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The initial management of patients with lung cancer is growing more complex in the context of an expanding number of precision medicine treatments. These challenges are accompanied by opportunities to deliver more efficacious and less toxic treatments to patients. Indications for these treatments are also expanding and patients with lung cancer across multiple stages now require biomarker testing. Given their role in the initial management of patients being diagnosed with lung cancer, pulmonologists must have fundamental knowledge regarding the importance, indications, and implications of biomarker testing across the spectrum of histology and stage. The purpose of this review is to provide fundamental knowledge regarding biomarker testing, its incorporation into the initial diagnostic and staging evaluation, and guidance for working within a multi-disciplinary team to achieve timely and comprehensive biomarker testing to direct the use of precision medicine treatments., (Copyright © 2024. Published by Elsevier Inc.)

Worldwide, lung cancer is the most common killer among cancers, advanced disease has worse outcomes, earlier stage detection leads to better outcomes, and high-quality screening has a favorable net benefit. With the mortality reduction recognized from annual low-radiation dose computed tomography by screening those at high risk, there has been consideration that this benefit could translate to those who have never smoked. There have been several large-scale, single-arm, observational trials in Asia in persons with light to no smoking histories, with or without a family history of lung cancer, which have revealed high or higher lung cancer detection rates than previously reported in high-risk persons who currently or formerly smoked. The Early Detection Program for Lung Cancer in Taiwan, of nearly 50,000 persons, revealed that the cancer detection rate for those screened with low-radiation dose computed tomography was more than twofold higher in light- or never-smokers with a family history of lung cancer compared with high-risk persons with more than 30 or more pack-years exposure and meeting U.S. Preventative Services Task Force criteria for screening. In addition, more than 90% of the cancers detected in those with a family history were in early stage. On the basis of those findings, the researchers concluded that screening first-degree relatives of those with a family history of lung cancer, irrespective of smoking history, would lead to a decrease in lung cancer mortality. We believe that the findings in this cohort and others like it represent substantial overdiagnosis and that the harms associated with screening a population that has a low likelihood of developing lethal cancers have not been thoroughly considered. Here, we provide our perspective and consider the potential benefits and harms of screening populations outside those currently eligible using the U.S. Preventative Services Task Force criteria., Competing Interests: Disclosure Dr. Silvestri reports research relationships with Delfi, Nucleix and Freenome and research and consulting relationship with Biodesix. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Financial/Nonfinancial Disclosures None declared.

Background: Despite advances in precision medicine for non-small cell lung cancer (NSCLC), biomarker testing for these therapies remain frequently underused, delayed, and inequitable. Pulmonologists often play a critical role in the initial diagnostic steps for patients with lung cancer, and previous data show variability in their knowledge and practices regarding biomarker testing. The purpose of this study is to better understand how pulmonologists view their role in lung cancer care., Research Question: With the increasing importance of biomarker testing and precision medicine, how do pulmonologists view their role in lung cancer care?, Study Design: An electronic survey consisting of 31 items focused on attitudes and practices regarding diagnostic steps for NSCLC was randomly distributed to a sample of practicing pulmonologists in the American College of Chest Physicians (CHEST) analytics database. Inferential statistics were performed using χ 2 tests and multivariable logistic regression models., Results: A total of 401 pulmonologists responded to the survey. Most (92%) were general pulmonologists, and more than half (62%) indicate they order biomarker testing. Longer practice tenure, higher case volumes, and participation in a multidisciplinary tumor board were associated with ordering biomarkers (P < .05). Pulmonology was identified to have the leading responsibility for the initial diagnostic biopsy by most respondents (83%) and less often for staging (45%), leading discussions about biomarker testing with patients (28%), and for ordering biomarkers (22%). The most common reasons for not ordering biomarkers included the following: oncology was responsible (84%), it was not within their scope of practice (46%), or lack of the necessary knowledge (51%)., Interpretation: Pulmonologists vary in their practices for ordering biomarkers, and many defer this responsibility to oncology. Despite the role of bronchoscopy and pulmonology societal guidelines for staging, many defer leadership of this process. Many pulmonologists lack the necessary resources and multidisciplinary infrastructure likely required to efficiently accomplish biomarker testing., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. H. F. received honoraria from the American College of Chest Physicians related to this project, ownership of Merck stock, consulting with AstraZeneca. M. A. R. reports receiving a fee from the American College of Chest Physicians to cover the labor costs associated with design, programming, data analysis, and reporting. G. A. S. reports receiving honoraria from the American College of Chest Physicians related to this project; consulting with AstraZeneca, research and consulting from Olympus, consultant and research support Biodesix, research support Exact Sciences, consultant and research support Nucleix, consultant and research support Seer, research support Amgen. None declared (P. J. N.)., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Financial/Nonfinancial Disclosures None declared.

Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J. S. K. discloses consulting/advisory (Ambu, Biodesix, Inc., Boston Scientific, Cook, Intuitive, Level Ex, Medtronic, Pinnacle Biologics, Pulmonx), research funding (Lung Therapeutics, PrognomiQ), honoraria (Pinnacle Biologics), speaker’s bureau (Biodesix, Inc., Veracyte), stock ownership (Doximity), and travel/accommodations/expenses (Auris); M. A. P. discloses honoraria (Medtronic, Philips, Astra Zeneca), consulting (Medtronic, Philips, Intuitive, Johnson & Johnson, Pfizer, Noah Medical, Galvanize Therapeutics, PreView Medical), research funding (Intuitive, Medtronic, Philips, Biodesix, Inc.), speaker’s bureau (Johnson & Johnson, United Therapeutics, Biodesix, Inc.), and travel/accommodations/expenses (Intuitive, Johnson & Johnson, Astra Zeneca, Pfizer, Noah Medical); T. P. discloses employment (Biodesix, Inc.); G. A. S. discloses research funding (Biodesix, Inc.) and consulting (Biodesix, Inc.). None declared (K. J. L.).

Background: Lung cancer screening (LCS) with low-dose CT (LDCT) imaging was recommended in 2013, making approximately 8 million Americans eligible for LCS. The demographic characteristics and outcomes of individuals screened in the United States have not been reported at the population level., Research Question: What are the outcomes among people screened and entered in the American College of Radiology's Lung Cancer Screening Registry compared with those of trial participants?, Study Design and Methods: This was a cohort study of individuals undergoing baseline LDCT imaging for LCS between 2015 and 2019. Predictors of adherence to annual screening were computed. LDCT scan interpretations by Lung Imaging Reporting and Data System (Lung-RADS) score, cancer detection rates (CDRs), and stage at diagnosis were compared with National Lung Cancer Screening Trial data., Results: Adherence was 22.3%, and predictors of poor adherence included current smoking status and Hispanic or Black race. On baseline screening, 83% of patients showed negative results and 17% showed positive screening results. The overall CDR was 0.56%. The percentage of people with cancer detected at baseline was higher in the positive Lung-RADS categories at 0.4% for Lung-RADS category 3, 2.6% for Lung-RADS category 4A, 11.1% for Lung-RADS category 4B, and 19.9% for Lung-RADS category 4X. The cancer stage distribution was similar to that observed in the National Lung Cancer Screening Trial, with 53.5% of patients receiving a diagnosis of stage I cancer and 14.3% with stage IV cancer. Underreporting into the registry may have occurred., Interpretation: This study revealed both the positive aspects of CT scan screening for lung cancer and the challenges that remain. Findings on CT imaging were correlated accurately with lung cancer detection using the Lung-RADS system. A significant stage shift toward early-stage lung cancer was present. Adherence to LCS was poor and likely contributes to the lower than expected cancer detection rate, all of which will impact the outcomes of patients undergoing screening for lung cancer., (Copyright © 2023 American College of Chest Physicians. All rights reserved.)

Background: Guided bronchoscopy is increasingly used to diagnose peripheral pulmonary lesions (PPLs). A meta-analysis published in 2012 demonstrated a pooled diagnostic yield of 70%; however, recent publications have documented yields as low as 40% and as high as 90%., Research Question: Has the diagnostic yield of guided bronchoscopy in patients with PPLs improved over the past decade?, Study Design and Methods: A comprehensive search was performed of studies evaluating the diagnostic yield of differing bronchoscopic technologies used to reach PPLs. Study quality was assessed using the Quality assessment of diagnostic accuracy of studies (QUADAS-2) assessment tool. Number of lesions, type of technology used, overall diagnostic yield, and yield by size were extracted. Adverse events were recorded. Meta-analytic techniques were used to summarize findings across all studies., Results: A total of 16,389 lesions from 126 studies were included. There was no significant difference in diagnostic yield prior to 2012 (39 studies; 3,052 lesions; yield 70.5%) vs after 2012 (87 studies; 13,535 lesions; yield 69.2%) (P > .05). Additionally, there was no significant difference in yield when comparing different technologies. Studies with low risk of overall bias had a lower diagnostic yield than those with high risk of bias (66% vs 71%, respectively; P = .018). Lesion size > 2 cm, presence of bronchus sign, and reports with a high prevalence of malignancy in the study population were associated with significantly higher diagnostic yield. Significant (P < .0001) between-study heterogeneity was also noted., Interpretation: Despite the reported advances in bronchoscopic technology to diagnose PPLs, the diagnostic yield of guided bronchoscopy has not improved., (Copyright © 2023 American College of Chest Physicians. All rights reserved.)

Lung cancer remains the leading cause of cancer-related mortality for men and women in the United States. Screening for lung cancer with annual low-dose CT is saving lives, and the continued implementation of lung screening can save many more. In 2015, the CMS began covering annual lung screening for those who qualified based on the original United States Preventive Services Task Force (USPSTF) lung screening criteria, which included patients 55 to 77 year of age with a 30 pack-year history of smoking, who were either currently using tobacco or who had smoked within the previous 15 years. In 2021, the USPSTF issued new screening guidelines, decreasing the age of eligibility to 80 years of age and pack-years to 20. Lung screening remains controversial for those who do not meet the updated USPSTF criteria, but who have additional risk factors for the development of lung cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Lung cancer remains the leading cause of cancer-related mortality in the United States. The National Lung Screening Trial (NLST) demonstrated a 20% reduction in lung cancer mortality resulting from lung cancer screening (LCS) with an additive reduction from smoking abstinence. However, successful smoking cessation within LCS is variable., Research Question: What patient and treatment factors are associated with attempts to quit smoking among those screened for lung cancer?, Study Design and Methods: In a secondary analysis of the American College of Radiology Imaging Network arm of the NLST, patient demographics, patient smoking behaviors, and tobacco treatment variables were stratified by patient smoking status. The Cox proportional hazards ratio was used to evaluate each variable's effect on attempting to quit smoking., Results: Seven thousand three hundred sixty-nine patients were smoking actively at enrollment in the NLST. Of the patients who reported they were smoking, 73.4% did not receive any pharmacologic tobacco treatment. More patients who attempted to quit received pharmacologic tobacco treatment than those who continued to smoke: (nicotine replacement therapy [NRT], 18.0% vs 12.4% [P < .01]; bupropion, 7.9% vs 6.9% [P = .02]; both NRT and bupropion, 5.6% vs 3.9% [P < .01]). Stable users were more likely to be women (47.8% vs 43.8%; P < .01), to be African American (8.2% vs 6.3%; P = .007), to be unmarried (43.2% vs 36.9% [P < .01]), and to have less than a college education (47.7% vs 42.3%; P < .01). Patients with high dependence who received dual therapy with bupropion and NRT showed the highest likelihood of quit attempt (hazard ratio, 2.07; 95% CI, 1.75-2.44)., Interpretation: In this analysis, only one-quarter of patients who underwent LCS and who smoked were treated with pharmacologic therapy, which is associated with increased likelihood of attempting to quit. Certain characteristics are associated with difficulty with attempting to quit smoking. Those with high nicotine dependence benefitted most from dual pharmacologic therapy., (Copyright © 2022. Published by Elsevier Inc.)

Background: Pretreatment invasive nodal staging is paramount for appropriate treatment decisions in non-small cell lung cancer. Despite guidelines recommending when to perform staging, many studies suggest that invasive nodal staging is underused. Attitudes and barriers to guideline-recommended staging are unclear. The National Lung Cancer Roundtable initiated this study to better understand the factors associated with guideline-adherent nodal staging., Research Question: What are the knowledge gaps, attitudes, and beliefs of thoracic surgeons and pulmonologists about invasive nodal staging? What are the barriers to guideline-recommended staging?, Study Design and Methods: A web-based survey of a random sample of pulmonologists and thoracic surgeons identified as members of American College of Chest Physicians (CHEST) was conducted in 2019. Survey domains included knowledge of invasive nodal staging guidelines, attitudes and beliefs toward implementation, and perceived barriers to guideline adherence., Results: Among 453 responding physicians, 29% were unaware that invasive nodal staging guidelines exist. Among the 320 physicians who knew guidelines exist, attitudes toward the guidelines were favorable, with 91% agreeing guidelines are generalizable and 90% agreeing that recommendations improved their staging and treatment decisions. Approximately 80% responded that guideline recommendations are based on satisfactory levels of scientific evidence, and 50% stated a lack of evidence linking adherence to guidelines to changes in management or better patient outcomes. Nearly 9 in 10 physicians reported at least one barrier to guideline adherence. The most common barriers included patient anxiety associated with treatment delays (62%), difficulty implementing guidelines into routine practice (52%), and time delays of additional testing (51%)., Interpretation: Among physicians who responded to our survey, more than one-quarter were unaware of invasive nodal staging guidelines. Attitudes toward guideline recommendations were positive, although 20% reported insufficient evidence to support staging algorithms. Most physicians reported barriers to implementing guidelines. Multilevel interventions are likely needed to increase rates of guideline-recommended invasive nodal staging., (Copyright © 2022. Published by Elsevier Inc.)

Background: Bronchial thermoplasty is a device-based treatment for subjects ≥ 18 years of age with severe asthma poorly controlled with inhaled corticosteroids and long-acting beta-agonists. The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma (PAS2) study collected data on patients with severe asthma undergoing this procedure., Research Question: What are the 5-year efficacy and safety results in patients with severe asthma who have undergone bronchial thermoplasty?, Study Design and Methods: This was a prospective, open-label, observational, multicenter study conducted in the United States and Canada. Subjects 18 to 65 years of age who were taking inhaled corticosteroids ≥ 1,000 μg/d (beclomethasone or equivalent) and long-acting beta-agonists ≥ 80 μg/d (salmeterol or equivalent) were included. Severe exacerbations, hospitalization, ED visits, and medication usage were evaluated for the 12 months prior to and at years 1 through 5 posttreatment. Spirometry was evaluated at baseline and at years 1 through 5 posttreatment., Results: A total of 284 subjects were enrolled at 27 centers; 227 subjects (80%) completed 5 years of follow-up. By year 5 posttreatment, the proportion of subjects with severe exacerbations, ED visits, and hospitalizations was 42.7%, 7.9%, and 4.8%, respectively, compared with 77.8%, 29.4%, and 16.1% in the 12 months prior to treatment. The proportion of subjects on maintenance oral corticosteroids decreased from 19.4% at baseline to 9.7% at 5 years. Analyses of subgroups based on baseline clinical and biomarker characteristics revealed a statistically significant clinical improvement among all subgroups., Interpretation: Five years after treatment, subjects experienced decreases in severe exacerbations, hospitalizations, ED visits, and corticosteroid exposure. All subgroups demonstrated clinically significant improvement, suggesting that bronchial thermoplasty improves asthma control in different asthma phenotypes., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT01350336; URL: www., Clinicaltrials: gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: Lung cancer screening (LCS) decreases lung cancer mortality; however, that reduction depends upon screening adherence. The purpose of this study was to determine factors associated with adherence rate for LCS among patients with negative baseline CT results in a multi-integrated health care network., Methods: A retrospective analysis was conducted among patients with negative baseline CT results in a multi-integrated health care network LCS program between January 2015 and January 2020. The two outcomes were adherence for the first and second subsequent LCS studies. Negative baseline result was defined as a Lung CT Screening Reporting and Data System score 0, 1, or 2. Adherence was defined as undergoing a follow-up study within 11 to 15 months of a prior scan. Multivariable logistic regression was used to determine significant predictors of adherence, adjusting for patient demographics, median household income (on the basis of geocoding ZIP codes from the US Census Bureau), smoking history, screening sites, and provider specialty., Results: A total of 30.7% (512 of 1,668) and 16.3% (270 of 1,660) of patients were adherent for the first two annual subsequent screens, respectively. First-year adherence was higher among former smokers and varied by site and provider specialty. Second-year adherence was higher among former smokers and varied by site, provider specialty, and pack-years smoked., Conclusions: Adherence to LCS in a multihospital integrated health care network was poor and even lower at year 2. The identified factors associated with adherence may serve as targets to increase LCS adherence and decrease lung cancer mortality., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Targeted therapies for advanced non-small cell lung cancer (NSCLC) with oncogenic drivers have caused a paradigm shift in care. Biomarker testing is needed to assess eligibility for these therapies. Pulmonologists often perform bronchoscopy, providing tissue for both pathologic diagnosis and biomarker analysis. We performed this survey to define the existing knowledge and practices regarding the pulmonologists' role in biomarker testing for advanced NSCLC., Research Question: What is the current knowledge and practice of pulmonologists regarding biomarker testing and targeted therapies in advanced NSCLC?, Study Design and Methods: This cross-sectional study was performed using an electronic survey of a random sample of 7,238 pulmonologists. Questions focused on diagnostic steps and biomarker analyses for NSCLC., Results: A total of 453 pulmonologists responded. Respondents vary by reported lung cancer patient volume, ranging from 51% evaluating one to four new cases per month to 19% evaluating > 10 cases per month. Interventional training, academic practice setting, and higher volume of endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) were associated with increased knowledge of practice guidelines for the number of recommended passes during EBUS-TBNA (P < .05). Academic pulmonologists more commonly performed or referred for EBUS-TBNA than community pulmonologists (96% and 83%, respectively; P < .0005). Higher testing rates were associated with interventional training, academic setting, and the presence of an institutional policy, whereas lower testing rates were associated with general pulmonologists, practice in community settings, and lack of a guiding institutional policy (P < .05)., Interpretation: Substantial differences among pulmonologists' evaluation of advanced NSCLC, variation in knowledge of available biomarkers and the importance of targeted therapies, and differences in institutional coordination likely lead to underutilization of biomarker testing. Interventional training appears to drive improved knowledge and practice for biomarker testing more than practice setting. Improvements are needed in tissue acquisition and interdisciplinary coordination to ensure universal and comprehensive testing for eligible patients., (Copyright © 2021. Published by Elsevier Inc.)

Background: Low-dose chest CT screening for lung cancer has become a standard of care in the United States, in large part because of the results of the National Lung Screening Trial (NLST). Additional evidence supporting the net benefit of low-dose chest CT screening for lung cancer, and increased experience in minimizing the potential harms, has accumulated since the prior iteration of these guidelines. Here, we update the evidence base for the benefit, harms, and implementation of low-dose chest CT screening. We use the updated evidence base to provide recommendations where the evidence allows, and statements based on experience and expert consensus where it does not., Methods: Approved panelists reviewed previously developed key questions using the Population, Intervention, Comparator, Outcome format to address the benefit and harms of low-dose CT screening, and key areas of program implementation. A systematic literature review was conducted using MEDLINE via PubMed, Embase, and the Cochrane Library on a quarterly basis since the time of the previous guideline publication. Reference lists from relevant retrievals were searched, and additional papers were added. Retrieved references were reviewed for relevance by two panel members. The quality of the evidence was assessed for each critical or important outcome of interest using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Meta-analyses were performed when enough evidence was available. Important clinical questions were addressed based on the evidence developed from the systematic literature review. Graded recommendations and ungraded statements were drafted, voted on, and revised until consensus was reached., Results: The systematic literature review identified 75 additional studies that informed the response to the 12 key questions that were developed. Additional clinical questions were addressed resulting in seven graded recommendations and nine ungraded consensus statements., Conclusions: Evidence suggests that low-dose CT screening for lung cancer can result in a favorable balance of benefit and harms. The selection of screen-eligible individuals, the quality of imaging and image interpretation, the management of screen-detected findings, and the effectiveness of smoking cessation interventions can impact this balance., (Copyright © 2021 American College of Chest Physicians. All rights reserved.)

Background: Low-dose chest CT screening for lung cancer has become a standard of care in the United States, in large part because of the results of the National Lung Screening Trial (NLST). Additional evidence supporting the net benefit of low-dose chest CT screening for lung cancer, and increased experience in minimizing the potential harms, has accumulated since the prior iteration of these guidelines. Here, we update the evidence base for the benefit, harms, and implementation of low-dose chest CT screening. We use the updated evidence base to provide recommendations where the evidence allows, and statements based on experience and expert consensus where it does not., Methods: Approved panelists reviewed previously developed key questions using the Population, Intervention, Comparator, Outcome format to address the benefit and harms of low-dose CT screening, and key areas of program implementation. A systematic literature review was conducted using MEDLINE via PubMed, Embase, and the Cochrane Library on a quarterly basis since the time of the previous guideline publication. Reference lists from relevant retrievals were searched, and additional papers were added. Retrieved references were reviewed for relevance by two panel members. The quality of the evidence was assessed for each critical or important outcome of interest using the Grading of Recommendations, Assessment, Development and Evaluation approach. Meta-analyses were performed where appropriate. Important clinical questions were addressed based on the evidence developed from the systematic literature review. Graded recommendations and ungraded statements were drafted, voted on, and revised until consensus was reached., Results: The systematic literature review identified 75 additional studies that informed the response to the 12 key questions that were developed. Additional clinical questions were addressed resulting in seven graded recommendations and nine ungraded consensus statements., Conclusions: Evidence suggests that low-dose CT screening for lung cancer can result in a favorable balance of benefit and harms. The selection of screen-eligible individuals, the quality of imaging and image interpretation, the management of screen-detected findings, and the effectiveness of smoking cessation interventions can impact this balance., (Copyright © 2021 American College of Chest Physicians. All rights reserved.)

Background: Lung cancer is a leading cause of cancer incidence and death in the United States. Risk factor-based guidelines and risk model-based strategies are used to identify patients who could benefit from low-dose chest CT (LDCT) screening. Few studies compare guidelines or models within the same cohort. We evaluate lung cancer screening performance of two risk factor-based guidelines (US Preventive Services Task Force 2014 recommendations [USPSTF-2014] and National Comprehensive Cancer Network Group 2 [NCCN-2]) and two risk model-based strategies, Prostate Lung Colorectal and Ovarian Cancer Screening (PLCOm2012) and the Bach model) in the same occupational cohort., Research Question: Which risk factor-based guideline or model-based strategy is most accurate in detecting lung cancers in a highly exposed occupational cohort?, Study Design and Methods: Fire Department of City of New York (FDNY) rescue/recovery workers exposed to the September 11, 2001 attacks underwent LDCT lung cancer screening based on smoking history and age. The USPSTF-2014, NCCN-2, PLCOm2012 model, and Bach model were retrospectively applied to determine how many lung cancers were diagnosed using each approach., Results: Among the study population (N = 3,953), 930 underwent a baseline scan that met at least one risk factor or model-based LDCT screening strategy; 73% received annual follow-up scans. Among the 3,953, 63 lung cancers were diagnosed, of which 50 were detected by at least one LDCT screening strategy. The NCCN-2 guideline was the most sensitive (79.4%; 50/63). When compared with NCCN-2, stricter age and smoking criteria reduced sensitivity of the other guidelines/models (USPSTF-2014 [44%], PLCOm2012 [51%], and Bach[46%]). The 13 missed lung cancers were mainly attributable to smoking less and quitting longer than guideline/model eligibility criteria. False-positive rates were similar across all four guidelines/models., Interpretation: In this cohort, our findings support expanding eligibility for LDCT lung cancer screening by lowering smoking history from ≥30 to ≥20 pack-years and age from 55 years to 50 years old. Additional studies are needed to determine its generalizability to other occupational/environmental exposed cohorts., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The diagnosis of peripheral pulmonary lesions (PPL) continues to present clinical challenges. Despite extensive experience with guided bronchoscopy, the diagnostic yield has not improved significantly. Robotic-assisted bronchoscopic platforms have been developed potentially to improve the diagnostic yield for PPL. Presently, limited data exist that evaluate the performance of robotic systems in live human subjects., Research Question: What is the safety and feasibility of robotic-assisted bronchoscopy in patients with PPLs?, Study Design and Methods: This was a prospective, multicenter pilot and feasibility study that used a robotic bronchoscopic system with a mother-daughter configuration in patients with PPL 1 to 5 cm in size. The primary end points were successful lesion localization with the use of radial probe endobronchial ultrasound (R-EBUS) imaging and incidence of procedure related adverse events. Robotic bronchoscopy was performed in patients with the use of direct visualization, electromagnetic navigation, and fluoroscopy. After the use of R-EBUS imaging, transbronchial needle aspiration was performed. Rapid on-site evaluation (ROSE) was used on all cases. Transbronchial needle aspiration alone was sufficient when ROSE was diagnostic; when ROSE was not diagnostic, transbronchial biopsy was performed with the use of the robotic platform, followed by conventional guided bronchoscopic approaches at the discretion of the investigator., Results: Fifty-five patients were enrolled at five centers. One patient withdrew consent, which left 54 patients for data analysis. Median lesion size was 23 mm (interquartile range, 15 to 29 mm). R-EBUS images were available in 53 of 54 cases. Lesion localization was successful in 51 of 53 patients (96.2%). Pneumothorax was reported in two of 54 of the cases (3.7%); tube thoracostomy was required in one of the cases (1.9 %). No additional adverse events occurred., Interpretation: This is the first, prospective, multicenter study of robotic bronchoscopy in patients with PPLs. Successful lesion localization was achieved in 96.2% of cases, with an adverse event rate comparable with conventional bronchoscopic procedures. Additional large prospective studies are warranted to evaluate procedure characteristics, such as diagnostic yield., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT03727425; URL: www.clinicaltrials.gov., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Over decades, there have been several alterations to cigarettes, including the addition of filters and flavoring. However, lung cancer remains the leading cause of cancer-related death in the United States., Research Question: The aim of this study was to examine the association of type of cigarette on nicotine dependence in the setting of lung cancer screening., Study Design and Methods: This study is a secondary analysis of the American College of Radiology Imaging Network arm of the National Lung Screening Trial. Tobacco dependence was evaluated by using the Fagerstrӧm Test for Nicotine Dependence, the Heaviness of Smoking Index, and time to first cigarette. Clinical outcomes, including nicotine dependence and tobacco abstinence, were assessed with descriptive statistics and χ 2 tests, stratified according to cigarette tar level, flavor, and filter. Logistic regression was used to study the influence of variables on smoking abstinence., Results: More than one-third of individuals presenting for lung cancer screening are highly addicted to nicotine and smoke within 5 min of waking up. Smokers of unfiltered cigarettes were more nicotine dependent compared with filtered cigarette smokers (OR, 1.32; P < .01). Although smokers of light/ultralight cigarettes had lower dependence (OR, 0.76, P < .0001), there was no difference in smoking abstinence compared with regular cigarette smokers. There was no difference in outcomes when comparing smokers of menthol vs unflavored cigarettes., Interpretation: In a screening population, the type of cigarette smoked is associated with different levels of dependence. Eliciting type of cigarette and time to first cigarette has the potential to allow for tailored tobacco treatment interventions within this context., (Copyright © 2020 American College of Chest Physicians. All rights reserved.)

Background: Adherence to annual low-dose CT was 95% in the National Lung Screening Trial and must be replicated to achieve mortality benefit from screening., Research Question: How do we determine adherence rates within the Veterans Affairs Lung Cancer Screening Demonstration Project and identify factors predictive of adherence?, Study Design and Methods: A secondary data analysis of the Lung Cancer Screening Demonstration Project that was conducted at eight Veterans Affairs medical centers was performed to determine adherence to follow up imaging and to determine factors predictive of adherence., Results: A total of 2,103 patients were screened. The adherence to screening from baseline scan (T0) to first follow-up scan (T1) was 82.2% and 65.2% from T1 to second follow-up scan (T2). Logistic regression modeling showed that presence of a nodule and the site of lung cancer screening were predictive of adherence. After three rounds of screening, 1,343 patients (64%) who underwent baseline screening underwent both subsequent annual low-dose CT scans; 225 patients (11%) had only one subsequent low-dose CT; 0.4% did not have a T1 scan but did have a T2 scan; 70 patients (3%) died, and 36 patients (1.7%) were diagnosed with lung cancer. There was significant variation in screening adherence across the eight sites, which ranged from 63% to 94% at T1 and 52% to 82% at T2 (P < .05)., Interpretation: Despite a centralized program design with dedicated navigator and registry to assist with adherence to annual lung cancer screening, variations between sites suggest that active follow-up strategies are needed to optimize adherence. For the mortality benefit from lung cancer screening to be recognized, adherence to annual screening must achieve higher rates., (Published by Elsevier Inc.)

Background: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic., Methods: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario., Results: Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non-small-cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non-small-cell lung cancer., Conclusions: There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care., (Copyright © 2020 American College of Chest Physicians, published by Elsevier Inc; RSNA; and The American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Bronchoscopy is commonly used to evaluate suspicious lung lesions. The yield is likely dependent on patient, radiographic, and bronchoscopic factors. Few studies have assessed these factors simultaneously while also including the preprocedure physician-assessed probability of cancer (pCA) when assessing yield., Methods: This study is a secondary data analysis from a prospective multicenter trial. Diagnostic yield of standard bronchoscopy with biopsy ± fluoroscopy, endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA), electromagnetic navigation, and combination bronchoscopies was assessed. Definitions for diagnostic and nondiagnostic bronchoscopies were rigorously predefined. The association of diagnostic yield with individual variables was examined by using univariate and multivariate logistic regression analyses where appropriate., Results: A total of 687 patients were included from 28 sites. Overall diagnostic yield was 69%; 80% for EBUS, 55% for bronchoscopy with biopsy ± fluoroscopy, 57% for electromagnetic navigation, and 74% for combination procedures (P < .001). Patients with larger, central lesions with adenopathy were significantly more likely to undergo a diagnostic bronchoscopy. Patients with pCA < 10% and 10% to 60% had lower yields (44% and 42%, respectively), whereas pCA > 60% yielded a positive result in 77% (P < .001). In multivariate logistic regression, the use of EBUS-TBNA, larger sized lesions, and central location were significantly associated with a diagnostic bronchoscopy. Seventeen percent of those with a malignant diagnosis and 28% of those with a benign diagnosis required secondary procedures to establish a diagnosis., Conclusions: This study is the first to assess the yield of bronchoscopy according to physician-assessed pCA in a large, prospective multicenter trial. The yield of bronchoscopy varied greatly according to physician suspicion that cancer is present, the patients' clinical/radiographic features, and the type of procedure performed. Of the procedures performed, EBUS-TBNA was the most likely to provide a diagnosis., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: The field of biomarker development is evolving to assist in determining benign from malignant pulmonary nodules. Although a prospective clinical utility would best to show how a biomarker affects patient treatment and outcomes, we sought to begin to understand how the results might alter management by determining how physicians would use the results of a rule-in blood test to manage pulmonary nodules., Materials and Methods: Pulmonologists and thoracic surgeons in the American College of Chest Physicians clinician database were invited to participate in an online survey. The participant demographic data were collected. Four hypothetical clinical vignettes were presented. The participants accessed the pretest probability (probability of cancer [pCA]) for malignancy and chose the management strategies as the case progressed. The management strategies chosen before and after the result of a rule-in biomarker test were compared and assessed for guideline concordance., Results: Of the 455 eligible participants who had opened the survey, 416 (92%) completed it: 332 pulmonologists and 84 thoracic surgeons. Although 91% of the participants were very comfortable managing nodules, depending on the case, 30% to 62% incorrectly assessed the pCA, with 22% to 62% overestimating the risk and 8% to 51% underestimating the risk. After a rule-in blood test result, the clinician change in management moved in the right direction in some cases but, in others, the physicians used the results incorrectly. Pulmonologists and thoracic surgeons differed in the management strategies, with surgeons recommending surgery more often., Conclusions: Although the use of biomarker testing for pulmonary nodule evaluation is promising, without proper physician education, the potential for harm exists. Clinical utility studies are needed to appropriately inform the effect of biomarker use., (Published by Elsevier Inc.)

Background: Shared decision-making is an essential element of low-dose CT (LDCT) screening for lung cancer. Understanding patient-level outcomes from the National Lung Screening Trial (NLST) is critical to effectively communicate risks and benefits of screening to patients., Methods: We performed a secondary analysis of data collected in the NLST. We determined outcomes of each LDCT scan performed in the NLST (downstream evaluation, complications, lung cancer diagnoses), and compared outcomes at the test level with outcomes calculated at the patient level for those randomized to LDCT screening. To assess the impact of COPD on patient outcomes, we compared outcomes among patients with and without COPD., Results: Of 75,138 LDCT scans, 14.2% led to a diagnostic study and 1.5% to an invasive procedure, with 0.3% of LDCT scans resulting in a procedure-related complication and 0.1% in a serious complication. Among 24,453 patients who underwent LDCT screening, 30.5% underwent a diagnostic study and 4.2% an invasive procedure, with 0.9% of screened patients experiencing a procedure-related complication and 0.3% a serious complication. Patients with COPD (defined by self-report) were more likely to need a diagnostic study (adjusted OR [aOR], 1.29; P < .01) and an invasive procedure (aOR, 1.41; P < .01) and more likely to experience a complication (aOR, 1.83; P < .01) and a serious complication (aOR, 1.78; P = .01). Patients with COPD also were more likely to be diagnosed with lung cancer (aOR, 1.43; P < .01)., Conclusions: We provide important patient-level data from the NLST that can be used to guide shared decision-making. The risk-to-benefit ratio of screening may vary significantly in some patients, such as those with COPD, in whom both risks and benefits of screening may be increased., (Copyright © 2019 American College of Chest Physicians. All rights reserved.)

Background: While the complexity of flexible bronchoscopy has increased, standard options for moderate sedation medications have not changed in three decades. There is a need to improve moderate sedation while maintaining safety. Remimazolam was developed to address shortcomings of current sedation strategies., Methods: A prospective, double-blind, randomized, multicenter, parallel group trial was performed at 30 US sites. The efficacy and safety of remimazolam for sedation during flexible bronchoscopy were compared with placebo and open-label midazolam., Results: The success rates were 80.6% in the remimazolam arm, 4.8% in the placebo arm (P < .0001), and 32.9% in the midazolam arm. Bronchoscopy was started sooner in the remimazolam arm (mean, 6.4 ± 5.82 min) compared with placebo (17.2 ± 4.15 min; P < .0001) and midazolam (16.3 ± 8.60 min). Time to full alertness after the end of bronchoscopy was significantly shorter in patients treated with remimazolam (median, 6.0 min; 95% CI, 5.2-7.1) compared with those treated with placebo (13.6 min; 95% CI, 8.1-24.0; P = .0001) and midazolam (12.0 min; 95% CI, 5.0-15.0). Remimazolam registered superior restoration of neuropsychiatric function compared with placebo and midazolam. Safety was comparable among all three arms, and 5.6% of the patients in the remimazolam group had serious treatment-emergent adverse events as compared with 6.8% in the placebo group., Conclusions: Remimazolam administered under the supervision of a pulmonologist was effective and safe for moderate sedation during flexible bronchoscopy. In an exploratory analysis, it demonstrated a shorter onset of action and faster neuropsychiatric recovery than midazolam., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Screening with low-dose CT scan has been shown to reduce mortality from lung cancer in those at risk based on age and smoking history. While lung cancer screening (LCS) is recommended by the United States Preventative Services Task Force and many professional societies, it has been recognized that the decision to be screened is complex due to a close balance of risk and benefit; therefore, shared decision-making is considered an essential component of effective LCS. The Centers for Medicare and Medicaid Services provides coverage for LCS following a mandated shared-decision making (SDM) visit. Here we review the concept of SDM, facilitators and barriers, evidence and knowledge gaps, and novel considerations for SDM within LCS., (Published by Elsevier Inc.)

Background: New technology has resulted in bronchoscopy being increasingly used for diagnosing pulmonary lesions. Reported yield from these procedures varies widely with few randomized clinical trials. This study compares the diagnostic yield of a thin bronchoscope and radial endobronchial ultrasound (R-EBUS) with standard bronchoscopy and fluoroscopy (SB-F) in lung lesions., Methods: Patients presenting for diagnostic bronchoscopic evaluation at five centers were randomized to undergo SB-F or R-EBUS with a thin bronchoscope (TB-EBUS). If SB-F was nondiagnostic, crossover to the TB-EBUS arm was allowed. Data on patient demographics, radiographic features, and final pathologic or radiographic follow-up were collected. Statistical comparisons were made by Fisher exact test, χ 2 test, and Student t test. Bivariate and multivariate analyses were performed to determine predictors of diagnostic yield., Results: One hundred and ninety-seven patients were included in the final analyses. There was no difference in demographics, lesion size, or location between study arms. The average lesion size was 31.2 mm (SD, 10.8 mm). Bronchoscopy was diagnostic in 87 patients (44%). Although the diagnostic yield was higher in the TB-EBUS arm compared with the SB-F arm (49% vs 37%), this difference was not statistically significant (P = .11). Among those with nondiagnostic bronchoscopic findings in the standard arm, 87% (n = 46) crossed over to TB-EBUS, resulting in a diagnosis in seven additional patients (15% of 46)., Conclusions: Bronchoscopy with or without a thin scope and R-EBUS had a poor diagnostic yield for pulmonary lesions. Future work should focus on improvements in technique and technology advances that ensure a higher likelihood of obtaining a diagnosis., (Published by Elsevier Inc.)

Background: Lung nodules are a diagnostic challenge, with an estimated yearly incidence of 1.6 million in the United States. This study evaluated the accuracy of an integrated proteomic classifier in identifying benign nodules in patients with a pretest probability of cancer (pCA) ≤ 50%., Methods: A prospective, multicenter observational trial of 685 patients with 8- to 30-mm lung nodules was conducted. Multiple reaction monitoring mass spectrometry was used to measure the relative abundance of two plasma proteins, LG3BP and C163A. Results were integrated with a clinical risk prediction model to identify likely benign nodules. Sensitivity, specificity, and negative predictive value were calculated. Estimates of potential changes in invasive testing had the integrated classifier results been available and acted on were made., Results: A subgroup of 178 patients with a clinician-assessed pCA ≤ 50% had a 16% prevalence of lung cancer. The integrated classifier demonstrated a sensitivity of 97% (CI, 82-100), a specificity of 44% (CI, 36-52), and a negative predictive value of 98% (CI, 92-100) in distinguishing benign from malignant nodules. The classifier performed better than PET, validated lung nodule risk models, and physician cancer probability estimates (P < .001). If the integrated classifier results were used to direct care, 40% fewer procedures would be performed on benign nodules, and 3% of malignant nodules would be misclassified., Conclusions: When used in patients with lung nodules with a pCA ≤ 50%, the integrated classifier accurately identifies benign lung nodules with good performance characteristics. If used in clinical practice, invasive procedures could be reduced by diverting benign nodules to surveillance., Trial Registry: ClinicalTrials.gov; No.: NCT01752114; URL: www.clinicaltrials.gov)., (Published by Elsevier Inc.)