules who underwent curative surgery, and 247 and 60 cases were pathologically confirmed malignant and benign lung lesions, respectively. Plasma samples from each patient were collected before surgery and performed low-depth (5×) whole-genome sequencing. We extracted cell-free DNA characteristics and determined radiomic features. We built models to classify the malignancy using our data and further validated models with 2 independent lung nodule cohorts. ResultsOur models using one type of profile were able to distinguish lung cancer and benign lung nodules at an area under the curve metrics of 0.69 to 0.91 in the study cohort. Integrating all the 5 base models using cell-free DNA profiles, the cell-free DNA–based ensemble model achieved an area under the curve of 0.95 (95% CI, 0.92-0.97) in the study cohort and 0.98 (95% CI, 0.96-1.00) in the validation cohort. At a specificity of 95.0%, the sensitivity reached 80.0% in the study cohort. With the same threshold, the specificity and sensitivity had similar performances in both validation cohorts. Furthermore, the performance of area under the curve reached 0.97 in both the study and validation cohorts when considering the radiomic profile. ConclusionsThe cell-free DNA profiles-based method is an efficient noninvasive tool to distinguish malignancies and high-risk but pathologically benign lung nodules.

Multilevel approaches to address disparities in lung cancer screening: a study protocol

BackgroundLow-dose computed tomography (lung cancer screening) can reduce lung cancer-specific mortality by 20–24%. Based on this evidence, the United States Preventive Services Task Force recommends annual lung cancer screening for asymptomatic high-risk individuals. Despite this recommendation, utilization is low (3–20%). Lung cancer screening may be particularly beneficial for African American patients because they are more likely to have advanced disease, lower survival, and lower screening rates compared to White individuals. Evidence points to multilevel approaches that simultaneously address multiple determinants to increase screening rates and decrease lung cancer burden in minoritized populations. This study will test the effects of provider- and patient-level strategies for promoting equitable lung cancer screening utilization.MethodsGuided by the Health Disparities Research Framework and the Practical, Robust Implementation and Sustainability Model, we will conduct a quasi-experimental study with four primary care clinics within a large health system (MedStar Health). Individuals eligible for lung cancer screening, defined as 50–80 years old, ≥ 20 pack-years, currently smoking, or quit < 15 years, no history of lung cancer, who have an appointment scheduled with their provider, and who are non-adherent to screening will be identified via the EHR, contacted, and enrolled (N = 184 for implementation clinics, N = 184 for comparison clinics; total N = 368). Provider participants will include those practicing at the partner clinics (N = 26). To increase provider-prompted discussions about lung screening, an electronic health record (EHR) clinician reminder will be sent to providers prior to scheduled visits with the screening-eligible participants. To increase patient-level knowledge and patient activation about screening, an inreach specialist will conduct a pre-visit phone-based educational session with participants. Patient participants will be assessed at baseline and 1-week post-visit to measure provider-patient discussion, screening intentions, and knowledge. Screening referrals and screening completion rates will be assessed via the EHR at 6 months. We will use mixed methods and multilevel assessments of patients and providers to evaluate the implementation outcomes (adoption, feasibility, acceptability, and fidelity).DiscussionThe study will inform future work designed to measure the independent and overlapping contributions of the multilevel implementation strategies to advance equity in lung screening rates.Trial registrationClinicalTrials.gov, NCT04675476. Registered December 19, 2020.

The radiologist's role in lung cancer screening.

Lung cancer is still the deadliest cancer in men and women worldwide. This high mortality is related to diagnosis in advanced stages, when curative treatment is no longer an option. Large randomized controlled trials have shown that lung cancer screening (LCS) with low-dose computed tomography (CT) can detect lung cancers at earlier stages and reduce lung cancer-specific mortality. The recent publication of the significant reduction of cancer-related mortality by 26% in the Dutch-Belgian NELSON LCS trial has increased the likelihood that implementation of LCS in Europe will move forward. Radiologists are important stakeholders in numerous aspects of the LCS pathway. Their role goes beyond nodule detection and nodule management. Being part of a multidisciplinary team, radiologists are key players in numerous aspects of implementation of a high quality LCS program. In this non-systematic review we discuss the multifaceted role of radiologists in LCS.

Abstract IA16: Lung Cancer Risk Assessment in Diverse Populations: One Size Cannot Fit All

Abstract Lung cancer is the leading cause of cancer related deaths in the United States with an estimate of over 200,000 new cases and 135,720 deaths in 2020. Despite the development of precision therapies, immunotherapy and improved surgical techniques, the overall 5-year survival has remained below that of many other malignancies and significant disparities continue to persist. Black American males tend to present with later-stage disease, are less likely to undergo appropriate staging and thus, have a higher lung cancer mortality. The National Lung Screening Trial I (NLST) determined that low-dose CT (LDCT) screening could reduce lung cancer specific mortality by nearly 20% and overall mortality by 6.7%. However, studies suggest that clinically useful models for improved lung cancer risk stratification will be essential to the identification of those most likely to benefit from screening while minimizing unnecessary screening and associated risks. In NLST, only 4% of enrolled participants were Black Americans. Recent investigation demonstrates that current screening eligibility criteria are insufficient in identifying Black Americans at risk for lung cancer a large percentage of whom are diagnosed at a younger age than White Americans and with less tobacco consumption. As a result, current draft recommendations include reducing both age and smoking screening eligibility to 50 years of age and 20 pack years respectively with a goal of narrowing gaps in disparities in early lung cancer diagnosis and outcome. Here, we will review current models for lung cancer risk stratification that incorporate sociodemographic factors, comorbid illnesses and non-invasive biomarkers and discuss their clinical application to diverse populations. Citation Format: Patrick Nana-Sinkam. Lung Cancer Risk Assessment in Diverse Populations: One Size Cannot Fit All [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA16.

Cancer-Specific Mortality, All-Cause Mortality, and Overdiagnosis in Lung Cancer Screening Trials: A Meta-Analysis.

Benefit of lung cancer screening using low-dose computed tomography (LDCT) in reducing lung cancer-specific and all-cause mortality is unclear. We undertook a meta-analysis to assess its associations with outcomes. We searched the literature and previous systematic reviews to identify randomized controlled trials comparing LDCT screening with usual care or chest radiography. We performed meta-analysis using a random effects model. The primary outcomes were lung cancer-specific mortality, all-cause mortality, and the cumulative incidence ratio of lung cancer between screened and unscreened groups as a measure of overdiagnosis. Meta-analysis was based on 8 trials with 90,475 patients that had a low risk of bias. There was a significant reduction in lung cancer-specific mortality with LDCT screening (relative risk = 0.81; 95% CI, 0.74-0.89); the estimated absolute risk reduction was 0.4% (number needed to screen = 250). The reduction in all-cause mortality was not statistically significant (relative risk = 0.96; 95% CI, 0.92-1.01), but the absolute reduction was consistent with that for lung cancer-specific mortality (0.34%; number needed to screen = 294). In the studies with the longest duration of follow-up, the incidence of lung cancer was 25% higher in the screened group, corresponding to a 20% rate of overdiagnosis. This meta-analysis showing a significant reduction in lung cancer-specific mortality, albeit with a tradeoff of likely overdiagnosis, supports recommendations to screen individuals at elevated risk for lung cancer with LDCT.

Improving identification of candidates for lung cancer screening in a high risk population

BackgroundLow dose computerized tomography (LDCT) has been shown to reduce lung cancer specific mortality by 20 %. Despite U.S. Preventive Services Task Force (USPSTF) endorsement, screening of appropriate patients in the U.S. remains low, at 1.9 %. The goal of this study was to assess the number and type of patients that would qualify for lung cancer screening based upon recommendations by various guidelines. MethodsWe prospectively collected a patient reported questionnaire, including smoking history, family history, exposure history, and demographics, from April-October 2017 from new consults in the Department of Radiation Oncology and Otolaryngology (ORL). Patients smoking status and patient factors were collected and reported. Patients qualifying for screening by USPSTF, the National Comprehensive Cancer Network (NCCN), and Tammemagi scoring criteria were identified. Multivariate analysis assessed the factors associated with positive criteria for screening and the sensitivity of each criterion was calculated. ResultsThere were 546 new consults during the study period and 528 successfully completed the questionnaire. A total of 104/528 (20 %) patients who completed questionnaires qualified for screening based on any guideline. After exclusion of active lung cancer (n = 19), poor prognosis (n = 24), and CT as part of surveillance (n = 16), 45 (8.5 %) patients would require LDCT. Of the entire population, 10 %, 11 % and 18 % of patients qualified based on USPSTF, NCCN, and Tammemagi, which was reduced to 4.9 %, 5.3 %, and 7.8 %, respectively after exclusions. Patients with head and neck cancer (40 %), skin cancer (27 %), and prostate cancer (11 %) accounted for the majority of patients eligible for screening after exclusions. The sensitivity of the USPSTF, NCCN, and Tammemagi criteria in patients with a diagnosis of lung cancer (n = 26) was 38.5 % (CI95 20.2 %–59.4 %), 46.2 % (CI95 26.6 %–66.6 %), and 61.5 % (CI95 40.6 %–79.8 %), respectively. ConclusionsWe successfully identified 9 % of an oncology population at consultation who could benefit from lung cancer screening in survivorship. Distribution of a written or electronic questionnaire at consultation is a simple, low cost, effective method of identifying patients who would benefit from LDCT.

Abstract IA15: Role of environment in genetic predisposition: Lessons from tobacco studies

Abstract While it is well recognized that tobacco smoke is the leading cause of preventable cancer mortality and morbidity, efforts to control its impact on population health have been only partially successful. In this talk we describe population characteristics relating to nicotine dependence. Among those who initiate tobacco smoking, about 80% become dependent, but even among this set there is a variable degree of dependence, affecting the propensity to quit. Twin and family studies have shown a very strong impact of genetic factors on smoking behavior, which is a relatively easier behavior to measure. Therefore, massive studies involving about 500,000 individuals have now been completed and these give comprehensive descriptions of the genetic profiles that influence tobacco smoking initiation, smoking behavior, and cessation. Genetic analysis of lung cancer risk and nicotine dependence identified a region of chromosome 15q25.1 that is strongly implicated in influence risk for both diseases. Further research using retrospective data from population studies and tobacco cessation trials showed a profound influence of genotypes on propensity to quit smoking and an interaction between efficacy of pharmacologic intervention and successful tobacco cessation. These findings, along with observations about similar striking effects of CYP2A6 variation on smoking behavior, have led to the design and conduct of novel studies that integrate genetic information into the allocation of participants into tobacco cessation trials, which we will discuss. As it is the primary driver of lung cancer risk, tobacco smoking is a key driver in identifying individuals who will benefit from low-dose spiral CT, which is among the only screening protocols that has a proven impact in reducing overall mortality and which also results in a striking stage shift for lung cancer and a substantial reduction in lung cancer-specific mortality. Despite the individual benefits of screening, the cost of lung cancer screening remains high and current guidelines, which restrict access to the highest risk participants, exclude from consideration most cases of lung cancer. Towards building improved risk prediction models for lung cancer, we discuss results from lung cancer genetic studies that have identified multiple genetic factors predisposing to lung cancer risk and that can identify biomarkers and host-specific factors that associate with lung cancer risk and identify more susceptible individuals. We similarly describe findings from large head and neck cancer studies that have identified sets of susceptibility loci according to the histology or location of the cancers. Finally, we discuss future goals in integrating genetic and biomarker information for further streamlining risk assessment for lung cancer and identifying gaps and needs for risk assessment in smoking-related diseases. Citation Format: Christopher I. Amos, Laura Bierut, Margaret R. Spitz, James McKay. Role of environment in genetic predisposition: Lessons from tobacco studies [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr IA15.

P3.11-26 Results of Initial Low-Dose Computed Tomographic Screening for Lung Cancer from a Single-Institution in China

Lung cancer screening using low-dose computed tomography (LDCT) has been reported to reduce lung cancer-specific mortality for smokers at high risk in patients of the United States. However, there are very few LDCT screening results from Chinese patients. We here report the screening findings at the initial round of LDCT screening program from a single-institution population-based cohort in China. We conducted a retrospective study of a single-institution population-based LDCT screening program for lung cancer. Patients participated LDCT in Taizhou Hospital of Enze Medical Center were eligible. All noncalcified nodules with long-axis diameters of 4mm or greater in the axial plane were considered to be positive for potential lung cancer according to NLST definition. If more than three nodules were found, one dominant nodules were selected for this analysis. From July 2017 through December 2017, a total of 8611 participants with LDCT screening were included in this report. A total of 78 participants with history of cancer and 437 participants were follow-up procedures were excluded in this analysis. Of the remaining 8096 participants, the median age was 51 years (range, 16-97 years). A total of 1516 (18.8%) participants were younger than 40 years, 5264 (65.2%) were 40-64 years and 1316 (16.3%) were greater than 64 years. The total proportion of positive nodules was 21.8%, slightly higher in females (535/2258, 23.7%) than males (1233/5838, 21.1%). Lung cancer was diagnosed in 26 participants (0.32%) (11 males and 14 females) of the 1768 positive nodules. The comprehensive demographics of 26 lung cancer patients (included one patients with multiple metastases tumor from pancreas) is shown table 1. The overall rate of positive nodules is similar to previous reports, and the overall cancer detection rate by LDCT in our cohort was lower than previous reports from others (0.36-3.3%).

Optimizing the lung cancer screening interval: the world is waiting.

Although lung cancer is the leading cause of cancer death throughout the world, until recently, there has not been an accepted screening test for this deadly disease. Fortunately, the National Lung Screening Trial (NLST) has now shown that screening with low dose computed tomography (CT) can reduce lung cancer-specific mortality by 20% compared to chest radiography (1). This test thus has the potential to substantially reduce lung cancer deaths throughout the world.

The Association between Smoking Abstinence and Mortality in the National Lung Screening Trial.

Smoking is the largest contributor to lung cancer risk, and those who continue to smoke after diagnosis have a worse survival. Screening for lung cancer with low-dose computed tomography (LDCT) reduces mortality in high-risk individuals. Smoking cessation is an essential component of a high-quality screening program. To quantify the effects of smoking history and abstinence on mortality in high-risk individuals who participated in the NLST (National Lung Screening Trial). This is a secondary analysis of a randomized controlled trial (NLST). Measurements included self-reported demographics, medical and smoking history, and lung cancer-specific and all-cause mortality. Cox regression was used to study the association of mortality with smoking status and pack-years. Kaplan-Meier survival curves were examined for differences in survival based on trial arm and smoking status. Current smokers had an increased lung cancer-specific (hazard ratio [HR], 2.14-2.29) and all-cause mortality (HR, 1.79-1.85) compared with former smokers irrespective of screening arm. Former smokers in the control arm abstinent for 7 years had a 20% mortality reduction comparable with the benefit reported with LDCT screening in the NLST. The maximum benefit was seen with the combination of smoking abstinence at 15 years and LDCT screening, which resulted in a 38% reduction in lung cancer-specific mortality (HR, 0.62; 95% confidence interval, 0.51-0.76). Seven years of smoking abstinence reduced lung cancer-specific mortality at a magnitude comparable with LDCT screening. This reduction was greater when abstinence was combined with screening, highlighting the importance of smoking cessation efforts in screening programs.

Metformin use and survival from lung cancer: A population-based cohort study

Preclinical evidence suggests that metformin, a widely prescribed anti-diabetic drug, may inhibit lung cancer progression. We investigated whether metformin use was associated with decreased risk of cancer-specific mortality in lung cancer patients. This study included newly diagnosed lung cancer patients (identified from English National Cancer Data Repository, 1998–2009) with type 2 diabetes (based on UK Clinical Practice Research Datalink prescriptions and diagnosis records). Lung cancer deaths occurring up to 2012 were identified using Office of National Statistics mortality data and the association between metformin use (before and after diagnosis) and risk of lung cancer-specific mortality was calculated using Cox regression models. In analysis of 533 patients, we found a weak non-significant reduction in lung cancer-specific mortality with metformin use after diagnosis (adjusted HR, 0.86; 95% CI, 0.68–1.09). No association was evident for metformin use before diagnosis and cancer-specific mortality in analysis of 1350 patients (adjusted HR, 0.97; 95% CI, 0.86, 1.11). Associations were similar by duration of use. In addition, after adjustment for potential confounders, there was little evidence of an association between the use of other anti-diabetic medications (either before or after diagnosis) and lung cancer-specific mortality; including sulfonylureas, insulin or other anti-diabetic medications (such as thiazolidinediones). Overall, the results from this population-based study provide little evidence of a protective association between metformin use and cancer mortality in lung cancer patients.

Lung cancer screening with low-dose computed tomography: Experiences from a tertiary hospital in Taiwan.

Lung cancer screening using low-dose computed tomography (CT) has been reported to reduce lung cancer-specific mortality for smokers at high risk. However, despite different characteristics of lung cancer in Asia, there are few data concerning this specific population for screening. We aim to analyze the performance of lung cancer screening with low-dose CT concurrent with chest radiography in Taiwan, with reference to international experience. During the 1-year period from January 2012 to December 2012, we conducted a retrospective, single-center population-based screening program for lung cancer in the setting of annual medical examinations. Participants were asymptomatic adults without prior history of any cancer. Low-dose CT and chest radiography were offered to all individuals. Baseline CT evaluations were defined as positive if any noncalcified nodule≥4mm in diameter, which were then classified as solid, pure ground-glass or partial ground-glass opacity. Of 3339 individuals, we detected 34 cancers, yielding an overall cancer detection rate of 1.02%. There was a particularly high cancer detection rate of 6.2% (8/129) in the high-risk group aged younger than 50years with a positive family history of all types of cancers in first-degree relatives. Adenocarcinomas accounted for 88% (30/34) of cancers and 99% of them were early-stage (including carcinoma in situ and Stage I). The probability of cancers was significant higher in nodules with interval growth (odds ratio 257.89, p=0.0002). There was no significant difference in the probability of cancers between ground glass opacity nodules and solid nodules (odds ratio 1.16, p=0.72). Of all screen-detected cancers, 61.76% (21/34) were chest radiographically occult. Low-dose CT is effective to detect early lung cancers. Further establishment of selection criteria for lung cancer screening, specifically for Asian individuals, is definitely warranted.

Is chest X-ray screening for lung cancer in smokers cost-effective? Evidence from a population-based study in Italy.

BackgroundAfter implementation of the PREDICA annual chest X-ray (CXR) screening program in smokers in the general practice setting of Varese-Italy a significant reduction in lung cancer-specific mortality (18 %) was observed. The objective of this study covering July 1997 through December 2006 was to estimate the cost-effectiveness of this intervention.MethodsWe examined detailed information on lung cancer (LC) cases that occurred among smokers invited to be screened in the PREDICA study (Invitation-to-screening Group, n = 5815 subjects) to estimate costs and quality-adjusted life-years (QALYs) from LC diagnosis until death. The control group consisted of 156 screening-eligible smokers from the same area, uninvited and unscreened, who developed LC and were treated by usual care. We calculated the incremental net monetary benefit (INMB) by comparing LC management in screening participants (n = 1244 subjects) and in the Invitation-to-screening group versus control group.ResultsThe average number of QALYs since LC diagnosis was 1.7, 1.49 and 1.07, respectively, in screening participants, the invitation-to-screening group, and the control group. The average total cost (screening + management) per LC case was higher in screening participants (€17,516) and the Invitation-to-screening Group (€16,167) than in the control group (€15,503). Assuming a maximum willingness to pay of €30,000/QALY, we found that the intervention was cost-effective with high probability: 79 % for screening participation (screening participants vs. control group) and 95 % for invitation-to-screening (invitation-to-screening group vs. control group).ConclusionsBased on the PREDICA study, annual CXR screening of high-risk smokers in a general practice setting has high probability of being cost-effective with a maximum willingness to pay of €30,000/QALY.

Integration of lung cancer screening into practice is lacking.

Integration of lung cancer screening into practice is lacking.

Exosomal protein FAM3C as a potential novel biomarker for non-small cell lung cancer.

e22162 Background: Low-dose computed tomography screening has been shown to reduce lung cancer-specific mortality, but has a high false-positive detection rate. The discovery of biomarkers for lung...

Lung Cancer Screening

The National Lung Screening Trial demonstrated that lung cancer screening with three annual low-dose computed tomographic scans has the potential to reduce lung cancer-specific mortality by 20% in an older population of heavy smokers. This was a great achievement by the National Lung Screening Trial (NLST) investigators, but this should be viewed as an important first step in an unfinished process. Many major questions remain about how to best realize this mortality reduction in a practical real-world context. Screening for lung cancer will be most effective if it is accompanied by continued research into risk modeling, patient communication strategies, and biomarkers. For clinicians establishing a program of lung cancer screening, we encourage this to be done in a responsible fashion, adhering to practices specified in the design of the NLST, and with careful attention given to proper management of screen-detected abnormalities and maintenance of screening registries.

Radiation Risk of Lung Cancer Screening

Lung cancer screening with low dose computed tomography (CT) is the only method ever proven to reduce lung cancer-specific mortality in high-risk current and former cigarette smokers. Radiation exposure from annual screening CT examinations and subsequent CT and nuclear medicine testing to further evaluate positive screening CTs is sometimes raised as a reason to avoid screening and is often misunderstood. With all testing, there are potential benefits and risks. As we sit on the brink of widespread adoption of lung cancer screening CT, we aim to explain why the risks associated with radiation exposure from lung cancer screening are very low and should not be used to avoid screening or dissuade individuals who qualify for screening CT to participate in a lung cancer screening program.

Implementation of a Lung Cancer-Screening Program

The National Lung Screening Trial (NLST) demonstrated that lung cancer screening with three annual low-dose CT scans has the potential to reduce lung cancer-specific mortality by 20 % among a population of older heavy smokers. Many questions should be raised to convert this efficacy into effective clinical practice. Screening for lung cancer will be most effective if it is conducted solely for high-risk individuals that can benefit from cancer treatment. Ongoing screening should be accompanied by continued research into risk modeling, communication strategies, and biomarkers. For clinicians establishing lung cancer screening programs, this should be done responsibly, adhering to practices specified in the design of the NLST, and with careful attention given to proper management of screen-detected abnormalities and maintenance of screening registries.

Molecular biomarkers for future screening of lung cancer

The Landmark National Lung Screening Trial established the potential for low dose CT screening (LDCT) to reduce lung cancer-specific mortality in high-risk patients as defined by smoking history and age. However, the prevalence of lung cancer in asymptomatic smokers selected based on the NLST criteria is low. Recent advances have facilitated biomarker discovery for early diagnosis of lung cancer through the analysis of surrogate tissues, including airway epithelium, sputum, exhaled breath, and blood. Although a number of candidate diagnostic biomarkers have been described, none have been validated for use in the clinical setting. The NLST ACRIN biomarker repository is a valuable resource of annotated biological specimens that were collected during the NLST trial, which has the potential to facilitate validation of candidate biomarkers for early diagnosis identified in discovery trials. It will be important to perform retrospective and prospective analysis of biomarkers to screen for lung cancer. The review below summarizes some of our understanding of biomarkers in screening.

Computed Tomography Screening for Lung Cancer

Low-dose computed tomography (CT) screening was shown to reduce lung cancer-specific mortality in a large randomized trial of a high-risk population. The decision to pursue CT screening for lung cancer is a timely question raised by individuals at risk of lung cancer and by their health care practitioners. To discuss the evidence for use of chest x-rays and low-dose CT in screening for lung cancer; to describe potential benefits, harms, and uncertainties of CT screening; and to review current guidelines for CT screening. MEDLINE and the Cochrane Library were searched from 1984 to 2012. Additional citations were obtained from lists of references from select research and review articles on this topic. Evidence was graded using the American Hospital Association level of evidence guidelines. Low-dose CT screening has been associated with a 20% reduction in lung cancer mortality in a large randomized controlled trial (National Lung Screening Trial [NLST]) of a high-risk population. Mortality data have not yet been reported for 5 other randomized controlled trials, and the sample sizes were too small to detect a meaningful difference in 2 other completed trials. A major risk of CT screening is a high false-positive rate, with associated risks and costs associated with follow-up CT scans and the potential for more invasive diagnostic procedures. Published guidelines for screening indicate a consensus that screening may be indicated for individuals who meet entry criteria for the NLST, but some guidelines expand their recommendations for screening beyond these criteria. Individuals at high risk of lung cancer who meet the criteria for CT screening in published guidelines should participate in an informed and shared decision-making process by discussing the potential benefits, harms, and uncertainties of screening with their physicians.