Large Cell Carcinoma Research Articles

Comparative study of the genomic landscape and tumor microenvironment among large cell carcinoma of the lung, large cell neuroendocrine of the lung, and small cell lung cancer.

Deciphering the genomic profiles and tumor microenvironment (TME) in large cell carcinomas of the lung (LCC), large cell neuroendocrine of the lung (LCNEC), and small cell lung cancer (SCLC) might contribute to a better understanding of lung cancer and then improve outcomes. Ten LCC patients, 12 LCNEC patients, and 18 SCLC patients were enrolled. Targeted next-generation sequencing was used to investigate the genomic profiles of LCC, LCNEC, and SCLC. Tumor-infiltrating lymphocytes (TILs) within cancer cell nests and in cancer stroma were counted separately. Precise 60% of LCNEC patients harbored classical non-small cell lung cancer driver alterations, occurring in BRAF, KRAS, ROS1, and RET. More than 70% of SCLC patients harbored TP53-RB1 co-alterations. Moreover, 88.9%, 40%, and 77.8% of LCC, LCNEC, and SCLC cases had a high tumor mutation burden level with more than 7 mutations/Mb. Furthermore, high index of CD68+ CD163+ (TILs within cancer cell nests/ TILs within cancer cell nests and in cancer stroma, P = .041, 548 days vs not reached) and CD163+ TILs (P = .041, 548 days vs not reached) predicted a shorter OS in SCLC. Our findings revealed the distinct genomic profiles and TME contexture among LCC, LCNEC, and SCLC. Our findings suggest that stratifying LCNEC/SCLC patients based on TME contexture might help clinical disease management.

GATA3 expression in primary lung carcinomas: correlation with histopathologic features and TTF-1, napsin A, and p40 expression

This study assessed the expression of GATA3 in primary lung carcinomas and correlated it with tumor histology and immunostains routinely utilized in the work up of primary lung cancers. Tissue microarrays (TMAs) were constructed from a cohort of 184 non-small cell carcinomas, stained with GATA3, p40, TTF-1, and napsin A, and analyzed semi-quantitatively. All TMA cases with GATA3 expression were further analyzed using corresponding whole slide sections. Positive GATA3 staining was present in 16 cases (9%), including 7 squamous cell carcinomas (SqCCs) (4%), 4 adenocarcinomas (AdCs) (2%), 2 adenosquamous carcinomas (AdSqCs) (1%), 2 large cell carcinomas (LCCs) (1%), and 1 sarcomatoid carcinoma (SC) (<1%). Among tumor histotypes, SqCC was more likely to stain with GATA3 (7/49, 14%), while AdC was less likely (4/111, 4%) (p=0.04). In GATA3-positive cases, high-level expression was observed in 9 cases (56%), including 5 p40-positive SqCCs (3 were nonkeratinizing), 1 p40-positive AdSqC (negative for TTF-1 and napsin A), and 1 AdC (solid), 1 LCC, and 1 SC, each negative for p40, TTF-1, and napsin A). Low-level GATA3 expression was found in 3 AdCs (1 was lepidic and 2 were acinar predominant), 2 SqCCs (keratinizing), 1 AdSqC, and 1 LCC. These findings indicate that GATA3 expression occurs in a minor but significant proportion of primary non-small cell lung carcinomas, most often involves SqCC, and tends to show increasing levels of expression in more poorly differentiated subtypes. Caution should be exercised when interpreting GATA3 expression, and a panel of immunostains should be utilized when assigning tumor origin.

A 5 Year Tertiary Centre Experience of Frequency &amp; Risk Factors Association with Primary and Secondary Lung Cancers

Introduction: Lung cancer is one of the commonest cancers worldwide having either small cell or non-small cell types and smoking is its major risk factor. We intend to study distribution of various lung malignancies and their association with various risk factors in a Pakistani population sample.&#x0D; Aims &amp; Objectives: To evaluate the frequency of types of primary and secondary lung cancers in a sample of the Pakistani population and see their association with age, gender, and smoking.&#x0D; Place and duration of study: The department of Pulmonology, Shaikh Zayed Hospital, Federal Postgraduate Medical Institute, Lahore, Pakistan, from August 2017 to August 2022 (5 years).&#x0D; Material &amp; Methods: Analysis of retrospective data of 156 consecutive patients age 40-70 years diagnosed with primary or secondary lung cancers. Data were stored and analyzed using IBM-SPSS version 23.0. Diagnosis was established through fibreoptic (FOB), or rigid bronchoscopies or CT and U/S guided percutaneous lung biopsies, P- value&lt;0.05 was taken as significant&#x0D; Results: There were 156 samples, among them 37.8% were found with age group 41 – 60 years old, 31.4% with age group 61 – 70 years old, mean age of subjects was 58.3 (SD=±14.9) years. 82.1% were of male gender, 42.9% were non- smokers, 25% were found with less than or equal to 25 smoking pack years, median smoking pack years were 30 with range 5 – 100 smoking pack years. Distribution of primary lung malignancy revealed; 28.8% having Squamous cell carcinoma, 35.3% with Adenocarcinoma, 13.5% with small cell carcinoma, 2.6% with large cell carcinoma and 5.8% with primary lung carcinoid tumors. Secondary deposits of cancer in lungs were found in 22 (14.1%) subjects. Pearson Chi Square test showed significant association of primary type of cancer with age group, gender, and smoking pack years (p &lt;0.01).&#x0D; Conclusion: Adenocarcinoma was most frequent lung malignancy followed by Squamous cell carcinoma and small cell carcinoma was less frequent. Advancing age, male gender and cigarette smoking are strongly associated with the diagnosis of lung cancer.

Updated Views in Targeted Therapy in the Patient with Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is the most frequent form of lung cancer and represents a set of histological entities that have an ominous long-term prognosis, for example, adenocarcinoma, squamous carcinoma and large cell carcinoma. Both small cell and non-small cell lung cancer are the main causes of oncological death and the oncological diseases with the highest incidence worldwide. With regard to clinical approaches for NSCLC, several advances have been achieved in diagnosis and treatment; the analysis of different molecular markers has led to the development of new targeted therapies that have improved the prognosis for selected patients. Despite this, most patients are diagnosed in an advanced stage, presenting a limited life expectancy with an ominous short-term prognosis. Numerous molecular alterations have been described in recent years, allowing for the development of therapies directed against specific therapeutic targets. The correct identification of the expression of different molecular markers has allowed for the individualization of treatment throughout the disease course, expanding the available therapeutic arsenal. The purpose of this article is to summarize the main characteristics of NSCLC and the advances that have occurred in the use of targeted therapies, thus explaining the limitations that have been observed in the management of this disease.

Factors for incidence risk and prognosis of synchronous brain metastases in pulmonary large cell carcinoma patients: a population-based study

BackgroundPatients with pulmonary large cell carcinoma (LCC) have a high incidence of synchronous brain metastases (SBM) and a poor prognosis. Our study was to evaluate the predictive and prognostic value of the clinical characteristics of pulmonary LCC patients with SBM at initial diagnosis by utilizing the Surveillance, Epidemiology, and End Results (SEER) database.MethodsLCC patients, diagnosed from 2010 to 2019, were identified from the latest SEER database which was released in April 2022. Logistic regression and Cox regression were used to identify the predictive and prognostic factors for LCC patients with SBM. Propensity score matching (PSM) and Kaplan–Meier analyses were applied to assess different therapy modalities.ResultsA total of 1375 LCC patients were enrolled in this study and 216 (15.7%) of them had SBM at the initial diagnosis. The median overall survival (OS) of LCC patients with SBM was 4 months. Multivariate Cox regression identified age 60–79 (OR 0.57; 95% CI 0.41–0.78; p < 0.001), age ≥ 80 (OR 0.23; 95% CI 0.12–0.45; p < 0.001) and bone metastases (OR 1.75; 95% CI 1.22–2.51; p < 0.001) as significant independent predictors for developing SBM. Multivariable Cox regression revealed that age 60–79, T stage, bone metastases and chemotherapy were independent prognostic factor for OS. The surgery combined with chemotherapy and radiotherapy group, in which all patients were N0 stage and had no other site-specific metastases, exhibited the best median OS of 15 months.ConclusionsLCC patients with age < 60 or bone metastases were more likely to have SBM at initial diagnosis. Age, T stage, bone metastases and chemotherapy were independent prognostic factors for OS of LCC patients with SBM. Highly selected patients might achieve the best survival benefit from surgery combined with chemotherapy and radiotherapy.

Whole-genome characterization of large-cell lung carcinoma: A comparative analysis based on the histological classification.

Background: According to the 2015 World Health Organization classification, large cell neuroendocrine carcinoma (LCNEC) was isolated from Large-cell lung cancer (LCLC) tumors, which constitutes 2%-3% of non-small cell lung cancer (NSCLC). However, LCLC tumors are still fairly vaguely defined at the molecular level compared to other subgroups. Materials and Methods: In this study, whole-genome sequencing (WGS) was performed on 23 LCLC and 15 LCNEC tumor specimens. Meanwhile, data from the TCGA (586 LUADs and 511 LUSCs) and U Cologne (120 SCLCs) were analyzed and compared. Results: The most common driver mutations were found in TP53 (13/23, 57%), FAM135B (8/23, 35%) and FAT3 (7/23, 30%) in LCLC, while their counterparts in LCNEC were TP53 (13/15, 87%), LRP1B (6/15, 40%) and FAT1 (6/15, 40%). Notably, FAM135B mutations only occurred in LCLC (P = 0.013). Cosmic signature analysis revealed widespread defective DNA mismatch repair and tobacco-induced mutations in both LCLC and LCNEC. Additionally, LCNEC had a higher incidence of chromosomal copy number variations (CNVs) and structural variations (SVs) compared with LCLC, although the differences were not statistically significant. Particularly, chromothripsis SVs was significantly associated with CNVs. Furthermore, mutational landscape of different subtypes indicated differences between subtypes, and there seems to be more commonalty between our cohort and SCLC than with other subtypes. SMARCA4 mutations may be specific driver gene alteration in our cohort. Conclusion: Our results support that LCLC and LCNEC tumors follow distinct tumorigenic pathways. To our knowledge, this is the first genome-wide profiling comparison of LCLC and LCNEC.

Effect of Chemotherapy in Stage II–IV Large-Cell Lung Carcinoma and Construction of Its Predictive Nomograms: A SEER Analysis

Objectives: Large-cell lung carcinoma (LCLC) is generally poorly differentiated with a poor prognosis. This study aimed to explore the impact of chemotherapy on the prognosis of patients with stage II–IV LCLC and to construct nomograms to predict overall survival (OS) and cancer-specific survival (CSS). Methods: Propensity score matching analysis was used to balance the effects of baseline characteristics. The Kaplan-Meier method was used to analyze the prognostic impact of chemotherapy on LCLC patients. Cox regression analysis was used to identify prognostic risk factors, and then nomograms were constructed and validated. Results: Overall, we identified 2,532 patients with LCLC from the Surveillance, Epidemiology, and End Results (SEER) database. The chemotherapy group showed better OS and CSS compared to the non-/unknown chemotherapy group for stage II–IV LCLC patients (p < 0.05). Two nomograms were plotted based on the results of Cox regression analysis. The areas under the curves (AUCs) of 1-, 3-, and 5-year OS were 0.786, 0.824, and 0.837, and the AUCs of CSS were 0.785, 0.821, and 0.836, respectively. The calibration curves showed excellent agreement between the prediction and the actual observation, and the decision curve analysis demonstrated good clinical utility. Conclusions: Chemotherapy could improve the prognosis among stage II–IV LCLC patients. In addition, the nomograms showed good predictive ability, which could be useful in making clinical decisions.

Lung Segmentation of Chest Radiograph Using Circular Window Based Local Contrast Thresholding (CWLCT) and Adaptive Median Outlier (CWAMO)

Certain chest illnesses, such as TB, adenocarcinoma, squamous cell carcinoma, large cell carcinoma, atelectasis, etc., can be diagnosed in chest radiographs, and the development of a CAD system relies in part on accurate lung segmentation. In order to partition the lungs in chest radiographs, this work introduces an unsupervised learning approach based on a circular window and local thresholding. The procedure involves pre-processing, a preliminary estimate of the lung field, and the elimination of noise. Images are initially scaled down to 1024x1024 and enhanced using adaptive histogram equalization. Then chest radiographs are binarized using the proposed method. Based on the geometrical and special characteristics, lungs are separated from the chest radiographs. The final step in picture segmentation is the use of morphological processes. Local thresholding, omitting extraneous body parts, filling in gaps, and filtering regions based on their attributes all contribute to preliminary estimates of the lung field.Morphological processes are used as a means of eliminating background noise. A public bone shadow eliminated JSRT dataset consisting of 247 chest x-rays is used to measure the performance of the proposed method. The effectiveness of the proposed method results’ performance is evaluated by comparing it with Active Shape Model (ASM) based lung segmentation for various performance metrics such as F-score, overlap percentage, accuracy rate, sensitivity, specificity, and precision rates. All the parameters for the proposed method are over and above 90%. Our investigations indicate that the suggested method is an unsupervised learning approach that does not require any training.

The different prognostic factors between metastatic and nonmetastatic disease of esophageal neuroendocrine carcinoma.

The specific risk factors of metastatic and nonmetastatic esophageal neuroendocrine carcinoma (NEC) are still uncertain. Whether primary site surgery is necessary for all patients with esophageal NEC is unknown. Patients with esophageal NEC in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2014 were selected. STATA 12 was used to analyze the clinical and pathological features of esophageal NEC. In total, 241 patients with esophageal NEC were included. Metastatic patients had shorter overall survival than nonmetastatic patients (6.03 versus 11.90 months, respectively). Prognostic factors varied between metastatic and nonmetastatic esophageal NEC. The location of the primary tumor is a key point for the prognosis of esophageal NEC. For nonmetastatic esophageal NEC, patients with tumors in the upper third of the esophagus had the worst survival, and patients with metastatic esophageal NEC with a primary tumor in the lower part of the esophagus tended to have an increased risk of death. Moreover, age ≥68 years (hazard ratio [HR] = 2.05; 95% confidence interval [CI]: 1.28-3.31; P < 0.01) and large cell carcinoma (HR = 2.79; 95% CI: 1.30-6.00; P < 0.01) were independent risk factors in patients with metastatic esophageal NEC. Primary site resection benefited patients with nonmetastatic esophageal NEC (HR = 0.20; 95% CI: 0.07-0.56; P < 0.01) rather than patients with metastatic esophageal NEC (HR = 0.91; 95% CI: 0.29-2.83; P > 0.05). Our study presented that primary tumor location is an important risk factor for nonmetastatic esophageal NEC patients. Age and pathological type are important risk factors for patients with metastatic esophageal NEC. Nonmetastatic esophageal NEC will benefit from primary tumor resection. Systematic treatment is recommended for metastatic esophageal NEC.

Bioinformatics analysis identifies key genes of prognostic value in lung cancer

Lung cancer is the most common human malignancy worldwide and can be divided into different types of carcinomas depending on their pathological features. Advances in medical science and technology have led to the identification of some lung cancer-related marker genes, including EGFR (epidermal growth factor receptor), BRAF (B-Raf proto-oncogene), RAS (RAS proto-oncogene, GTPase) and HER2 (human epidermal growth factor receptor 2). However, the underlying biomarker and key genes associated with different types of lung cancer are still poorly understood. In this study, we analyzed a GEO (Gene Expression Omnibus) dataset and identified 28 upregulated intersection DEGs (different expression genes) and 125 downregulated intersection DEGs among AC (adenocarcinoma), PTC (primary typical carcinoid), PLCC (primary large cell carcinoma), PLCNC (primary large cell lung carcinoma) and PSCLC (primary small cell lung carcinoma). Through PPI (protein-protein interaction) network analysis, we identified 14 genes among the DEGs, namely MFAP4 (microfibril-associated protein 4), PDZD2 (PDZ domain containing 2), FBLN1 (fibulin 1), FBLN5 (fibulin 5), EFEMP1 (EGF containing fibulin extracellular matrix protein 1), KDR (kinase insert domain receptor), S1PR1 (sphingosine-1-phosphate receptor 1), CAV1 (caveolin 1), GRK5 (G protein-coupled receptor kinase 5), EDNRA (endothelin receptor type A), EDNRB (endothelin receptor type B), CALCRL (calcitonin receptor-like receptor), PTGER4 (prostaglandin E receptor 4), and ADRB1 (adrenoceptor beta 1), which were found to be downregulated in different subtypes of lung cancer and associated with poor survival outcomes. In addition, most of the screened DEGs demonstrated good predictive ability in LUAD (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma). Among them, MFAP4 was found to promote cell proliferation while also suppressing cell migration and angiogenesis. In summary, we propose MFAP4, PDZD2, FBLN1, FBLN5, EFEMP1, KDR, S1PR1, CAV1, GRK5, EDNRA, EDNRB, CALCRL, PTGER4 and ADRB1 as potential prognostic markers in lung cancer patients.

Development of Medical Image Analytics by Deep Learning Model for Prediction and Classification of CT Image Diseases

The CT images of Lung illnesses or diseases that damage the lungs and weaken the respiratory system. Lung cancer is one of the topmost causes of death in humans around the world. Humans have a better chance of surviving if they are detected early. The average survival rate of persons with lung cancer increases from 14 to 49 percent if the disease is detected early. While computed tomography (CT) is significantly more effective than X-ray, a complete diagnosis requires a combination of imaging techniques that complement each other. But, because there are multiple phases of cancer that develop into different types of tumors with varying sizes and risks, finding lung cancer does not predict the risk of cancer. A deep neural network is constructed and tested for detecting lung cancer CT images. This research work analyses different types of tumor sizes such as large cell carcinoma, normal, squamous cell carcinoma, and adenocarcinoma. Also, the lung tumors are detected and predicted with the help of computer vision methods such as Residual neural network (ResNet), Convolutional neural network (CNN). Finally, the results of all the methods are compared and various parameters were calculated. Thus, the proposed method (ResNet) gives an optimal solution on comparison with respect to all the parameters.

Oral higher dose prednisolone to prevent stenosis after endoscopic submucosal dissection for early esophageal cancer.

Esophageal stenosis is one of the main complications of endoscopic submucosal dissection (ESD) for the treatment of large-area superficial esophageal squamous cell carcinoma and precancerous lesions (≥ 3/4 of the lumen). Oral prednisone is useful to prevent esophageal stenosis, but the curative effect remains controversial. To share our experience of the precautions against esophageal stenosis after ESD to remove large superficial esophageal lesions. Between June 2019 and March 2022, we enrolled patients with large superficial esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia experienced who underwent ESD. Prednisone (50 mg/d) was administered orally on the second morning after ESD for 1 mo, and tapered gradually (5 mg/wk) for 13 wk. In total, 14 patients met the inclusion criteria. All patients received ESD without operation-related bleeding or perforation. There were 11 patients with ≥ 3/4 and < 7/8 of lumen mucosal defects and 1 patient with ≥ 7/8 of lumen mucosal defect and 2 patients with the entire circumferential mucosal defects due to ESD. The longitudinal extension of the esophageal mucosal defect was < 50 mm in 3 patients and ≥ 50 mm in 11 patients. The esophageal stenosis rate after ESD was 0% (0/14). One patient developed esophageal candida infection on the 30th d after ESD, and completely recovered after 7 d of administration of oral fluconazole 100 mg/d. No other adverse events of oral steroids were found. Oral prednisone (50 mg/d) and prolonged prednisone usage time may effectively prevent esophageal stricture after ESD without increasing the incidence of glucocorticoid-related adverse events. However, further investigation of larger samples is required to warrant feasibility and safety.

CIGB-300 Anticancer Peptide Differentially Interacts with CK2 Subunits and Regulates Specific Signaling Mediators in a Highly Sensitive Large Cell Lung Carcinoma Cell Model.

Large cell lung carcinoma (LCLC) is one form of NSCLC that spreads more aggressively than some other forms, and it represents an unmet medical need. Here, we investigated for the first time the effect of the anti-CK2 CIGB-300 peptide in NCI-H460 cells as an LCLC model. NCI-H460 cells were highly sensitive toward CIGB-300 cytotoxicity, reaching a peak of apoptosis at 6 h. Moreover, CIGB-300 slightly impaired the cell cycle of NCI-H460 cells. The CIGB-300 interactomics profile revealed in more than 300 proteins that many of them participated in biological processes relevant in cancer. Interrogation of the CK2 subunits targeting by CIGB-300 indicated the higher binding of the peptide to the CK2α' catalytic subunit by in vivo pull-down assays plus immunoblotting analysis and confocal microscopy. The down-regulation of both phosphorylation and protein levels of the ribonuclear protein S6 (RPS6) was observed 48 h post treatment. Altogether, we have found that NCI-H460 cells are the most CIGB-300-sensitive solid tumor cell line described so far, and also, the findings we provide here uncover novel features linked to CK2 targeting by the CIGB-300 anticancer peptide.

Histopathological characterization of lung tumours at the University Teaching Hospital, Lusaka, Zambia: a pilot study.

There are limited data on histological classification of primary lung cancer from sub-Saharan Africa. Furthermore, the time trends of age-truncated incidence rates of lung cancer by histological phenotype in Zambia are also unknown. The objective of this study was to determine histological types of lung tumours at the University Teaching Hospital (UTH) in Lusaka, Zambia. This was a retrospective pilot study of lung tumour biopsies collected from the histopathology laboratory at the UTH over a period of one year. Tissue sections were stained and when seen, lung cancer was classified using standard histological methods. Data were analysed using IBM SSPS version 23. A total of 23 lung cancer tissues were retrieved. Histological types included eleven (47.8%) squamous cell carcinoma (SCC), six (26.1%) adenocarcinoma, two (8.7%) small cell carcinoma, two (8.7%) large cell carcinoma, 1 (4.3%) inflammatory myofibroblastic tumours and 1 (4.3%) pleural pulmonary blastoma. The results showed that the most affected age group was 60-69 years with most of the histological subtype in this age group being SCC. There was no statistically significant difference of histological subtypes across age groups, p=0.12. This study has shown that the most commonly diagnosed type of primary lung cancer is squamous cell carcinoma. More data are needed to further corroborate this observation.

Two Cases of Retroperitoneal Fibrosis During Anti-programmed Cell Death 1 Antibody Treatment

Background. Retroperitoneal fibrosis is characterized by fibrosis around the abdominal aorta and iliac arteries. Two-thirds of reported cases had idiopathic causes. Idiopathic retroperitoneal fibrosis is thought to result from a local inflammatory reaction to antigens in the atherosclerotic plaques of the abdominal aorta. Therefore, it is thought that idiopathic retroperitoneal fibrosis may be a manifestation of a systemic autoimmune or inflammatory disease. In contrast, anti-programmed cell death 1 (anti-PD-1) antibodies may overexpress innate immunity. There have been only two case reports on retroperitoneal fibrosis during anti-PD-1 antibody treatment. We encountered two cases of retroperitoneal fibrosis during anti-PD-1 antibody treatment. Cases. Case 1 involved a 57-year-old man who experienced recurrence of squamous cell lung carcinoma after resection. More than 75% of his cancer cells were positive for programmed cell death ligand 1 (PD-L1). He experienced urinary urgency after one year and six months of nivolumab treatment. Computed tomography revealed a homogeneous plaque that was isodense with muscle surrounding the abdominal aorta and iliac arteries. Positron emission tomography revealed the accumulation of fluorodeoxyglucose at the same site. The serum IgG4 level was normal. Although a biopsy specimen was not obtained, the patient was diagnosed with retroperitoneal fibrosis. The patient was treated with steroids. Case 2 involved a 64-year-old man with pulmonary large cell carcinoma. An analysis of the cancer cells revealed that 50-74% of the cells were positive for PD-L1. Lower back pain appeared after one year and 11 months of pembrolizumab treatment. Computed tomography revealed right hydronephrosis and homogeneous plaque on the right side of the abdominal aorta. Although a biopsy specimen was not obtained, the patient was diagnosed with retroperitoneal fibrosis. The patient improved once with steroids but relapsed. Conclusion. We hypothesized that the administration of anti-PD-1 antibodies may have affected the onset of retroperitoneal fibrosis.

Immunotherapeutics in lung cancers: from mechanistic insight to clinical implications and synergistic perspectives.

Lung cancer is one of the highly lethal forms of cancer whose incidence has worldwide rapidly increased over the past few decades. About 80-85% of all lung cancer cases constitute non-small cell lung cancer (NSCLC), with adenocarcinoma, squamous cell carcinoma and large cell carcinoma as the main subtypes. Immune checkpoint inhibitors have led to significant advances in the treatment of a variety of solid tumors, significantly improving cancer patient survival rates. The cytotoxic drugs in combination with anti-PD-(L)1 antibodies is a new method that aims to reduce the activation of immunosuppressive and cancer cell prosurvival responses while also improving direct cancer cell death. The most commonly utilized immune checkpoint inhibitors for patients with non-small cell lung cancer are monoclonal antibodies (Atezolizumab, Cemiplimab, Ipilimumab, Pembrolizumab etc.) against PD-1, PD-L1, and CTLA-4. Among them, Atezolizumab (TECENTRIQ) and Cemiplimab (Libtayo) are engineered monoclonal anti programmed death ligand 1 (PD-L1) antibodies that inhibit binding of PD-L1 to PD-1 and B7.1. As a result, T-cell proliferation and cytokine synthesis are inhibited leading to restoring the immune homeostasis to fight cancer cells. In this review article, the path leading to the introduction of immunotherapeutic options in lung cancer treatment is described, with analyzing the benefits and shortages of the current immunotherapeutic drugs. In addition, possibilities to co-administer immunotherapeutic agents with standard cancer treatment modalities are also considered.

Non-small cell lung cancer with MET exon 14 skip mutation: case report

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, making up 80-85% of all lung malignancies. It can be further subdivided into different types. The three main subtypes are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Traditionally, NSCLCs have been treated with a combination of chemotherapy, surgery, and/or radiation therapy. However, with the advent of genotype subtype analysis and targeted therapy it has become possible to have individualized treatment options for patients with NSCLC. We present a case report of a 68-year-old female with NSCLC. Patient initially only received radiation therapy due to her not being a surgical candidate. While initial treatment was responsive, later imaging showed metastasis of disease. Subsequent genotype analysis of the patient's tumor indicated a MET exon 14 skipping mutation which qualified her for treatment with Capmatinib (Tabrecta). Patients on Capmatinib have minimal side effects and better efficacy than traditional chemotherapy. Patients with MET exon 14 skipping mutations should be considered for Capmatinib therapy.

Neuroendocrine Carcinoma of the Prostate – a Case Report

"Poorly differentiated neuroendocrine carcinomas are rare. Most of them arise from the lung, and only 9% are found in extrapulmonary sites. In the prostate, neuroendocrine cells are more commonly present compared to other organs of the genitourinary tract. We present the case of a 67-year-old male patient who was investigated for constipation, loss of appetite and pelvic-perineal pain; a large prostatic mass was discovered upon further investigation. After a thorough work-up and multidisciplinary approach, the patient was diagnosed with de novo small cell neuroendocrine carcinoma of the prostate with multiple metastases. He underwent five cycles of chemotherapy with cisplatin and etoposide before we evaluated the therapeutic response by CT scan, which showed partial response according to RECIST v 1.1. Due to significant nephrotoxicity, the treatment was discontinued after the 6th cycle and a follow-up after three months was recommended. The rarity of this case made the diagnosis process challenging, but an accurate diagnosis was possible with the multidisciplinary team`s involvement. The treatment was initiated according to the international guidelines concerning extrapulmonary poorly differentiated neuroendocrine carcinomas/ large or small cell carcinomas. Although the evaluation showed partial response, small cell neuroendocrine carcinoma of the prostate is an aggressive tumor with a poor prognosis. "

Appendiceal neuroendocrine tumour association in a patient with a large sarcomatoid renal cell carcinoma

Renal cell carcinoma (RCC) can develop into sarcomatoid differentiation which demonstrates aggressive biological behavior evident by the rapid progression of the tumour with multiple metastases. Though the appendiceal neuroendocrine tumour (NET) has a good prognosis, the prognosis can be worse when associated with the sarcomatoid RCC (sRCC). A 45-year-old female patient presented to the emergency department with a 2-month history of worsening right upper abdominal pain, nausea, vomiting, and significant weight loss. Computed tomography (CT) revealed heterogeneously enhancing solid cystic mass lesions arising from a lower pole of the right kidney with a tumour thrombus involving the entire right renal vein and extending into the inferior vena cava (IVC). The patient underwent radical nephrectomy and appendectomy and was managed conservatively due to the poor prognosis. After four weeks, she presented with severe right upper abdominal pain, and Magnetic resonance imaging (MRI) indicated a possible liver metastasis and tumour necrosis. In three weeks, the patient died of respiratory failure following multiple organ dysfunction syndrome (MODS). This case report outlines a presentation of sRCC with biologically aggressive disease progression and a rare association with appendiceal NET. CT, MRI, and PET scans can be helpful in the diagnosis and monitoring of disease progression. Early identification of the sRCC and appendiceal NET will contribute to better outcomes of the disease and complications. The prognostic elements and similar genetic patterns of sRCC and appendiceal NET would be of great clinical interest.

The Clinical Characteristics and Treatments for Large Cell Carcinoma Patients Older than 65 Years Old: A Population-Based Study.

Pulmonary large cell carcinoma, a type of non-small cell lung cancer (NSCLC), is a rare neoplasm with poor prognosis. In this study, our aim was to investigate the impact of radiation sequences with surgery for stage III/IV LCC patients between different age groups, especially in the elderly patients. The patients with LCC and other types of NSCLC in the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2015 were retrospectively analyzed. Then we divided the LCC patients into two age groups: &lt;65 years old group and ≥65 years old group. Propensity score method (PSM) was used to control potential differences between different groups. The overall survival (OS) of LCC patients and other types of NSCLC patients were evaluated by Kaplan-Meier analysis. Univariate and multivariate Cox regression analysis were employed to explore the independent risk factors of OS. The forest plots of HRs for OS were generated to show the above outcomes more visually. In total, 11,349 LCC patients and 129,118 other types of NSCLC patients were enrolled in this study. We divided LCC patients into &lt;65 years old group (4300) and ≥65 years old group (7049). LCC patients was more common in whites (81.4%), males (58.3%), elderly (≥65 years old: 62.1%), east regions (52.7%), upper lobe (51.6%), right-origin of primary (55.4%), with advanced grade (54.2%) or stage (76.7%). After PSM, Kaplan-Meier analysis and multivariate Cox analysis showed significantly worse survival prognosis for LCC patients compared to other types of NSCLC, especially in the group ≥65 years old (HR: 1.230; 95% CI: 1.171-1.291; p &lt; 0.001). For LCC patients, there were some risk survival factors including whites, males, not upper lobe, advanced stage, elder age at diagnosis, bone metastasis, liver metastasis, singled status, no lymphadenectomy, no surgery, and no chemotherapy (p &lt; 0.05). In LCC patients ≥65 years old, radiation after surgery had significantly better impact on overall survival outcomes (HR: 0.863, 95% CI: 0.765-0.973, p = 0.016), whereas radiation prior to surgery (HR: 1.425, 95% CI: 1.059-1.916, p = 0.019) had significantly worse impact on prognosis of patients. In LCC patients &lt;65 years old, radiation sequences with surgery had no significant impact on the OS of patients (p = 0.580), but ≥4 LNRs had significantly survival benefits to prognosis (HR:0.707, 95% CI: 0.584-0.855). Elderly LCC patients had worse malignant tumors than young patients, of which the majority were diagnosed as stage III/IV tumors. Postoperative radiotherapy may achieve a better prognosis for stage III/IV LCC patients older than 65 years old compared to other radiation sequences with surgery.