Background & Aims: Hepatic encephalopathy (HE) is a serious neuropsychiatric sequela emerging in the advanced stages of cirrhosis. The gut microbiota plays an important role in the development of HE. The aim of the study was to analyze the dynamic interplay between microbiota and Blastocystis in cirrhotic patients with or without encephalopathy. Methods: The study was designed as cross-sectional study. A total of 37 patients from the Ankara city, admitted to the University Hospital within a 6-month period prior to enrolment into the study were included in the study. After the regular health checks, clinical histories, clinical examinations, and Psychometric HE Score (PHES) points, patients’ MELD and CTP scores were recorded. The fecal microbiota configurations were characterized by targeting hypervariable regions V3 and V4 of the 16S rRNA gene using Illumina MiSeq System. Results: Blastocystis spp. were detected in 21.6% (n = 8) of all cirrhotic patients. When those were analyzed by subgroups, four of them were subtype 2, three were subtype 3 and one was subtype 1. Blastocystis spp. were not found in any of the patients with HE; however, they were detected in 38.1% of the patients without HE. Also the increase in the bacterial diversity was observed along with the absence of Blastocystis. It was suggested that there was an inverse relationship between Blastocystis spp. and advanced stages of HE and the structure and composition of gut microbiota. Conclusion: The absence of Blastocystis spp. is associated with the HE severity and dysbiosis in the gut microbiota. Abbreviations: Bl: Blastocystis; CTP: Child-Turcotte-Pugh; DNA: deoxyribonucleic acid; HE: hepatic encephalopathy; IBD: inflammatory bowel disease; IBS: irritable bowel syndrome; MELD: Model for End Stage Liver Disease; MHE: Minimal hepatic encephalopathy; NASH: Non-alcoholic steatohepatitis; PBC: Primary Biliary Cirrhosis; PCR: Polymerase Chain Reaction; PHES: Psychometric Hepatic Encephalopathy Score; rRNA: ribosomal ribonucleic acid.

Background and Objectives: Although breast cancer is the most common type of cancer among women, bilateral breast cancer (BBC) remains exceedingly rare. BBC can present as either synchronous (SBBC) or metachronous (MBBC) disease. Data regarding the clinical characteristics of BBC are limited. In this study, we aimed to share our multicenter, retrospective experience on the clinicopathological and demographic features of SBBC and MBBC, their survival outcomes, and the factors influencing survival, in light of current knowledge. Material and Method: A total of 125 patients who were treated and followed between 2015 and 2024 across six different centers were included in the study. The patients were categorized into synchronous (SBBC) and metachronous (MBBC) groups. Their clinicopathological characteristics were analyzed, along with disease-free survival (DFS) and 5-year overall survival (OS) outcomes. Results: DFS was 5.7 years in the SBBC group and 5.6 years in the MBBC group (p = 0.95). The 5-year OS rate was 95.2% in the MBBC group and 80.7% in the SBBC group (p = 0.035). Hormone receptor negativity was identified as an independent risk factor for lower DFS in the overall patient cohort (HR: 0.55, 95% CI: 0.31–0.98, p = 0.04). Conclusion: Significant differences were found between the SBBC and MBBC groups in terms of hormone receptor status, presence of an invasive lobular carcinoma component, recurrence/metastasis status, and molecular subtype discordance between the two primary tumors. Although DFS did not significantly differ between the groups, the 5-year OS was significantly higher in the MBBC group. In multivariate regression analysis, hormone receptor negativity was identified as an independent risk factor for decreased DFS among all BBC patients. Our study is noteworthy for shedding light on the clinical features of BBC in the context of current knowledge and for its multicenter design.

Background and Objectives: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers and remains a leading cause of cancer-related mortality worldwide. EGFR-targeted tyrosine kinase inhibitors (TKIs) have substantially improved outcomes in EGFR-mutant NSCLC; however, primary and acquired resistance continues to limit their long-term efficacy. HER3 (receptor tyrosine-protein kinase ErbB3), a member of the ErbB receptor family, has been implicated in TKI resistance through heterodimerization with EGFR and HER2, leading to downstream PI3K/AKT pathway activation. Despite its biological plausibility as a resistance mediator, the clinical significance of HER3 expression as a prognostic and predictive biomarker in EGFR-mutant NSCLC has not been thoroughly characterized in real-world cohorts. Materials and Methods: This retrospective, single-center study included 52 patients diagnosed with EGFR-mutant NSCLC who received TKI therapy at Afyonkarahisar Health Sciences University between January 2011 and September 2023. HER3 protein expression was evaluated by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tumor tissue sections using the Huabio anti-HER3 antibody (clone PD00-44, 1:2000 dilution). Staining in more than 30% of tumor cells was considered HER3-positive; membranous staining intensity was scored on a 1–3 scale. Progression-free survival (PFS1, PFS2) and overall survival (OS) were analyzed using the Kaplan–Meier method and log-rank test. Statistical significance was set at p < 0.05. Results: Of 52 patients (55.8% female; mean age 64.5 years), 59.6% received chemotherapy and 40.4% received an EGFR TKI as first-line treatment; erlotinib constituted 71.2% of targeted therapies. In the first-line TKI group, HER3-negative patients had a numerically longer median PFS1 compared with HER3-positive patients (14.0 vs. 7.1 months; p = 0.285); however, this difference did not reach statistical significance and should be interpreted with caution given the small sample size. In contrast, among patients receiving first-line chemotherapy, HER3 staining status did not meaningfully affect PFS1 (4.1 vs. 2.5 months; p = 0.063). In second-line treatment, HER3-positive patients who received TKI after prior chemotherapy demonstrated a PFS2 comparable to or slightly exceeding that of HER3-negative patients (21.8 vs. 19.8 months; p = 0.49), suggesting that the sequencing of chemotherapy before TKI may attenuate the adverse effect of HER3 positivity. Median OS was 15.1 months in HER3-negative patients and 12.7 months in HER3-positive patients (p = 0.824); this numerical difference of approximately 3 months did not reach statistical significance and should therefore be interpreted cautiously. Among patients receiving TKI in the first line, HER3-positive patients had a shorter median OS than HER3-negative patients (9.6 vs. 14.2 months), whereas those receiving TKI in the second line showed a trend toward longer OS in HER3-positive patients (20.5 vs. 17.2 months). Conclusions: HER3 expression was associated with reduced first-line TKI efficacy in EGFR-mutant NSCLC, suggesting a possible role for HER3 in primary TKI resistance; however, these findings are exploratory and did not reach statistical significance. The observation that HER3-positive patients who received chemotherapy before TKI demonstrated outcomes comparable to HER3-negative patients raises the hypothesis that treatment sequencing may potentially influence the impact of HER3 positivity, though this requires prospective validation before any clinical conclusions can be drawn. These results suggest that HER3 expression may warrant further investigation as a candidate biomarker for treatment sequencing decisions and as a potential therapeutic target in EGFR-mutant NSCLC. Prospective studies evaluating chemotherapy–TKI sequencing and HER3-directed agents such as patritumab deruxtecan (HER3-DXd) in HER3-positive patients are needed to confirm these preliminary observations.

Background: Vandetanib and cabozantinib are the approved first-line antiangiogenic multikinase inhibitors (aaMKIs) for metastatic medullary thyroid carcinoma (MTC); however, real-world data on their comparative efficacy, optimal sequencing, and outcomes beyond the first-line setting remain limited. We report multicenter real-world outcomes from a large Turkish cohort. Methods: In this retrospective multicenter cohort study, we analyzed data from 24 oncology referral centers across Türkiye. Patients with histologically confirmed metastatic MTC who received systemic therapy between December 2011 and December 2024 were included. The primary endpoint was progression-free survival (PFS), assessed separately for first-line (PFS1) and second-line (PFS2) therapy. Overall survival (OS) and prognostic factors were evaluated using Kaplan–Meier and Cox proportional hazards analyses. Results: A total of 115 patients were included (median age 47.4 years; 63.5% male). In the first-line setting, vandetanib (47.8%) and cabozantinib (30.4%) were the most frequently used agents. Median PFS1 was 40.8 months with vandetanib and was not reached with cabozantinib; both were significantly superior to chemotherapy (median PFS1 4.9 months; log-rank p < 0.001). In the second-line setting, median PFS2 was not reached with cabozantinib and was 32.5 months with vandetanib. Sequential use of cabozantinib and vandetanib across the first two lines was associated with a median time to second progression of 114 months, compared with 39 months in patients receiving any other TKI combination (p = 0.003). Second-line use of cabozantinib or vandetanib was independently associated with improved OS (HR 0.40, 95% CI 0.16–0.98; p = 0.046). On multivariate analysis, younger age (HR 0.16, 95% CI 0.03–0.72; p = 0.017) and bone metastasis (HR 0.29, 95% CI 0.11–0.73; p = 0.009) were independent prognostic factors for OS. Conclusions: In this real-world cohort of patients with metastatic MTC, cabozantinib and vandetanib demonstrated durable efficacy across treatment lines, substantially outperforming alternative TKIs and chemotherapy. Sequential use of both approved aaMKIs was associated with prolonged disease control. These findings suggest a potential association between access to both agents and improved outcomes. They are consistent with their central role in treatment sequencing, particularly in settings with limited access to selective RET inhibitors. Given the retrospective design and small subgroup sizes, these results should be interpreted as exploratory and hypothesis-generating.

Background/Objectives Immune checkpoint inhibitors are frequently used to treat advanced non-small cell lung cancer (NSCLC). Drug clearance also varies depending on patient-related factors. Therefore, the lung immune prognostic index (LIPI), based on inflammatory markers, may help predict prognosis. Early changes in LIPI may predict treatment response and survival. Methods This multicenter study included 707 patients with NSCLC. LIPI was calculated at baseline and one month after treatment initiation. Patients were categorized into two groups: those with stable or improved LIPI scores and those with worsened LIPI scores. Survival outcomes and prognostic significance were analyzed. Results Median progression free survival was 9 months in patients with stable or improved LIPI and 6 months in those with worsened LIPI (p = 0.005). Median overall survival was 15 months in the stable/improved LIPI group and 9 months in the worsened LIPI group (p = 0.001). Conclusion Changes in LIPI can be assessed using routine laboratory tests as early as the second treatment cycle, allowing early prediction of treatment response. Baseline LIPI values and changes in LIPI can predict prognosis.