Blood-based DNA methylation biomarkers have great potential for the early detection of lung cancer (LC). Here, we investigated the association between HYAL2 methylation in peripheral blood and LC.

Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was performed to measure the methylation levels of 4 CpG sites in HYAL2 gene in two independent case-control studies (168 LC cases and 167 controls in Study I, 677 LC cases and 833 controls in Study II). Logistic regression adjusted for covariates was conducted for odds ratios (ORs) and 95% confidence intervals (CIs). Non-parametric tests were applied for the comparisons of stratified groups.

Hypomethylation of all 4 CpG sites in HYAL2 was associated with early-stage LC in the two studies (ORs range from 1.91 to 3.07 in Study I, ORs range from 1.39 to 1.86 in Study II, p < 0.05 for all). The associations were still significant for the very early-stage LC patients (stage I). Subgroup analysis indicated that the associations could be enhanced by male gender and older age. Moreover, decreased HYAL2 methylation was correlated with increased tumor size, tumor length and stage.

Our results suggested blood-based HYAL2 hypomethylation as a potential biomarker for LC early detection.

Systemic chemotherapy plus immune checkpoint inhibitors (ICIs) are first-line treatment for advanced non-small cell lung cancer (NSCLC). However, elderly patients typically have comorbidities that tend to limit the use of chemotherapy at standard dosage and frequency. Drug-eluting bead bronchial arterial chemoembolisation (DEB-BACE)/bronchial arterial chemoembolization (BACE) represents options in such patients.

This is a retrospective analysis. We screened all elderly patients (aged ≥70 years) undergoing treatment with immunotherapy plus DEB-BACE/BACE for pathologically confirmed stage III-IV NSCLC with negative driver gene mutations from October 2019 to December 2023 at our hospital. The response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 criteria.

The final analysis included 46 patients (median age: 76 years; 42 men and 4 women). Eastern Cooperative Oncology Group (ECOG) performance status was either 1 or 2. The median progression-free survival and overall survival were 9.1 months (95% confidence interval [CI]: 8.4-9.9) and 18.2 months (95% CI: 16.5-19.9), respectively, after a median follow-up of 20.3 months (95% CI: 19.5-21.1) in all populations. The most prevalent adverse events (AEs) were myelosuppression (76.1%, 35/46), followed by decreased appetite (71.7%, 33/46), nausea (65.2%, 30/46), and fatigue (54.3%, 25/46). The rate of any grade and grade ≥3 immune-related AEs was 34.8% (16/46) and 6.5% (3/46), respectively. No patients experienced treatment-related deaths, haemoptysis, or unexpected embolisation.

DEB-BACE/BACE combined with immunotherapy was effective and well tolerated in elderly patients with advanced NSCLC.

The upper lobe is the most common site of primary lung cancer, however, very few reports focus on its prognosis. This study aims to identify prognostic factors of lung cancer in the upper lobe, as well as to establish an effective nomogram for individualized overall survival (OS) prediction.

Patients diagnosed with lung cancer were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database for the period of 2010-2017,as recorder in the 2021 SEER database release. The demographic characteristics and OS differed in the primary sites of the upper, middle and lower lobes were drawn. The primary upper lobe lung cancer patients were further stratified by the risk indicators including Mets at DX-bone, stage, histology, grade and sex; and their OS differences in stratification were compared by the Kaplan-Meier method and the Log-Rank test. The univariate and the multivariate Cox regression were employed to determine the independent prognostic factors for the primary upper lobe lung cancer and to build a nomogram model for its OS prediction.

Depending on the different primary sites of lung cancer occurrence, all the collected patients were divided into three groups of the upper lobe (30295 individuals), the middle lobe (2801 individuals) and the lower lobe (16757 individuals), where the upper lobe group gained our attention with the largest population and an overwhelmingly low OS compared to the middle lobe group (P <0.0001). With the results of the univariate and multivariate Cox regression model analyses, age, sex, grade, histology type, stage, regional lymph nodes removed, bone metastasis and liver metastasis were selected as the prognostic factors and a prediction nomogram model was built. The calibration curves showed no significant bias from the reference line and the concordance index between the survival nomogram prediction and the actual outcome for 2-year and 3-year OS was 0.761 (95% CI, 0.757-0.765). The time-dependent receiver operating characteristic curves showed that the areas under curve for 2-year and 3-year OS were 0.840 and 0.836, respectively.

A novel nomogram was established which achieved good performance in predicting the probability of OS in the primary upper lobe lung cancer, indicating its potential value in individualized prediction of the clinical outcome in these patients.

Limited research has explored the effect of high-density lipoprotein cholesterol (HDL-C) on lung cancer's seven autoantibodies (7-AABs). This study investigated the association between serum HDL-C and 7-AABs among 5,574 Chinese adults aged ≥ 18 years from January 2018 to December 2023.

This cross-sectional study utilized physical examination data from the Department of Health Management at Henan Provincial People's Hospital. The associations between HDL-C and autoantibodies, such as tumor protein 53(P53), SRY-box containing gene 2 (SOX2), and ATP-dependent RNA helicase 4-5 (GBU4-5), were modeled using a restricted cubic spline logistic regression model.

After the adjustment for factors, such as age and body mass index, the binary logistic regression model showed distinct correlations between serum HDL-C levels and autoantibodies, including P53, SOX2, and 7-AABs. Restricted cubic spline logistic regression analysis indicated that the increased level of serum HDL-C was associated with a decreased risk of positive P53 (all participants: HDL-C: 1.227-1.366 mmol/L, P HDL-C=0.028), SOX2 (all participants: HDL-C ≥ 1.227 mmol/L, P HDL-C =0.021; all women: HDL-C ≥ 1.224 mmol/L, P HDL-C=0.037), GBU4-5 (all women: HDL-C ≥ 1.269 mmol/L, P HDL-C=0.039), and 7-AABs (all women: HDL-C ≥ 1.224 mmol/L, P HDL-C=0.015). In women, HDL-C levels between 1.163 and 1.224 mmol/L correlated with an increased risk of positive 7-AABs test results.

Elevated HDL-C levels exhibited an independent association with a reduced risk of positivity for 7-AABs of lung cancer, especially in the female physical examination population. These findings suggest that high HDL-C levels may play a role in hindering lung cancer development with gender differences. However, further confirmation is still needed in the future.

The optimal configuration of a smoking cessation intervention in a lung cancer screening (LCS) setting has not yet been established.

To evaluate the efficacy of 3 tobacco treatment strategies of increasing integration and intensity in the LCS setting.

In this randomized clinical trial, LCS-eligible current smokers were randomized into 3 treatments: quitline (QL), QL plus (QL+), or integrated care (IC). The study was conducted from July 2017 to June 2022 at a hospital-based tobacco treatment clinic in Houston, Texas.

The QL intervention group had quitline referral and 12-week nicotine replacement therapy (NRT). The QL+ group had quitline referral plus 12-week NRT or pharmacotherapy prescribed by the LCS clinician. The IC group had 12-week NRT or prescription pharmacotherapy and counseling provided by tobacco treatment specialists within the LCS health care environment.

The original primary outcome was biochemically verified 7-day point prevalence abstinence at 6 months; however, this was changed to self-reported abstinence during the conduct of the study due to COVID-19 pandemic restrictions.

Of 630 participants, 320 (50.8%) were male, and the median (IQR) age was 59 (55-64) years. Participants smoked a median (IQR) of 20 (15-25) cigarettes per day. Each cohort (QL, QL+, and IC) was composed of 210 participants. The median (IQR) number of counseling sessions was 4 (2-5) sessions for both QL and QL+ and 8 (7-9) sessions for IC. At 3 months, 53 participants (25.2%) in QL, 57 (27.1%) in QL+, and 78 (37.1%) in IC reported abstinence. IC outperformed both QL (odds ratio [OR], 1.75 [95% CI, 1.15-2.66]; P = .01) and QL+ (OR, 1.58 [95% CI, 1.05-2.40]; P = .03). At 6 months, IC maintained the highest rate of abstinence with 68 individuals (32.4%), followed by QL+ at 58 (27.6%) and QL at 43 (20.5%). IC outperformed QL at this time point (OR, 1.86 [95% CI, 1.19-2.89]; P = .01). In the bayesian analysis, IC demonstrated a higher probability of positive absolute risk differences (ARDs) in abstinence at 3 months vs QL (ARD, 0.12) with 99% probability of positive ARD, and QL+ (ARD, 0.10) with 98% probability of positive ARD. This advantage was maintained at 6 months with ARDs of 0.12 for QL (probability of positive ARD, 99%) and 0.05 for QL+ (probability of positive ARD, 86%).

In this randomized clinical trial, IC involving medication and intensive counseling provides the best opportunity for smoking cessation relative to QL counseling, with or without LCS clinician-managed medication. Although IC consistently outperformed QL and QL+, differences with QL+ were reduced at 6 months, suggesting QL+ could be considered in low-resource settings.

ClinicalTrials.gov Identifier: NCT03059940.

Low-radiation techniques should be used to detect and follow lung nodules on CT images, but reducing radiation dose to ultra-low-dose CT with submilliSievert dose level would drastically impede image quality and sensitivity for nodule detection. This study investigated the feasibility of using DenseNet to suppress image noise in ultra-low-dose CT for lung cancer screening. DenseNet was trained using input-label pairs from 1, 2, 4, and 6 patients. After training, the model was tested with chest CT from 14 patients that were not used in training process. Seven patients have solid nodules and 7 patients have subsolid nodules. Root mean square error (RMSE) and peak signal-to-noise ratio (PSNR) were calculated to quantify the difference between reference and test images. The contrast-to-noise ratio (CNR) between lung nodule and lung parenchyma was calculated to evaluate the target detectability of chest CT. Subjective image quality assessment was performed using 4-point ranking scale to evaluate the visual quality of CT images perceived by end user. Substantial improvements in RMSE and PSNR were observed after denoising. The lung nodules in denoised images could be distinguished more easily in comparison with those in the original ultra-low-dose CT, which is supported by the CNRs and subjective image quality scores. The comparison of intensity profiles for lung nodules demonstrated that the image noise in ultra-low-dose CT could be suppressed effectively after denoising without causing edge blurring or variation in Hounsfield unit (HU) values. A two-sample t-test revealed no statistically significant differences between full-dose CT and denoised ultra-low-dose CT in the evaluation of lung nodules, lung parenchyma, paraspinal muscle, or vertebral body. Since the linear no-threshold model suggests that no amount of ionizing radiation is entirely risk-free, the quest for further dose reduction remains a consistently important focus in radiology. Overall, our findings suggest that DenseNet could be a viable approach for reducing image noise in ultra-low-dose CT scans used for lung cancer screening.

Coronary artery calcification (CAC) is a well-known cardiovascular risk factor. In the past year, the CAC score has been investigated in lung cancer (LC) screening, suggesting promising results in terms of mortality risk assessment. Nevertheless, its role in patients with LC is still to be investigated. This study aimed to evaluate the performance of a fully automated CAC scoring alone and combined with a prognostic index on the basis of perioperative routine blood tests in predicting 5-year survival of patients with stage I LC.

This study included 536 consecutive patients with stage I LC who underwent preoperative chest computed tomography followed by surgical resection. The CAC score was measured by commercially available, fully automated artificial intelligence software. The primary outcome was the 5-year overall survival rate.

A total of 110 patients (20.5%) had a CAC score greater than or equal to 400, 149 (27.8%) between 100 and 399, and 277 (51.7%) had less than 100. Male smokers had the highest CAC values: 32% compared with only 17% of nonsmokers. Females had lower CAC values compared with males both in smokers and nonsmokers: CAC greater than or equal to 400 only for 10% of smoking females and 0% in nonsmoking females. The 5-year survival was 80.3% overall, 84.7% in CAC less than 100, 77.5% in CAC 100 to 399, and 73.5% in CAC greater than or equal to 400 (p = 0.0047).

We observed that the CAC score predicted the 5-year overall survival in patients with resected stage I LC, both alone and combined with the modified routine blood test score. These results open new prospects for the prevention of noncancer mortality in patients with early-stage LC.

With the widespread use of Low-dose computed tomography (LDCT) in the chest, more and more people will be detected with pulmonary nodules. The presence of uncertainty following the detection of these nodules can impose significant psychological distress. This study aimed to investigate personality traits, psychological distress, and their impact on pulmonary nodule patients in China.

We conducted a cross-sectional survey of adults with pulmonary nodules accidently discovered by LDCT in the chest from the respiratory outpatient department.

A total of 224 patients with pulmonary nodules were included in this study. The prevalence of anxiety among patients with pulmonary nodules was found to be 47.8 %, while the prevalence of depression was reported to be 44.2 %. The present study also demonstrated a higher prevalence of anxiety among female patients with pulmonary nodules compared to their male counterparts, with mild anxiety being the predominant manifestation. The multivariate logistic regression analysis revealed that age (OR = 0.926, P < 0.01), gender (OR = 3.24, P < 0.01), number of pulmonary nodules (OR = 0.586, P < 0.05), lung cancer-related characteristics (OR = 5.423, P < 0.01), PTSD (OR = 5.715, P < 0.01), and Extroversion personality traits (OR = 1.087, P < 0.05) were significant factors contributing to anxiety in patients with pulmonary nodules. Similarly, (OR = 0.891, P < 0.01), gender (OR = 2.981, P < 0.05), duration (OR = 0.663, P < 0.05), lung cancer-related characteristics (OR = 5.707, P < 0.01), PTSD (OR = 4.420, P < 0.01)emerged as key factors associated with depression in this patient population.

Approximately 50 % of patients with pulmonary nodules exhibit negative affective states. Furthermore, as time progresses, the negative emotional burden of anxiety and depression in individuals with pulmonary nodules tends to alleviate.

Distinguishing between benign and malignant pulmonary nodules based on CT imaging features such as the spiculation sign and/or lobulation sign remains challenging and these nodules are often misinterpreted as malignant tumors. this retrospective study aimed to develop a prediction model to estimate the likelihood of benign and malignant lung nodules exhibiting spiculation and/or lobulation signs.

A total of 500 patients with pulmonary nodules from June 2022 to August 2024 were retrospectively analyzed. Among them, 190 patients with spiculation sign and lobar sign or both on CT scan were included in this study. This investigation collected the clinical information, preoperative chest CT imaging characteristics, and postoperative histopathologic results from patients.Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, from which a prediction model and nomogram were developed. In addition, The model performance was assessed through receiver operating characteristic(ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA).

In our study, 190 patients with pulmonary nodules underwent lung biopsy in 10 patients and surgical resection in 180 patients, of whom 53 were benign nodules and 137 were malignant nodules. When combined with the spiculation sign or (and) the lobulation sign, the vascular cluster sign, bronchial architectural distortion, bubble-like translucent area, nodule density, and CEA were found to be significant independent predictors for determining the benignity and malignancy of pulmonary nodules. The nomogram prediction model demonstrated high predictive accuracy with an area under the ROC curve (AUC) of 0.904. Furthermore, the model's calibration curve demonstrated adequate calibration. DCA confirmed the prediction model's validity.

The model can assist clinicians in making more accurate preoperative diagnoses and in guiding clinical decision-making regarding treatment, potentially reducing unnecessary surgical interventions.

Despite the importance of early detection for lung cancer outcomes, staging disparities among the growing US Hispanic population remain underexplored. This population-based study aimed to identify racial/ethnic disparities among non-Hispanic White, non-Hispanic Black, and Hispanic (including specific subgroups) patients in stage at diagnosis for potentially curable non-small cell lung cancer (NSCLC).

Incident NSCLC cases (2005-2018) were extracted from the Florida cancer registry. Stage was categorized as early (localized/regional) or advanced (distant). Multivariable logistic regression assessed the association between race/ethnicity and stage at diagnosis, adjusting for socioeconomic status, smoking, and clinical factors.

Among 157 034 NSCLC patients, 47.8% were diagnosed at an advanced stage. Multivariable models showed higher odds of advanced-stage diagnosis for non-Hispanic Blacks (adjusted odds ratio [ORadj] = 1.22, 95% confidence interval [CI] = 1.17 to 1.26) and Hispanics (ORadj = 1.03, 95% CI = 1.00 to 1.08) compared with non-Hispanic Whites. Regional differences were stark for Hispanics compared with non-Hispanic Whites: ORadj = 0.96 (95% CI = 0.91 to 1.01) in South Florida vs 1.12 (95% CI = 1.05 to 1.19) in the rest of Florida. In South Florida, Central Americans (ORadj = 1.49, 95% CI = 1.20 to 1.85) were the only Hispanic group showing a staging disadvantage compared with non-Hispanic Whites.

Pronounced disparities in NSCLC staging among non-Hispanic Black and Hispanic populations, with notable regional variations within Florida's Hispanic communities, indicate that targeted interventions could significantly enhance early detection. The relative advantage observed in nearly all minority groups in multicultural South Florida compared with the rest of Florida underscores the need for future research exploring how specific Hispanic and multiracial sociocultural contexts can positively influence the landscape of cancer early detection across the United States.

Literature suggests that there is a close relationship between chronic obstructive pulmonary disease (COPD) and cardiovascular (CV) disease. The aim of this study was to assess whether the presence of coronary calcium (CC) on chest computed tomography (CT) in asymptomatic COPD patients is associated with an increased risk of CV events and mortality.

A systematic review of the literature was performed following PRISMA recommendations. Studies published in the last 20 years in four databases (PubMed, Web of Science, Embase and MEDLINE) were included.

Three hundred fifty articles were identified, eight of them met the selection criteria. The included studies, conducted between 2013 and 2024, were predominantly multicentre cohort studies. The meta-analysis showed that the presence of CC on chest CT of COPD patients is an independent predictor of CV events (hazard ratio 1.44, 95% CI 1.22-1.70) and associated with an increased mortality during the follow-up period (hazard ratio 1.57, 95% CI 1.35-1.83).

Our analysis suggests that the identification of CC on chest CT scans of COPD patients may be useful in the early detection and treatment of CV disease in asymptomatic patients. Prospective, multicentre studies confirming our findings are needed to explore the potential impact of early detection and treatment of CV risk in COPD patients.

Lung cancer screening is still in an early phase compared to other cancer screening programs, despite its high lethality particularly when diagnosed late. Achieving early diagnosis is crucial to obtain optimal outcomes.

In this review, we will address the current evidence on lung cancer screening through low-dose computed tomography (LDCT) and its impact on mortality reduction, existing screening recommendations, patient eligibility criteria, screening frequency and duration, benefits and harms, cost-effectiveness and some insights on lung cancer screening implementation and adoption. Additionally, new non-imaging, noninvasive biomarkers with high diagnostic potential are also briefly highlighted.

LDCT screening in a prespecified population based on age and smoking history proved to reduce lung cancer mortality. Optimization of the target population and management of LDCT pitfalls can further improve lung cancer screening efficiency and cost-effectiveness. Novel screening technologies and biomarkers being studied can potentially be game-changers in lung cancer screening and diagnosis.

Recent advances in lung cancer treatment have led to dramatic improvements in 5-year survival rates. And yet, lung cancer remains the leading cause of cancer-related mortality, in large part, because it is often diagnosed at an advanced stage, when cure is no longer possible. Lung cancer screening (LCS) is essential for intercepting the disease at an earlier stage. Unfortunately, LCS has been poorly adopted in the United States, with less than 5% of eligible patients being screened nationally. This article will describe the data supporting LCS, the obstacles to LCS implementation, and the promising opportunities that lie ahead.

Foreign-born populations in the United States have markedly increased, yet cancer trends remain unexplored. Survey-based Population-Adjusted Rate Calculator (SPARC) is a new tool for evaluating nativity differences in cancer mortality.

Using SPARC, we calculated 3-year (2016-2018) age-adjusted mortality rates and rate ratios for common cancers by sex, age group, race and ethnicity, and nativity. Trends by nativity were examined for the first time for 2006-2018. Traditional cancer statistics draw populations from decennial censuses. However, nativity-stratified populations are from the American Community Surveys, thus involve sampling errors. To rectify this, SPARC employed bias-corrected estimators. Death counts came from the National Vital Statistics System.

Age-adjusted mortality rates were higher among US-born populations across nearly all cancer types, with the largest US-born, foreign-born difference observed in lung cancer among Black women (rate ratio = 3.67, 95% confidence interval [CI] = 3.37 to 4.00). The well-documented White-Black differences in breast cancer mortality existed mainly among US-born women. For all cancers combined, descending trends were more accelerated for US-born compared with foreign-born individuals in all race and ethnicity groups with changes ranging from -2.6% per year in US-born Black men to stable (statistically nonsignificant) among foreign-born Black women. Pancreas and liver cancers were exceptions with increasing, stable, or decreasing trends depending on nativity and race and ethnicity. Notably, foreign-born Black men and foreign-born Hispanic men did not show a favorable decline in colorectal cancer mortality.

Although all groups show beneficial cancer mortality trends, those with higher rates in 2006 have experienced sharper declines. Persistent disparities between US-born and foreign-born individuals, especially among Black people, necessitate further investigation.

To investigate the computed tomography (CT) characteristics of air-containing space and its specific patterns in neoplastic and non-neoplastic ground glass nodules (GGNs) for clarifying their significance in differential diagnosis.

From January 2015 to October 2022, 1328 patients with 1,350 neoplastic GGNs and 462 patients with 465 non-neoplastic GGNs were retrospectively enrolled. Their clinical and CT data were analyzed and compared with emphasis on revealing the differences of air-containing space and its specific patterns (air bronchogram and bubble-like lucency [BLL]) between neoplastic and non-neoplastic GGNs and their significance in differentiating them.

Compared with patients with non-neoplastic GGNs, female was more common (P < 0.001) and lesions were larger (P < 0.001) in those with neoplastic ones. Air bronchogram (30.1% vs. 17.2%), and BLL (13.0% vs. 2.6%) were all more frequent in neoplastic GGNs than in non-neoplastic ones (each P < 0.001), and the BLL had the highest specificity (93.6%) in differentiation. Among neoplastic GGNs, the BLL was more frequently detected in the larger (14.9 ± 6.0 mm vs. 11.4 ± 4.9 mm, P < 0.001) and part-solid (15.3% vs. 10.7%, P = 0.011) ones, and its incidence significantly increased along with the invasiveness (9.5-18.0%, P = 0.001), whereas no significant correlation was observed between the occurrence of BLL and lesion size, attenuation, or invasiveness.

The air containing space and its specific patterns are of great value in differentiating GGNs, while BLL is a more specific and independent sign of neoplasms.

Low-dose computed tomography (LDCT) has been shown useful in early lung cancer detection. This study aimed to develop a novel deep learning model for detecting pulmonary nodules on chest LDCT images.

In this secondary analysis, three lung nodule datasets, including Lung Nodule Analysis 2016 (LUNA16), Lung Nodule Received Operation (LNOP), and Lung Nodule in Health Examination (LNHE), were used to train and test deep learning models. The 3D region proposal network (RPN) was modified via a series of pruning experiments for better predictive performance. The performance of each modified deep leaning model was evaluated based on sensitivity and competition performance metric (CPM). Furthermore, the performance of the modified 3D RPN trained on three datasets was evaluated by 10-fold cross validation. Temporal validation was conducted to assess the reliability of the modified 3D RPN for detecting lung nodules.

The results of pruning experiments indicated that the modified 3D RPN composed of the Cross Stage Partial Network (CSPNet) approach to Residual Network (ResNet) Xt (CSP-ResNeXt) module, feature pyramid network (FPN), nearest anchor method, and post-processing masking, had the optimal predictive performance with a CPM of 92.2%. The modified 3D RPN trained on the LUNA16 dataset had the highest CPM (90.1%), followed by the LNOP dataset (CPM: 74.1%) and the LNHE dataset (CPM: 70.2%). When the modified 3D RPN trained and tested on the same datasets, the sensitivities were 94.6%, 84.8%, and 79.7% for LUNA16, LNOP, and LNHE, respectively. The temporal validation analysis revealed that the modified 3D RPN tested on LNOP test set achieved a CPM of 71.6% and a sensitivity of 85.7%, and the modified 3D RPN tested on LNHE test set had a CPM of 71.7% and a sensitivity of 83.5%.

A modified 3D RPN for detecting lung nodules on LDCT scans was designed and validated, which may serve as a computer-aided diagnosis system to facilitate lung nodule detection and lung cancer diagnosis.

Observational studies have suggested a link between severe mental illness (SMI) and risk of lung carcinoma (LC); however, causality has not been established. In this study, we conducted a two-sample, two-step Mendelian randomization (MR) investigation to uncover the etiological influence of SMI on LC risk and quantify the mediating effects of known modifiable risk factors. We obtained summary-level datasets for schizophrenia, major depressive disorder (MDD), and bipolar disorder (BD) from the Psychiatric Genomics Consortium (PGC). Data on single nucleotide polymorphisms (SNPs) associated with lung carcinoma (LC) were sourced from a recent large meta-analysis by McKay et al. We employed two-sample MR and two-step MR utilizing the inverse variance weighted method for causal estimation. Sensitivity tests were conducted to validate causal relationships. In two-sample MR, we identified schizophrenia as a risk factor for LC (OR = 1.06, 95% CI 1.02-1.11, P = 3.48E-03), while MDD (OR = 1.18, 95% CI 0.98-1.42, P = .07) and BD (OR = 1.07, 95% CI 0.99-1.15, P = .09) showed no significant association with LC. In the two-step MR, smoking accounted for 24.66% of the schizophrenia-LC risk association, and alcohol consumption explained 7.59% of the effect. Schizophrenia is a risk factor for lung carcinoma, and smoking and alcohol consumption are the mediating factors in this causal relationship. LC screening should be emphasized in individuals with schizophrenia, particularly in those who smoke and consume alcohol regularly.

Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings.

High-risk subjects were defined as being >55 years of age and active smokers or formers who had quit within 15 years (>30 pack/y). A PLCOm2012 threshold >2% was chosen. Subject outreach was streamlined through media campaign and general practitioners' engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the "Maisonneuve risk re-calculation model", and a threshold <0.6% was chosen for the biennial round.

In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M/F 62/38%), with a mean PLCOm2012 of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers.

LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.

To investigate the distribution pattern of V1+2 d in the left superior pulmonary vein and its clinical significance.

A retrospective analysis was conducted using three-dimensional computed tomographic bronchography and angiography (3D-CTBA) data from 500 lung cancer patients. Statistical analyses were performed to evaluate the incidence and drainage patterns of the three sub-branches of V1+2 d, namely V1+2 d1, V1+2 d2 and V1+2 d3. Furthermore, clinical data from 10 patients' lesions involving V1+2 d were reviewed to illustrate the impact of adjacency to V1+2 d on the surgical approach.

The incidences of V1+2 d1, V1+2 d2 and V1+2 d3 were 100%, 76.4% and 100% respectively. The relative interlobar distribution sizes of B3 a and B1+2 c and the left upper division (LUD) vein type influenced the incidence of V1+2 d2 (p < 0.05; p < 0.001). V1+2 d2 predominantly occurred in B3 a = B1+2 c and B1+2 c > B3 a patterns. V1+2 d2 was entirely absent in the B3 a > B1+2 c pattern. V1+2 d2 exhibited a higher incidence in both the central vein (CV) type and the noncentral vein (NCV) type when compared to the semi-central vein (SCV) type (100% vs. 100% vs. 64.8%). The most prevalent venous drainage pattern was the three sub-branches of V1+2 d constituting a major trunk to drain (41.2%). All 10 cases with lesions involving V1+2 d successfully underwent sublobar resection with no complications, and the surgical margin was ≥2 cm.

The three sub-branches of V1+2 d exhibit a high incidence with diverse distribution patterns, yet a discernible pattern exists. For inter- or multi-intersegmental nodules involving V1+2 d, combined segmentectomy and subsegmentectomy or combined subsegmentectomy can ensure the safe margin.

Background: Lung cancer screening is not limited to low dose computed tomography (LDCT). Recently, molecular biomarkers have been shown to have the potential to improve the current state of early lung cancer detection. The current study determined the efficiency of seven autoantibodies against tumor-associated antigens (7-AABs) and tumor markers in patients with lung cancer. Materials and Methods: An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 7-AABs and tumor markers in 354 patients with lung cancer and 108 patients with benign pulmonary disease under care at Ethics Committee of Tianjin Medical University General Hospital. Results: The sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic (ROC) curve of 7-AABs were 30.0%, 84.3%, 86.3%, and 0.61, respectively. When combining the 7-AABs and tumor markers, the sensitivity was 68.6%, the specificity was 52.8%, and the area under the ROC curve was 0.72. The 7-AABs positive expression rate in lung cancer patients was significantly higher than patients with benign pulmonary diseases (30.1% vs 15.7%); however, the 7-AABs positive expression rate was affected by clinical features and pathologic stages. When combining 7-AABs and tumor markers, the combined 7-AABs and tumor marker positive expression rate increased to 68.6%. Conclusion: Based on this study and previous literature, the supplemental diagnostic value of 7-AABs has been confirmed; however, due to the low sensitivity, the value of 7-AABs alone in lung cancer screening is limited. The combination of 7-AABs and tumor markers has improved sensitivity and positivity, but decreased specificity, which makes their performance in cancer screening and early detection worthy of further research.

In 2023, Journal of Primary Care and Community Health published the results of 4 outstanding studies in which investigators aimed to explore and improve clinician and eligible individuals' knowledge of the rationale for lung cancer screening (LCS). Their results highlighted the underutilization of LCS, particularly for certain high risk populations, and the continued disparities in screening seen between groups of eligible individuals. Here, key findings from those 2023 Journal of Primary Care and Community Health reports, along with salient findings of other recent LCS reports, are discussed. The bases for the United States Preventive Task Force (USPSTF) LCS recommendations, barriers primary care providers face, the perspective of eligible individuals, importance of shared decision-making (SDM) and disparities between groups in LCS are reviewed along with potential strategies to ensure that more eligible individuals are offered LCS.

Lung cancer is the leading cause of cancer death, but the advent of lung cancer screening using low-dose computed tomography offers a tremendous opportunity to improve lung cancer outcomes. Unfortunately, implementation of lung cancer screening has been hampered by substantial barriers and remains suboptimal. Specifically, the commentary emphasizes the intersectionality of smoking history and several important sociodemographic characteristics and identities that should inform lung cancer screening outreach and engagement efforts, including socioeconomic considerations (e.g., health insurance status), racial and ethnic identity, LGBTQ + identity, mental health history, military experience/veteran status, and geographic residence in addressing specific community risk factors and future interventions in efforts to make strides toward equitable lung cancer screening.

Members of the Equitable Implementation of Lung Cancer Screening Interest Group with the Cancer Prevention and Control Network (CPCRN) provide a critical commentary based on existing literature regarding smoking trends in the US and lung cancer screening uptake to propose opportunities to enhance implementation and support equitable distribution of the benefits of lung cancer screening.

The present commentary utilizes information about historical trends in tobacco use to highlight opportunities for targeted outreach efforts to engage communities at high risk with information about the lung cancer screening opportunity. Future efforts toward equitable implementation of lung cancer screening should focus on multi-level implementation strategies that engage and work in concert with community partners to co-create approaches that leverage strengths and reduce barriers within specific communities to achieve the potential of lung cancer screening.

The prognosis of conventionally diagnosed lung cancer patients is still rather poor. Two large, randomized trials using screening by low dose CT could demonstrate that early detection in persons with smoking as risk factor can improve this prognosis. Early detection of lung cancer can be achieved by structured screening programs using low dose CT for persons at increased risk, but in addition also by consequent management of incidental pulmonary nodules, which are seen on imaging for other reasons. Integral part of these programs should be prevention measures, especially a consequent, repeated, low-threshold offer of a service for smoking cessation. Programs for lung cancer screening for persons at increased risk are only beneficial for the screenees and cost-effective, if the various parts of the program are optimally integrated and coordinated and all necessary disciplines (especially respiratory medicine, radiology, pathology, thoracic surgery, radiotherapy) are included in a multidisciplinary manner. For Germany the certified lung cancer centres in structured cooperation with physicians in private practice (respiratory physicians, radiologists, general practitioners) would be a good option. It is essential that there is a good perception for the need of early detection of lung cancer in politics and the public and that the persons at risk are reached, contacted and motivated by various methods.

Non-small cell lung cancer (NSCLC) accounts for more than 80 % of all lung cancers, and its 5-year survival rate can be greatly improved by early diagnosis. However, early diagnosis remains elusive because of the lack of effective biomarkers. In this study, we aimed to develop an effective diagnostic model for NSCLC based on a combination of circulating biomarkers.

Tissue-deregulated long noncoding RNAs (lncRNAs) in NSCLC were identified in datasets retrieved from the Gene Expression Omnibus (GEO, n=727) and The Cancer Genome Atlas (TCGA, n=1,135) databases, and their differential expression was verified in paired local plasma and exosome samples from NSCLC patients. Subsequently, LASSO regression was used to screen for biomarkers in a large clinical population, and a logistic regression model was used to establish a multi-marker diagnostic model. The area under the receiver operating characteristic (ROC) curve (AUC), calibration plots, decision curve analysis (DCA), clinical impact curves, and integrated discrimination improvement (IDI) were used to evaluate the efficiency of the diagnostic model.

Three lncRNAs-PGM5-AS1, SFTA1P, and CTA-384D8.35 were consistently expressed in online tissue datasets, plasma, and exosomes from local patients. LASSO regression identified nine variables (Plasma CTA-384D8.35, Plasma PGM5-AS1, Exosome CTA-384D8.35, Exosome PGM5-AS1, Exosome SFTA1P, Log10CEA, Log10CA125, SCC, and NSE) in clinical samples that were eventually included in the multi-marker diagnostic model. Logistic regression analysis revealed that Plasma CTA-384D8.35, exosome SFTA1P, Log10CEA, Exosome CTA-384D8.35, SCC, and NSE were independent risk factors for NSCLC (p<0.01), and their results were visualized using a nomogram to obtain personalized prediction outcomes. The constructed diagnostic model demonstrated good NSCLC prediction ability in both the training and validation sets (AUC=0.97).

In summary, the constructed circulating lncRNA-based diagnostic model has good NSCLC prediction ability in clinical samples and provides a potential diagnostic tool for NSCLC.

Shared Decision-Making to discuss how the benefits and harms of lung cancer screening align with patient values is required by the US Centers for Medicare and Medicaid and recommended by multiple organizations. Barriers at organizational, clinician, clinical encounter, and patient levels prevent SDM from meeting quality standards in routine practice. We developed an implementation plan, using the socio-ecological model, for Shared Decision-Making for lung cancer screening for the Department of Veterans Affairs (VA) New England Healthcare System. Because understanding the local context is critical to implementation success, we sought to proactively tailor our original implementation plan, to address barriers to achieving guideline-concordant lung cancer screening.

We conducted a formative evaluation using an ethnographic approach to proactively identify barriers to Shared Decision-Making and tailor our implementation plan. Data consisted of qualitative interviews with leadership and clinicians from seven VA New England medical centers, regional meeting notes, and Shared Decision-Making scripts and documents used by providers. Tailoring was guided by the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS).

We tailored the original implementation plan to address barriers we identified at the organizational, clinician, clinical encounter, and patient levels. Overall, we removed two implementation strategies, added five strategies, and modified the content of two strategies. For example, at the clinician level, we learned that past personal and clinical experiences predisposed clinicians to focus on the benefits of lung cancer screening. To address this barrier, we modified the content of our original implementation strategy Make Training Dynamic to prompt providers to self-reflect about their screening beliefs and values, encouraging them to discuss both the benefits and potential harms of lung cancer screening.

Formative evaluations can be used to proactively tailor implementation strategies to fit local contexts. We tailored our implementation plan to address unique barriers we identified, with the goal of improving implementation success. The FRAME-IS aided our team in thoughtfully addressing and modifying our original implementation plan. Others seeking to maximize the effectiveness of complex interventions may consider using a similar approach.

As lung cancer screening is rolled-out, there is a need to develop an effective quality assurance (QA) framework around radiology reporting to ensure optimal implementation. Here, we report a structured QA process for low-dose CT (LDCT) scans performed in the Yorkshire Lung Screening Trial.

Negative LDCT scans were single read after using computer-aided detection software. The radiology QA process included reviewing 5% of negative scans selected at random, and all cases with a subsequent diagnosis of extrapulmonary cancer or interval lung cancer not detected on the baseline scan. Radiologists were not informed of the reason for review and original radiology reports were scored as either "satisfactory", "satisfactory with learning points", or "unsatisfactory".

From 6650 participants undergoing LDCT screening, 208 negative scans were reviewed alongside 11 cases with subsequent extrapulmonary cancer and 10 cases with interval lung cancer. Overall, only three reports were ultimately judged "unsatisfactory", 1% of randomly selected negative scans (n = 2/208) and one interval lung cancer scan (n = 1/10). Four out of a total of five cases judged "satisfactory with learning points" were related to oesophageal abnormalities where the participant was subsequently diagnosed with oesophageal cancer.

The described process attempts to minimise bias in retrospective review of screening scans, and may represent a framework for future QA of national screening programmes.

This study describes a structured QA process for a lung cancer screening programme, involving blinded second-read of LDCT screening scans to ensure fair, constructive audit of clinical performance.

The incidence and mortality of hepatocellular carcinoma (HCC) have been increasing around the world. Current guidelines recommend HCC screening in high-risk population. However, the strength of evidence of benefits and harms of HCC screening to support the recommendation was unclear. The objective is to systematically synthesize current evidence on the benefits and harms of HCC screening.

We searched PubMed and nine other databases until August 20, 2021. We included cohort studies and RCTs that compared the benefits and harms of screening and non-screening in high-risk population of HCC. Case series studies that reported harms of HCC screening were also included. Pooled risk ratio (RR), according to HCC screening status, was calculated for each benefit outcome (e.g., HCC mortality, survival rate, proportion of early HCC), using head-to-head meta-analysis. The harmful outcomes (e.g., proportion of physiological harms provided by non-comparative studies were pooled by prevalence of meta-analysis. Analysis on publication bias and quality of life, subgroup analysis, and sensitivity analysis were also conducted.

We included 70 studies, including four random clinical trials (RCTs), 63 cohort studies,three case series studies. The meta-analysis of RCTs showed HCC screening was significantly associated with reduced HCC mortality (RR [risk ratio], 0.73 [95% CI, 0.56-0.96]; I 2 = 75.1%), prolonged overall survival rates (1-year, RR, 1.72 [95% CI, 1.13-2.61]; I 2 = 72.5%; 3-year, RR, 2.86 [95% CI, 1.78-4.58]; I 2 = 10.1%; and 5-year, RR, 2.76 [95% CI, 1.37-5.54]; I 2 = 28.3%), increased proportion of early HCC detection (RR, 2.68 [95% CI, 1.77-4.06]; I 2 = 50.4%). Similarly, meta-analysis of cohort studies indicated HCC screening was more effective than non-screening. However, pooled proportion of physiological harms was 16.30% (95% CI: 8.92%-23.67%) and most harms were of a mild to moderate severity.

The existing evidence suggests HCC screening is more effective than non-screening in high-risk population. However, harms of screening should not be ignored.

There is a need for biomarkers that improve accuracy compared with current demographic risk indices to detect individuals at the highest lung cancer risk. Improved risk determination will enable more effective lung cancer screening and better stratification of lung nodules into high or low-risk category. We previously reported discovery of a biomarker for lung cancer risk characterized by increased prevalence of TP53 somatic mutations in airway epithelial cells (AEC). Here we present results from a validation study in an independent retrospective case-control cohort.

Targeted next generation sequencing was used to identify mutations within three TP53 exons spanning 193 base pairs in AEC genomic DNA.

TP53 mutation prevalence was associated with cancer status (P < 0.001). The lung cancer detection receiver operator characteristic (ROC) area under the curve (AUC) for the TP53 biomarker was 0.845 (95% confidence limits 0.749-0.942). In contrast, TP53 mutation prevalence was not significantly associated with age or smoking pack-years. The combination of TP53 mutation prevalence with PLCOM2012 risk score had an ROC AUC of 0.916 (0.846-0.986) and this was significantly higher than that for either factor alone (P < 0.03).

These results support the validity of the TP53 mutation prevalence biomarker and justify taking additional steps to assess this biomarker in AEC specimens from a prospective cohort and in matched nasal brushing specimens as a potential non-invasive surrogate specimen.

Nearly half of the 14.8 million US adults eligible for lung cancer screening (LCS) smoke cigarettes. The optimal smoking cessation program components for the LCS setting are unclear.

To assess the effect of adding a referral to prescription medication therapy management (MTM) to the tobacco longitudinal care (TLC) program among patients eligible for LCS who smoke and do not respond to early tobacco treatment and to assess the effect of decreasing the intensity of TLC among participants who do respond to early treatment.

This randomized clinical trial included patients who currently smoked cigarettes daily and were eligible for LCS. Recruitment took place at primary care centers and LCS programs at 3 large health systems in the US and began in October 2016, and 18-month follow-up was completed April 2021.

(1) TLC comprising intensive telephone coaching and combination nicotine replacement therapy for 1 year with at least monthly contact; (2) TLC with MTM, MTM offered pharmacist-referral for prescription medications; and (3) Quarterly TLC, intensity of TLC was decreased to quarterly contact. Intervention assignments were based on early response to tobacco treatment (abstinence) that was assessed either 4 weeks or 8 weeks after treatment initiation.

Self-reported, 6-month prolonged abstinence at 18-month.

Of 636 participants, 228 (35.9%) were female, 564 (89.4%) were White individuals, and the median (IQR) age was 64.3 (59.6-68.8) years. Four weeks or 8 weeks after treatment initiation, 510 participants (80.2%) continued to smoke (ie, early treatment nonresponders) and 126 participants (19.8%) had quit (ie, early treatment responders). The 18 month follow-up survey response rate was 83.2% (529 of 636). Across TLC groups at 18 months follow-up, the overall 6-month prolonged abstinence rate was 24.4% (129 of 529). Among the 416 early treatment nonresponders, 6-month prolonged abstinence for TLC with MTM vs TLC was 17.8% vs 16.4% (adjusted odds ratio [aOR] 1.13; 95% CI, 0.67-1.89). In TLC with MTM, 98 of 254 participants (39%) completed at least 1 MTM visit. Among 113 early treatment responders, 6-month prolonged abstinence for Quarterly TLC vs TLC was 24 of 55 (43.6%) vs 34 of 58 (58.6%) (aOR, 0.54; 95% CI, 0.25-1.17).

In this randomized clinical trial, adding referral to MTM with TLC for participants who did not respond to early treatment did not improve smoking abstinence. Stepping down to Quarterly TLC among early treatment responders is not recommended. Integrating longitudinal tobacco cessation care with LCS is feasible and associated with clinically meaningful quit rates.

ClinicalTrials.gov Identifier: NCT02597491.

Interstitial lung abnormalities (ILA) are relatively common incidental findings in participants undergoing low-dose CT screening for lung cancer. Some ILA are transient and inconsequential, but others represent interstitial lung disease (ILD). Lung cancer screening therefore offers the opportunity of earlier diagnosis and treatment of ILD for some screening participants.

The prevalence of ILA in participants in the baseline screening round of the Yorkshire Lung Screening Trial is reported, along with the proportion referred to a regional ILD service, eventual diagnoses, outcomes and treatments.

Of 6650 participants undergoing screening, ILA were reported in 169 (2.5%) participants. Following review in a screening review meeting, 56 participants were referred to the ILD service for further evaluation (0.8% of all screening participants). 2 participants declined referral, 1 is currently awaiting review and the remaining 53 were confirmed as having ILD. Eventual diagnoses were idiopathic pulmonary fibrosis (n=14), respiratory bronchiolitis ILD (n=4), chronic hypersensitivity pneumonitis (n=2), connective tissue disease/rheumatoid arthritis-related ILD (n=4), asbestosis (n=1), idiopathic non-specific interstitial pneumonia (n=1), sarcoidosis (n=1) and pleuroparenchymal fibroelastosis (n=1). Twenty five patients had unclassifiable idiopathic interstitial pneumonia. Overall, 10 people received pharmacotherapy (7 antifibrotics and 3 prednisolone) representing 18% of those referred to the ILD service and 0.15% of those undergoing screening. 32 people remain under surveillance in the ILD service, some of whom may require treatment in future.

Lung cancer screening detects clinically significant cases of ILD allowing early commencement of disease-modifying treatment in a proportion of participants. This is the largest screening cohort to report eventual diagnoses and treatments and provides an estimate of the level of clinical activity to be expected by ILD services as lung cancer screening is implemented. Further research is needed to clarify the optimal management of screen-detected ILD.

ISRCTN42704678.

To assess automated coronary artery calcium (CAC) and quantitative emphysema (percentage of low attenuation areas [%LAA]) for predicting mortality and lung cancer (LC) incidence in LC screening. To explore correlations between %LAA, CAC, and forced expiratory value in 1 second (FEV 1 ) and the discriminative ability of %LAA for airflow obstruction.

Baseline low-dose computed tomography scans of the BioMILD trial were analyzed using an artificial intelligence software. Univariate and multivariate analyses were performed to estimate the predictive value of %LAA and CAC. Harrell C -statistic and time-dependent area under the curve (AUC) were reported for 3 nested models (Model survey : age, sex, pack-years; Model survey-LDCT : Model survey plus %LAA plus CAC; Model final : Model survey-LDCT plus selected confounders). The correlations between %LAA, CAC, and FEV 1 and the discriminative ability of %LAA for airflow obstruction were tested using the Pearson correlation coefficient and AUC-receiver operating characteristic curve, respectively.

A total of 4098 volunteers were enrolled. %LAA and CAC independently predicted 6-year all-cause (Model final hazard ratio [HR], 1.14 per %LAA interquartile range [IQR] increase [95% CI, 1.05-1.23], 2.13 for CAC ≥400 [95% CI, 1.36-3.28]), noncancer (Model final HR, 1.25 per %LAA IQR increase [95% CI, 1.11-1.37], 3.22 for CAC ≥400 [95%CI, 1.62-6.39]), and cardiovascular (Model final HR, 1.25 per %LAA IQR increase [95% CI, 1.00-1.46], 4.66 for CAC ≥400, [95% CI, 1.80-12.58]) mortality, with an increase in concordance probability in Model survey-LDCT compared with Model survey ( P <0.05). No significant association with LC incidence was found after adjustments. Both biomarkers negatively correlated with FEV 1 ( P <0.01). %LAA identified airflow obstruction with a moderate discriminative ability (AUC, 0.738).

Automated CAC and %LAA added prognostic information to age, sex, and pack-years for predicting mortality but not LC incidence in an LC screening setting. Both biomarkers negatively correlated with FEV 1 , with %LAA enabling the identification of airflow obstruction with moderate discriminative ability.

Pulmonary and extrapulmonary incidental findings are frequently identified on CT scans performed for lung cancer screening. Uncertainty regarding their clinical significance and how and when such findings should be reported back to clinicians and participants persists. We examined the prevalence of non-malignant incidental findings within a lung cancer screening cohort and investigated the morbidity and relevant risk factors associated with incidental findings. We quantified the primary and secondary care referrals generated by our protocol.

The SUMMIT study (NCT03934866) is a prospective observational cohort study to examine the performance of delivering a low-dose CT (LDCT) screening service to a high-risk population. Spirometry, blood pressure, height/weight and respiratory history were assessed as part of a Lung Health Check. Individuals at high risk of lung cancer were offered an LDCT and returned for two further annual visits. This analysis is a prospective evaluation of the standardised reporting and management protocol for incidental findings developed for the study on the baseline LDCT.

In 11 115 participants included in this analysis, the most common incidental findings were coronary artery calcification (64.2%) and emphysema (33.4%). From our protocolised management approach, the number of participants requiring review for clinically relevant findings in primary care was 1 in 20, and the number potentially requiring review in secondary care was 1 in 25.

Incidental findings are common in lung cancer screening and can be associated with reported symptoms and comorbidities. A standardised reporting protocol allows systematic assessment and standardises onward management.

Environmental and occupational exposures have been associated with an increased risk of different types of cancers, although the exact mechanisms of higher carcinogenesis risk are not always well understood. Lung cancer is the leading cause of global cancer mortality, and, also, genitourinary neoplasms are among the main causes of cancer-related deaths in Western countries. The purpose of this review is to describe the main environmental and occupational factors that increase the risk of developing lung and genitourinary cancers and to investigate carcinogenesis mechanisms that link these agents to cancer onset. Further objectives are to identify methods for the prevention or the early detection of carcinogenic agents and, therefore, to reduce the risk of developing these cancers or to detect them at earlier stages.

Though decreasing in incidence and mortality in the USA, lung cancer remains the deadliest of all cancers. For a significant number of patients, the emergency department (ED) provides the first pivotal step in lung cancer prevention, diagnosis, and management. As screening recommendations and treatments advance, ED providers must stay up-to-date with the latest lung cancer recommendations. The purpose of this review is to identify the many ways that emergency providers may intersect with the disease spectrum of lung cancer and provide an updated array of knowledge regarding detection, management, complications, and interdisciplinary care.

Lung cancer, encompassing 10-12% of cancer-related emergency department visits and a 66% admission rate, is the most fatal malignancy in both men and women. Most patients presenting to the ED have not seen a primary care provider or undergone screening. Ultimately, half of those with a new lung cancer diagnosis in the ED die within 1 year. Incidental findings on computed tomography are mostly benign, but emergency staff must be aware of the factors that make them high risk. Radiologic presentations range from asymptomatic nodules to diffuse metastatic lesions with predominately pulmonary symptoms, and some may present with extra-thoracic manifestations including neurologic. The short-term prognosis for ED lung cancer patients is worse than that of other malignancies. Screening offers new hope through earlier diagnosis but is underutilized which may be due to racial and socioeconomic disparities. New treatments provide optimism but lead to new complications, some long-term. Multidisciplinary care is essential, and emergency medicine is responsible for the disposition of patients to the appropriate specialists at inpatient and outpatient centers.

ED providers are intimately involved in all aspects of lung cancer care. Risk factor modification and referral for lung cancer screening are opportunities to further enhance patient care. In addition, with the advent of newer cancer therapies, ED providers must stay vigilant and up-to-date with all aspects of lung cancer including disparities, staging, symptoms of disease, prognosis, treatment, and therapy-related complications.

Due to lack of effective biomarkers for non-small cell lung cancer (NSCLC), many patients are diagnosed at an advanced stage, which leads to poor prognosis. Dysregulation of N6-methyladenosine (m⁶A) RNA contributes significantly to tumorigenesis and tumor progression. However, the diagnostic value of m⁶A RNA status in peripheral blood to screen NSCLC remains unclear.

Peripheral blood samples from 152 NSCLC patients and 64 normal controls (NCs) were applied to assess the m⁶A RNA levels. Bioinformatics and qRT-PCR analysis were performed to identify the specific immune cells in peripheral blood cells and investigate the mechanism of the alteration of m⁶A RNA levels.

Robust elevation of m⁶A RNA levels of peripheral blood cells was exhibited in the NSCLC group. Moreover, the m⁶A levels increased as NSCLC progressed, and reduced after treatment. The m⁶A levels contained area under the curve (AUC) was 0.912, which was remarkably greater than the AUCs for CEA (0.740), CA125 (0.743), SCC (0.654), and Cyfra21-1 (0.730). Furthermore, the combination of these traditional biomarkers with m⁶A levels elevated the AUC to 0.970. Further analysis established that the expression of m⁶A erasers FTO and ALKBH5 were both markedly reduced and negatively correlated with m⁶A levels in peripheral blood of NSCLC. Additionally, GEO database and flow cytometry analysis implied that FTO and ALKBH5 attributes to peripheral CD4⁺ T cells proportion and activated the immune functions of T cells.

These findings unraveled that m⁶A RNA of peripheral blood immune cells was a prospective biomarker for the diagnosis of NSCLC.

The optimal management of small but growing nodules remains unclear. The SUMMIT study nodule management algorithm uses a specific threshold volume of 200 mm3 before referral of growing solid nodules to the multidisciplinary team for further investigation is advised, with growing nodules below this threshold kept under observation within the screening programme. Malignancy risk of growing solid nodules of size >200 mm3 at initial 3-month interval scan was 58.3% at a per-nodule level, compared with 13.3% in growing nodules of size ≤200 mm3 (relative risk 4.4, 95% CI 2.17 to 8.83). The positive predictive value of a combination of nodule growth (defined as percentage volume change of ≥25%), and size >200 mm3 was 65.9% (29/44) at a cancer-per-nodule basis, or 60.5% (23/38) on a cancer-per-participant basis. False negative rate of the protocol was 1.9% (95% CI 0.33% to 9.94%). These findings support the use of a 200 mm3 minimum volume threshold for referral as effective at reducing unnecessary multidisciplinary team referrals for small growing nodules, while maintaining early-stage lung cancer diagnosis.