LDCT lung cancer screening eligibility and use of CT scans for lung cancer among sexual minorities

ObjectiveTo compare eligibility for lung cancer screening and receipt of a CT scan for lung cancer among sexual minorities.MethodsSecondary data analysis of cross-sectional data from older U.S. adults in the Behavioral Risk Factor Surveillance System survey during the 2017 cycle (n = 20,685).ResultsRates of eligibility for low-dose helical computed tomography (LDCT) were roughly twice as high among sexual minorities than among heterosexuals (21.1% vs. 11.7%). The odds of gay men and lesbian women indicating eligibility for LDCT screening were four to five times higher when compared to their heterosexual peers. No statistically significant differences were found between sexual minorities and heterosexuals with respect to having a CT scan for lung cancer in the past year.ConclusionsThere are potential sexual-identity-related disparities in the utilization of lung cancer screening among eligible smokers. Interventions are needed to increase awareness and uptake of lung cancer screening in order to detect and manage this common form of cancer in the U.S.     

Recent advances in human sweat metabolomics for lung cancer screening

Introduction

Lung cancer is the leading cause of cancer related mortality owing to the advanced stage it is usually detected because the available diagnostic tests are expensive and invasive; therefore, they cannot be used for general screening.

Objectives

To increase robustness of previous biomarker panels—based on metabolites in sweat samples—proposed by the authors, new samples were collected within different intervals (4 months and 2 years), analyzed at different times (2012 and 2014, respectively) by different analysts to discriminate between LC patients and smokers at risk factor.

Methods

Sweat analysis was carried out by LC–MS/MS with minimum sample preparation and the generated analytical data were then integrated to minimize variability in statistical analysis.

Results

Panels with capability to discriminate LC patients from smokers at risk factor were obtained taken into account the variability between both cohorts as a consequence of the different intervals for samples collection, the times at which the analyses were carried out and the influence of the analyst. Two panels of metabolites using the PanelomiX tool allow reducing false negatives (95 % specificity) and false positives (95 % sensitivity). The first panel (96.9 % specificity and 83.8 % sensitivity) is composed by monoglyceride MG(22:2), muconic, suberic and urocanic acids, and a tetrahexose; the second panel (81.2 % specificity and 97.3 % sensitivity) is composed by the monoglyceride MG(22:2), muconic, nonanedioic and urocanic acids, and a tetrahexose.

Conclusion

The study has allowed obtaining a prediction model more robust than that obtained in the previous study from the authors.

     

Association between lung cancer screening and smoking cessation

IntroductionAdults with high-risk smoking histories benefit from annual lung cancer screening. It is unclear if there is an association between lung cancer screening and smoking cessation among U.S. adults who receive screening.MethodsWe performed this population-based cross-sectional study using data from the Behavioral Risk Factor Surveillance System (2017–2020). We defined individuals eligible for lung cancer screening as adults 55–80 years old with ≥ 30 pack-year smoking history who were currently smoking or quit within the last 15 years. We assessed the association between lung cancer screening and current smoking status.ResultsBetween 2017 and 2020, 12,382 participants met screening criteria. Current smoking was reported by 5685 (45.9 %) participants, of whom 40.4 % (2298) reported a cessation attempt in the prior year. Lung cancer screening was reported by only 2022 (16.3 %) eligible participants. Lung cancer screening was associated with lower likelihood of currently smoking (odds ratio [OR] 0.705, 95 % CI 0.626–0.793) compared to individuals who did not receive screening. Screening was also associated with higher likelihood of reporting a cessation attempt in the prior year (OR 1.562, 95 % CI 1.345–1.815) compared to individuals who did not receive screening.ConclusionsReceipt of lung cancer screening was associated with lower smoking rates and more frequent cessation attempts among U.S. adults. Better implementation of lung cancer screening programs is critical and may profoundly increase smoking cessation in this population at risk of developing lung cancer.     

An up to date look at lung cancer screening

Lung cancer is the leading cause of cancer-related death worldwide. At the time of initial presentation, most patients are at an advance stage of disease and have a poor associated prognosis. Those diagnosed and treated at earlier stages have a significantly better outcome with five year survival for stage I disease approaching 75%. Ideally a screening strategy for lung cancer would detect disease at an earlier stage and allow for potential surgical cure. The purpose of this review is to examine past and current evidence as it relates to lung cancer screening.     

Five microRNAs in plasma as novel biomarkers for screening of early-stage non-small cell lung cancer

Background

In order to find novel noninvasive biomarkers with high accuracy for the screening of early-stage non-small cell lung cancer (NSCLC), we investigate the predictive power of 5 microRNAs (miR-20a, miR-145, miR-21, miR223 and miR-221) as potential biomarkers in early-stage NSCLC.

Methods

In training set, 25 early-stage NSCLC patients and 25 matched healthy controls are included to assess the miRNA expression profile between early-stage NSCLC patients and healthy controls by real-time RT-PCR. We found that five of these miRNAs (miR-20a, miR-223, miR-21, miR-221 and miR-145) levels in NSCLC patients were significantly dysregulated compared with the healthy groups and thus were selected to validation set. Therefore, a validation experiment was further performed to investigate the potential predictive power of these five miRNAs based on 126 early-stage NSCLC patients, 42 NCPD patients and 60 healthy controls. The receiver operating characteristic (ROC) curves were generated for the five miRNAs.

Results

ROC curve analyses suggested that these five plasma miRNAs could be promising biomarkers for NSCLC, with relatively high AUC values as follows: miR-20a, 0.89 with 95% CI of [0.85-0.93]; miR-223, 0.94 with 95% CI of [0.91-0.96]; miR-21, 0.77 with 95% CI of [0.71-0.83]; miR-155, 0.92 with 95% CI of [0.89-0.96]; miR-145, 0.77 with 95% CI of [0.71-0.83]. Stratified analyses indicated that plasma miR-20a, miR-223, miR-21 and miR-145 showed better predictive value in smokers than in non-smokers, while miR-155 might be more suitable for non-smokers. In addition, all of these five miRNAs could differentiate NSCLC from controls with a higher accuracy in advanced stage and squamous carcinoma subgroups.

Conclusions

In conclusion, our study suggested that five plasma miRNAs (miR-20a, miR-145, miR-21, miR-223 and miR-221) can be used as promising biomarkers in early screening of NSCLC. Nevertheless, further validation and optimizing improvement should be performed on larger sample to confirm our results.     

A segmentation tool for pulmonary nodules in lung cancer screening: Testing and clinical usage

PurposeWith the future goal of defining a large dataset based on low-dose CT with labelled pulmonary lesions for lung cancer screening (LCS) research, the aim of this work is to propose and evaluate into a clinical context a tool for semi-automatic segmentation able to facilitate the process of labels collection from a LCS study (COSMOS, Continuous Observation of SMOking Subjects).MethodsConsidering a preliminary set of manual annotations, a segmentation model based on a 2D-Unet was trained from scratch. Contour quality of the final 2D-Unet was assessed on an internal test set of manual annotations and on a subset of the public available LIDC dataset used as external test set. The tool for semi-automatic segmentation was then designed integrating the tested model into a Graphical User Interface. According to the opinion of two clinical users, the percentage of lesions properly contoured through the tool was quantified (Acceptance Rate, AR). The variability between segmentations derived by the two readers was estimated as mean percentage of difference (MPD) between the two sets of volumes and comparing the likelihood of malignancy derived from Volume Doubling Time (VDT).ResultsPerformance in test sets were found similar (DICE ~ 0.75(0.15)). Accordingly, a good mean AR (80.1%) resulted from the two readers. Variability in terms of MPD was equal to 23.6% while 2.7% was the VDTs percentage of disagreement.ConclusionsA semi-automatic segmentation tool was developed and its applicability evaluated into a clinical context demonstrating the efficacy of the tool in facilitating the collection of labelled data.     

Biomarkers for screening of lung cancer and pre-neoplastic lesions in a high risk Chilean population

Background

The mortality of lung cancer (LC), increases each year in the world, in spite of any advances, in development of new drugs to advance stages of LC. The high incidence of LC has been associated with smoking habit, genetic diversity and environmental pollution. Antofagasta region has been reported to have the highest LC mortality rate in Chile and its inhabitants were exposed to arsenic in their drinking water in concentrations as high as 870 μg/L. Non-invasive techniques such as biomarkers (Automatic Quantitative Cytometry: AQC and DR70) and Auto Fluorescence Bronchoscopy (AFB) might be potentially useful as a supplementary diagnostic approach and early detection. Early detection is one of the most important factors to intervene and prevent cancer progression in LC. This is a work of an ongoing prospective bimodality cancer surveillance study in high risk LC volunteers. Enrolment was done in subjects from Antofagasta and Metropolitan regions. In addition, we enrolled subjects who were suspected of having lung cancer. AQC, DR70 and AFB were used as tools in the detection of pre-neoplastic (PNL) and neoplastic lesions (NL).

Results

Half of the samples, classified as suspicious by AFB, were confirmed as metaplasia or dysplasia by histopathology. For LC, DR70 showed a higher sensitivity (95.8%) and specificity (91.9%) than AQC. However, for PNL AQC showed a higher sensitivity (91.9%) than DR70 (27.3%), although both with low PPV values. As a pre screener, both biomarkers might be employed as complementary tools to detect LC, especially as serially combined tests, with a sensitivity of 60% and a PPV of 65.2%. Additionally, the use of parallel combined tests might support the detection of PNL (sensitivity 91.2%; PPV 49.1%).

Conclusion

This work adds information on cellular and molecular biomarkers to complement imaging techniques for early detection of LC in Latin America that might contribute to formulate policies concerning screening of LC. Supported by INNOVA-CORFO, Chile.     

The association of urbanicity and travel time with lung cancer screening utilization

BackgroundTo examine 1) the rate of lung cancer screening (LCS) utilization in a large healthcare system in South Carolina; 2) associations of urbanicity and travel time with LCS utilization.MethodsLCS-eligible patients from 2019 were identified. The outcome was LCS utilization. The exposures were zip-code level urbanicity and travel time from the centroid of zip-code area to the nearest screening site (<10,10-<20, ≥20 min). Covariates included age, sex, race, marital status, insurance, body mass index, chronic obstructive pulmonary disease, Charlson Comorbidity Index (0, 1, 2, ≥3), and zip-code level median income. Chi-square tests and logistic regressions were employed.ResultsThe analysis included 6930 patients, among whom 1432 (20.66%) received LCS. After adjusting for covariates, living in a non-metropolitan area (adjusted odds ratio: 0.32; 95% confidence interval: 0.26–0.40) and having longer travel time (0.80 [0.65–0.98] and 0.68 [0.54–0.86] for 10-<20 and ≥20 min travel time, respectively, compared to <10 min travel time) were significantly associated with lower odds of LCS utilization.ConclusionsThe LCS utilization rate of a healthcare system was about 20% in 2019. Living in non-metropolitan areas or having longer travel time to LCS site were associated with lower LCS utilization.     

Discovery of ERBB3 inhibitors for non-small cell lung cancer (NSCLC) via virtual screening

As a member of the epidermal growth factor receptor family (EGFR) of receptor tyrosine kinases, ERBB3 plays an important role in mediating cellular growth and differentiation. Recent research works identified that CD74-NRG1 fusions lead to overexpression of the EGF-like domain of NRG1, and thus activate ERBB3 and PI3K-AKT signaling pathways. The fusion was detected in lung adenocarcinomas, and served as an important oncogenic factor for ERBB3 driven cancers. A sequential virtual screening strategy has been applied to ERBB3 crystal structure using databases of natural products and Chinese traditional medicine compounds, and led to identification of a group of small molecular compounds potentially capable of blocking ERBB3. Six small molecular compounds were selected for in vitro analysis. Five of these molecules significantly inhibited the growth of A549 cells. Among them, compound VS1 is the most promising one with IC₅₀ values of 269.75 μM, comparing to the positive control of nimustine hydrochloride with IC₅₀ values of 264.14 μM. With good specificity and predicted ADMET results, our results support the feasibility by using a pharmacophore of the compound VS1 for designing and optimization of ERBB3 inhibitors.