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Background: Lung cancer is a leading public health concern worldwide. Previous evidence suggests that chronic obstructive pulmonary disease (COPD) and asthma may contribute to its development. However, whether these common chronic pulmonary diseases are causal factors of lung cancer remained unclear. Methods: Summary statistics from genome-wide association studies (GWAS) were used for Mendelian randomization (MR) analysis. Genetic data for COPD were obtained from the Global Biobank Meta-Analysis Initiative, and asthma data were retrieved from the UK Biobank cohort. Suitable instrumental variables were selected based on quality control measures. GWAS summary data for lung cancer were obtained from a large study involved 85,716 participants. MR analysis was performed using various methods, and sensitivity analyses were conducted. Multivariable MR (MVMR) analysis was employed to account for potential confounding factors. Results: Our MR analysis revealed a significant causal association between COPD and lung cancer, including its subtypes such as lung squamous cell carcinoma, lung adenocarcinoma, and small cell lung carcinoma. Genetically predicted COPD was associated with a 64% increased risk of lung cancer and a 2.3 to 2.8-fold increased risk of the different subtypes. However, in the MVMR analysis adjusting for smoking, alcohol drinking, and body mass index, the association between COPD and lung cancer became non-significant. No significant association was observed between asthma (childhood-onset and adult-onset) and lung cancer and its histological subtypes. Conclusions: Our study suggests a potential causal association between COPD and lung cancer. However, this association became non-significant after adjusting for smoking in the multivariable analysis. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Paraneoplastic Neurological Syndromes (PNS) represent a heterogeneous group of diseases associated with the presence of neoplasm. The appearance of PNS can precede cancer diagnosis. The estimated frequency amongst cancer patients is about 1%. Malignant tumors represent a serious health problem and are the second leading cause of death in Poland. The aim of this study is to collect information about PNS focusing on cancers mostly diagnosed in Polish adults. REVIEW METHODS: The analysis was conducted based on information regarding PNS gathered from PubMed and Google Scholar within the context of selected cancers. THE STATE OF KNOWLEDGE: PNS develop from an autoimmune reaction in which onconeural antibodies are produced. The recent classification divides PNS to high risk, indicating a likely paraneoplastic origin and intermediate risk, if this association is less evident. Diagnosis is difficult and usually relies on exclusion methods. The symptoms described are non-specific and the diagnostic process may require the involvement of various specialists. The main approaches include cancer treatment, especially tumor removal and immunotherapy, which in certain may prove to be effective. SUMMARY: Although PNS is relatively rare, its detectability has recently increased. Many syndromes are especially associated with lung cancer (mainly small cell carcinoma). Breast and prostate cancers have also shown associations with certain syndromes. They can present with nonspecific symptoms related to different organ systems. Awareness and understanding of this phenomenon can be helpful amongst many specialists. [ABSTRACT FROM AUTHOR]

Background: Former research has emphasized a correlation between lung cancer (LC) and sepsis, but the causative link remains unclear. Method: This study used univariate Mendelian Randomization (MR) to explore the causal relationship between LC, its subtypes, and sepsis. Linkage Disequilibrium Score (LDSC) regression was used to calculate genetic correlations. Multivariate MR was applied to investigate the role of seven confounding factors. The primary method utilized was inverse-variance-weighted (IVW), supplemented by sensitivity analyses to assess directionality, heterogeneity, and result robustness. Results: LDSC analysis revealed a significant genetic correlation between LC and sepsis (genetic correlation = 0.325, p = 0.014). Following false discovery rate (FDR) correction, strong evidence suggested that genetically predicted LC (OR = 1.172, 95% CI 1.083-1.269, p = 8.29 × 10-5, Pfdr = 2.49 × 10-4), squamous cell lung carcinoma (OR = 1.098, 95% CI 1.021-1.181, p = 0.012, Pfdr = 0.012), and lung adenocarcinoma (OR = 1.098, 95% CI 1.024-1.178, p = 0.009, Pfdr = 0.012) are linked to an increased incidence of sepsis. Suggestive evidence was also found for small cell lung carcinoma (Wald ratio: OR = 1.156, 95% CI 1.047-1.277, p = 0.004) in relation to sepsis. The multivariate MR suggested that the partial impact of all LC subtypes on sepsis might be mediated through body mass index. Reverse analysis did not find a causal relationship (p > 0.05 and Pfdr > 0.05). Conclusion: The study suggests a causative link between LC and increased sepsis risk, underscoring the need for integrated sepsis management in LC patients. [ABSTRACT FROM AUTHOR]

Background: Growing evidence has shown that atopic dermatitis (AD) may decrease lung cancer (LC) risk. However, the causality between the two diseases is inconsistent and controversial. Therefore, we explored the causal relationship between AD and different histological subtypes of LC by using the Mendelian randomization (MR) method. Materials and methods: We conducted the MR study based on summary statistics from the genome‐wide association studies (GWAS) of AD (10,788 cases and 30,047 controls) and LC (29,266 cases and 56,450 controls). Instrumental variables (IVs) were obtained after removing SNPs associated with potential confounders. We employed inverse‐variance weighted (IVW), MR‐Egger, and weighted median methods to pool estimates, and performed a comprehensive sensitivity analysis. Results: The results of the IVW method suggested that AD may decrease the risk of developing lung adenocarcinoma (LUAD) (OR = 0.91, 95% CI: 0.85‐0.97, P = 0.007). Moreover, no causality was identified between AD and overall LC (OR = 0.96, 95% CI: 0.91–1.01, P = 0.101), lung squamous cell carcinoma (LUSC) (OR = 1.04, 95% CI: 0.96–1.036, P = 0.324), and small cell lung carcinoma (SCLC) (OR = 0.95, 95% CI: 0.82–1.10, P = 0.512). A comprehensive sensitivity test showed the robustness of our results. Conclusion: The present study indicates that AD may decrease the risk of LUAD in the European population, which needs additional investigations to identify the potential molecular mechanisms. [ABSTRACT FROM AUTHOR]

Background: Previous studies have highlighted the crucial role of immune cells in lung cancer development; however, the direct link between immunophenotypes and lung cancer remains underexplored. Methods: We applied two-sample Mendelian randomization (MR) analysis, using genetic variants as instruments to determine the causal influence of exposures on outcomes. This method, unlike traditional randomized controlled trials (RCTs), leverages genetic variants inherited randomly at conception, thus reducing confounding and preventing reverse causation. Our analysis involved three genome-wide association studies to assess the causal impact of 731 immune cell signatures on lung cancer using genetic instrumental variables (IVs). We initially used the standard inverse variance weighted (IVW) method and further validated our findings with three supplementary MR techniques (MR-- Egger, weighted median, and MR-PRESSO) to ensure robustness. We also conducted MR--Egger intercept and Cochran's Q tests to assess heterogeneity and pleiotropy. Additionally, reverse MR analysis was performed to explore potential causality between lung cancer subtypes and ident ified immunophenotypes, using R software for all statistical calculations. Results: Our MR analysis identified 106 immune signatures significantly associated with lung cancer. Notably, we found five suggestive associations across all sensitivity tests (P<0.05): CD25 on IgD- CD24- cells in small cell lung carcinoma (ORIVW =0.885; 95% CI: 0.798--0.983; PIVW =0.022); CD27 on IgD+ CD24+ cells in lung squamous cell carcinoma (ORIVW =1.054; 95% CI: 1.010-- 1.100; PIVW =0.015); CCR2 on monocyte cells in lung squamous cell carcinoma (ORIVW =0.941; 95% CI: 0.898--0.987; PIVW =0.012); CD123 on CD62L+ plasmacytoid dendritic cells (ORIVW =0.958; 95% CI: 0.924--0.992; PIVW =0.017) as well as on plasmacytoid dendritic cells (ORIVW =0.958; 95% CI: 0.924--0.992; PIVW =0.017) in lung squamous cell carcinoma. Conclusion: This study establishes a significant genomic link between immune cells and lung cancer, providing a robust basis for future clinical research aimed at lung cancer management. [ABSTRACT FROM AUTHOR]

Background: Pneumothorax is a non-physiological collection of air in the pleural space. Pneumothoraces can be broadly divided into Primary, Secondary, and Traumatic. Cancer of the lung is a known cause of secondary pneumothorax in both primary and metastatic lesions, however, pneumothorax as the presentation of lung cancer is exceedingly rare. Non-small cell lung carcinoma (NSCLC) has been reported in the literature to present with a pneumothorax, particularly in adeno/squamous cell carcinomas. It is almost completely unheard of for small cell lung carcinoma (SCLC) to present with a pneumothorax. Case Presentation: We present the case of a 62-year-old male patient, presenting twice in two months with spontaneous pneumothorax. The initial management involved admission and chest drain insertion. The patient has a past medical history of COPD and a significant smoking history. On the second admission, he underwent a video-assisted thoracoscopic (VATS) bullectomy and talc pleurodesis. The pathology report of the resected specimen confirmed SCLC with extensive infiltration. No gross evidence of metastatic spread was present on CT. Due to the R1 resection and significant risk of recurrence, the management plan included four cycles of adjuvant chemotherapy with carboplatin and etoposide, and radiotherapy as a consideration upon completion. Conclusions: Pneumothorax as the presentation of lung cancer imparts a very poor prognosis, however the reasons for this are largely unknown. Furthermore, the mechanisms underlying spontaneous pneumothorax in lung cancer are also not well understood. [ABSTRACT FROM AUTHOR]

This study investigated the association between lung cancer and waterpipe smoking, which is an emerging global public health concern. Multicentre case-control study. This study included 627 cases and 3477 controls from the Iranian Study of Opium and Cancer (IROPICAN) study, which was conducted between 2017 and 2020. One frequency-matched control for each lung cancer patient was selected by age, gender and residential place; however, this study used controls of four cancer types in the analyses. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence intervals (CIs). Additional analyses were performed among 181 lung cancer cases and 2141 controls who were not cigarette smokers or opium or nass/pipe users. The odds of lung cancer were higher among waterpipe smokers than never-smokers (OR = 1.3, 95% CI: 1.0–1.7). Results showed a higher OR of lung cancer for those who smoked the waterpipe daily (OR = 2.1, 95% CI: 1.4–3.0), smoked more than two heads per day (OR = 2.7, 95% CI: 1.8–4.0), had smoked for >20 years (OR = 1.9, 95% CI: 1.3–2.7), smoked more than 20 head-years (OR = 2.8, 95% CI: 1.9–4.1) and initiated smoking before the age of 30 years (OR = 1.7, 95% CI: 1.1–2.5). The association was only statistically significant for squamous cell carcinomas (OR = 1.8, 95% CI 1.2–2.7). Furthermore, this study observed a higher OR of lung cancer among exclusive waterpipe smokers (OR = 2.3, 95% CI: 1.6, 3.5). Waterpipe smoking was associated with an increased risk of lung cancer. The association was stronger with higher frequency, duration and intensity of exposure to waterpipe smoking. The association increases in exclusive waterpipe smokers, which is likely due to controlling for residual confounding by cigarette smoking and opium consumption, and higher exposure levels in this subpopulation. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the feasibility of deep learning (DL) based on multiparametric MRI to differentiate the pathological subtypes of brain metastasis (BM) in lung cancer patients. This retrospective analysis collected 246 patients (456 BMs) from five medical centers from July 2016 to June 2022. The BMs were from small-cell lung cancer (SCLC, n = 230) and non-small-cell lung cancer (NSCLC, n = 226; 119 adenocarcinoma and 107 squamous cell carcinoma). Patients from four medical centers were assigned to training set and internal validation set with a ratio of 4:1, and we selected another medical center as an external test set. An attention-guided residual fusion network (ARFN) model for T1WI, T2WI, T2-FLAIR, DWI, and contrast-enhanced T1WI based on the ResNet-18 basic network was developed. The area under the receiver operating characteristic curve (AUC) was used to assess the classification performance. Compared with models based on five single-sequence and other combinations, a multiparametric MRI model based on five sequences had higher specificity in distinguishing BMs from different types of lung cancer. In the internal validation and external test sets, AUCs of the model for the classification of SCLC and NSCLC brain metastasis were 0.796 and 0.751, respectively; in terms of differentiating adenocarcinoma from squamous cell carcinoma BMs, the AUC values of the prediction models combining the five sequences were 0.771 and 0.738, respectively. DL together with multiparametric MRI has discriminatory feasibility in identifying pathology type of BM from lung cancer. [ABSTRACT FROM AUTHOR]

The current guidelines for the treatment of non-small cell lung cancer encourage local curative treatment for selected patients with oligometastases. This study evaluated the surgical results of total en bloc spondylectomy (TES) for isolated spinal metastases originating from lung cancer in carefully selected patients. We retrospectively reviewed 14 patients (7 men and 7 women) who underwent TES for spinal metastases originating from lung cancer between 2000 and 2017. The primary outcome measure was the postoperative overall survival time. The histological types included adenocarcinoma (n = 12), pleomorphic carcinoma (n = 1), and small cell lung carcinoma (SCLC) (n = 1 patient). We assessed postoperative survival using Kaplan–Meier analysis and the log-rank test. The median postoperative survival time was 83.0 months (6–162 months) in 13 patients with non-small cell lung carcinoma (NSCLC) and 6 months in 1 patient with SCLC. The 3-, 5-, and 10-year overall survival rates in patients with NSCLC were 61.5%, 53.8%, and 15.4%, respectively. Poor postoperative performance status (PS) and Frankel grade, and preoperative irradiation to the vertebrae to be resected were significantly associated with short-term survival after TES in patients with NSCLC (p < 0.05). The surgical results of TES for spinal metastases of lung cancer were relatively favorable among carefully selected patients. TES may be indicated for spinal metastases of lung cancer in patients with controlled primary lung cancer, NSCLC histology, prospect of good postoperative PS, and preferably no irradiation to the target vertebrae. [ABSTRACT FROM AUTHOR]

An increasing number of studies point to an association between mitochondrial proteins (MPs) and lung cancer (LC). However, the causal relationship between MPs and LC remains unclear. Consequently, our study employed a bidirectional Mendelian randomization (MR) analysis to explore the causal association between MPs and different pathological types of LC. A two-sample MR study was performed using the genome-wide association study (GWAS) data publicly available. We applied the primary inverse variance weighted (IVW) method along with additional MR methods to validate the causality between MPs and different pathological types of LC. To ensure the robustness of our findings, sensitivity analyses were employed. Moreover, we performed a bi-directional MR analysis to determine the direction of the causal association. We identified a total of seven MPs had significant causal relationships on overall LC, lung squamous cell carcinoma (LUSC), and small cell lung carcinoma (SCLC). We found two MPs had significant associations with overall LC, four MPs had significant associations with LUSC, and four MPs had significant associations with SCLC. Additionally, an MP was found to have a nominal relationship with LUSC. Moreover, no causality was found between MPs and lung adenocarcinoma (LUAD). Bidirectional MR showed no reverse effect between identified MPs and different pathological types of LC. In general, our findings of this MR study suggest causal associations of specific MPs with overall LC, LUSC, and SCLC. However, no such causality was found in LUAD. [ABSTRACT FROM AUTHOR]

Background: The second most common cancer and the main cause of death from cancer worldwide is lung cancer. The stage of the cancer, mutation, and histological type all affect the prognosis and course of treatment. There is no adequate data about histological subtypes lung cancer in our area. The aim of this study is to evaluate the smoking status, histological subtypes, clinicoepidemiological profile, and interdependencies among those suffering from lung cancer. Materials and Methods: This cross-sectional study was conducted in Department of Pulmonary Medicine, Government Medical College, Thrissur, Kerala, India. From May 2, 2021, until May 7, 2022. Histopathologicaly confirmed lung cancer patients were studied. The data was collected by using a semi-structured proforma, and SPSS 20 was used for analysis. Results: The mean age of the patients (n=124) was 63.42 + 9.11 (SD) years. The common symptoms were cough (71.8%), breathlessness (62.9%), chest pain (35.5%), and loss of weight (31.5%). Among the patients 86.3% are males and 80.6% are smokers. Adenocarcinoma was the commonest histopathological subtype (45.9%) followed by squamous cell carcinoma (37.9%), small cell carcinoma (10.5%) and other neuroendocrine tumors (5.6%). Squamous cell carcinoma was the commonest subtype among males (42.1%) and smokers (44.6%). Adenocarcinoma remained commonest among females (82.3%) and non-smokers (87%). Cough was significantly higher in squamous cell and small cell carcinomas (p=0.04). Dyspnea remained the most prevalent symptom in adenocarcinoma (64.9%). Conclusion: Adenocarcinoma was the commonest subtype. Squamous cell carcinoma had higher prevalence among males and smokers; adenocarcinoma was higher among females and non-smokers. The commonest symptom was cough. Cough was significantly higher in squamous cell and small cell carcinomas. Dyspnoea was the most prevalent symptom in adenocarcinoma. [ABSTRACT FROM AUTHOR]

Lung cancer ranks as the second most prevalent cancer globally and is the primary contributor to neoplastic-related deaths. The approach to its treatment relies on both tumour staging and histological type determination. Data indicate that the prognosis of lung cancer is strongly linked to its clinical stage, underscoring the importance of early diagnosis in enhancing patient outcomes. Consequently, the choice of an appropriate diagnostic method holds significant importance in elevating both the early detection rate and prognosis of lung cancer. This paper aims to assess computer tomography features specific to the most common lung cancer types (adenocarcinoma, squamous cell carcinomas and small cell lung cancer). Data were collected retrospectively from CT scans of 58 patients pathologically diagnosed with lung cancer. The following CT features were evaluated and recorded for each case: location, margins, structure, lymph node involvement, cavitation, vascular bundle-thickening, bronchial obstruction, and pleural involvement. Squamous cell carcinoma (SQCC) and small cell lung cancer (SCLC) showed a higher incidence of central location, while adenocarcinoma (ADC) showed a significant predilection for a peripheral location. Internal cavitation was mostly observed in SQCC, and a solid structure was observed in almost all cases of ADC. These features can provide information about the prognosis of the patient, considering that NSCLCs are more frequent but tend to demonstrate positive results for targetable driver mutations, such as EGFR, thereby increasing the overall survival. In addition, SCLC presents with early distant spreads, which limits the opportunity to investigate the evolution of tumorigenesis and gene alterations at early stages but can have a rapidly positively response to chemotherapy. The location of the lung cancer exhibits distinct forecasts, with several studies suggesting that peripheral lung tumours offer a more favourable prognosis. Cavity formation appears correlate with a poorer prognosis. Histopathological analysis is the gold standard for diagnosing the type of lung cancer; however, using CT scanning for the purpose of a rough, but fast, preliminary diagnosis has the potential to shorten the waiting time for treatment by helping clinicians and patients to know more about the diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the application value of serum cytokeratin 19 fragment (CYFRA21-1) combined with nerve-specific enolase (NSE), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC-Ag) in the diagnosis of lung cancer (LC). Methods: A total of 831 cases of LC, 360 cases of benign lung disease (BLD) and 102 healthy controls, were enrolled. The data were processed using SPSS, GraphPad Prism, and MedCalc software. Results: The tumor marker (TM) levels in the LC and BLD groups were significantly higher than those in the control group; the CYFRA21-1, NSE, and CEA levels in the patients with LC were higher than in those with BLD. In particular, the increase was predominantly observed for the levels of CEA and CYFRA21-1 in adenocarcinoma (LUAD), CYFRA21-1 and SCC-Ag in squamous cell carcinoma (LUSC), and NSE in small cell carcinoma (SCLC). The CYFRA21-1, NSE, and CEA levels were significantly higher in stage IV than in other stages in LC. Univariate binary logistic analysis showed that increased levels of all four TMs were risk factors for BLD and LC. The area under the curve (AUC) of CYFRA21-1 was most effective in distinguishing patients with BLD or LC from the controls and in distinguishing patients with BLD and LC. The AUCs of combined CYFRA21-1, NSE, and CEA were increased to 0.755, 0.922, and 0.783, respectively, with no significant difference with the AUC of the four combined tests. In the histological classification, the best predictors were CEA, for LUAD, CYFRA21-1 for LUSC, and NSE for SCLC. Moreover, the expression levels of CYFRA21-1, NSE, and CEA significantly decreased after each treatment course. Conclusions: The combined assay of CYFRA21-1, NSE, and CEA addresses the aspects of accuracy, sensitivity, specificity, and economic cost and should be considered as a potential diagnostic test in LC. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer remains the number one public health burden related to cancer worldwide. The integration of genomic profiling with in-depth proteomic profiling has introduced a new dimension of molecular cancer research, termed proteogenomics. This new-born scientific field is anticipated to fill significant knowledge gaps created by transitioning from the genome to the proteome and assist in the discovery of novel treatment pathways for lung cancer patients. This review consists of a comprehensive investigation of recent studies undertaken in the lung cancer proteogenomics setting, focusing on how elucidation of such features can evoke tangible clinical outcomes. Background: Lung cancer is associated with a high incidence of mortality worldwide. Molecular mechanisms governing the disease have been explored by genomic studies; however, several aspects remain elusive. The integration of genomic profiling with in-depth proteomic profiling has introduced a new dimension to lung cancer research, termed proteogenomics. The aim of this review article was to investigate proteogenomic approaches in lung cancer, focusing on how elucidation of proteogenomic features can evoke tangible clinical outcomes. Methods: A strict methodological approach was adopted for study selection and key article features included molecular attributes, tumor biomarkers, and major hallmarks involved in oncogenesis. Results: As a consensus, in all studies it becomes evident that proteogenomics is anticipated to fill significant knowledge gaps and assist in the discovery of novel treatment options. Genomic profiling unravels patient driver mutations, and exploration of downstream effects uncovers great variability in transcript and protein correlation. Also, emphasis is placed on defining proteogenomic traits of tumors of major histological classes, generating a diverse portrait of predictive markers and druggable targets. Conclusions: An up-to-date synthesis of landmark lung cancer proteogenomic studies is herein provided, underpinning the importance of proteogenomics in the landscape of personalized medicine for combating lung cancer. [ABSTRACT FROM AUTHOR]

Lung cancer remains the leading cause of cancer-related mortality, with 1.8 million deaths per year. Small cell lung cancer and non-small cell lung cancer (NSCLC) are the main cancer types. Approximately 85% of cases are NSCLC, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. In this reported treatment case, the tumor histological type changed after targeted therapy, which has not been previously well documented. The patient was a 67-year-old woman diagnosed with squamous cell carcinoma via bronchoscopy. She received five neoadjuvant immune monotherapies. The lesion shrank but then progressed, with a diagnosis of small cell carcinoma via bronchoscopy. This finding suggests that tumor acquisition of resistance as manifested by cancer-type changes needs consideration and study in the application of this particular type of immunotherapy. [ABSTRACT FROM AUTHOR]

Lung cancer is a deadly type of malignancy that poses a significant threat to human health. Accurately identifying the subtypes of lung cancer is critical for effective treatment. However, conventional methods for determining subtypes, such as histological examination, are invasive and time-consuming. In order to overcome this problem, a non-invasive approach for predicting lung cancer subtypes using multi-modality images with a hybrid model is proposed in this study. The model combines attention-based Convolutional Neural Networks (CNNs) and machine learning classifiers to achieve this objective. The model employs a soft-attention mechanism to focus on the pathological areas and extract both global and local features from the images. The stack-based ensemble classifier employs logistic regression as a meta-learner and four machine learning classifiers, including Support Vector Machine (SVM), Naive Bayes, Random Forest, and J48. The classifier categorizes lung cancer into Adenocarcinoma (ADC), Squamous Cell Carcinoma (SQC), and Small Cell Carcinoma (SCC). The suggested model validated using publically accessible datasets (Lung-PET-CT-DX, Lung1, and Lung3) achieved superior performance, with a validation accuracy of 98.8%, an F1-score of 0.986, and a Matthews Correlation Coefficient (MCC) of 0.988. [ABSTRACT FROM AUTHOR]

Rationale: Particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5) is an established cause of lung cancer, but the association with ultrafine particulate matter (UFP; aerodynamic diameter < 0.1 μm) is unclear. Objectives: To investigate the association between UFP and lung cancer overall and by histologic subtype. Methods: The Los Angeles Ultrafines Study includes 45,012 participants aged ≤50 years in southern California at enrollment (1995-1996) followed through 2017 for incident lung cancer (n = 1,770). We estimated historical residential ambient UFP number concentrations via land use regression and back extrapolation using PM2.5. In Cox proportional hazards models adjusted for smoking and other confounders, we estimated associations between 10-year lagged UFP (per 10,000 particles/cm³ and quartiles) and lung cancer overall and by major histologic subtype (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). We also evaluated relationships by smoking status, birth cohort, and historical duration at the residence. Measurements and Main Results: UFP was modestly associated with lung cancer risk overall (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.99-1.08]). For adenocarcinoma, we observed a positive trend among men; risk was increased in the highest exposure quartile versus the lowest (HR, 1.39 [95% CI, 1.05-1.85]; P for trend = 0.01) and was also increased in continuous models (HR per 10,000 particles/cm3, 1.09 [95% CI, 1.00-1.18]), but no increased risk was apparent among women (P for interaction = 0.03). Adenocarcinoma risk was elevated among men born between 1925 and 1930 (HR, 1.13 [95% CI, 1.02-1.26] per 10,000) but not for other birth cohorts, and was suggestive for men with ≤10 years of residential duration (HR, 1.11 [95% CI, 0.98-1.26]). We found no consistent associations for women or other histologic subtypes. Conclusions: UFP exposure was modestly associated with lung cancer overall, with stronger associations observed for adenocarcinoma of the lung. [ABSTRACT FROM AUTHOR]

In lung cancer, metastasis to the liver, bones, brain, and adrenal glands is more commonly observed, whereas pancreatic metastasis from lung cancer is relatively rare. We present a case of a patient with an 8-year history of lung adenocarcinoma (LUAD) who was admitted to our institution exhibiting symptoms consistent with acute pancreatitis. Subsequent histopathological examination through puncture confirmed the occurrence of pancreatic metastasis originating from small cell lung cancer (SCLC). During a multidisciplinary team discussion, we reached a consensus in diagnosing the patient with post-transformation small cell carcinoma alongside moderately severe pancreatitis, which was determined to be a consequence of pancreatic metastasis. The patient received a regimen of etoposide and cisplatin chemotherapy. This unique clinical case highlights the importance of further investigating the factors contributing to pancreatic metastasis in patients with lung cancer, as the underlying mechanisms remain unclear. Understanding these exceptional metastatic events is vital in devising effective therapeutic strategies and improving patient prognosis. Our findings emphasize the need for continued surveillance and comprehensive management of lung cancer patients, particularly those with resistant forms of the disease, to promptly identify and address the progression of metastatic events to uncommon sites such as the pancreas. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the primary cause of cancer-related deaths in China. This study analysed the incidence and survival trends of lung cancer from 2011 to 2020 in Fujian Province, southeast of China, and provided basis for formulating prevention and treatment strategies. Methods: The population-based cancer data was used to analyse the incidence of lung cancer between 2011 and 2020, which were stratified by sex, age and histology. The change of incidence trend was analysed using Joinpoint regression. The relative survival of lung cancer with onset in 2011–2014, 2015–2017 and 2018–2020 were calculated using the cohort, complete and period methods, respectively. Results: There were 23,043 patients diagnosed with lung cancer in seven registries between 2011 and 2020, with an age-standardized incidence rate (ASIR) of 37.7/100,000. The males ASIR increased from 51.1/100,000 to 60.5/100,000 with an annual percentage change (APC) of 1.5%. However, females ASIR increased faster than males, with an APC of 5.7% in 2011–2017 and 21.0% in 2017–2020. Compared with 2011, the average onset age of males and females in 2020 was 1.5 years and 5.9 years earlier, respectively. Moreover, the proportion of adenocarcinoma has increased, while squamous cell carcinoma and small cell carcinoma have decreased over the past decade. The 5-year relative survival of lung cancer increased from 13.8 to 23.7%, with a greater average increase in females than males (8.7% and 2.6%). The 5-year relative survival of adenocarcinoma, squamous cell carcinoma and small cell carcinoma reached 47.1%, 18.3% and 6.9% in 2018–2020, respectively. Conclusions: The incidence of lung cancer in Fujian Province is on the rise, with a significant rise in adenocarcinoma, a younger age of onset and the possibility of overdiagnosis. Thus, Fujian Province should strengthen the prevention and control of lung cancer, giving more attention to the prevention and treatment of lung cancer in females and young populations. [ABSTRACT FROM AUTHOR]

OBJECTIVE Lung cancer (LC) is the leading cause of cancer death worldwide. Multiple studies have shown tumor progression and prognosis to be associated with immune status and nutritional condition. Alterations in blood lipid levels have been demonstrated to be a risk factor for LC. In the present study, we evaluate the effect of blood parameters on brain metastasis in LC. METHODS Patients identified with brain metastases during diagnosis or therapy and who subsequently underwent radiation therapy were included in the study. Patient characteristics, laboratory parameters, pathologic subtype, disease stage, treatment modalities, and outcome following treatment were recorded, and the patients' PFS and OS were calculated. RESULTS Univariate analysis revealed neutrophil, low-density lipoprotein (LDL), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein levels to be significantly different between groups according to brain metastases. In a subgroup analysis based on cancer subtypes, LDL and lymphocyte levels were found to be significantly different in squamous cancer, while LDL was different in the undifferentiated subtype. OS was different in the NLR low and high groups, favoring the NLR low group (p=0.015; OS: 12 vs. 9 months), and the monocyte/lymphocyte ratio was significant in terms of OS favoring the low group with a cutoff value of 0.56 (p=0.002; OS: 13 vs. 9 months). CONCLUSION Our study identified differences in the inflammatory and lipid profiles of LC patients in terms of brain metastases and survival. Other than the literature, LDL levels were different among groups and may be considered a valid subject for future study. [ABSTRACT FROM AUTHOR]

Lung cancer is highly aggressive, which has a high mortality rate. Major types encompass lung adenocarcinoma, lung squamous cell carcinoma, lung adenosquamous carcinoma, small cell carcinoma, and large cell carcinoma. Lung adenocarcinoma and lung squamous cell carcinoma together account for more than 80% of cases. Diverse subtypes demand distinct treatment approaches. The application of precision medicine necessitates prompt and accurate evaluation of treatment effectiveness, contributing to the improvement of treatment strategies and outcomes. Medical imaging is crucial in the diagnosis and management of lung cancer, with techniques such as fluoroscopy, computed radiography (CR), digital radiography (DR), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)/CT, and PET/MRI being essential tools. The surge of radiomics in recent times offers fresh promise for cancer diagnosis and treatment. In particular, PET/CT and PET/MRI radiomics, extensively studied in lung cancer research, have made advancements in diagnosing the disease, evaluating metastasis, predicting molecular subtypes, and forecasting patient prognosis. While conventional imaging methods continue to play a primary role in diagnosis and assessment, PET/CT and PET/MRI radiomics simultaneously provide detailed morphological and functional information. This has significant clinical potential value, offering advantages for lung cancer diagnosis and treatment. Hence, this manuscript provides a review of the latest developments in PET-related radiomics for lung cancer. [ABSTRACT FROM AUTHOR]

Small cell transformation was one mechanism by which EGFR-mutation NSCLC acquired resistance after tyrosine kinase inhibitors (TKIs) treatment. A few reports of small cell transformation occurred in other oncogene-driven lung cancers. We found the first case of transformation of a RET-rearranged lung adenocarcinoma to SCLC after selpercatinib, a novel highly selective RET TKIs. Whole-exome sequencing (WES) was used to explore alteration in gene expression in tumor tissue at initial diagnosis and after transformation into small cell carcinoma. We found that transformed into SCLC tumor tissue had inactivation of RB1 and TP53, with RET fusion was still present. In addition, the APOBEC family of cytidine deaminases appeared amplification. Although RET rearrangement still existed, using another RET TKIs was ineffective, and etoposide plus platinum might be an effective rescue treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung are now classified as lung neuroendocrine carcinomas (NECs) and have different treatment strategies compared with non-SCLC. Although these NECs are less frequently resected by surgery, the diagnosis of LCNEC is particularly difficult in some cases because staining for neuroendocrine markers is necessary in addition to morphological features. In our retrospective study of pathology specimens from 42 surgically resected SCLCs and 44 LCNECs, we demonstrated that immunohistochemical staining with Musashi-1, a marker of neural stem cells, more diffusely and intensely stained SCLC and LCNEC tissues. The findings of this study may improve and simplify the diagnosis of NECs in surgical and biopsy specimens and increase the opportunity to provide more appropriate treatment for patients. Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have recently been grouped as lung neuroendocrine carcinomas (NECs). Because these lung NECs are clinically malignant and their treatment strategies differ from those of non-SCLC, the quality of diagnosis has a significant prognostic impact. The diagnosis of LCNEC requires positive immunohistochemical staining with chromogranin A, synaptophysin, and CD56, along with a morphological diagnosis, and insulinoma-associated protein 1 (INSM1) has been proposed as an additional marker but is still not an ideal or better marker. We investigated Musashi-1 as a novel immunohistochemical marker in 42 patients with SCLCs and 44 with LCNECs who underwent lung resection between 1998 and 2020 at our institution. We found Musashi-1 expression in 98% (41/42) SCLC and in 90% (40/44) LCNEC. These findings were similar to CD56 expression and superior to synaptophysin, chromogranin A, and INSM1. Musashi-1 also tended to show more diffuse and intense staining, especially in LCNEC, with more cases staining > 10% than any other existing markers (Musashi-1, 77%; INSM1, 45%; chromogranin A, 34%; synaptophysin, 41%; and CD56, 66%). In conclusion, we identified Musashi-1 as a novel immunohistochemical staining marker to aid in the diagnosis of lung NEC. [ABSTRACT FROM AUTHOR]

The rs2736100 (A > C) polymorphism of the second intron of Telomerase reverse transcriptase (TERT) has been confirmed to be closely associated with the risk of Lung cancer (LC), but there is still no unified conclusion on the results of its association with LC. This study included Genome-wide association studies (GWAS) and case–control studies reported so far on this association between TERT rs2736100 polymorphism and LC to clarify such a correlation with LC and the differences in it between different ethnicities and different types of LC. Relevant literatures published before May 7, 2022 on 'TERT rs2736100 polymorphism and LC susceptibility' in PubMed, EMbase, CENTRAL, MEDLINE databases were searched through the Internet, and data were extracted. Statistical analysis of data was performed in Revman5.3 software, including drawing forest diagrams, drawing funnel diagrams and so on. Sensitivity and publication bias analysis were performed in Stata 12.0 software. The C allele of TERT rs2736100 was associated with the risk of LC (Overall population: [OR] = 1.21, 95%CI [1.17, 1.25]; Caucasians: [OR] = 1.11, 95%CI [1.06, 1.17]; Asians: [OR] = 1.26, 95%CI [1.21, 1.30]), and Asians had a higher risk of LC than Caucasians (C vs. A: Caucasians: [OR] = 1.11 /Asians: [OR]) = 1.26). The other gene models also showed similar results. The results of stratified analysis of LC patients showed that the C allele was associated with the risk of Non-small-cell lung carcinoma (NSCLC) and Lung adenocarcinoma (LUAD), and the risk of NSCLC and LUAD in Asians was higher than that in Caucasians. The C allele was associated with the risk of Lung squamous cell carcinoma (LUSC) and Small cell lung carcinoma(SCLC) in Asians but not in Caucasians. NSCLC patients ([OR] = 1.27) had a stronger correlation than SCLC patients ([OR] = 1.03), and LUAD patients ([OR] = 1.32) had a stronger correlation than LUSC patients ([OR] = 1.09).In addition, the C allele of TERT rs2736100 was associated with the risk of LC, NSCLC and LUAD in both smoking groups and non-smoking groups, and the risk of LC in non-smokers of different ethnic groups was higher than that in smokers. In the Asians, non-smoking women were more at risk of developing LUAD. The C allele of TERT rs2736100 is a risk factor for LC, NSCLC, and LUAD in different ethnic groups, and the Asian population is at a more common risk. The C allele is a risk factor for LUSC and SCLC in Asians but not in Caucasians. And smoking is not the most critical factor that causes variation in TERT rs2736100 to increase the risk of most LC (NSCLC, LUAD). Therefore, LC is a multi-etiological disease caused by a combination of genetic, environmental and lifestyle factors. [ABSTRACT FROM AUTHOR]

Lung cancer is the second most common cancer worldwide, yet the distribution by histological subtype remains unknown. We aimed to quantify the global, regional, and national burden of lung cancer incidence for the four main subtypes in 185 countries and territories. In this population-based study, we used data from Cancer Incidence in Five Continents Volume XI and the African Cancer Registry Network to assess the proportions of adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma among all lung cancers by country, sex, and age group and subsequently applied these data to corresponding national (GLOBOCAN) estimates of lung cancer incidence in 2020. Unspecified morphologies were reallocated to specified subtypes. Age-standardised incidence rates were calculated using the world standard population to compare subtype risks worldwide, adjusted for differences in age composition between populations by country. In 2020, there were an estimated 2 206 771 new cases of lung cancer, with 1 435 943 in males and 770 828 in females worldwide. In males, 560 108 (39%) of all lung cancer cases were adenocarcinoma, 351 807 (25%) were squamous cell carcinoma, 163 862 (11%) were small-cell carcinoma, and 115 322 (8%) were large-cell carcinoma cases. In females, 440 510 (57%) of all lung cancer cases were adenocarcinoma, 91 070 (12%) were squamous cell carcinoma, 68 224 (9%) were small-cell carcinoma, and 49 246 (6%) were large-cell carcinoma cases. Age-standardised incidence rates for adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma, respectively, were estimated to be 12·4, 7·7, 3·6, and 2·6 per 100 000 person-years in males and 8·3, 1·6, 1·3, and 0·9 per 100 000 person-years in females worldwide. The incidence rates of adenocarcinoma exceeded those of squamous cell carcinoma in 150 of 185 countries in males and in all 185 countries in females. The highest age-standardised incidence rates per 100 000 person-years for adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma, respectively, for males occurred in eastern Asia (23·5), central and eastern Europe (17·5), western Asia (7·2), and south-eastern Asia (11·0); and for females occurred in eastern Asia (16·0), northern America (5·4), northern America (4·7), and south-eastern Asia (3·4). The incidence of each subtype showed a clear gradient according to the Human Development Index for male and female individuals, with increased rates in high and very high Human Development Index countries. Adenocarcinoma has become the most common subtype of lung cancer globally in 2020, with incidence rates in males exceeding those of squamous cell carcinoma in most countries, and in females in all countries. Our findings provide new insights into the nature of the global lung cancer burden and facilitates tailored national preventive actions within each world region. None. [ABSTRACT FROM AUTHOR]

Objective: The approval of immunotherapy (I-O) for the treatment of late-stage non-small cell lung cancer (NSCLC) opened new perspectives in improving survival outcomes. However, survival data have not yet been provided from the period of the Covid-19 pandemic. The aims of our study were to assess and compare survival outcomes of patients with advanced LC receiving systemic anticancer treatment (SACT) before and after the approval of immunotherapy in Hungary, and to examine the impact of pandemic on survival outcomes using data from the Hungarian National Health Insurance Fund (NHIF) database. Methods: This retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with advanced stage lung cancer (LC) (ICD-10 C34) between 1 January 2011 and 31 December 2021 and received SACT treatment without LC-related surgery. Survival rates were evaluated by year of diagnosis, sex, age, and LC histology. Results: In total, 35,416 patients were newly diagnosed with advanced LC and received SACT during the study period (mean age at diagnosis: 62.1-66.3 years). In patients with non-squamous cell carcinoma, 3-year survival was significantly higher among those diagnosed in 2019 vs. 2011-2012 (28.7% [95% CI: 26.4%-30.9%] vs. 14.45% [95% CI: 13.21%-15.69%], respectively). In patients with squamous cell carcinoma, 3-year survival rates were 22.3% (95% CI: 19.4%-25.2%) and 13.37% (95% CI: 11.8%-15.0%) in 2019 and 2011-2012, respectively, the change was statistically significant. Compared to 2011-2012, the hazard ratio of survival change for non-squamous cell carcinoma patients was 0.91, 0.82, and 0.62 in 2015-2016, 2017-2018, and 2019, respectively (p<0.001 for all cases). In the squamous cell carcinoma group, corresponding hazard ratios were 0.93, 0.87, and 0.78, respectively (p<0.001 for all cases). Survival improvements remained significant in both patient populations during the Covid-19 pandemic (2020-2021). No significant improvements were found in the survival of patients with small cell carcinoma. Platinum-based chemotherapy was the most common first-line treatment in all diagnostic periods, however, the proportion of patients receiving first- or second-line immunotherapy significantly increased during the study period. Conclusion: 3-year survival rates of NSCLC almost doubled among patients with non-squamous cell carcinoma and significantly improved at squamous cell carcinoma over the past decade in Hungary. Improvements could potentially be attributable by the introduction of immunotherapy and were not offset by the Covid-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is one of the most frequent neoplasms and is associated with serious oncologic emergencies (OE). We performed a retrospective study to characterize OE in lung cancer patients admitted to the pulmonology department to determine the effects of the SARS-CoV2 pandemic. Materials and Methods: A total number of 82 patients were admitted with an emergency, mostly brain metastasis (n=37; 45.1%), followed by superior vena cava syndrome (n=13; 15.9%), cardiac tamponade (n=7; 8.5%), large pleural effusion (n=7; 8.5%), severe pulmonary embolism (n=6; 7.3%), spinal cord syndrome (n=6; 7.3%), massive hemoptysis (n=3; 3.7%), stridor (n=2; 2.4%) and atelectasis (n=1; 1.2%). Clinical and pathological data were retrieved from clinical charts including demographic information, smoking status, cancer histology, clinical stage at diagnosis, anticancer treatment, time between LC diagnosis until the OE, outcomes of OE treatment, and overall survival after OE. Results: The predominant histology was adenocarcinoma (n=59; 71.9%) and 86.8% of the patients (n=71) were in stage IV. OE was the disease presentation in 45.2% (n=37) and 6-month mortality was 75.6%. Neurologic emergencies were associated with a lower risk of 6-month mortality compared to cardiovascular and respiratory [OR 0.255 (CI 0.72-0.90), p=0.035)]. Younger patients (p=0.011), metastatic disease (p=0.02), no cancer treatment (p<0.001), and small cell carcinoma (SCLC) (p=0.016) had a shorter time between cancer diagnosis and the event. Conclusion: OE occurred mostly in men with metastatic adenocarcinomas. Younger patients, SCLC, metastatic disease, and no cancer treatment were associated with a shorter time between lung cancer diagnosis until the occurrence of an OE and brain metastasis with a better prognosis. There were no differences between patients admitted in 2019 and 2020 that could be related to the access to healthcare services during the SARS-COV2 pandemic. [ABSTRACT FROM AUTHOR]

Objectives: Pulmonary embolism (PE) is a life‐threatening complication that can occur in patients with lung cancer. In this study, we aimed to identify risk factors and examine the clinical characteristics of advanced lung cancer patients with PE. Methods: We conducted a retrospective review of patients admitted to our two hospitals between January 2020 and June 2022. The case group consisted of patients with lung cancer and PE, and a closely matched control group was included to identify risk factors. Statistical analysis was conducted using R language. Results: A total of 4957 patients were reviewed, and 162 patients (comprising 54 cases and 108 controls) were included in this study. The prevalence of lung cancer with PE in the study population was 1.08%. The majority of patients were male, and the most common histological subtype was adenocarcinoma (67%), followed by squamous cell carcinoma, small cell carcinoma, and poorly differentiated non‐small cell lung cancer. The majority of patients had a high performance status (PS) score, with 50% experiencing respiratory failure (mainly hypoxia) and 33% with deep vein thrombosis (DVT). Forty‐eight percent of patients were diagnosed with concurrent PE. Further analysis showed that PE was an independent predictor of poor survival, and a PS score of >1 was an independent risk factor for PE in patients with lung cancer. Conclusion: Our study provides valuable insights into the epidemiology and prognosis of PE in lung cancer patients and suggests that a poor ECOG PS, which has not been previously reported, is an independent risk factor for PE. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer is a highly aggressive malignancy that causes significant morbidity and mortality. The incidence of lung cancer has been increasing in the past few decades. Cytology aids in the initial evaluation and diagnosis of patients with lung cancer. Currently, the classification of lung carcinoma has expanded beyond small cell lung carcinoma and Non-Small Cell Lung Carcinoma (NSCLC). Precise subtyping of poorly differentiated NSCLC into adenocarcinoma and Squamous Cell Carcinoma (SCC) has a direct impact on patient management and prognosis. The morphologic diagnosis forms the basis and is further supplemented by a panel of immunohistochemical markers. Immunohistochemistry (IHC) is important in cases with poorly differentiated morphology or partial sampling. The IHC panel used includes Tumour Protein p63 (p63) and Thyroid Transcription Factor (TTF1) for subtyping lung cancer. Aim: The present study was conducted with the aim of studying the age and gender distribution, risk factors, cytohistopathological association, and formulating an effective IHC panel for the precise yet effective subtyping of poorly differentiated lung malignancies. Materials and Methods: This cross-sectional study included cases retrieved from the Archives of Pathology Department, SRM Medical College and Research Centre, Chennai, Tamil Nadu, India, between July 2012 and July 2016. The cases included had a diagnosis of lung malignancy (confirmed by cytology/biopsy) or were suspected of having malignancy based on clinical/radiological findings. The study period was from July 2015 to August 2016. The cytology and biopsy slides were reviewed, and the malignancy was classified according to the World Health Organisation (WHO) classification of lung malignancies (2021). IHC was performed on the cases using the markers p63 and TTF1 as a dual regimen. Diagnosis and subtyping of tumours were done based on histomorphology, and the tumours were reclassified based on IHC findings. The data were statistically analysed using SPSS software version 25 and the ROC curve. Results: The mean age of the patients was 60.9 years. The study included a total of 50 cases of lung carcinoma, with an average age of 60.9 years (ranging from 30 to 88 years). Among the cases, 35 (70%) had a positive smoking history. A concordant cytohistopathological association was observed in 26 (52%) of cases. Adenocarcinoma was the predominant subtype, accounting for 21 (42%) of cases. Tumour cells in adenocarcinoma showed positive staining for TTF-1, with the marker exhibiting 100% sensitivity and 83% specificity. In SCC, tumour cells were positive for p63, with the marker demonstrating 92% sensitivity and 82% specificity. Both markers showed effective sensitivity and specificity when used as a dual regimen. Conclusion: Although lung cancer is typically diagnosed in the elderly population, there has been an increase in cases among younger individuals due to urbanisation. Smoking remains an important risk factor for lung malignancy. Exfoliative cytology alone is not sufficient for the diagnosis of lung malignancies and should be supplemented with biopsy for more accurate results. Adenocarcinoma was found to be the most common subtype in our study. The IHC panel of p63 and TTF-1 proved to be an effective regimen for classifying poorly differentiated lung carcinomas. [ABSTRACT FROM AUTHOR]

Alveolar macrophages (AMs) are resident macrophages in the lungs; however, whether the number of AMs plays a role in the lung neuroendocrine tumor (NET) prognosis remains unclear. We counted the number of AMs located around the tumor (peritumoral alveolar macrophages [pAMs]) and the number of AMs located apart from the tumor (distant macrophages; dAMs). In 73 cases of neuroendocrine carcinoma (NEC: small cell lung carcinoma and large cell neuroendocrine carcinoma), the group that contained higher pAMs (≥86/μm2) revealed shorter recurrent‐free survival (RFS) than those with lower pAMs (<86/μm2) (p = 0.005). Bivariate analysis showed that the number of pAMs was an independent predictor of a poor RFS. In contrast, in the carcinoid tumor cohort (n = 29), there was no statistically significant correlation between the two groups with high and low numbers of pAMs in RFS (p = 0.113). Furthermore, we examined the correlation between genomic alterations and the number of pAMs in NEC, but no significant correlation was observed. In conclusion, the number of pAMs is a prognostic factor for NEC in the lung and pAMs may contribute to tumor progression within the peritumoral microenvironment. [ABSTRACT FROM AUTHOR]

Background: Histopathological transformation between different types of lung cancer cells has been reported following a variety of anti-tumor treatments. Examples include transformation from lung adenocarcinoma to squamous-cell carcinoma (SCC) and transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC). Case report: A patient with intermittent hemoptysis for 2 days underwent a computed tomography (CT) scan that revealed interstitial pneumonia in addition to two enlarged paratracheal lymph nodes: one on the right (4R) and one on the left (4L) measuring 10 and 7 mm in diameter, respectively (Fig. 1). There was no evidence of a lung or bronchial mass. Bronchoscopy identified an endoluminal primary mass in a superior segmental bronchus of the left lower lobe and pathological examination following surgery confirmed it to be SCC. At 15 months post operation, a CT scan detected that the 4R lymph node had increased in size from 10 to 16 mm in diameter. At the next follow-up 7 months later, a CT scan showed that the R4 lymph node had further increased in size from 16 to 40 mm in the short axis, making it difficult for a surgeon to resect it "en bloc" immediately. The maximum standardized uptake value was 7.5 on PET-CT images. One month following completion of one cycle of neoadjuvant chemotherapy with gemcitabine and nedaplatin, a further CT scan indicated that the lymph node had decreased in size from 40 to 30 mm in the short axis. A complete mediastinal lymphadenectomy via open thoracotomy was performed and the lymph node was resected. Histological examination identified a main large cell neuroendocrine carcinoma (LCNEC) component with a small fraction of small cell carcinoma, confirmed by immunohistochemical analysis and genetic evidence. Conclusion: Histopathological transformation from SCC to LCNEC with a small fraction of SCLC may have occurred spontaneously without any treatment. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (PD-L1) therapy for advanced non-small-cell lung cancer (NSCLC) has variable outcomes. Tumor subtypes based on PD-L1 expression, histopathology, mutation burden is required for patient stratification and formulation of treatment guidelines. Lung cancers (n=57) diagnosed at Pathology department, VPCI (2018-2021) were retrospectively analyzed. PD-L1(SP263) expressed by tumor cells [low (<1%), medium (1-49%), high (≥50%)] was correlated with histopathology, microenvironment, EGFR, KRAS expression. Patients were categorized into high and low risk based on their: i) gender: males (n=47, 30-89 years), females (n=10, 45-80 years); ii) smoking history: males 26/47 (45.61%), females 1/10 (10%); iii) tumor subtyping: squamous cell carcinoma 15/57 (26.32%), adenocarcinoma 6/57 (17.54%), NSCLC-undifferentiated 24/57 (42.10%), adenosquamous carcinoma 5/57 (8.77 %), carcinosarcoma 4/57 (7.02%), small cell carcinoma 1/57 (1.75%); iv) inflammatory tumor microenvironment/TILs 44/57 (77.1%); iv) PD-L1 positivity-31/57 (54.3%); v) concomitant EGFR/KRAS positivity. PD-L1positive cases showed squamous/undifferentiated histopathology, concomitant EGFR+ (9/20, 45%) and KRAS+ (8/15, 53.3%), smoking+ (21/31,67.74%).PD-L1 negative cases (26/57, 45.6%), were EGFR+ (2/14, 14.28%) and KRAS+ (6/19, 31.5%). The high-risk lung cancer subtypes show squamous/undifferentiated histopathology, inflammatory microenvironment, male preponderance, smoking history, higher concomitant PD-L1, KRAS and EGFR positivity. Lung cancer subtyping can predict clinical response/resistance of patients prior to initiation of PD-L1 inhibitor therapies and can be used to guide therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic spinal cord compression (MSCC) is characterised by the compression of the spinal cord due to direct or metastatic spread to the vertebrae, potentially leading to neurological deficits. This condition constitutes an urgent situation in oncology, demanding swift diagnosis and immediate intervention due to the considerable risk of spinal cord damage and irreversible neurological repercussions. Spinal tumours resulting from the metastasis of lung cancer are particularly connected with an unfavourable prognosis, often displaying rapid advancement and limited survival. Treatment approaches encompass a combination of radiotherapy and potential surgery, which are tailored to each patient's situation. Within this retrospective study, our goal was to pinpoint prognostic elements that impact the survival rates of lung cancer patients experiencing MSCC. Identifying such prognostic factors associated with shorter or longer survival subsequent to MSCC could contribute to tailoring distinct, more or less intensive therapeutic strategies for these individuals. Purpose: Metastatic spinal cord compression (MSCC) is a severe complication of cancer that can lead to irreversible neurological impairment, necessitating prompt recognition and intervention. This retrospective, single-centre study aimed to determine the prognostic factors and survival rates among patients presenting with MSCC secondary to lung cancer. Methods and Materials: We identified 74 patients with epidural metastases-related spinal cord compression and a history of lung cancer through the electronic database of Medway Maritime Hospital in the United Kingdom (UK), spanning the period from April 2016 to September 2021. Among them, 39 were below 55 years old, while 35 were aged 55 years or older; 24 patients were diagnosed with small cell lung cancer (SCLC), and 50 patients had non-small cell lung cancer (NSCLC). Results: The median overall survival (OS) was 5.5 months, with 52 out of 74 patients dying within 6 months of diagnosis with MSCC. For the entire cohort, the statistically significant variables on multi-variate analysis were cancer type (NSCLC had improved OS), the number of involved vertebrae (one to two vertebrae involvement had improved OS), and the time taken to develop motor deficits (≤10 days to develop motor deficits had worsened OS). For the NSCLC cohort, the statistically significant variables on multivariate analysis were molecular alterations (patients with epidermal growth factor receptor (EGFR) mutation), pre-treatment ambulatory status, Eastern Cooperative Oncology Group (ECOG) performance status, and the time taken to develop motor deficits. Conclusions: Within the entire cohort, patients diagnosed with NSCLC and spinal metastases affecting one to two vertebrae exhibited enhanced OS. Within the NSCLC subgroup, those with EGFR mutations who were ambulatory and possessed an ECOG performance status of 1–2 demonstrated improved OS. In both the entire cohort and the NSCLC subgroup, the development of motor deficits within a period of ≤10 days was associated with poor OS. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common malignant diseases, being the most common in men. Many complex factors contribute to its occurrence, smoking being the most important. A period of asymptomatic course, a period of manifestations of the disease and a period of complications may differ. Early diagnosis is important. The prognosis is always serious, especially when diagnosed in late stages, as it is in a large percentage of cases. Prevention includes combating harmful agents. Our goal is to show the factors increasing the probability of the occurrence, presentation of the clinical symptoms, prevention, prognosis, diagnosis and treatment of small cell lung carcinoma. The subject of our research is tracking the practical steps in diagnosis, treatment and monitoring of patients with small cell lung carcinoma. We present a clinical case of a patient with small cell lung carcinoma and her clinical history. For the purposes of the study, the following methods were used: documentary - documentary sources related to the problem were studied; empirical - tracking the clinical sequence of the undertaken diagnostic and therapeutic strategies. Cases of small cell lung carcinoma have a strong correlation with smoking. It is necessary to control external factors as much as possible, as well as to adequately monitor chronic inflammatory processes in the lungs. Given the poor prognosis and frequent diagnosis at an advanced stage, comprehensive examinations should be conducted, helping early diagnosis, as well as researching and developing new ones. [ABSTRACT FROM AUTHOR]

Background: Many epidemiological studies have shown that idiopathic pulmonary fibrosis (IPF) is a risk factor for lung cancer (LC), but these studies do not provide direct evidence of a causal association between the two diseases. We investigated the causal association between IPF and different pathological types of LC based on the Mendelian randomization (MR) study. Methods: The genome-wide association study (GWAS) data of IPF and LC were obtained from the latest published articles, and instrumental variables (IVs) for analysis were obtained after screening and eliminating the confounders. MR Analysis was carried out with the help of random effects inverse variance weighting (re-IVW), MR-egger, and weighted median method, and a comprehensive sensitivity test was conducted. Results: The results of re-IVW analysis showed that IPF may increase the risk of lung squamous cell carcinoma (LUSC) (OR = 1.045, 95% CI 1.011 to 1.080, P = 0.008). In addition, no causal relationship was found between IPF and overall LC (OR = 0.977, 95% CI 0.933 to 1.023, P = 0.32), lung adenocarcinoma (LUAD) (OR = 0.967, 95% CI 0.903 to 1.036, P = 0.345) and small cell lung carcinoma (SCLC) (OR = 1.081, 95% CI 0.992 to 1.177, P = 0.074). A comprehensive sensitivity analysis ensured the reliability of the study. Conclusion: In conclusion, from the perspective of genetic association, we found that IPF is an independent risk factor for LUSC and may increase the risk of LUSC, but no such causal relationship was found in LUAD and SCLC. [ABSTRACT FROM AUTHOR]

In lung and prostate adenocarcinomas, neuroendocrine (NE) transformation to an aggressive derivative resembling small cell lung cancer (SCLC) is associated with poor prognosis. We previously described dependency of SCLC on the nuclear transporter exportin 1. Here, we explored the role of exportin 1 in NE transformation. We observed up-regulated exportin 1 in lung and prostate pretransformation adenocarcinomas. Exportin 1 was up-regulated after genetic inactivation of TP53 and RB1 in lung and prostate adenocarcinoma cell lines, accompanied by increased sensitivity to the exportin 1 inhibitor selinexor in vitro. Exportin 1 inhibition prevented NE transformation in different TP53/RB1-inactivated prostate adenocarcinoma xenograft models that acquire NE features upon treatment with the aromatase inhibitor enzalutamide and extended response to the EGFR inhibitor osimertinib in a lung cancer transformation patient-derived xenograft (PDX) model exhibiting combined adenocarcinoma/SCLC histology. Ectopic SOX2 expression restored the enzalutamide-promoted NE phenotype on adenocarcinoma-to-NE transformation xenograft models despite selinexor treatment. Selinexor sensitized NE-transformed lung and prostate small cell carcinoma PDXs to standard cytotoxics. Together, these data nominate exportin 1 inhibition as a potential therapeutic target to constrain lineage plasticity and prevent or treat NE transformation in lung and prostate adenocarcinoma. Editor's summary: Lung and prostate adenocarcinomas can undergo neuroendocrine (NE) transformation, which results in a more aggressive tumor and worst prognosis for patients. Here, Quintanal-Villalonga et al. explored the role of exportin 1 in this NE transformation and saw that it was elevated after inactivation of TP53 and RB1. This increase resulted in an increased sensitivity to an exportin 1 inhibitor, selinexor, which additionally sensitized NE-transformed mouse models to standard chemotherapy. This suggests exportin 1 as a potential therapeutic target to both prevent and treat NE-transformed lung and prostate adenocarcinomas that requires further study. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

Introduction: Cutaneous metastases (CM) revealing lung carcinoma are extremely rare, accounting for 0.8%. The diagnosis is guided by histology and immunohistochemistry. Treatment is palliative. The prognosis is poor. Case presentation: This is a retrospective study of the available clinical and histological records of four North African patients with CM revealing lung cancer treated at our institute between 2004 and 2010. Three men and one woman were registered. The mean age was 54.5 years (38–74 years). Two patients had primary adenocarcinoma, one patient had small cell carcinoma and one had squamous cell carcinoma. Treatment was based on chemotherapy in two cases and antalgic radiotherapy in two cases, one patient underwent surgical resection as the lesion was infected. The overall survival after diagnosis was between one and four months. Conclusions: A skin nodule can be the first symptom revealing lung cancer. A rare clinical presentation that should not be taken for a benign nodule, the biopsy and histological study with immunohistochemistry confirm the diagnosis. [ABSTRACT FROM AUTHOR]

There has been controversy over whether to radiologically follow up or use local treatment for asymptomatic small-sized brain metastases from primary lung cancer. For brain tumors without local treatment, we evaluated potential factors related to the brain progression and whether systemic therapy controlled the tumor. We analyzed 96 patients with asymptomatic small-sized metastatic brain tumors from lung cancer. These underwent a radiologic follow-up every 2 or 3 months without local treatment of brain metastases. The pathologies of the tumors were adenocarcinoma (n = 74), squamous cell carcinoma (n = 11), and small cell carcinoma (n = 11). The primary lung cancer was treated with cytotoxic chemotherapy (n = 57) and targeted therapy (n = 39). Patients who received targeted therapy were divided into first generation (n = 23) and second or third generation (n = 16). The progression-free survival (PFS) of brain metastases and the overall survival (OS) of patients were analyzed depending on the age, tumor pathology, number, and location of brain metastases, the extent of other organ metastases, and chemotherapy regimens. The median PFS of brain metastases was 7.4 months (range, 1.1–48.3). Targeted therapy showed statistically significant PFS improvement compared to cytotoxic chemotherapy (p = 0.020). Especially, on univariate and multivariate analyses, the PFS in the second or third generation targeted therapy was more significantly improved compared to cytotoxic chemotherapy (hazard ratio 0.229; 95% confidence interval, 0.082–0.640; p = 0.005). The median OS of patients was 13.7 months (range, 2.0–65.0). Univariate and multivariate analyses revealed that the OS of patients was related to other organ metastases except for the brain (p = 0.010 and 0.020, respectively). Three out of 52 patients with brain recurrence showed leptomeningeal dissemination, while the recurrence patterns of brain metastases were mostly local and/or distant metastases (94.2%). Of the 52 patients who relapsed, 25 patients received local brain treatment. There was brain-related mortality in two patients (2.0%). The intracranial anti-tumor effect was superior to cytotoxic chemotherapy in the treatment of asymptomatic small-sized brain metastases with targeted therapy. Consequently, it becomes possible to determine the optimal timing for local brain treatment while conducting radiological follow-up for these tumors, which do not appear to increase brain-related mortality. Furthermore, this approach has the potential to reduce the number of cases requiring brain local treatment. [ABSTRACT FROM AUTHOR]

Background: Distant organ metastasis is a common event in lung cancer (LC). However, the preferential metastatic pattern of different pathological types of LC and its effect on prognosis have not been comprehensively elucidated. This study aimed to explore the distant metastasis pattern and construct nomograms predicting the metastasis and survival of LC patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: LC data were downloaded from the SEER database to conduct logistic regression and investigate risk factors for developing organ metastasis. A Cox regression analysis was conducted to investigate prognostic factors of LC. A Kaplan-Meier analysis was used to estimate overall survival outcomes. Nomograms were constructed to predict the probability of organ metastasis and the 1-, 3- and 5-year survival probability of LC patients. Receiver operating characteristic curves were used to evaluate the diagnostic accuracy of the nomograms. All statistical analyses were conducted within R software. Results: The liver is the most common metastatic organ of small cell carcinoma. The brain is the most likely metastasis site of large cell carcinoma, and bone is the most likely metastasis site for squamous cell carcinoma and adenocarcinoma. Patients with triple metastases (brain-bone-liver) have the worst prognosis, and for nonsquamous carcinoma with single organ metastasis, liver metastases conferred the worst prognosis. Our nomograms based on clinical factors could predict the metastasis and prognosis of LC patients. Conclusion: Different pathological types of LC have different preferential metastatic sites. Our nomograms showed good performance in predicting distant metastasis and overall survival. These results will provide a reference for clinicians and contribute to clinical evaluations and individualized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Artificial intelligence and emerging data science techniques are being leveraged to interpret medical image scans. Traditional image analysis relies on visual interpretation by a trained radiologist, which is time-consuming and can, to some degree, be subjective. The development of reliable, automated diagnostic tools is a key goal of radiomics, a fast-growing research field which combines medical imaging with personalized medicine. Radiomic studies have demonstrated potential for accurate lung cancer diagnoses and prognostications. The practice of delineating the tumor region of interest, known as segmentation, is a key bottleneck in the development of generalized classification models. In this study, the incremental multiple resolution residual network (iMRRN), a publicly available and trained deep learning segmentation model, was applied to automatically segment CT images collected from 355 lung cancer patients included in the dataset "Lung-PET-CT-Dx", obtained from The Cancer Imaging Archive (TCIA), an open-access source for radiological images. We report a failure rate of 4.35% when using the iMRRN to segment tumor lesions within plain CT images in the lung cancer CT dataset. Seven classification algorithms were trained on the extracted radiomic features and tested for their ability to classify different lung cancer subtypes. Over-sampling was used to handle unbalanced data. Chi-square tests revealed the higher order texture features to be the most predictive when classifying lung cancers by subtype. The support vector machine showed the highest accuracy, 92.7% (0.97 AUC), when classifying three histological subtypes of lung cancer: adenocarcinoma, small cell carcinoma, and squamous cell carcinoma. The results demonstrate the potential of AI-based computer-aided diagnostic tools to automatically diagnose subtypes of lung cancer by coupling deep learning image segmentation with supervised classification. Our study demonstrated the integrated application of existing AI techniques in the non-invasive and effective diagnosis of lung cancer subtypes, and also shed light on several practical issues concerning the application of AI in biomedicine. [ABSTRACT FROM AUTHOR]

The aim of this descriptive study is to analyze the cost for the treatment of NSCLC and SCLC patients (2014–2019) in Finland. The primary objective is to understand recent (2014–2019) cost developments. The study is retrospective and based on hospital register data. The study population consists of NSCLC and SCLC patients diagnosed in four out of the five Finnish university hospitals. The final sample included 4047 NSCLC patients and 766 SCLC patients. Cost of the treatment in lung cancer is increasing. Both the average cost of the first 12 months as well as the first 24 months after diagnosis increases over time. For patients diagnosed in 2014, the average cost of the first 24 months was 19,000 €and for those diagnosed in 2015 22,000 €. The annual increase in the nominal 24-month costs was 10.4% for NSCLC and 7.3% for SCLC patients. The average cost per patient has increased annually for both NSCLC and SCLC. Possible explanations to the cost increase are increased medicine costs (especially in NSCLC), and the increased percentage of patients being actively treated. [ABSTRACT FROM AUTHOR]

Ciliated muconodular papillary tumor/bronchiolar adenoma (CMPT/BA) is a recently introduced benign lung tumor. It remains unclear whether CMPT/BA is associated with a specific type of lung cancer (LC). We studied the clinicopathological characteristics and genetic profiles of the coexisting primary LC and CMPT/BA (LCCM) cases. We identified eight LCCM (0.4%) from the resected Stage 0–III primary LC (n = 1945). The LCCM cohort was male‐dominant (n = 8), elderly (median 72 years old), and most were smokers (n = 6). In addition to the adenocarcinoma (n = 8), we detected two squamous cell carcinomas and one small cell carcinoma—in some cases, multiple cancer. The target sequence/whole exome sequence (WES) revealed no shared mutations between CMPT/BA and LC. One exceptional case was invasive mucinous adenocarcinoma harboring an HRAS mutation (I46N, c.137T>A), but it was likely to be a single nucleotide polymorphism based on variant allele frequency (VAF). Other driver mutations in LC included EGFR (InDel, n = 2), BRAF(V600E) (n = 1), KRAS (n = 2), GNAS (n = 1), and TP53 (n = 2). BRAF(V600E) was the most frequent mutation in CMPT/BA (60%). In contrast, LC showed no specific trend in driver gene mutations. In conclusion, our study revealed differences in the gene mutation profiles of CMPT/BA and LC in coexisting cases, suggesting mostly independent clonal tumorigenesis of CMPT/BA from LC. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most commonly diagnosed cancer types. Studying the molecular changes that occur in lung cancer is important to understand tumor formation and identify new therapeutic targets and early markers of the disease to decrease mortality. Glycosaminoglycan chains play important roles in various signaling events in the tumor microenvironment. Therefore, we have determined the quantity and sulfation characteristics of chondroitin sulfate and heparan sulfate in formalin-fixed paraffin-embedded human lung tissue samples belonging to different lung cancer types as well as tumor adjacent normal areas. Glycosaminoglycan disaccharide analysis was performed using HPLC-MS following on-surface lyase digestion. Significant changes were identified predominantly in the case of chondroitin sulfate; for example, the total amount was higher in tumor tissue compared to the adjacent normal tissue. We also observed differences in the degree of sulfation and relative proportions of individual chondroitin sulfate disaccharides between lung cancer types and adjacent normal tissue. Furthermore, the differences in the 6-O-/4-O-sulfation ratio of chondroitin sulfate were different between the lung cancer types. Our pilot study revealed that further investigation of the role of chondroitin sulfate chains and enzymes involved in their biosynthesis is an important aspect of lung cancer research. [ABSTRACT FROM AUTHOR]

The transformation from non‐small‐cell lung cancer (NSCLC) to small‐cell lung cancer (SCLC) is one of the mechanisms of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) resistance. Previous studies exhibited that the median transformation time was 17.8 months for NSCLC to SCLC. Here we introduced a case of lung adenocarcinoma (LADC) with EGFR19 exon deletion mutation in which the pathological transformation emerged only 1 month after lung cancer surgery and receiving EGFR‐TKI inhibitor. Eventually, the pathological examination confirmed the patient experienced a transformation from LADC to SCLC with EGFR, tumor protein p53 (TP53), RB transcriptional corepressor 1 (RB1), and SRY‐box transcription factor 2 (SOX2) mutation. Although the transformation of LADC with EGFR‐mutant into SCLC after targeted therapy was frequent, the pathological results of most patients were only biopsy specimens, which cannot rule out the existence of mixed pathological components of the primary tumor. In this case, the patient's postoperative pathology was sufficient to exclude the probability of mixed tumor components, confirming that the patient's pathological change was indeed transformation from LADC to SCLC. In addition, primary drug resistance in such a short time after surgery and osimertinib‐targeted therapy has not been reported before. We detected the molecular state of this patient before and after SCLC transformation through targeted gene capture and high‐throughput sequencing, and also found for the first time that the mutations of EGFR, TP53, RB1, and SOX2 continue to exist before and after transformation, but the mutation abundance is different. In our paper, the occurrence of small‐cell transformation is affected largely by these gene mutations. [ABSTRACT FROM AUTHOR]

Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are two types of high-grade neuroendocrine carcinomas of the lung with poor prognosis. LCNEC has not been thoroughly studied due to its rarity, data are also lacking regarding the survival comparison and prognosis analysis of patients with locally advanced or metastatic LCNEC and SCLC. Methods: Data of patients with LCNEC, SCLC, and other NSCLC who were diagnosed from 1975 to 2019 were extracted from the Surveillance, Epidemiology and End Results (SEER) database to estimate incidence. Those in stage III-IV and being diagnosed from 2010 to 2015 were utilized further to investigate their clinical characteristics and prognosis. Propensity score matching (PSM) analyses at a ratio of 1:2 was used to compare their survival outcomes. Nomograms of LCNEC and SCLC were established with internal validation, and the nomogram of SCLC was externally validated by 349 patients diagnosed in Cancer hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 1, 2012 to December 31, 2018. Results: The incidence of LCNEC has been increasing in recent decades, meanwhile that of SCLC and other types of NSCLC were decreasing. A total of 91,635 lung cancer patients, including 785 with LCNEC, 15,776 with SCLC, and 75,074 with other NSCLC were enrolled for further analysis. The survival of stage III-IV LCNEC resembles that of SCLC, and significantly worse than other types of NSCLC before and after PSM analysis. In pretreatment prognostic analysis, age, T stage, N stage, M stage, bone metastasis, liver metastasis, and brain metastasis were found to be associated with the survival of both LCNEC and SCLC, besides sex, bilaterality, and lung metastasis were additional prognostic factors for SCLC. Two nomograms and convenient online tools respectively for LCNEC and SCLC were established accordingly with favorable predicting accuracy of < 1-year, < 2-year, < 3-year survival probabilities. In external validation of the SCLC nomogram with a Chinese cohort, the AUCs of 1-year, 2-year and 3-year ROC were 0.652, 0.669, and 0.750, respectively. All the results of 1-, 2-, 3- year variable-dependent ROC curves verified the superior prognostic value of our nomograms for LCNEC and SCLC over the traditional T/N/M staging system. Conclusions: Based on large sample-based cohort, we compared the epidemiological trends and survival outcomes between locally advanced or metastatic LCNEC, SCLC, and other NSCLC. Furthermore, two prognostic evaluation approaches respectively for LCNEC and SCLC might present as practical tools for clinicians to predict the survival outcome of these patients and facilitate risk stratification. [ABSTRACT FROM AUTHOR]

SMARCA4-deficient non-small cell carcinoma is an aggressive neoplasm with poor outcome. Several studies have highlighted its immunochemistry, pathophysiology, and underlying mechanisms, but studies of its definite treatment are few. Here, we report on a 69-year-old male with heterogenous pathological presentations of SMARCA4-deficient non-small cell carcinoma. He initially presented with neck lymphadenopathies. Immunohistochemistry staining and genomic profiling confirmed the diagnosis of SMARCA4-deficient non-small cell carcinoma. The patient responded well to immune checkpoint inhibitors with nivolumab. However, new lesions with various pathological presentations and various responses to nivolumab appeared during the treatment course. The patient survived more than 3 years from the initial diagnosis. This case shows the efficacy of nivolumab to treat SMARCA4-deficient non-small cell lung carcinoma. [ABSTRACT FROM AUTHOR]

Background and objectives: Lung cancer is the most common cause of cancer‐related death worldwide in both sexes. Evidence suggests the role of genetic factors in lung cancer. Studying of such factors can help understand the cancer prognosis. Overexpression of the human epidermal growth factor receptor‐2 (HER2/neu) protein is considered an important prognostic factor in breast cancer, but its role has not been confirmed in lung cancer. Therefore, the present study aimed to investigate the role of its expression in patients with lung cancer. Materials and methods: In this cross‐sectional study, patients aged >18 years who were referred to Afzalipoor Hospital, Kerman, Iran, from 2016 to 2017, and were diagnosed with lung cancer were enrolled into the study if they had a pathological sample of their cancerous lung. Their demographics were recorded, and the sample was sectioned and stained to measure HER2/neu gene expression according to DAKO instructions using heat‐induced antigen retrieval (HIER) enzyme marker. Results: The samples of 100 patients with lung cancer were evaluated (84% men and 16% women) with a mean age of 61.34 years (standard deviation of 12.51 years). HER2/neu expression was significantly associated with the type of cancer and was highest in adenocarcinoma and zero in small cell carcinoma (P < 0.001), but not with patients' sex, age, smoking status and family history of cancer (P > 0.05). Conclusion: These results emphasized the overexpression of HER2/neu in different types of lung cancer, which can be used further for therapeutic purposes. The results showed that HER2/neu was overexpressed not only in adenocarcinoma but also in other types, like squamous cell carcinoma. Therefore, all subtypes of non‐small cell lung carcinoma should be considered for anti‐HER2 therapies, and further research is required for small cell lung carcinoma. [ABSTRACT FROM AUTHOR]