Global Epidemiology of Lung Cancer.

While lung cancer has been the leading cause of cancer-related deaths for many years in the United States, incidence and mortality statistics - among other measures - vary widely worldwide. The aim of this study was to review the evidence on lung cancer epidemiology, including data of international scope with comparisons of economically, socially, and biologically different patient groups. In industrialized nations, evolving social and cultural smoking patterns have led to rising or plateauing rates of lung cancer in women, lagging the long-declining smoking and cancer incidence rates in men. In contrast, emerging economies vary widely in smoking practices and cancer incidence but commonly also harbor risks from environmental exposures, particularly widespread air pollution. Recent research has also revealed clinical, radiologic, and pathologic correlates, leading to greater knowledge in molecular profiling and targeted therapeutics, as well as an emphasis on the rising incidence of adenocarcinoma histology. Furthermore, emergent evidence about the benefits of lung cancer screening has led to efforts to identify high-risk smokers and development of prediction tools. This review also includes a discussion on the epidemiologic characteristics of special groups including women and nonsmokers. Varying trends in smoking largely dictate international patterns in lung cancer incidence and mortality. With declining smoking rates in developed countries and knowledge gains made through molecular profiling of tumors, the emergence of new risk factors and disease features will lead to changes in the landscape of lung cancer epidemiology

Following Patients with Severe Coronary Artery Calcifications Detected by Low-Dose CT Scan for Lung Cancer Screening

Introduction: Recommendations for lose-dose CT screening for lung cancer (LC) targets a population at concomitant risk for coronary disease. Coronary artery calcifications (CAC) are an independent predictor of cardiovascular events among screening patients, and atherosclerotic cardiovascular disease (ASCVD) was the leading cause of death in the National Lung Screening Trial. In this study, we tested the hypothesis that patients with severe CAC undergo more risk factor modification when seen by a cardiologist. Methods: A chart review assessing patients found to have severe CAC on screening LDCT between January 2018 and April 2019 was conducted. Patient demographics, medical history, and cardiology data were obtained from the electronic medical record. Results: Of 580 patients who underwent LC screening, forty patients (6.9%) had severe CAC. 70% of these patients (28/40) had ASCVD at baseline. Twenty-three patients (57.5%) were subsequently seen by a cardiologist. Of these patients, 12 (52.2%) were started on or had a dose increase in cardiac medications; 9 (39.1%) underwent stress testing; 12 (52.2%) had an echocardiogram; and 3 patients (13.0%) underwent coronary angiography. Among the 17 patients not seen by a cardiologist, 2 patients (11.8%) had an increase in cardiac medications, and none underwent cardiac procedures. Discussion: Patients with severe CAC detected on LDCT screening have a high incidence of known ASCVD. Those who are referred to Cardiology undergo procedures and medication changes at a higher rate than patients not seen by a cardiologist. Future directions should include examining the impact of cardiac interventions on ASCVD mortality in this population

Sociodemographic Background Characteristics of Patients Who Participate in a Lung Cancer Screening Program

Introduction: Despite decreasing lung cancer incidence and mortality rates, disparities in prevalence and outcomes persist between Black and White patients. Secondary analysis of the National Lung Screening Trial found screening with low-dose CT (LDCT) reduced lung cancer mortality more in Blacks than Whites. However, it is unknown if racial disparities exist in screening results, and the involved sociodemographic factors. Objective: The study aims to analyze characteristics that may predict screening outcomes (Lung-RADS category) in patients who received LDCT through the Jefferson Lung Cancer Screening Program (LCSP). Methods: Retrospective data (n=733, May 2015 to July 2017) were merged with prospective data (n=292, January to September 2018). Lung-RADS scores were categorized into a binary variable (negative=1 and 2 vs. positive=3, 4A, 4B, and 4X). Chi-square and multivariate logistic regression were conducted to examine risk factors (race, gender, age, marital status, smoking status, COPD, and BMI). Results: Of 1025 total participants, 688 met eligibility criteria and underwent LDCT. In adjusted analysis, age and marital status were associated with Lung-RADS result. Older patients (aOR=1.04, 95% CI=1.01-1.08) and never-married patients (aOR=1.88, 95% CI=1.09-3.26) had significantly higher odds of a positive screen. An interaction between race and gender was also identified. Compared to White women, White men (aOR=2.13, 95% CI=1.08-4.19) and Black men (aOR=2.10, 95% CI=1.01-4.42) had higher odds of positive screening results. Discussion: Despite no main effect of race on screening results, an interaction existed between race and gender. These findings can be further explored to develop education programs for earlier detection and treatment, increasing screening awareness in vulnerable populations

Characteristics Associated With Early vs. Late Adoption of Lung Cancer Screening

Background: Although lung cancer screening (LCS) reduces lung cancer mortality among high-risk individuals, uptake overall remains low. With all cancer screening modalities, a period of diffusion among medical providers and the public is expected, with screening uptake exhibiting a distribution among early vs. late adoption. We aimed to characterize individuals undergoing LCS based upon the timeframe of screening adoption. Methods: This retrospective study examined patients who underwent LCS between January 2015 – December 2022 in a centralized LCS program. Based on United States Preventive Services Task Force (USPSTF) criteria for LCS, early and late adopters of LCS – defined by time from eligibility to screening completion – were compared. A multivariable regression model was constructed to identify factors associated with early adoption of LCS. Results: Among patients screened during the study period, 90.4% were eligible based on USPSTF 2013 criteria, and 9.6% were eligible based on USPSTF 2021 criteria. Of the USPSTF 2013 eligible persons, multivariable analysis demonstrated Black/African-American individuals and current smokers had significantly greater odds of early adoption (aOR 1.428 and 1.514, respectively). Those without a family history of lung cancer or without a personal history of cancer had significantly lower odds of early adoption of LCS. Conclusions: Early adopters were more likely to report Black/African-American race or current smoking status after adjustment for covariates. Future research should examine how screening diffuses across the overall LCS-eligible population, as well as identify factors that drive and inhibit diffusion to create programs and policies with the ultimate goal of increasing timely LCS uptake

Incidental Findings on LDCT for Lung Cancer Screening: Prevalence and Clinical Management

Objectives To define the frequency of incidental findings on low-dose CT (LDCT) scans among patients undergoing lung cancer screening. To determine the current reporting methods for incidental findings and measure the frequency of clinical follow-up

Detection of lung carcinoma arising from ground glass opacities (GGO) after 5 years - A retrospective review

Pure ground glass opacities (GGO) may indicate pre-invasive subtypes of lung carcinoma. These neoplasms typically demonstrate indolent patterns of growth; Fleischner Society guidelines recommend up to five years of serial imaging. Our aim was to determine the frequency of diagnosed carcinoma arising from GGO detected beyond 5 years of surveillance. We reviewed pathologic diagnoses of lung carcinoma (n = 442) between 2016 and 2018 of a tertiary academic hospital and National Cancer Institute-designated cancer center to identify all cancers that arose from ground glass opacities detected on CT scan. Of the 442 cases of lung carcinoma, 32 (7%) were found that arose from pure GGOs and were ultimately diagnosed as cancer. Among the subgroup of GGOs, 78% (n = 25) were diagnosed within five years of surveillance, but up to 22% (n = 7) required between five and twelve years of serial follow up prior to definitive diagnosis. In order to detect 95% of cancers, GGOs would need to be followed for 7.9–12.7 years based upon a Kaplan-Meier estimate (p = 0.05). No patients who had lung carcinoma arising from GGOs died (0/32) within a follow-up time of one to three years. These data suggest that a greater number of lung carcinomas would be detected upon routine follow up of GGOs that extended beyond the current recommendation of five years. The overall survival of the cohort was 100%, consistent with existing data that these cancers are indolent. It is unknown whether a higher detection rate from longer interval follow up would impact overall survival

Black patients referred to a lung cancer screening program experience lower rates of screening and longer time to follow-up.

BACKGROUND: Racial disparities are well-documented in preventive cancer care, but they have not been fully explored in the context of lung cancer screening. We sought to explore racial differences in lung cancer screening outcomes within a lung cancer screening program (LCSP) at our urban academic medical center including differences in baseline low-dose computed tomography (LDCT) results, time to follow-up, adherence, as well as return to annual screening after additional imaging, loss to follow-up, and cancer diagnoses in patients with positive baseline scans. METHODS: A historical cohort study of patients referred to our LCSP was conducted to extract demographic and clinical characteristics, smoking history, and lung cancer screening outcomes. RESULTS: After referral to the LCSP, blacks had significantly lower odds of receiving LDCT compared to whites, even while controlling for individual lung cancer risk factors and neighborhood-level factors. Blacks also demonstrated a trend toward delayed follow-up, decreased adherence, and loss to follow-up across all Lung-RADS categories. CONCLUSIONS: Overall, lung cancer screening annual adherence rates were low, regardless of race, highlighting the need for increased patient education and outreach. Furthermore, the disparities in race we identified encourage further research with the purpose of creating culturally competent and inclusive LCSPs

Interrogating Genes That Mediate Chlamydia trachomatis Survival in Cell Culture Using Conditional Mutants and Recombination

Intracellular bacterial pathogens in the family Chlamydiaceae are causes of human blindness, sexually transmitted disease, and pneumonia. Genetic dissection of the mechanisms of chlamydial pathogenicity has been hindered by multiple limitations, including the inability to inactivate genes that would prevent the production of elementary bodies. Many genes are also Chlamydia-specific genes, and chlamydial genomes have undergone extensive reductive evolution, so functions often cannot be inferred from homologs in other organisms. Conditional mutants have been used to study essential genes of many microorganisms, so we screened a library of 4,184 ethyl methanesulfonate-mutagenized Chlamydia trachomatis isolates for temperature-sensitive (TS) mutants that developed normally at physiological temperature (37°C) but not at nonphysiological temperatures. Heat-sensitive TS mutants were identified at a high frequency, while cold-sensitive mutants were less common. Twelve TS mutants were mapped using a novel markerless recombination approach, PCR, and genome sequencing. TS alleles of genes that play essential roles in other bacteria and chlamydia-specific open reading frames (ORFs) of unknown function were identified. Temperature-shift assays determined that phenotypes of the mutants manifested at distinct points in the developmental cycle. Genome sequencing of a larger population of TS mutants also revealed that the screen had not reached saturation. In summary, we describe the first approach for studying essential chlamydial genes and broadly applicable strategies for genetic mapping in Chlamydia spp. and mutants that both define checkpoints and provide insights into the biology of the chlamydial developmental cycle. IMPORTANCE: Study of the pathogenesis of Chlamydia spp. has historically been hampered by a lack of genetic tools. Although there has been recent progress in chlamydial genetics, the existing approaches have limitations for the study of the genes that mediate growth of these organisms in cell culture. We used a genetic screen to identify conditional Chlamydia mutants and then mapped these alleles using a broadly applicable recombination strategy. Phenotypes of the mutants provide fundamental insights into unexplored areas of chlamydial pathogenesis and intracellular biology. Finally, the reagents and approaches we describe are powerful resources for the investigation of these organisms

Racial disparities in occupational risks and lung cancer incidence: Analysis of the National Lung Screening Trial.

The relationship between racial disparities in occupational risk and lung cancer diagnosis is not well defined. We examined occupational exposure to asbestos, silica, and other workplace chemicals, fumes, or dusts as reported in the National Lung Screening Trial (NLST). Descriptive analyses and multivariate logistic regression models were performed. Among the NLST study cohort, 3.9% were diagnosed with lung cancer. African-Americans had a higher rate of lung cancer diagnosis than White individuals (4.3% vs. 3.9%). About 28% reported at least one occupational exposure, including 6.5% exposed to silica and 4.7% to asbestos. African-Americans reported occupational exposure more frequently than White participants, including exposures to asbestos and silica. In a multivariate model, the interactions of all measures of occupational exposures and smoking status were significant. Current smokers with occupational exposures had higher odds of lung cancer diagnosis (aOR = 2.01, 95% CI = 1.76-2.30 for any exposure as well as higher odds after silica (aOR = 2.35, 95% CI = 1.89-2.91) or asbestos (aOR = 1.97, 95% CI = 1.52-2.56) exposure compared to former smokers without any exposures. African-Americans had higher odds of lung cancer diagnosis than White individuals (aOR = 1.24 to 1.25, 95% CI = 1.01-1.54). Our findings indicate that we need more effective public health prevention programs, especially for minorities who may have disproportionately greater occupational exposures due to socioeconomic constructs and barriers. Interventions may include education about occupational risks and lung cancer screening or instituting workplace policies for smoke-free environments with tobacco cessation support

Tumor Doubling Time of Pulmonary Carcinoid Tumors Measured by CT

Introduction: Pulmonary carcinoid tumor (PCT) is a rare neuroendocrine lung cancer that is known clinically to be a slow-growing neoplasm. Few studies have established the true growth rate of these tumors when followed over time by radiography. Therefore, we sought to determine PCT tumor doubling time using longitudinal Computed Tomography (CT) scans. Nodule guidelines may misclassify early PCT nodules with a small diameter as benign if tumor growth is too slow to be appreciable on follow up radiographic scans completed between six months and two years after initial detection. Methods: We performed a retrospective analysis of available CT imaging of all PCTs treated at Thomas Jefferson University Hospital between 2006-2020 where radiographic follow up occurred prior to biopsy or resection. Nodule dimensions were measured manually using Phillips Intellispace PACS or retrieved from radiology reports. Tumor doubling time was calculated for all tumors demonstrating definitive growth (an increase in average diameter ≥ 2 mm) over a follow up interval of at least two years. Results: Fifteen patients had pathologically proven PCT with pre-resection observation times exceeding two years. 12/15 (80%) were typical carcinoids and 3/15 were atypical. 11/12 of the typical PCTs demonstrated definitive growth with a median doubling time of 140 weeks (mean = 161 ± 105 weeks). Discussion: The median doubling time of typical PCT was 141 weeks, or almost three years. It is conceivable that PCTs detected early with small diameter may be mistaken for benign non-growing lesions when followed for less than two years in low-risk patients