Background: Comprehensive molecular profiling is essential for precision oncology in non-small cell lung cancer (NSCLC). However, genomic data from Eastern European populations, including Romania, remain limited. Methods: We analyzed 398 consecutive NSCLC cases tested at the PATHOS Molecular Pathology Laboratory (Cluj-Napoca, Romania) between April 2024 and February 2025 using the Ion Torrent™ Genexus™ System and the Oncomine™ Dx Target Test, which evaluates SNVs/indels in 46 genes, fusions in 23 genes, and CNVs in 19 genes from FFPE samples. Results: The cohort was predominantly male (66%) with a median age of 67 years. Adenocarcinoma represented 70% of cases with known histology. Genomic profiling revealed a high frequency of actionable alterations. KRAS mutations were the most common (29.1%), with p.G12C detected in 10.3% of all the cases. EGFR mutations were present in 14.3% of patients, mostly exon 19 deletions and L858R substitutions. BRAF alterations (5.3%) included both V600E and non-V600E variants. RET alterations were detected as eight missense mutations, two canonical fusions (KIF5B–RET, CCDC6–RET), one amplification, and three transcript imbalances. EML4-ALK fusions (1.77%), ERBB2 mutations/amplifications (3.0%), and FGFR1/FGFR3 amplifications were also observed. Conclusions: This study provides the first large-scale molecular snapshot of NSCLC in Romania. While the overall genomic profiles align with Western populations, the higher frequency of KRAS p.G12C and FGFR amplifications highlights the value of region-specific data to support targeted therapies in Eastern Europe.

Lung cancer is the leading cause of cancer deaths worldwide, with non-small cell lung cancer (NSCLC) being most common. This study examines how patient and tumor characteristics influences NSCLC treatment in Romania, Bulgaria, and Serbia, highlighting regional disparities and aiming to improve outcomes. This retrospective cohort study of stage IV NSCLC patients in Romania, Bulgaria, and Serbia analyzed the impact of patient and tumor characteristics on treatment choices, timelines for diagnosis, biomarker testing, and imaging, using regression analyses. The study included 840 stage IV NSCLC patients (mean age 64.2 years) across Romania, Bulgaria, and Serbia, with 280 patients per country. Overall, chemo-immunotherapy (CIT) was most common (38.1 %), followed by immunotherapy (31.2 %). Bulgaria and Romania favored CIT, while Serbia's options were limited by reimbursement. Factors influencing treatment included programmed death-ligand 1 (PD-L1) status and gene mutation profile in Bulgaria, weight loss and appetite in Romania, and smoking status and symptoms in Serbia. Testing and treatment initiation times varied, with Serbia showing the shortest times. PD-L1 status and Eastern Cooperative Oncology Group performance were crucial across all countries. Common symptoms included chest pain, cough, shortness of breath, and general pain, with varying frequencies across countries. This retrospective three-country real-world cohort shows marked regional differences in first-line treatment and timing for stage IV NSCLC. Beyond clinical factors, health-system elements, reimbursement, biomarker-testing availability/turnaround, and access to chemo-immunotherapy, shape care. Addressing these offers policy-level opportunities to improve equitable, guideline-concordant treatment. Initiated after the most heated phase of the COVID-19 pandemic and conducted without contingency measures, thus study highlights the need for personalized medicine and improved healthcare infrastructure to address disparities in treatment and testing times. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer worldwide. In this retrospective cohort study we examined how patient and tumor characteristics influences NSCLC treatment in Romania, Bulgaria, and Serbia, and revealed significant regional differences in baseline characteristics, treatment preferences, and influencing factors for stage IV NSCLC in these countries.

Purpose. Different combination modalities between an anti-PD-1/PD-L1 agent and a platinum-based chemotherapy or another checkpoint inhibitor (with or without a short course or full course of a platinum doublet) proved superior to chemotherapy alone in multiple clinical trials, but these strategies were not directly compared. The aim of this study is to report the real-world data results with different immunotherapy combinations in a series of patients treated in consecutive cohorts at the Ion Chiricuță Oncology Institute. Methods. A total of 122 patients were successively enrolled in three cohorts: (1A) nivolumab + ipilimumab (18 patients), (1B) nivolumab + ipilimumab + short-course chemotherapy (33 patients), and (2) pembrolizumab plus full-course chemotherapy (71 patients). Endpoints included overall survival (OS), progression-free survival (PFS), objective response (ORR), and univariate and multivariate exploratory analysis of prognostic factors. RESULTS. Median follow-up in the consecutive cohorts 1A, 1B, and 2 was 83 versus 59 versus 14.2 months. Median OS and PFS for all patients were 22.2 and 11.5 months, respectively, and 2-year actuarial OS and PFS were 49% and 35%, respectively. For the nivolumab + ipilimumab (cohorts 1A and 1B) versus pembrolizumab combinations (cohort 2), median OS was 14 vs. 24.8 months (p = 0.18) and 2-year actuarial survival 42% vs. 53%; median PFS was 8.6 vs. 12.7 months (p = 0.41) and 2-year actuarial PFS 34% vs. 35%; response rates were 33.3% vs. 47.9% (p = 0.22). Older age, impaired PS (2 versus 0–1), corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate analysis of survival (limited to 2 years follow-up). The 5-year long-term survival was 30.5% and 18.8% for cohorts 1A and 1B, respectively (not enough follow-up for cohort 2). Conclusions. Efficacy results using different immunotherapy combination strategies were promising and not significantly different between protocols at 2 years. Real-world efficacy and long-term results in our series were in line with those reported in the corresponding registration trials.

Background/Objectives: Our goal was to evaluate the effectiveness of tract sealing agents in reducing pneumothorax and chest drainage insertion following CT-guided lung biopsy (CLB), and to assess the certainty of supporting evidence. Methods: A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines (PROSPERO: CRD42024608747). Four health science databases (ScienceDirect, PubMed, Scopus, and Cochrane Library) were searched up to 13 October 2025. Randomized controlled trials and cohort studies reporting tract sealing after CLB were included. Outcomes were post-procedural pneumothorax and pleural drainage insertion. Both were analyzed as dichotomous variables using random-effects meta-analysis with the Mantel–Haenszel method. Statistical heterogeneity was assessed using the I² statistic. Results were considered statistically significant for p < 0.05. Study quality was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and the Risk Of Bias In Non-randomized Studies—of Interventions, Version 2 (ROBINS-I V2) tool for cohort studies. Results: A total of 3328 records were initially retrieved, with 37 studies (13,107 patients, 7161 male and 4526 female) meeting the inclusion criteria. Sealing agents included saline solution, hydrogel plug, gelatin sponge, autologous blood patch, saline + rapid roll-over, hemocoagulase, gelatin sponge + hemocoagulase, and fibrin glue. Meta-analysis demonstrated significant reductions in pneumothorax and drainage insertion with saline solution (pneumothorax: OR = 0.35; 95% CI 0.25–0.48; p < 0.00001; drainage: OR = 0.22, 95% CI 0.11–0.43; p < 0.00001), gelatin sponge (pneumothorax: OR = 0.44, 95% CI 0.37–0.53; p < 0.00001; drainage: OR = 0.40, 95% CI 0.29–0.54; p < 0.00001), autologous blood patch (pneumothorax: OR = 0.50, 95% CI 0.40–0.62; p < 0.00001; drainage: OR = 0.40, 95% CI 0.27–0.59; p < 0.00001), and hydrogel plug (pneumothorax: OR = 0.65, 95% CI 0.50–0.85; p = 0.001; drainage: OR = 0.44, 95% CI 0.25–0.76; p < 0.004). Conclusions: Saline solution, hydrogel plug, gelatin sponge, and autologous blood patch are sealing agents that are effective at lowering the risk of pneumothorax and drainage insertion following CLB.

Upfront Next-Generation Sequencing (NGS) is increasingly recommended in advanced NSCLC to guide targeted therapy. This prospective single-center study in Romania evaluated routine, upfront NGS in advanced NSCLC at baseline (tissue and/or liquid) and progression (liquid). Baseline FoundationOne NGS (tissue/liquid) was performed in 119 consecutive stage IV NSCLC patients, along with PD-L1 immunohistochemistry (IHC, SP263). Liquid biopsy was repeated at progression. Turnaround time (TAT), the prevalence of actionable targets, and clinical utility were assessed. Patients were predominantly male (68.1%) with a median age of 62 years (range 30–86). Most had ECOG PS 0–1 (79%) and non-squamous histology (67.2%). Never-smokers accounted for 25.2%. The median TAT for the NGS results was 9 days (range 5–21). Overall, 671 genetic alterations were detected in 149 genes. The mean number of distinct mutations per patient dropped from 5.6 at baseline to 4.3 at progression. Tissue samples yielded more alterations (6 per patient) than baseline liquid biopsies (4.6). Squamous tumors had more alterations (7.1 vs. 4.8 in non-squamous), and the number of smokers exceeded that of never-smokers (6 vs. 4.5). TP53 was the most frequent (70.59%). Actionable variants were found in 74.8% of patients, though only 35.3% received personalized therapy, largely due to performance status deterioration, reimbursement, or trial availability barriers. Common targets in non-squamous tumors included EGFR (21%), KRAS G12C (11%), NF1 (11%), and ERBB2 (6%); in squamous tumors, common targets included NF1 (24%), PIK3CA (18%), and ERBB2 (8%). Among smokers, driver mutations were often NF1 (15%), PIK3CA (11%), KRAS G12C (9%), and ERBB2 (8%); never-smokers were dominated by EGFR (45%), NF1 (15%), and KRAS G12C (8%). TMB ≥ 10 mut/Mb was seen in 26.9%; no patients were MSI-H. PD-L1 TPS was <1% in 33% of patients, 1–49% in 20%, ≥50% in 18%, and unknown in 29%. Upfront NGS offers rapid, comprehensive genomic data, guiding tailored therapies and trials in advanced NSCLC. Liquid rebiopsy at progression further refines treatment decisions.