Non-small Cell Carcinoma Research Articles

Changes in glycocalyx-related biochemical parameters during lung resection in non-small cell carcinoma cases : A pilot study

Objective: Non-small cell lung cancer (NSCLC) is one of the most common neoplasms with high mortality rates, and new studies are needed to understand its characteristics better. This study aimed to determine the changes in the glycocalyx structure related to surgery regarding histopathologic subtypes and to evaluate the correlation of these changes on the development of metastasis and mortality. Material and methods: Serum levels of hyaluronan, VEGF-A, FGF-10, BMP-2, and BMP-4 were measured before and after surgery in 42 patients with NSCLC. The alterations in serum levels of studied markers were evaluated as related to metastasis status and mortality in post-operative 18-24 months. Results: Our study included 15 adenocarcinoma and 27 squamous cell carcinoma cases. Pre- and post-operative values of serum hyaluronan, VEGF-A, FGF-10, and BMP-2 showed significant differences for the whole group (p=0.006, p=0.001, p=0.002, and p=0.004, respectively). Post-operative BMP-2 values also correlated with hyaluronan and VEGF-A values. Post-operative values of hyaluronan and VEGF-A values found incorrelation with metastasis and mortality, while BMP-2 with metastasis and FGF-10 with mortality. Serum values of hyaluronan, VEGF-A, FGF-10 and BMP-2 differed significantly in-between the pre- and post-operative measurements in adenocarcinoma cases (p=0.020, p=0.009, p=0.003, and p=0.011, respectively) , but not that of squamous cell carcinoma. Conclusion: Pre- and post-operative changes in serum hyaluronan, VEGF-A, FGF-10 and BMP-2 values may be associated with metastasis and/or mortality in NSCLC. These findings were also more prominent in adenocarcinoma cases, though further extended studies are needed for a better conclusion.

The Relationship Between Clinical Risk Factors and Patient’s Survival Rate in Non-Small Cell Lung Carcinoma Cases: A Cross-Sectional Study

Background: Non-small cell carcinoma (NSCLC) is the most common type of lung cancer. Risk factors for lung cancer include smoking, genetic factors, chronic lung disease, lung infections, radon exposure, air pollution, exposure to carcinogenic substances in the workplace and other risk factors. The significance of each of these risk factors differs by sex, race and region in a given country. Purpose: The study was conducted to assess the analysis of risk factors, treatment response and survival of NSCLC patients. Methods: Cross sectional and survival analysis, patients undergoing diagnostic and treatment at Dr. Wahidin Sudirohusodo Makassar period January 2017-December 2019. Anamnesis of risk factors and survival by telephone and patient medical record data. Results: There are 100 patients who fulfill the inclusion criteria; Subject characteristics were mostly male (64%), age >45 years (84%), Bugis ethnicity (50%), farmer occupation (27%), active smokers (60%), consume filter cigarettes (75%), and has severe brinkman index (BI) (51.6%). About 40% of the subjects were non-smokers, 50% of whom were passive smokers. Severe IB and high-risk occupations by type of KPKBSK were significant (p = 0.02 and p = 0.01). Age <45 years, median survival was better than age 45 years (8 months versus 4 months), p = 0.002. Subjects receiving EGFR-TKI had a better median survival of 7 months, platinum doublet 6 months, did not receive treatment for 2 months, p = <0.05. Conclusion: Brinkman Index (BI) and high-risk occupation based on NSCLC type are significant. Age < 45 years had a good median survival. Subjects who received TKI had a better median survival. Keywords: Non-small cell lung carcinoma, clinical risk factors, survival rate.

Early stage NSCLS patients' prognostic prediction with multi-information using transformer and graph neural network model.

We proposed a population graph with Transformer-generated and clinical features for the purpose of predicting overall survival (OS) and recurrence-free survival (RFS) for patients with early stage non-small cell lung carcinomas and to compare this model with traditional models. The study included 1705 patients with lung cancer (stages I and II), and a public data set for external validation (n=127). We proposed a graph with edges representing non-imaging patient characteristics and nodes representing imaging tumour region characteristics generated by a pretrained Vision Transformer. The model was compared with a TNM model and a ResNet-Graph model. To evaluate the models' performance, the area under the receiver operator characteristic curve (ROC-AUC) was calculated for both OS and RFS prediction. The Kaplan-Meier method was used to generate prognostic and survival estimates for low- and high-risk groups, along with net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis. An additional subanalysis was conducted to examine the relationship between clinical data and imaging features associated with risk prediction. Our model achieved AUC values of 0.785 (95% confidence interval [CI]: 0.716-0.855) and 0.695 (95% CI: 0.603-0.787) on the testing and external data sets for OS prediction, and 0.726 (95% CI: 0.653-0.800) and 0.700 (95% CI: 0.615-0.785) for RFS prediction. Additional survival analyses indicated that our model outperformed the present TNM and ResNet-Graph models in terms of net benefit for survival prediction. Our Transformer-Graph model was effective at predicting survival in patients with early stage lung cancer, which was constructed using both imaging and non-imaging clinical features. Some high-risk patients were distinguishable by using a similarity score function defined by non-imaging characteristics such as age, gender, histology type, and tumour location, while Transformer-generated features demonstrated additional benefits for patients whose non-imaging characteristics were non-discriminatory for survival outcomes. The study was supported by the National Natural Science Foundation of China (91959126, 8210071009), and Science and Technology Commission of Shanghai Municipality (20XD1403000, 21YF1438200).

Correlation Study on the Expression of INSR, IRS-1, and PD-L1 in Nonsmall Cell Lung Cancer.

Objective To study the expression and correlation of insulin receptor (INSR), insulin receptor substrate-1 (IRS-1), and programmed cell death ligand-1 (PD-L1) in nonsmall cell lung cancer (NSCLC). Methods 45 lung cancer tissues and 30 adjacent normal tissues of NSCLC patients diagnosed in the Second Affiliated Hospital of Shandong First Medical University from June 2019 to August 2020 were selected. The expressions of INSR, IRS-1, and PD-L1 proteins in tumor tissues and adjacent tissues of NSCLC were detected by immunohistochemical staining. Results The expression of INSR and IRS-1 in NSCLC was significantly higher than that in adjacent normal lung tissue (P < 0.05). INSR expression had statistical significance with the degree of pathological differentiation of nonsmall cell carcinoma (P = 0.031), but had no significant association with age, gender, pathological type, TNM stage, and lymph node metastasis status (P > 0.05). There was no significant correlation between IRS-1 positive expression and NSCLC patients' age, gender, pathological typing, degree of differentiation, TNM stage, and lymph node metastasis (P > 0.05). PD-L1 positive expression was correlated with lymph node metastasis of NSCLC (P = 0.028), while there was no significant correlation with gender, age, pathological type, TNM stage, and pathological differentiation degree of NSCLC patients (P > 0.05). Spearman correlation analysis showed that PD-L1 protein expression had a significant positive correlation with IRS-1 protein expression (r = 0.373), but was not correlated with the expression of INSR protein. Conclusion IRS-1 may be involved in the regulation of PD-L1 expression and mediate the occurrence of tumor immune escape, which is expected to become a new target for NSCLC immunotherapy and provide new clinical evidence for immunosuppressive therapy.

КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ ТЕРАПИИ МЕТАСТАТИЧЕСКОГО НЕМЕЛКО– КЛЕТОЧНОГО РАКА ЛЕГКОГО ДЕМОНСТРИРУЮТ МНОГООБЕЩАЮЩИЕ РЕЗУЛЬТАТЫ: КОНГРЕСС ASCO 2022

Lung cancer (LC) is a commonly diagnosed malignant tumor that annually claims the lives of about 1.8 million peoples. In the Russian Federation, the group of tumors of the respiratory organs: trachea, bronchi and lung occupies the third place (9.4%, both sexes) in the structure of oncological morbidity after malignant neoplasms of the skin with melanoma (15.0%), breast (11.6% ). Up to 80% of detected malignant lung tumors are non-small cell carcinoma (NSCLC). Among patients with NSCLC, stage IIIB-IV of the process is diagnosed in 70% of cases. The median survival of patients in this group is 4-5 months, and only 10% of them survive 1 year from the moment of diagnosis. This study explored the most advanced clinical developments in the treatment of metastatic NSCLC discussed at the ASCO Annual Congress – 2022: new treatment options for mNSCLC with KRAS mutations and other targeted therapy strategies for mNSCLC. The reviewed clinical developments on targeted combination therapy for metastatic NSCLC show promising results and an acceptable drug safety profile for its personalized administration to patients after progression under standard treatment conditions. Presented at ASCO – 2022, the results of clinical trials of the latest drug molecules indicate their serious antitumor efficacy. Personalized methods of selective suppression of specific effector pathways of oncogenesis have certain clinical advantages.

PULMONARY SARCOMATOID CARCINOMA WITH EXTENSION INTO THE RIGHT PULMONARY VEIN AND LEFT ATRIUM

PULMONARY SARCOMATOID CARCINOMA WITH EXTENSION INTO THE RIGHT PULMONARY VEIN AND LEFT ATRIUM

S1676 Things Are Not Always What They Seem: A Rare Case of Pancreatic Carcinoma Manifesting Through Cutaneous Metastasis

Introduction: Pancreatic cancer is an aggressive disease that commonly metastasizes to the liver, lung, and peritoneum. Cutaneous metastasis is a rare occurrence with an incidence of only 2.0%. We present a case of metastatic pancreatic adenocarcinoma primarily presenting as a cutaneous nodule. Case Description/Methods: A 50-year-old male was undergoing outpatient evaluation for a raised, left scalp lesion along with neck nodules. Associated symptoms included an unintentional 30lb weight loss. Outpatient CT soft tissue neck revealed numerous necrotic lateral neck lymph nodes, lytic lesion with epidural soft tissue extension at C2-4, and occlusion/thrombosis of the left subclavian, brachiocephalic, and left internal jugular veins (Figure). Given these findings, the patient was referred to the Emergency Department (ED). At time of ED arrival, vital signs were stable along with initial laboratory values. CTA PE study showed no pulmonary embolism but revealed numerous pulmonary and bilateral adrenal nodules, multifocal liver and osseous lesions, and widespread lymphadenopathy. Additionally, CT head demonstrated a left scalp soft tissue lesion. Follow up CT abdomen/pelvis revealed a 2.8 x 2.2 x 1.8 cm ill-defined pancreatic lesion and confirmed widespread metastasis including to the muscles. Additional testing revealed elevated cancer markers with Cancer antigen 19-9 (CA 19-9) of 5418 U/mL and carcinoembryonic antigen (CEA) of 63.8 ng/mL. Pathology from initial scalp lesion biopsy showed fragments of necrotic dermis with small foci of poorly differentiated carcinoma. Biopsies of the right and left neck masses revealed poorly differentiated adenocarcinoma of uncertain primary. Therefore, liver biopsy was performed and confirmed non-small cell carcinoma of pancreatobiliary origin. Further imaging to determine treatment course discovered intracranial metastasis and cervical spine disease resulting in cord compression. Ultimately, the patient underwent 4 out of 10 fractions of palliative radiation to the cervical spine but passed away after transitioning to comfort care one month after diagnosis. Discussion: There are less than 25 documented cases of pancreatic cancer with cutaneous involvement; however, it is even more rare that cutaneous involvement prompts initial diagnosis. The umbilicus is the most common site of cutaneous involvement and is referred to as the Sister Mary Joseph Nodule. Involvement of the soft tissue of the scalp and neck is much less common and poorly documented making this case extremely unique.Figure 1.: Axial contrast enhanced CT of the abdomen shows a 2.8 cm ill-defined hypoattenuating mass in the pancreatic tail (A) with multifocal metastatic liver lesions and bilateral adrenal metastasis (B). Axial CT image of the pelvis shows a metastatic lesion in the right rectus femoris muscle (C). On liver biopsy, H&E, 40X,(S21-41666) revealed high grade carcinoma with vesiculated nuclei, prominent nucleoli (D), CA 19-9 IHC 20X diffuse positivity in tumor cells (E) and CK AE1/3 IHC, 20X, diffusely positivee for pancytokeratin in tumor cells confirming carcinoma (F). Axial CT of the head shows a 2.4 cm nodular left parietal scalp soft tissue lesion (G) which was also seen on clinical examination (H). Biopsy of the scalp lesion (H&E, 40X) demonstrated high grade carcinoma with vesiculated nuclei, prominent nucleoli and mitoses (I), histologically similar to liver biopsy findings.

CHARACTERISTICS OF NON-SMALL CELL LUNG CARCINOMA AND THE RESULT OF EPIDERMAL GROWTH FACTOR RECEPTOR TEST

Lung carcinoma is cancer that develops from the abnormal proliferation of lung epithelial cells. Lung carcinoma has two forms: Non-Small Cell Lung Carcinoma (NSCLC) and Small Cell Lung Carcinoma (SCLC). NSCLC makes up 85% of lung carcinomas cases. EGFR overexpression is often seen in NSCLC. This research aims to discuss and provide information about the patient's characteristics, smoking status, functional status, clinical stage, histopathological diagnosis, and EGFR test of NSCLC. This research is a literature study that collects, manages, uses and reviews research data from scientific journals, previous research manuscripts, and textbooks. The literature review results were that most patients with NSCLC were found in the 55–65 age group. NSCLC can happen to both genders. NSCLC was found in smokers and non-smokers. The patient's functional status was mostly "very dependent". The clinical stage of NSCLC patients is often found in stages III and IV. The most common histopathological diagnosis of NSCLC was adenocarcinoma. EGFR results can be positive or negative; most occur in the adenocarcinoma subtype. EGFR overexpression in NSCLC occurs due to somatic mutations in the tyrosine kinase domain, causing continuous signal transduction and phosphorylation.

The effect of some trace elements on the expression of telomerase gene in lung cancer

Lung cancer is a disorder that begins due to genetic and epigenetic changes. These changes cause the activation of oncogenes and the inactivation of tumor suppressor genes. Various factors influence the expression of these genes. In this research, we investigated the relationship between the number of trace elements zinc and copper and the ratio of these two in serum with the expression of the telomerase enzyme gene in lung cancer. For this purpose, we included 50 people with lung cancer in the study as the case group and 20 patients with non-tumor lung diseases as the control group. The TRAP assay method measured the telomerase activity in biopsy samples of lung tumor tissue. Also, serum copper and zinc were measured by atomic absorption spectrometry. The results showed that the mean serum concentration of copper and the ratio of copper to zinc in patients were significantly higher than in the controls (120.8 ± 5.7 versus 107.2 ± 6.5μg/dL)(P<0.05). However, there is no significant difference in the mean serum concentration of zinc between the two groups (p > 0.05). The patients' mean ratio of copper to zinc is significantly higher than the control group (1.6 ± 0.4 versus 1.1 ± 0.2)(p < 0.05). The average level of telomerase enzyme activity of patients showed a significant difference from the control group 32.8 ± 16.1 vs. zero percent) (p < 0.01). There is a direct and significant correlation between the serum level of copper and the level of telomerase enzyme activity in patients (r = 0.36 and p < 0.05). A positive correlation was observed between total serum copper concentration and the increasing age of patients (r = 0.39 and p < 0.01). The correlation between the ratio of copper to zinc and the serum copper concentration of the patients was positive and significant (r = 0.36 and p < 0.05), but the correlation between the amount of serum zinc and the ratio of copper to zinc was negative and significant (r = -0/ 72 and p < 0.01). The average copper serum concentration of people with small cell carcinoma (123.7 ± 2.8 μg/dL) compared to non-small cell carcinoma (117.6 ± 4.8 μg/dL) is high and significant (P< 0.05). Patients with small cell carcinoma had a high mean telomerase concentration (112 ± 0.57%) and significantly compared to non-small cell carcinomas (6.4 ± 2.5%)(P < 0.05). This situation regarding the zinc element and the ratio of copper to zinc in non-small cell carcinomas compared to small cell carcinomas were evaluated as non-significant (P>0.05). Based on the obtained results, it can be assumed that determining the amount of zinc and copper and the telomerase enzyme activity in lung cancer can have a biological role in the initiation and progression of tumor tissue, which requires more studies.

Lung cancer screening with low-dose CT integrated with pulmonary care in a public hospital in southern Brazil: results from the first 712 patients.

To describe the performance of a pulmonologist-led lung cancer screening program using low dose CT (LDCT) in a cohort of outpatients with stable respiratory diseases in the Brazilian public health care system. This was a retrospective analysis of the first two rounds of lung cancer screening of patients enrolled in the program. Inclusion criteria were being between 55 and 80 years of age, being a current or former smoker (smoking cessation ≤ 15 years), and having a smoking history ≥ 30 pack-years. LDCT results were interpreted in accordance with the Lung CT Screening Reporting and Data System, and those with a score of 3 or 4 were considered positive screening. Incidental pleuropulmonary findings were sought in all reports. LDCTs were requested for 791 patients during the study period, and 712 patients (90%) met the screening criteria. The mean patient age was 63 years, and most participants were current smokers (56%) with emphysema (78.5%) and other pleuropulmonary findings on CT (64%). Screening was positive in 14.0% and 5.6% of the cases in the first and second screening rounds, respectively. Lung cancer was detected in 1.5% of the patients in both first and second rounds (positive predictive value: 11.0% and 26.6%, respectively). The rate of early-stage (TNM I or II) screen-detected non-small cell carcinoma was 64.3%. Of the patients with positive screening, 19% were lost to follow-up before investigation was complete. The results of this screening program suggest its adequate performance in a cohort of patients with significant respiratory morbidity. The loss to follow-up rate highlights the need for constant monitoring and interventions to ensure adherence.

Targeting EGFR Exon 20 Insertion-mutated Cancers – New Perspectives in Head and Neck Cancers – Lessons to Learn from Non-small Cell Carcinoma (NSCLC)

Mutations in the tyrosine kinase (TKD) domain of the epidermal growth factor receptor (EGFR) are involved in the unfavorable therapeutic response through resistance to targeted molecular therapy. Data from the clinical experience of non-small cell lung carcinoma (NSCLC) treatment demonstrate the benefit of tyrosine kinase inhibitors (TKIs) in cases of EGFR mutation. The next generation sequencing technique (NGS) allows the identification of hot spots involved in mutations, exon 20 insertion being associated with the unfavorable response. Exon 20 insertions are more common in head and neck squamous cell carcinoma (HNSCC) compared to NSCLC, which could explain a resistance to targeted therapy in head and neck cancers. Taking into account the data reported in the NSCLC, Amivantamab, a bi-specific EGFR-MET antibody with potential immune cell modulation of activity, but also other innovative therapies validated in exon 20 EGFR mutation could be part of the therapy of sino-nasal cancer, but also of other HNSCC sites exon 20 mutant EFGR.

Diagnostic accuracy and adequacy of peripheral pulmonary nodules samples obtained by transthoracic needle aspiration.

To examine the adequacy of samples and accuracy of transthoracic needle aspiration (TTNA) in patients with peripheral pulmonary nodule (PPN) diagnosis. This retrospective study included 248 patients who underwent TTNA of PPN and subsequent diagnostic and therapeutic surgical procedures during a 5-year period at the Institute for Pulmonary Diseases of Vojvodina. The following were analysed: adequacy of cytological samples for diagnosis and molecular testing, tumour localisation and dimensions, and cytological and histopathological characteristics. The adequacy of the cytological samples was 93.15%. The proportion of adequate-diagnostic samples was higher in patients in whom the largest diameter of the lesion was >4cm, and this difference showed statistical significance. Tumour localisation was not statistically significant for the adequacy of samples for cytological analysis. Cytological samples of lung adenocarcinoma had high projected adequacy for EGFR analyses of 91.55%, not dependent on the size and location of the lesion. The most commonly diagnosed lung tumour was adenocarcinoma (45.51%). Patients with a cytological diagnosis of non-small cell carcinoma not otherwise specified, after histopathological analyses, had adenocarcinoma in most cases (53.85%). The overall accuracy of TTNA in the diagnosis of PPN was 71%. The method's accuracy was 75.24% for malignant tumours, while it was 28.57% for benign tumours. The accuracy of cytological analysis for the histological type of tumour was 84.18%. Transthoracic needle aspiration with cytological analysis is an effective and highly sensitive method in determining the aetiology of PPN.

Neoadjuvant Stereotactic Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis of the Literature and Ongoing Clinical Trials.

Simple SummaryThe available treatment strategies for patients with brain metastases remain suboptimal, with current research focused on identifying therapies intended to improve patient outcomes while reducing the risk of treatment-related complications. Several studies have investigated the role of pre-operative neoadjuvant stereotactic radiotherapy, and have proposed it as a valid alternative to post-operative adjuvant stereotactic radiotherapy. The aim of our systematic review was to comprehensively analyze the current literature and ongoing clinical trials evaluating neoadjuvant stereotactic radiotherapy in patients with brain metastases, describing treatment protocols and related outcomes. Early evidence suggests that neoadjuvant stereotactic radiotherapy may offer rates of local control and overall survival comparable to those obtained with adjuvant postoperative SRS, but comparative studies are currently lacking. In addition, neoadjuvant stereotactic radiotherapy shows low rates of post-treatment radiation necrosis and leptomeningeal metastases. Ongoing clinical trials aim to evaluate long-term outcomes in large patient cohorts, with some focused on comparing neoadjuvant stereotactic radiotherapy to adjuvant stereotactic radiosurgery.Background: Brain metastases (BMs) carry a high morbidity and mortality burden. Neoadjuvant stereotactic radiotherapy (NaSRT) has shown promising results. We systematically reviewed the literature on NaSRT for BMs. Methods: PubMed, EMBASE, Scopus, Web-of-Science, Cochrane, and ClinicalTrial.gov were searched following the PRISMA guidelines to include studies and ongoing trials reporting NaSRT for BMs. Indications, protocols, and outcomes were analyzed using indirect random-effect meta-analyses. Results: We included 7 studies comprising 460 patients with 483 BMs, and 13 ongoing trials. Most BMs originated from non-small lung cell carcinoma (41.4%), breast cancer (18.7%) and melanoma (43.6%). Most patients had single-BM (69.8%) located supratentorial (77.8%). Patients were eligible if they had histologically-proven primary tumors and ≤4 synchronous BMs candidate for non-urgent surgery and radiation. Patients with primary tumors clinically responsive to radiotherapy, prior brain radiation, and leptomeningeal metastases were deemed non-eligible. Median planning target volume was 9.9 cm3 (range, 2.9–57.1), and NaSRT was delivered in 1-fraction (90.9%), 5-fraction (4.8%), or 3-fraction (4.3%), with a median biological effective dose of 39.6 Gy10 (range, 35.7–60). Most patients received piecemeal (76.3%) and gross-total (94%) resection after a median of 1-day (range, 1–10) post-NaSRT. Median follow-up was 19.2-months (range, 1–41.3). Actuarial post-treatment rates were 4% (95%CI: 2–6%) for symptomatic radiation necrosis, 15% (95%CI: 12–18%) and 47% (95%CI: 42–52%) for local and distant recurrences, 6% (95%CI: 3–8%) for leptomeningeal metastases, 81% (95%CI: 75–87%) and 59% (95%CI: 54–63%) for 1-year local tumor control and overall survival. Conclusion: NaSRT is effective and safe for BMs. Ongoing trials will provide high-level evidence on long-term post-treatment outcomes, further compared to adjuvant stereotactic radiotherapy.

EP16.03-019 Landscape of EGFR Extracellular Domain Mutations in Advanced Non Small Cell Lung Carcinoma

Plasma next generation sequencing (NGS) is a non-invasive method for tumor genomic profiling that offers personalized treatment options via cell free DNA analysis for patients with advanced cancers. Targeted therapies direct activity toward specific functional protein domain(s) to inhibit tumor cell survival. The EGFR protein is comprised of an extracellular domain (ECD) that spans amino acids 1-620 and an intracellular tyrosine kinase domain (TKD) that can be targeted in multiple cancer types. In advanced non-small cell carcinoma (NSCLC), EGFR directed-therapies mainly focus on mutations within the TKD.

Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and one year survival of lung cancer in Sanglah hospital

Background: Lung cancer is ranked third as the most common cancer in Indonesia. The one-year survival rate of advanced-stage non-small cell lung carcinoma (NSCLC) patient is quite low, that is 24.6%. Effective and inexpensive prognostic markers need to be further studied due to an increasing incidence of cancer. Inflammation plays an important role in tumorigenesis and research showed an association of NLR and PLR values with poor prognosis in patients with various solid tumors, but current cut off values still vary. This study wanted to determine the value of NLR, PLR and their relationship with the survival rate of advanced stage NSCLC patients at Sanglah hospital.Methods: A retrospective cohort study using the medical record of 96 advanced-stage NSCLC patients who underwent treatment since January 2018 in Sanglah hospital, was closely monitored for a year since diagnosed. Analysis was performed with ROC, Kaplan Meier analysis, log rank test, and time independent cox regression model.Results: The one-year survival rate of advanced stage NSCLC patient is 14.6%, with median survival 3.26 months. Cut off NLR&gt; 3.37, median survival 2.66, p=0.00. Cut off PLR&gt;178.55, median survival 3.26, p=0.35. Multivariate analysis showed that NLR, HR=2.75 and performance status, HR=1.78 were associated with survival.Conclusions: NLR with cut off &gt;3.37 is associated with one-year survival rate of advanced-stage NSCLC patient. PLR did not have any significant association with one-year survival rate of advanced-stage NSCLC patient.

Spindle cell tumor of the lung: A rare case

Spindle cell carcinoma of the lung is a rare, aggressive lung malignancy (non-small cell carcinoma) with a poor prognosis. This tumor accounts for approximately 0.4% of all lung malignancies, and due to its rarity, standard therapy is yet to be established for its management and treatment. The prevalence of this tumor is more common in males as compared to females (ratio of 4:1) and usually occurs in the sixth/seventh decade of life, more so in smokers. The authors report a case of a 79-year-old male patient who was incidentally detected and diagnosed with this rare lung carcinoma proven with a lung biopsy.

Mutually exclusive expression of EZH2 and H3K27me3 in non-small cell lung carcinoma

Enhancer of zeste homolog 2 (EZH2) epigenetically represses gene expression via trimethylation of lysine 27 on histone 3 (H3K27me3). Non-small cell carcinoma (NSCLC) has been reported to show high EZH2 and low H3K27me3 expression compared to normal lung tissues, but there are no studies examining the expression of EZH2 and H3K27me3 simultaneously with immunohistochemistry. In the present study, the expression of EZH2 and H3K27me3 was examined in surgically resected NSCLC. We enrolled 27 cases of squamous cell carcinoma (SCC), 73 cases of Lepidic, 77 of Papillary/Acinar, 51 of Solid, 31 of Micropapillary, and 12 of Mucinous subtypes of adenocarcinoma. First, we examined the expression of EZH2 and H3K27me3 in normal and metaplastic bronchial epithelium adjacent to NSCLC. Normal bronchial epithelium showed EZH2 expression in a limited number of basal cells and H3K27me3 expression in surface differentiated cells with cilia or mucus. In metaplastic bronchial epithelium, the number of EZH2-positive cells increased in multilayered basal cells, and H3K27me3-positive cells were observed in the superficial layer. Then, EZH2 and H3K27me3 expression was analyzed in NSCLC. Abundant EZH2 and rare H3K27me3 expression was detected in SCC, Papillary/Acinar, Solid and Micropapillary subtypes. In Mucinous subtype, EZH2 expression was hardly detected, and H3K27me3 expression was detected in almost all tumor cells. EZH2-expressing and H3K27me3-expressing tumor cells were similarly observed in Lepidic subtype, but double immunofluorescence revealed that EZH2 and H3K27me3 expression pattern was mutually exclusive. No co-expression of EZH2 and H3K27me3 was detected in all examined subtypes. To our knowledge, there have been no reports describing mutually exclusive expression pattern of EZH2 and H3K27me3.

Comprehensive genomic profiling of Finnish lung adenocarcinoma cohort reveals high clinical actionability and SMARCA4 altered tumors with variable histology and poor prognosis

IntroductionLung adenocarcinoma is the most common type of lung cancer and typically carries a high number of mutations. However, the genetic background of the tumors varies according to patients’ ethnic background and smoking status. Little data is available on the mutational landscape and the frequency of actionable genomic alterations in lung adenocarcinoma in the Finnish population. Materials and methodsWe evaluated the gene alteration frequencies of 135 stage I–IV lung adenocarcinomas operated at Turku University Hospital between 2004 and 2017 with a large commercial comprehensive genomic profiling panel. Additionally, we correlated the alterations in selected genes with disease outcomes in 115 stage I–III patients with comprehensive follow-up data. The genomic alterations in a sub-cohort of 30 never-smokers were assessed separately. ResultsSeventy percent of patients in the overall cohort and 77% in the never-smoker sub-cohort harbored an alteration or a genomic signature targetable by FDA and/or EMA approved drug for non-small cell carcinoma, respectively. In multivariable analysis for disease-specific survival, any alteration in SMARCA4 (DSS; HR 3.911, 95%CI 1.561–9.795, P=0.004) exhibited independent prognostic significance along with stage, tumor mutation burden, and predominant histological subtypes. ConclusionsOver two thirds of our overall cohort, and especially never-smokers had an actionable genomic alteration or signature. SMARCA4 alterations, detected in 7.4% of the tumors, independently predicted a shortened overall and disease-specific survival regardless of the alteration type. Most SMARCA4 alterations in our cohort were missense mutations associated with differentiated predominant histological subtypes and immunohistochemical SMARCA4/BRG1 and TTF-1 positive status.

Pten and p53 Loss in the Mouse Lung Causes Adenocarcinoma and Sarcomatoid Carcinoma.

Simple SummaryLung cancer is the world leading cause of cancer death. Therefore, a better understanding of the disease is needed to improve patient survival. In this work, we have deleted the tumor suppressor genes Pten and Trp53 in adult mouse lungs to analyze its impact on tumor formation. Double mutant mice develop Adenocarcinoma and Pulmonary Sarcomatoid Carcinoma, two different types of Non-Small Cell Carcinoma whose biological relationships are a matter of debate. The former is very common, with various models described and some therapeutic options. The latter is very rare with very poor prognosis, no effective treatment and lack of models reported so far. Interestingly, this study reports the first mouse model of pulmonary sarcomatoid carcinoma available for preclinical research.Lung cancer remains the leading cause of cancer deaths worldwide. Among the Non-Small Cell Carcinoma (NSCLC) category, Adenocarcinoma (ADC) represents the most common type, with different reported driver mutations, a bunch of models described and therapeutic options. Meanwhile, Pulmonary Sarcomatoid Carcinoma (PSC) is one of the rarest, with very poor outcomes, scarce availability of patient material, no effective therapies and no models available for preclinical research. Here, we describe that the combined deletion of Pten and Trp53 in the lungs of adult conditional mice leads to the development of both ADC and PSC irrespective of the lung targeted cell type after naphthalene induced airway epithelial regeneration. Although this model shows long latency periods and incomplete penetrance for tumor development, it is the first PSC mouse model reported so far, and sheds light on the relationships between ADC and PSC and their cells of origin. Moreover, human ADC show strong transcriptomic similarities to the mouse PSC, providing a link between both tumor types and the human ADC.

Potential of Vicenin-2 in Chitosan Encapsulated Basil (Ocimum sanctum Linn.) Leaf Extract as A Therapeutic Alternative Medicine for Non-small cell carcinoma lung cancer

This study aimed to analyze the production of chitosan-encapsulated vicenin-2 extracted from basil leaves and its effect on non-small cell carcinoma lung cancer. Vicenin-2 Extract from Chitosan-Encapsulated basil (Ocimum sanctum Linn.) leaf extract is produced by library research and laboratory practice. In non-small cell carcinoma lung cancer, vicenin-2, one of the components in basil leaves, and chitosan capsules, which are deacetylated chitin, had a substantial anticancer effect. It is required to investigate the effectiveness and safety of basil leaf powder containing mostly vicenin-2 and encapsulated in chitosan capsules.