Lung Cancer Cases Research Articles

Abstract A132: Missed Opportunities? Regional availability of Low Dose CT lung cancer screening facility locations in the year prior to diagnoses: A descriptive comparison of American Indian and Non-Hispanic White lung cancer patients in North Carolina

Abstract INTRODUCTION American Indians (AI) have much higher incidence rates of lung cancer (LC) compared with non-Hispanic Whites (NHW) in the US. While low-dose computed tomography (LDCT) screening facilitates early detection of lung cancer, it is unknown how available LDCT screenings are to racially and geographically diverse populations in North Carolina (NC). To address this gap in knowledge, we conducted a descriptive study to characterize incident LC cases among AIs and NHWs, the distance from their location at diagnosis to the nearest LDCT screening facility and explored whether distance was associated with late-stage LC diagnoses. Methods Data were obtained from the Cancer Information and Population Health Resource (CIPHR), which comprise data from NC Central Cancer Registry (CCR) as well as public and private health insurance claims for the state. We identified ZIP codes and dates of rendered service for facilities providing LDCT by searching through claims from 2015-20. In addition, we identified incident LC cases among AIs and NHWs aged ≥18 years, from 2015-19. We assembled lists of LDCT facilities that existed in the year prior to each incident LC case. We calculated the minimum centroid to centroid distance to all facilities. Clinical attributes included age at diagnosis, sex, histology, stage at diagnosis, and rurality as measured by Rural Urban Commuting Area. Risk ratios were calculated for late-stage LC diagnoses across a range of thresholds for patient’s distance to nearest LDCT screening facility for AIs and NHWs. Results We identified 388 AI and 26,867 NHW incident LC cases in NC between 2015-20. Compared to NHWs, the median age at diagnosis for AIs was 5 years younger (AI: 65 vs. NHW: 69); more frequently male (AI: 54% vs NHW: 51%); and almost twice as likely to reside in rural areas (AI: 52% vs. NHW: 28%). There were no differences in late-stage LC diagnoses (AI: 54% vs. NHW: 52%). For distance (in miles) to the nearest LDCT screening facility, the median [Interquartile range] was twice as high for AIs (9.9 miles [0.8, 16.30]) compared to NHWs (5.3 miles [0, 12.1]). Among NHWs, there were statistically significant associations between distance and late-stage LC diagnosis at the shortest distance threshold of 5 miles (RR=1.04; 95%CL: 1.02, 1.07) through the threshold of 30 miles (RR=1.10 95%CL: 1.05, 1.15). There was no association across any distance threshold among AI lung cancer patients. Conclusions The large difference in accessibility of LDCT screening was not strongly associated with metastatic lung cancer diagnoses, possibly because so many patients were diagnosed late, reflecting poor early detection across all populations. We found that 80% of AIs with LC lived more than 10 miles away from LDCT screening facilities. This geographic distance may increase difficulty accessing cancer care geographically, and contribute to suboptimal LC screening rates. If efforts are to be made to increase early detection and improve survival, accessibility needs to be addressed on different dimensions. Citation Format: Bradford E. Jackson, Marc Emerson, Daniel Carrizosa, Chris Baggett, Lisa Spees, Joel Begay, Ana Salas, Yadurshirni Raveendran, Tomi Akinyemiju, Rachel Denlinger-Apte, Stephanie Wheeler, Ronny Bell. Missed Opportunities? Regional availability of Low Dose CT lung cancer screening facility locations in the year prior to diagnoses: A descriptive comparison of American Indian and Non-Hispanic White lung cancer patients in North Carolina [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A132.

Prenatal exposure to maternal smoking and adult lung cancer risk: a nested case-control study using peripheral blood leukocyte DNA methylation prediction of exposure.

A prior study reported no association between prenatal smoking methylation scores and adult lung cancer risk adjusting for methylation-predicted adult smoking, without considering maternal smoking trends by birth cohort. To address this gap, we examined the association between prenatal smoking methylation scores and adult lung cancer, independent of methylation-predicted adult packyears and by birth cohort, in a study nested in CLUE II. Included were 208 incident lung cancer cases ascertained by cancer registry linkage and 208 controls matched on age, sex, and smoking. DNA methylation was measured in prediagnostic blood. We calculated two prenatal smoking scores, using 19 (Score-19) and 15 (Score-15) previously identified CpGs and a methylation-predicted adult packyears score. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for adult packyears score and batch effects. Score-15 was positively associated with lung cancer (per standard deviation, OR = 1.40, 95% CI = 1.10-1.79, P-trend = .006), especially in the 1930-1938 birth cohort (OR = 3.43, 95% CI = 1.55-7.60, P-trend = .002). Score-19 was associated only in the 1930-1938 birth cohort (OR = 2.12, 95% CI = 1.15-3.91). Participants with both prenatal scores below the median (vs all other combinations) had lower risk (OR = 0.44, 95% CI = 0.27-0.72), especially in the 1930-1938 birth cohort (OR = 0.16, 95% CI = 0.04-0.62). Among ever smokers, participants with higher prenatal smoking scores had higher risk, irrespective of adult packyears (low: OR = 2.81, 95% CI = 1.38-5.72, high: OR = 2.67, 95% CI = 1.03-6.95). This prospective study suggests a positive association between prenatal smoking exposure and adult lung cancer risk, especially in the 1930-1938 birth cohort, independent of active smoking. Future studies with multiple birth cohorts are needed.

Real-time delivered dose assessment in carbon ion therapy of moving targets

Abstract Purpose:
Real-time adaptive particle therapy is being investigated as a means to maximize the treatment delivery accuracy. To react to dosimetric errors, a system for fast and reliable verification of the agreement between planned and delivered doses is essential. This study presents a clinically feasible, real-time 4D-dose reconstruction system, synchronized with the treatment delivery and motion of the patient, which can provide the necessary feedback on the quality of the delivery.
Methods:
A GPU-based analytical dose engine capable of millisecond dose calculation for carbon ion therapy has been developed and interfaced with the next generation of the Dose Delivery System (DDS) in use at Centro Nazionale di Adroterapia Oncologica (CNAO). The system receives the spot parameters and the motion information of the patient during the treatment and performs the reconstruction of the planned and delivered 4Ddoses. After each iso-energy layer, the results are displayed on a graphical user interface by the end of the spill pause of the synchrotron, permitting verification against the reference dose.
The framework has been verified experimentally at CNAO for a lung cancer case based on a virtual phantom 4DCT. The patient’s motion was mimicked by a moving Ionization Chambers (ICs) 2D-array.
Results:
For the investigated static and 4D-optimized treatment delivery cases, real time dose reconstruction was-achieved with an average pencil beam dose calculation speed up to more than one order of magnitude smaller than the spot delivery. The reconstructed doses have been benchmarked against offline log-file based dose reconstruction with the TRiP98 treatment planning system, as well as QA measurements with the ICs 2D-array, where an average gamma-index passing rate (3%/3mm) of 99.8% and 98.3%, respectively, were achieved.
Conclusion:
This work provides the first real-time 4D-dose reconstruction engine for carbon ion therapy. The framework integration with the CNAO DDS paves the way for a swift transition to the clinics.

Repeated CT scans on 12,984 Asians to diagnose lung cancer once it is suspected.

In Taiwan, lung cancer remains the leading cause of cancer-related fatalities, resulting in substantial healthcare expenses. This research aims to evaluate both the frequency and the costs of low-dose computed tomography (LDCT) in individuals suspected of having lung cancer until their diagnosis of cancer. LDCT screening was not conducted on a population-wide scale, and asymptomatic participants had to cover the expenses for the screening personally or reimburse from other sources. If the screening results were positive or suspicious, National Health Insurance (NHI) could be utilized for subsequent follow-up examinations. This cohort study utilized the NHI Database and focused on individuals with suspected cases of lung cancer identified between 2010 and 2014.A total of 17,572 suspected new lung cancer cases were initially identified and assigned to the relevant International Classification of Diseases codes. Individuals with suspected lung cancer received a diagnosis following an average follow-up period of 2.24 (95%CI, 2.11-2.37) years, and required the use of 2.36 (95%CI, 2.20-2.51) repeated CT scans. The NHI expenditures incurred by the use of CT scans for monitoring suspected lung cancer cases were relatively modest.

A novel internal target volume definition based on velocity and time of respiratory target motion for external beam radiotherapy.

This study aimed to develop a novel internal target volume (ITV) definition for respiratory motion targets, considering target motion velocity and time. The proposed ITV was evaluated in respiratory-gated radiotherapy. An ITV modified with target motion velocity and time (ITVvt) was defined as an ITV that includes a target motion based on target motion velocity and time. The target motion velocity was calculated using four-dimensional computed tomography (4DCT) images. The ITVvts were created from phantom and clinical 4DCT images. The phantom 4DCT images were acquired using a solid phantom that moved with a sinusoidal waveform (peak-to-peak amplitudes of 10 and 20mm and cycles of 2-6s). The clinical 4DCT images were obtained from eight lung cancer cases. In respiratory-gated radiotherapy, the ITVvt was compared with conventional ITVs for beam times of 0.5-2s within the gating window. The conventional ITV was created by adding a uniform margin as the maximum motion within the gating window. In the phantom images, the maximum volume difference between the ITVvt and conventional ITV was -81.9%. In the clinical images, the maximum volume difference was -53.6%. Shorter respiratory cycles and longer BTs resulted in smaller ITVvt compared with the conventional ITV. Therefore, the proposed ITVvt plan could be used to reduce treatment volumes and doses to normal tissues.

Cost-effectiveness analysis of a lung cancer screening program in the Netherlands: a simulation based on NELSON and NLST study outcomes

Background In the Netherlands, lung cancer is the leading cause of cancer-related death, accounting for more than 10,000 annual deaths. Lung cancer screening (LCS) studies using low-dose computed tomography (LDCT) have demonstrated that early detection reduces lung cancer mortality. However, no LCS program has been implemented yet in the Netherlands. A national LCS program has the potential to enhance the health outcomes for lung cancer patients in the Netherlands. Objective and Methods This study evaluates the cost-effectiveness of LCS compared to no-screening in the Netherlands, by simulating the screening outcomes based on data from NEderlands–Leuvens Longkanker Screenings ONderzoek (NELSON) and National Lung Screening Trial (NLST). We simulated annual screening up to 74 years of age, using inclusion criteria from the respective studies. A decision tree and Markov model was used to predict the incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICERs) for the screening population. The analysis used a lifetime horizon and a societal perspective. Results Compared to no-screening, LCS resulted in an ICER of €5,169 per QALY for the NELSON simulation, and an ICER of €17,119 per QALY for the NLST simulation. The screening costs were highly impactful for the cost-effectiveness. The most influential parameter was the CT scan cost. Cost reduction for CT from €201 to €101 per scan would reduce the ICER to €2,335 using NELSON criteria. Additionally, LCS could prevent 15,115 and 12,611 premature lung cancer deaths, accompanied by 1.66 and 1.31 QALYs gained per lung cancer case for the NELSON and NLST simulations, respectively. Conclusion LCS was estimated to be cost-effective in the Netherlands for both simulations at a willingness-to-pay threshold of €20,000 per QALY. Using the NELSON criteria, less than €5,500 per QALY had to be spent. Lowering the cost per CT exam would lead to a further reduction of this amount.

Additional reporting of diffuse and homogeneous ROS-1 SP384 immunoreactivity enhances prediction of ROS1 fusion-positive non-small cell lung cancer.

ROS-1 immunohistochemistry (IHC) is a common method for screening ROS1 fusion in the clinical management of non-small cell lung cancer. The interpretation criteria for ROS-1 SP384 IHC, however, remain unestablished. Sixty-five non-small cell lung cancer cases underwent AmoyDx ROS1 fusion real-time polymerase chain reaction (PCR) study and ROS-1 SP384 IHC tests, which were retrieved for analysis. ROS-1 IHC tests were interpreted based on the established classifiers as well as the presence of diffuse homogeneous immunoreactivity. The diagnostic accuracies of these ROS-1 IHC interpretation methods were evaluated by comparing them with the ROS1 real-time PCR results. Previous ROS-1 IHC classifiers demonstrated high sensitivity for positive ROS1 real-time PCR results (100%), but they showed low specificities (25%-50%) and overall accuracies (58%-72%). In contrast, the diffuse homogeneous ROS-1 immunoreactivity predicted positive ROS1 real-time PCR results with much higher specificity (94%) and overall accuracy (95%), albeit with a slightly lower sensitivity (97%). Some cases that showed discrepancy between diffuse homogeneous ROS-1 immunoreactivity and real-time PCR results involved rare ROS1::LDLR fusion and suboptimal IHC staining. A 3-tier reporting system for ROS-1 SP384 IHC testing combining previous interpretation criteria and diffuse and homogeneous immunoreactivity may better predict ROS1 fusion status without decreasing specificity.

Identifying priority populations for lung cancer screening intervention using neighborhood-level factors and cancer registry data.

To evaluate the association of neighborhood level economic, environmental, and social indicators with lung cancer (LC) incidence and mortality. Data for adult incident LC cases in Allegheny County, Pennsylvania, diagnosed between 2015-2019 were obtained from Pennsylvania cancer registry. Cases were summarized at census-tract level. Publicly available data on neighborhood deprivation index (NDI), built environment, and racial isolation at census-tracts were linked to cases. Poisson regression was used to compute relative risk (RR) for LC incidence and mortality, adjusting for covariates. A total of 3256 LC cases were included in the analyses. About 68% were ≥65 years, 54% female, 14% Black or African American, and 63% deceased. Results of the multivariable model found that increasing quintiles (Q) of NDI were significantly associated with increasing risk of LC incidence and mortality. The RRs (95% confidence interval) of LC incidence for Q2, Q3, Q4 and Q5 were 1.36 (1.21-1.52), 1.55 (1.40-1.72), 1.68 (1.51-1.87), 2.08 (1.82-2.38), respectively, compared with Q1 (P trend <0.01). The corresponding RRs for LC mortality were 1.46 (1.27-1.68), 1.63 (1.42-1.88), 1.74 (1.51-2.01), 2.04 (2.02-2.88) (P trend <0.01). Targeted interventions for LC prevention and early detection in high NDI neighborhoods may be more effective to reduce LC health disparities.

Meta-analysis of Targeted Therapies in EGFR-mutated Non-Small Cell Lung Cancer: Efficacy and Safety of Osimertinib, Erlotinib, and Gefitinib as First-line Treatment.

Some of the non-small cell lung cancer (NSCLC) cases enhance somatic mutations of the epidermal growth factor receptor (EGFR) gene within the tyrosine kinase inhibitor (TKI) domain. In such cases, first-line treatments are EGFR-TKIs, including osimertinib, erlotinib, or gefitinib. Therefore, this meta-analysis aims to assess the safety and efficacy of first-line targeted therapies for EGFR-mutated advanced NSCLC patients, focusing on osimertinib, erlotinib, and gefitinib. A systematic electronic search was conducted on 3 electronic databases-Scopus, PubMed, and Web of Science-from inception to May 2024 to locate relevant trials reporting the safety and efficacy of osimertinib, erlotinib, or gefitinib in treating EGFR-mutated advanced NSCLC. No language or data restriction was applied to the search strategy. The assessed effects were objective response rate (ORR) and disease control rate (DCR). RoB 2 tool was utilized to determine the risk of bias while R programming language performed all the statistical synthesis. Out of 15,275 search results, only 19 trials were eligible for this meta-analysis. All the 3 EGFR-TKIs depicted effectiveness and safety among NSCLC patients, but osimertinib improved the ORR by 72% (95% CI: 65%, 78%) as compared with erlotinib (69% [95% CI: 58%, 79%]) and gefitinib (64% [95% CI: 64%, 78%]). Overall, the 3 EGFR-TKIs were effective by improving ORR 68% (95% CI: 63%, 73%). Similarly, osimertinib demonstrated highly effective impacts in disease control among NSCLC patients by 94% (95% CI: 91%, 97%) compared with gefitinib (68% [95% CI: 41%, 89%]). Overall, the 2 EGFR-TKIs were effective in disease control among NSCLC patients (82% [95% CI: 67%, 93%]). The pooled analyses have shown that erlotinib, gefitinib, and osimertinib are safe and effective first-line treatment options for patients with EGFR-mutated advanced NSCLC. The meta-analysis outcomes have demonstrated that osimertinib, erlotinib, or gefitinib positively impact overall response rate and disease control.

Combining rVAR2 and Anti-EpCAM to Increase the Capture Efficiency of Non-Small-Cell Lung Cancer Cell Lines in the Flow Enrichment Target Capture Halbach (FETCH) Magnetic Separation System.

Circulating tumor cells (CTCs) are detected in approximately 30% of metastatic non-small-cell lung cancer (NSCLC) cases using the CellSearch system, which relies on EpCAM immunomagnetic enrichment and Cytokeratin detection. This study evaluated the effectiveness of immunomagnetic enrichment targeting oncofetal chondroitin sulfate (ofCS) using recombinant VAR2CSA proteins (rVAR2) to improve the recovery of different NSCLC cell lines spiked into lysed blood samples. Four NSCLC cell lines-NCI-H1563, A549, NCI-H1792, and NCI-H661-were used to assess capture efficiency. The results demonstrated that the combined use of anti-EpCAM antibody and rVAR2 significantly enhanced the capture efficiency to an average of 88.2% compared with 40.6% when using only anti-EpCAM and 56.6% when using only rVAR2. These findings suggest that a dual-marker approach using anti-EpCAM and rVAR2 can provide a more robust and sensitive method for CTC enrichment in NSCLC, potentially leading to better diagnostic and prognostic outcomes.

Comparative study of lung cancer between smokers and nonsmokers: A real-world study based on the whole population from Tianjin City, China.

The purpose of this study was to examine the prevalence, clinical characteristics, and changing trends of non-smokers with lung cancer (LC) based on data from a population-wide cancer registry in northern China. The study used LC incidence and follow-up data from 2010 to 2019 from the Cancer Registry System of Tianjin city, which included 82769 cases. Trends in the incidence and proportion of non-smokers with LC were examined by joinpoint regression analysis. Life table and Cox survival analyses were used to calculate the survival rates and compare the death hazard ratios (HRs) in different groups, respectively. Among the 82769 new diagnosis cases of LC during 2010 to 2019, there were 34589 (41.8%) current smokers, 14913 (18.0%) ex-smokers, 28123 (34.0%) non-smokers, and 5144 (6.2%) unknowns. The proportion of non-smokers changed slightly from 2010 (35.36%) to 2019 (36.87%) (annual percentage change, APC= -0.01%, p>0.05). This proportion declined in men (2010 vs 2019; 22.06% vs 20.66%) and increased in women (2010 vs 2019; 53.02% vs 62.35%), and in the 0-44 years age group it showed an upward trend from 2015 to 2019 (APC=4.82%, 95% CI: 1.8-7.9). Compared with smokers with LC, non-smokers with LC were predominantly females (64.15% vs 27.26%), had a predominantly adenocarcinoma histological subtypes (76.71% vs 42.22%), and had a 20% lower risk of death than smokers (HR=0.80; 95% CI: 0.78-0.81). The proportion of non-smokers with LC was relatively high in northern China, with an increasing trend in the proportion of females and younger age groups. Non-smokers with LC had different epidemiological and clinical characteristics compared with smokers with LC.

No genetic causal association between human papillomavirus and lung cancer risk: a bidirectional two-sample Mendelian randomization analysis

IntroductionSeveral observational or retrospective studies have previously been conducted to explore the possible association between lung cancer and human papillomavirus (HPV) infection. However, there may be inconsistencies in the data and conclusions due to differences in study design and HPV testing methods. There are currently no studies that provide conclusive evidence to support the involvement of HPV in the occurrence and development of lung cancer. Therefore, the relationship between HPV and lung cancer remains controversial and uncertain. This study aimed to explore whether HPV infection is causally related to lung cancer risk by systematically performing a two-way Two-Sample Mendelian Randomization (TSMR) analysis.MethodsIn the International Lung Cancer Consortium (ILCCO) genome-wide association study dataset, we included 11,348 lung cancer (LUCA) cases, including 3275 squamous cell carcinoma (LUSC) cases, 3442 adenocarcinoma (LUAD) cases, and 15,861 cases of control. Using genetic variants associated with the HPV E7 protein as instrumental variables, we summarized statistics associated with HPV infection in the MRC IEU OpenGWAS database, which included the HPV-16 E7 protein and the HPV-18 E7 protein. Two-sample Mendelian randomization (MR) results are expressed as odds ratios (OR) and 95% confidence intervals (CI).ResultsBased on a comprehensive analysis of genome-wide association study (GWAS) data from public databases, we mainly used inverse-variance weighted (IVW) to estimate causal relationships, while using MR-Egger, weighted median, simple mode, and weighted mode, and other four methods as supplements. Two-sample MR Analysis revealed no causal relationship between exposure factors (HPV-16 E7 protein and HPV-18 E7 protein) and outcome factors (lung cancer (LUCA) and its subtypes squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD)) in forward MR Analysis using the IVW approach.HPV-16 E7 protein and LUCA and its subtypes LUSC and LUAD by IVW method results: [OR] = 1.002; 95% [CI]: 0.961 − 1.045; p = 0.920; [OR] = 1.023; 95% [CI]: 0.966 − 1.084; p = 0.438; [OR] = 0.994; 95% [CI]: 0.927 − 1.066; p = 0.872); HPV-18 E7 protein and LUCA and its subtypes LUSC and LUAD by IVW method results: [OR] = 0.965; 95% [CI]: 0.914 − 1.019; p = 0.197; [OR] = 0.933; 95% [CI]: 0.834 − 1.043; p = 0.222; [OR] = 1.028; 95% [CI]: 0.945 − 1.118; p = 0.524. It was observed through reverse MR that LUCA and its subtypes LUSC and LUAD were used as exposure factors, and HPV infection (HPV-16 E7 protein and HPV-18 E7 protein) was used as the outcome factors, the results of the IVW method are also invalid.LUCA and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.036; 95% [CI]: 0.761 − 1.411; p = 0.82; [OR] = 1.318; 95% [CI]: 0.949 − 1.830; p = 0.099; LUSC and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.123; 95% [CI]0.847 − 1.489; p = 0.421; [OR] = 0.931; 95% [CI]: 0.660 − 1.313; p = 0.682; LUAD and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.182; 95% [CI] 0.983 − 1.421; p = 0.075; [OR] = 1.017; 95% [CI]: 0.817 − 1.267; p = 0.877.Our results indicate that there is no causal relationship between genetically predicted HPV infection and LUCA and its subtypes LUSC and LUAD. In addition, in the reverse MR analysis, we did not observe a significant causal relationship between LUCA and its subtypes LUSC and LUAD on HPV infection.ConclusionsOur findings do not support a genetic association between HPV infection and lung cancer.

Wolf in sheep’s clothing: a case of primary lung adenosquamous carcinoma mimicking traumatic pulmonary pseudocyst

BackgroundTraumatic pulmonary pseudocyst is a rare “cystlike” lung lesion that typically develops following blunt chest trauma. It differs from lung cancer associated with cystic airspaces in terms of pathogenic mechanisms, clinical manifestations, and radiological features. Furthermore, there are few reports of the diagnostic bias between traumatic pulmonary pseudocyst and lung cancer associated with cystic airspaces. Here, we present a rare case of lung cancer associated with cystic airspaces that mimicks traumatic pulmonary pseudocyst.Case presentationA 61-year-old man with no chest medical or surgical history, no chest radiologic examination within the last five years, and no smoking history had an air-filled “cystlike” lesion surrounded by solid components and ground-glass opacities in the middle third of the right upper lobe of the lung during a computed tomography evaluation following blunt chest trauma. He was initially diagnosed with traumatic pulmonary pseudocyst and treated conservatively. On the third post-trauma day, he experienced hemoptysis, which was successfully treated with intravenous hemostatic medication. On the ninth post-trauma day, he exhibited a significant hemoptysis and a moderate dyspnea. A subsequent chest computed tomography scan demonstrated that the solid components had entered the lesion’s cavity and significantly expanded, and the surrounding ground-glass opacities had slightly enlarged. A contrast-enhanced chest computed tomography scan and a three-dimensional reconstruction computed tomography image confirmed that the solid components were a hematoma caused by damage to the right upper pulmonary vein. A right upper lobectomy was performed based on the concern about severe intrapulmonary bleeding. An intraoperative frozen section analysis showed significant bleeding in the lung parenchyma. Adenosquamous carcinoma was unexpectedly identified during the postoperative pathological examination of the resected specimen. A diagnosis of primary lung adenosquamous carcinoma was made. He was discharged on the seventh postoperative day and followed up for two years without any recurrence.ConclusionsThe potential of lung cancer associated with cystic airspaces should be considered for “cystlike” lung lesions discovered in elderly patients after blunt chest trauma. A comprehensive review of the medical history, meticulous analysis of the radiological findings, and close monitoring can help clinicians reduce the risk of diagnostic bias.

The association between plasma fatty acids and risk of lung cancer: a prospective cohort study of the UK Biobank.

Fatty acids (FAs) have emerged as significant contributors to tumorigenesis, yet prospective evidence regarding their specific effects on lung cancer risk remains scarce. To investigate the association between plasma FAs and lung cancer incidence, as well as a potential modification effect of genetic susceptibility on lung cancer risk. A cohort study was conducted involving 112,547 cancer-free participants from the UK Biobank, with measurements of plasma FAs, including saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) at baseline (2006-2010). Cox regression models were employed to assess lung cancer risk according to plasma FA quartiles or 1-SD increment. Furthermore, interaction between plasma FAs and polygenic risk score (PRS) was evaluated using an additive model. Over an average 10.9-year follow-up, 1122 lung cancer cases occurred. After multivariable adjustment, MUFAs were positively associated with lung cancer risk (hazard ratio [HR] per 1-SD = 1.32, 95% confidence interval [CI]: 1.13-1.54). In contrast, PUFAs, particularly n-3 PUFAs, n-6 PUFAs, docosahexaenoic acid, and linoleic acid, were associated with a lower risk of lung cancer, with HRs ranging from 0.79 (95% CI: 0.72-0.87) to 0.89 (95% CI: 0.83-0.95). SFAs were not significantly associated with lung cancer risk. Moreover, we observed an additive interaction between plasma PUFAs and genetic risk. Individuals with a high genetic risk and the lowest quartile of plasma PUFAs had the highest risk of lung cancer (HR = 2.20, 95% CI: 1.43-3.38). Our findings suggest that plasma PUFAs may serve as protective factors, while MUFAs represent risk factors for lung cancer, offering novel insights into lung cancer carcinogenesis and prevention.

343. DIAGNOSTIC VALUE OF ENDOBRONCHIAL ULTRASOUND-GUIDED TRANSESOPHAGEAL NEEDLE ASPIRATION (EBUS-TENA) IN LESIONS ADJACENT TO BOTH THE TRACHEA/BRONCHUS AND ESOPHAGUS

Abstract Objective To investigate the clinical diagnostic value of endobronchial ultrasound-guided transesophageal needle aspiration (EBUS-TENA) in lesions adjacent to both the trachea/bronchus and esophagus Methods The clinical data of 12 patients who underwent EBUS-TENA from February 2019 to February 2022 were collected. The operative physicians and nurses worked closely with each other and meticulously cared the patients. The vital signs changes were observed and recorded, as well as intraoperative adverse events and the acquired specimens. Results All the 12 patients underwent surgery successfully, and hair-like tissue strips were obtained in each case. There were 8 cases of central lung cancer and 4 cases of mediastinal tumor. The preoperative vital signs scores showed no significant difference with the intraoperative and postoperative scores (P&amp;gt;0.05). A few complications occurred, including 2 case of mild cough, 2 case of nausea and vomiting, with no symptoms of severe cough and dyspnea, haemorrhage, mediastinal infection, pneumothorax, mediastinal emphysema and other complications. Conclusion EBUS-TENA has significant effect in successfully obtaining pathological tissue specimens especially for lesions adjacent to both the trachea/bronchus and esophagus, improving disease positive diagnosis rate, reducing patients discomfort and the risk of surgery.

Predicting non-small cell lung cancer lymph node metastasis: integrating ctDNA mutation/methylation profiling with positron emission tomography-computed tomography (PET-CT) scan: protocol for a prospective clinical trial (LUNon-invasive Study).

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases and remains a leading cause of cancer-related death. Lymph node metastasis (LNM) significantly affects recurrence, survival rates, and treatment options. While lymph node sampling is standard for surgically removing operable NSCLC, it can lead to complications. Positron emission tomography-computed tomography (PET-CT) helps assess preoperative LNM despite false positive or negative rates. Additionally, circulating tumor DNA (ctDNA) detects minimal residual disease with high sensitivity and specificity. Whether ctDNA can predict LNM in operable NSCLC remains uncertain. Our goal is to develop a precise model for predicting NSCLC LNM using non-invasive ctDNA/methylation profiling combined with PET-CT imaging. This is a prospective study conducted in three stages. We will enroll patients with clinical stage I-IIIB [8th tumor, node, metastasis (TNM) staging] NSCLC requiring lobectomy plus lymph node sampling/dissection. The distribution of clinical stages in the enrolled population is as follows: clinical stage cN0 (n=100) and cN1/cN2 (n=100). During Stage 1, we will establish LNMs-specific ctDNA methylation signatures and compare negative predictive value (NPV) rates of LNMs using preoperative blood ctDNA somatic mutation/methylation alone or combined with PET-CT across different groups. For Stage 2, we will compare detection rates between ctDNA somatic mutation/methylation profiles alone or combined with PET-CT and traditional mediastinoscopy/endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). As for Stage 3, ctDNA-free interval (CFI) and disease-free survival between systematic lymph node presence and absence in patients will be compared with preoperative negative ctDNA profiling and/or PET-CT. In Stage 3, patients will be followed up for 5 years to collect recurrence and survival data. Post-surgery follow-up ctDNA tests will be conducted every 3 months for the first 2 years, every 6 months for years 3-4, and annually in year five. Demographics and baseline data will be summarized with mean, standard deviation, median, max, and min values. Tests will include t-tests, Welch/Behren-Fisher test, and Wilcoxon rank-sum test for continuous variables. Categorical data will be presented as counts/percentages and compared using χ2 test or Fisher's exact test. By utilizing preoperative ctDNA/methylation profiling in conjunction with PET-CT, this study is expected to yield substantial evidence for accurately predicting LNM before surgery. This will help inform surgeons in selecting the appropriate intraoperative lymph node dissection strategy for operable NSCLC patients. This study is registered on www.clinicaltrials.gov (NCT06358222).

Evaluation of risk prediction models to select lung cancer screening participants in Europe: a prospective cohort consortium analysis

Lung cancer risk prediction models might efficiently identify individuals who should be offered lung cancer screening. However, their performance has not been comprehensively evaluated in Europe. We aimed to externally validate and evaluate the performance of several risk prediction models that predict lung cancer incidence or mortality in prospective European cohorts. We analysed 240 137 participants aged 45-80 years with a current or former smoking history from nine European countries in four prospective cohorts from the pooled database of the Lung Cancer Cohort Consortium: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Finland), the Nord-Trøndelag Health Study (Norway), CONSTANCES (France), and the European Prospective Investigation into Cancer and Nutrition (Denmark, Germany, Italy, Spain, Sweden, the Netherlands, and Norway). We evaluated ten lung cancer risk models, which comprised the Bach, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 model (PLCOm2012), the Lung Cancer Risk Assessment Tool (LCRAT), the Lung Cancer Death Risk Assessment Tool (LCDRAT), the Nord-Trøndelag Health Study (HUNT), the Optimized Early Warning Model for Lung Cancer Risk (OWL), the University College London-Death (UCLD), the University College London-Incidence (UCLI), the Liverpool Lung Project version 2 (LLP version 2), and the Liverpool Lung Project version 3 (LLP version 3) models. We quantified model calibration as the ratio of expected to observed cases or deaths and discrimination using the area under the receiver operating characteristic curve (AUC). For each model, we also identified risk thresholds that would screen the same number of individuals as each of the US Preventive Services Task Force 2021 (USPSTF-2021), the US Preventive Services Task Force 2013 (USPSTF-2013), and the Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) criteria. Among the participants, 1734 lung cancer cases and 1072 lung cancer deaths occurred within five years of enrolment. Most models had reasonable calibration in most countries, although the LLP version 2 overpredicted risk by more than 50% in eight countries (expected to observed ≥1·50). The PLCOm2012, LCDRAT, LCRAT, Bach, HUNT, OWL, UCLD, and UCLI models showed similar discrimination in most countries, with AUCs ranging from 0·68 (95% CI 0·59-0·77) to 0·83 (0·78-0·89), whereas the LLP version 2 and LLP version 3 showed lower discrimination, with AUCs ranging from 0·64 (95% CI 0·57-0·72) to 0·78 (0·74-0·83). When pooling data from all countries (but excluding the HUNT cohort), 33·9% (73 313 of 216 387) of individuals were eligible by USPSTF-2021 criteria, which included 74·8% (1185) of lung cancers and 76·3% (730) of lung cancer deaths occurring over 5 years. Fewer individuals were selected by USPSTF-2013 and NELSON criteria. After applying thresholds to select a population of equal size to USPSTF-2021, the PLCOm2012, LCDRAT, LCRAT, Bach, HUNT, OWL, UCLD, and UCLI, models identified 77·6%-79·1% of future cases, although they selected slightly older individuals compared with USPSTF-2021 criteria. Results were similar for USPSTF-2013 and NELSON. Several lung cancer risk prediction models showed good performance in European countries and might improve the efficiency of lung cancer screening if used in place of categorical eligibility criteria. US National Cancer Institute, l'Institut National du Cancer, Cancer Research UK.

Association of alcohol with lung cancer risk in men with different growth hormone receptor genotypes

ObjectiveTo test whether genetic variants of the growth hormone receptor gene (GHR) modulate the effect of lifestyle variables on lung cancer (LC) risk. Materials and methodsThis population-based cohort study involved 6,439 men from the Japan-Hawaii Cancer study drawn from the Kuakini Honolulu Heart Program who were cancer-free at baseline examination (1965–1968; age 45–68 years) and followed-up until December 1999. We determined the association of GHR SNP rs4130113 genotypes GHR-AA (common allele A homozygotes) and GHR-G (minor allele G carriage) with alcohol drinking, BMI, physical activity and cigarette smoking in relation to LC and non-small cell LC (NSCLC). Results were expressed as hazard ratios and 95 % CIs estimated from Cox proportional hazard models. ResultsOver mean 26.7 ± 7.4 SD years follow-up, 190 LC cases, including 133 NSCLC cases, were diagnosed. After adjusting for age, education, alcohol intake, BMI, physical activity, cigarette smoking, green tea consumption and dietary saturated fat, main-effect Cox models showed that compared with GHR-AA, GHR-G was associated with protection against LC: HR = 0.75 (95 % CI, 0.56–1.00). Full Cox models showed GHR-G interacted with alcohol intake only (β = 1.171; p = 0.0003; drinks per week: β = 0.279; P = 0.0025). Stratified analyses showed that for GHR-AA, drinkers had reduced LC risk (HR = 0.53; 95 % CI, 0.34–0.84), and that <2 drinks/week had the strongest protection (HR = 0.39; 95 % CI, 0.18–0.84). In contrast, for GHR-G, alcohol drinkers had increased LC risk (HR = 1.74; 95 % CI, 1.11–2.75) which was dose-dependent (P for trend = 0.003). Results for NSCLC were similar. ConclusionIn men with the GHR-AA genotype, alcohol drinking at a low dose poses significantly less risk of LC compared with non-drinkers and higher alcohol consumption., the overall relationship being U-shaped. In contrast, in GHR minor allele carriers, alcohol posed a progressively greater risk of LC as amount consumed increased

The Diagnostic Value of Endobronchial Ultrasound-Guided Fine Needle Aspiration (EBUS-FNA) in Diagnosing FDG-PET-Avid Lymph Nodes in Extrapulmonary Malignancies.

Background and objective The accurate diagnosis of extrapulmonary malignancies with mediastinal lymphadenopathy is crucial for effective patient management. Endobronchial ultrasound-guided fine-needle aspiration(EBUS-FNA)has emerged as a valuable tool in assessingfluorodeoxyglucose (FDG)-positron emission tomography(PET)-avid lymph nodes (LNs).In this study, we aimed to evaluate the diagnostic value of EBUS-FNA in patients with mediastinal lymphadenopathy in extrapulmonary malignancies and compare its efficacy with PET-CT. Methodology Thisretrospective, cross-sectional study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, from February 2018 to February 2023. It included patients with extrapulmonary malignancies with mediastinal lymphadenopathy displaying abnormal PET-CT uptake, with LN diameters ≥5 mm, excluding lung cancer cases. Data on demographics, malignancy type, LN involvement, PET-CT findings, and EBUS-FNA histopathology were collected. EBUS-FNA procedures involved a 22-gauge needle, and samples were analyzed cytologically and histologically. SPSS Statistics version 20 (IBM Corp., Armonk, NY) was used to perform the statistical analysis. Results The study analyzed a total of 216 patients. Males comprised 56.3% of the cohort, and females 43.7%. The most common malignancy was lymphoma (33.0%), followed by breast cancer (12.6%). EBUS-FNA exhibited a sensitivity of 90.9% compared to PET-CT's sensitivity of 72.7%. Lymph node morphology on EBUS showed low echogenicity and irregular borders in malignant cases. Subcarinaland right hilar were the most frequently sampled lymph nodes. The study found significant differences in lymph node characteristics between non-malignant and malignant groups, with EBUS-FNA effectively identifying malignancies. Conclusions EBUS-FNA demonstrates high sensitivity and diagnostic utility in identifying malignant lymph nodes in patients with extrapulmonary malignancies. Its effectiveness in detecting true positive cases highlights its importance as a complementary diagnostic tool to PET-CT in oncological diagnostics.

M2 macrophage-derived lncRNA NORAD in EVs promotes NSCLC progression via miR-520g-3p/SMIM22/GALE axis

Non-small cell lung cancer (NSCLC) constitutes the majority of lung cancer cases, accounting for over 80%. RNAs in EVs play a pivotal role in various biological and pathological processes mediated by extracellular vesicle (EV). Long non-coding RNAs (lncRNAs) are widely associated with cancer-related functions, including cell proliferation, migration, invasion, and drug resistance. Tumor-associated macrophages are recognized as pivotal contributors to tumorigenesis. Given these insights, this study aims to uncover the impact of lncRNA NORAD in EVs derived from M2 macrophages in NSCLC cell lines and xenograft mouse models of NSCLC. EVs were meticulously isolated and verified based on their morphology and specific biomarkers. The interaction between lncRNA NORAD and SMIM22 was investigated using immunoprecipitation. The influence of SMIM22/GALE or lncRNA NORAD in EVs on glycolysis was assessed in NSCLC cell lines. Additionally, we evaluated the effects of M2 macrophage-derived lncRNA NORAD in EVs on cell proliferation and apoptosis through colony formation and flow cytometry assays. Furthermore, the impact of M2 macrophage-derived lncRNA NORAD in EVs on tumor growth was confirmed using xenograft tumor animal models. The results underscored the potential role of M2 macrophage-derived lncRNA NORAD in EVs in NSCLC. SMIM22/GALE promoted glycolysis and the proliferation of NSCLC cells. Furthermore, lncRNA NORAD in EVs targeted SMIM22 and miR-520g-3p in NSCLC cells. Notably, lncRNA NORAD in EVs promoted the proliferation of NSCLC cells and facilitated NSCLC tumor growth through the miR-520g-3p axis. In conclusion, M2 macrophage-derived lncRNA NORAD in EVs promotes NSCLC progression through the miR-520g-3p/SMIM22/GALE axis.