The Association of Immune-Related Adverse Events with the Efficacy of Atezolizumab in Previously Treated Advanced Non-Small-Cell Lung Cancer Patients: A Single-Center Experience.

Immune checkpoint inhibitors (ICIs) are pivotal in managing metastatic non-oncogene addicted non-small-cell lung cancer (NSCLC). They have unique toxicities known as immune-related adverse events (irAEs). Previous studies have linked irAEs during atezolizumab-based first-line treatments in advanced NSCLC with improved outcomes. This study explored the association between irAEs and the efficacy of atezolizumab in advanced NSCLC patients who had previously received platinum-based chemotherapy. The study involved 105 advanced NSCLC patients who received atezolizumab monotherapy after progressing on at least one line of platinum-based chemotherapy from a single academic institution in Serbia. Data were obtained from a hospital lung cancer registry. Among the participants, 63.8% were male, with the majority being current (53.3%) or former smokers (37.1%). About half had a good performance status (ECOG PS 0-1) at the start of atezolizumab treatment. irAEs occurred in 23 patients (21.9%). The median progression-free survival (mPFS) was significantly longer for patients with irAEs (13.03 months) compared to those without (3.4 months) (HR 0.365 [95% CI, 0.195-0.681], p = 0.002). irAEs and ECOG PS 0-1 were predictors of longer mPFS, with irAEs being more common in patients with good performance status (p = 0.01). irAEs were linked to improved mPFS in NSCLC patients treated with atezolizumab after multiple lines of platinum-based chemotherapy.

Correlation of Systemic Inflammation Parameters and Serum SLFN11 in Small Cell Lung Cancer-A Prospective Pilot Study.

BACKGROUND AND OBJECTIVES: The objective of this research was to analyze the correlation of the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), soluble programmed cell death ligand 1 (sPD-L1), and Schlafen 11 (SLFN11) with the response to first-line chemotherapy in a cohort of small cell lung cancer (SCLC) patients, and to determine their potential as predictive serum biomarkers. MATERIALS AND METHODS: A total of 60 SCLC patients were included. Blood samples were taken to determine CRP, sPD-L1, and SLFN11 levels. The first sampling was performed before the start of chemotherapy, the second after two cycles, and the third after four cycles of chemotherapy. RESULTS: The patients who died earlier during the study had NLR and SLFN11 concentrations significantly higher compared to the survivor group. In the group of survivors, after two cycles of chemotherapy, the NLR ratio decreased significantly (p < 0.01), but after four cycles, the NLR ratio increased (p < 0.05). Their serum SLFN11 concentration increased significantly (p < 0.001) after two cycles of chemotherapy, but after four cycles, the level of SLFN11 fell significantly (p < 0.01). CRP, NLR, and SLFN11 were significant predictors of patient survival according to Kaplan-Meier analysis. The combination of inflammatory parameters and SLFN11 with a cutoff value above the 75th percentile of the predicted probability was associated with significantly lower overall survival in SCLC patients (average survival of 3.6 months vs. 4.8 months). CONCLUSION: The combination of inflammatory markers and the levels of two specific proteins (sPD-L1, SLFN11) could potentially serve as a non-invasive biomarker for predicting responses to DNA-damaging therapeutic agents in SCLC.

Molecular profiling of rare thymoma using next-generation sequencing: meta-analysis.

BACKGROUND: Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on thymoma using articles based on the disease's next-generation sequencing (NGS) genomic profiling. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the prevalence of studies that discovered the genes and variants occurring in the less aggressive forms of the thymic epithelial tumors. Studies published before 12th December 2022 were identified through PubMed, Web of Science (WoS), and SCOPUS databases. Two reviewers have searched for the bases and selected the articles for the final analysis, based on well-defined exclusion and inclusion criteria. RESULTS: Finally, 12 publications were included in the qualitative as well as quantitative analysis. The three genes, GTF2I, TP53, and HRAS, emerged as disease-significant in the observed studies. The Odds Ratio for all three extracted genes GTF2I (OR = 1.58, CI [1.51, 1.66] p < 0.00001), TP53 (OR = 1.36, CI [1.12, 1.65], p < 0.002), and HRAS (OR = 1.02, CI [1.00, 1.04], p < 0.001). CONCLUSIONS: According to obtained data, we noticed that the GTF2I gene exhibits a significant prevalence in the cohort of observed thymoma patients. Moreover, analyzing published articles NGS has suggested GTF2I, TP53, and HRAS genes as the most frequently mutated genes in thymoma that have pathogenic single nucleotide variants (SNV) and Insertion/Deletion (InDel), which contribute to disease development and progression. These variants could be valuable biomarkers and target points specific to thymoma.

Soluble sPD-L1 and Serum Amyloid A1 as Potential Biomarkers for Lung Cancer.

BACKGROUND: The objective of this prospective study was to evaluate whether soluble programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) and serum amyloid A1 (SAA1) are potential diagnostic, predictive or prognostic biomarkers in lung cancer. METHODS: Lung cancer patients (n=115) with advanced metastatic disease, 101 with non-small cell lung cancer, NSCLC (77 EGFR wild-type NSCLC patients on chemotherapy, 15 EGFR mutation positive adenocarcinoma patients, 9 patients with mPD-L1 Expression ≥50% NSCLC - responders to immunotherapy), and 14 patients with small cell lung cancer (SCLC) were examined. ELISA method was used to determine sPD-L1 and SAA1 concentrations in patients' plasma. RESULTS: Significantly higher blood concentrations of sPD-L1 and SAA1 were noted in lung cancer patients compared with a healthy control group. In PD-L1+ NSCLC patients, a significantly higher sPD-L1 level was noticed compared to any other lung cancer subgroup, as well as the highest average SAA1 value compared to other subgroups. CONCLUSIONS: It seems that sPD-1/PD-L1 might be a potential biomarker, prognostic and/ or predictive, particularly in patients treated with immunotherapy. Serum amyloid A1 has potential to act as a good predictor of patients' survival, as well as a biomarker of a more advanced disease, with possibly good capability to predict the course of disease measured at different time points.

Clinical features of endobronchial tuberculosis.

BACKGROUND/AIM: Endobronchial tuberculosis (EBTB) is a specific type of pulmonary tuberculosis which often affect the tracheobronchial tree, and can be microbiologically and/or pathohistologically confirmed. The aim of the study was to determine the clinical features and diagnostic aspects of EBTB. METHODS: This retrospective study was conducted at the Clinic for Lung Diseases, Clinical Center of Serbia, Belgrade, from January 1997 to December 2007. All patients with EBTB confirmed by bronchoscopy with biopsy during a study period were analysed. Data included the patient's medical history, a physical exam, chest X-ray, mycobacterial analysis of sputum samples, endoscopic types and patohistological confirmation. RESULTS: In the study, 57.6% of the patients were males. The most frequent symptoms were cough (71.2%), malaise (54.20%), fever (49.2%), weight loss (40.7%), and hemoptysis (13.60%). Most of the patients were diagnosed within 30 days of symptoms onset. Sputum examination showed acid-fast bacilli in 31.4% of the patients, while sputum culture for tuberculosis bacilli were positive in 55.9% of the patients. The most common radiographic localization was in the upper lung lobes (63.5%). Cavities were present in 60.4% of the patients. The most common endoscopic subtype determined by bronchoscopy were nonspecific bronchitis (39.9%) and edematous-hyperemic subtype (36.4%). CONCLUSION: EBTB was more frequent among men, and among people in their fifties in our country. Detailed bronchoscopic examination, correlated with clinical and laboratory findings, will improve diagnostic rate and provide timely therapy.

Sarcoidosis of the pleura--A case report.

INTRODUCTION: Pleural involvement is an uncommon manifestation of sarcoidosis. It may manifest as pleural effusion, pneumothorax, pleural thickening and nodules, hydropneumothorax, trapped lung, hemothorax, or chylothorax. The incidence of pleural effusion with sarcoidosis ranges from 0% to 5% but has been reported to be as high as 7.5%. Pleural effusions complicate sarcoidosis in < 3% of patients. CASE REPORT: We reported a 64-year-old male patient with chronic multiorgan sarcoidosis. This patient developed pleural sarcoidosis with massive pleural effusion several years after the diagnosis of sarcoidosis. A definitive diagnosis of a sarcoid pleural effusion was based on a biopsy demonstrating noncaseating granuloma. The patient responded well to the treatment (methotrexate and methylprednisolone) with a complete withdrawal of pleural effusion following five weeks of the treatment beginning. CONCLUSION: The presented patient is a rare case of pleural involvement of sarcoidosis with massive effusion, who responded well to the treatment.