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Cancer interception refers to actively blocking the cancer development process by preventing progression of premalignancy to invasive disease. The rate-limiting steps for effective lung cancer interception are the incomplete understanding of the earliest molecular events associated with lung carcinogenesis, the lack of preclinical models of pulmonary premalignancy, and the challenge of developing highly sensitive and specific methods for early detection. Recent advances in cancer interception are facilitated by developments in next-generation sequencing, computational methodologies, as well as the renewed emphasis in precision medicine and immuno-oncology. This review summarizes the current state of knowledge in the areas of molecular abnormalities in lung cancer continuum, preclinical human models of lung cancer pathogenesis, and the advances in early lung cancer diagnostics.

Background Clinical utility data on pulmonary nodule (PN) risk stratification biomarkers are lacking. We aimed to determine the incremental predictive value and clinical utility of using an artificial intelligence (AI) radiomics-based computer-aided diagnosis (CAD) tool in addition to routine clinical information to risk stratify PNs among real-world patients. Methods We performed a retrospective cohort study of patients with PNs who underwent lung biopsy. We collected clinical data and used a commercially available AI radiomics-based CAD tool to calculate a Lung Cancer Prediction (LCP) score. We developed logistic regression models to evaluate a well-validated clinical risk prediction model (the Mayo Clinic model) with and without the LCP score (Mayo vs Mayo + LCP) using area under the curve (AUC), risk stratification table, and standardized net benefit analyses. Results Among the 134 patients undergoing PN biopsy, cancer prevalence was 61%. Addition of the radiomics-based LCP score to the Mayo model was associated with increased predictive accuracy (likelihood ratio test, P  =  .012). The AUCs for the Mayo and Mayo + LCP models were 0.58 (95% CI = 0.48 to 0.69) and 0.65 (95% CI = 0.56 to 0.75), respectively. At the 65% risk threshold, the Mayo + LCP model was associated with increased sensitivity (56% vs 38%; P  =  .019), similar false positive rate (33% vs 35%; P  =  .8), and increased standardized net benefit (18% vs -3.3%) compared with the Mayo model. Conclusions Use of a commercially available AI radiomics-based CAD tool as a supplement to clinical information improved PN cancer risk prediction and may result in clinically meaningful changes in risk stratification. [ABSTRACT FROM AUTHOR]

A multiplexed quantitative method for the analysis of three major unconjugated steroids in human serum by stable isotope dilution liquid chromatography-high resolution mass spectrometry (LC-HRMS) was developed and validated on a Q Exactive Plus hybrid quadrupole/Orbitrap mass spectrometer. This quantification utilized isotope dilution and Girard P derivatization on the keto-groups of testosterone (T), androstenedione (AD) and dehydroepiandrosterone (DHEA) to improve ionization efficiency using electrospray ionization. Major isomeric compounds to T and DHEA; the inactive epimer of testosterone (epiT), and the metabolite of AD, 5α-androstanedione (5α-AD) were completely resolved on a biphenyl column within an 18min method. Inter- and intra-day method validation using LC-HRMS with qualifying product ions was performed and acceptable analytical performance was achieved. The method was further validated by comparing steroid levels from 100μL of serum from young vs older subjects. Since this approach provides high-dimensional HRMS data, untargeted analysis by age group was performed. DHEA and T were detected among the top analytes most significantly different across the two groups after untargeted LC-HRMS analysis, as well as a number of other still unknown metabolites, indicating the potential for combined targeted/untargeted analysis in steroid analysis.

Lung cancer mortality rates, particularly non-small cell lung cancer (NSCLC), continue to present a significant global health challenge, and the adoption of lung cancer screening remains limited, often influenced by inequities in access to healthcare. Despite clinical evidence demonstrating the efficacy of annual screening with low-dose computed tomography (LDCT) and recommendations from medical organizations including the U.S. Preventive Services Task Force (USPSTF), the national lung cancer screening uptake remains around 5% among eligible individuals. Advancements in the clinical management of NSCLC have recently become more personalized with the implementation of blood-based biomarker testing. Extensive research into tumor-derived cell-free DNA (cfDNA) through fragmentation offers a novel method for improving early lung cancer detection. This review assesses the screening landscape, explores obstacles to lung cancer screening, and discusses how a plasma whole genome fragmentome test (pWGFrag-Lung) can improve lung cancer screening participation and adherence. [ABSTRACT FROM AUTHOR]

ObjectivesGenome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping.Materials and methodsWe genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p

Lung cancer screening with low-dose computed tomography has been shown to reduce lung cancer mortality. Nevertheless, it may also lead to potential harms, including complications arising from downstream invasive procedures. However, the magnitude of such potential harms in real-world practice remains unknown. The current study evaluated downstream use of invasive procedures and procedural complications after lung cancer screening in 5 diverse U.S. health care systems. Visual Abstract. Downstream Procedures and Complications Associated With Lung Cancer Screening.: Lung cancer screening with low-dose computed tomography has been shown to reduce lung cancer mortality. Nevertheless, it may also lead to potential harms, including complications arising from downstream invasive procedures. However, the magnitude of such potential harms in real-world practice remains unknown. The current study evaluated downstream use of invasive procedures and procedural complications after lung cancer screening in 5 diverse U.S. health care systems. Background: Lung cancer screening (LCS) using low-dose computed tomography (LDCT) reduces lung cancer mortality but can lead to downstream procedures, complications, and other potential harms. Estimates of these events outside NLST (National Lung Screening Trial) have been variable and lacked evaluation by screening result, which allows more direct comparison with trials. Objective: To identify rates of downstream procedures and complications associated with LCS. Design: Retrospective cohort study. Setting: 5 U.S. health care systems. Patients: Individuals who completed a baseline LDCT scan for LCS between 2014 and 2018. Measurements: Outcomes included downstream imaging, invasive diagnostic procedures, and procedural complications. For each, absolute rates were calculated overall and stratified by screening result and by lung cancer detection, and positive and negative predictive values were calculated. Results: Among the 9266 screened patients, 1472 (15.9%) had a baseline LDCT scan showing abnormalities, of whom 140 (9.5%) were diagnosed with lung cancer within 12 months (positive predictive value, 9.5% [95% CI, 8.0% to 11.0%]; negative predictive value, 99.8% [CI, 99.7% to 99.9%]; sensitivity, 92.7% [CI, 88.6% to 96.9%]; specificity, 84.4% [CI, 83.7% to 85.2%]). Absolute rates of downstream imaging and invasive procedures in screened patients were 31.9% and 2.8%, respectively. In patients undergoing invasive procedures after abnormal findings, complication rates were substantially higher than those in NLST (30.6% vs. 17.7% for any complication; 20.6% vs. 9.4% for major complications). Limitation: Assessment of outcomes was retrospective and was based on procedural coding. Conclusion: The results indicate substantially higher rates of downstream procedures and complications associated with LCS in practice than observed in NLST. Diagnostic management likely needs to be assessed and improved to ensure that screening benefits outweigh potential harms. Primary Funding Source: National Cancer Institute and Gordon and Betty Moore Foundation. [ABSTRACT FROM AUTHOR]