Muzaffer Uğraklı

Background and Objectives: This study aimed to compare the real-world outcomes of first-line pembrolizumab monotherapy (Mono-IO) versus pembrolizumab plus platinum-based chemotherapy (IO + ChT) in patients with metastatic non-small cell lung cancer (mNSCLC) and a PD-L1 tumor proportion score (TPS) ≥ 50%. Materials and Methods: This retrospective, multicenter, real-world study evaluated 148 patients with mNSCLC and PD-L1 expression ≥ 50% who received either first-line Mono-IO or IO + ChT. Overall survival (OS), progression-free survival (PFS), and clinical benefit rate were compared between the two treatment strategies. Additionally, clinical prognostic factors, patterns of progression, and post-progression treatments were analyzed. Survival outcomes were assessed using Kaplan–Meier estimates, multivariable Cox regression, and restricted mean survival time (RMST) analysis. Results: Patients in the Mono-IO group were significantly older (median 69 vs. 63 years; p < 0.001) and had a higher proportion of ECOG PS 2 (35.3% vs. 5.2%; p < 0.001). No significant differences were observed between Mono-IO and IO + ChT in median OS (32.0 vs. 26.0 months; p = 0.559) or PFS (19.6 vs. 19.4 months; p = 0.572). In an exploratory multivariable analysis adjusting for organ-specific metastases and antibiotic exposure, ECOG PS ≥ 1 (aHR: 1.86, 95% CI: 1.16–2.97; p = 0.009), antibiotic use (aHR: 1.85, 95% CI: 1.16–2.95; p = 0.010), and liver metastasis (aHR: 2.58, 95% CI: 1.16–5.74; p = 0.020) were independent predictors of worse OS. Conversely, PD-L1 TPS ≥ 90% (aHR: 0.56, 95% CI: 0.35–0.91; p = 0.018) was independently associated with superior OS. In exploratory subgroup analysis, a numerical survival trend favoring Mono-IO was observed in patients with PD-L1 TPS ≥ 90%, although this finding remains hypothesis-generating. Following disease progression, 64.7% of patients received no further systemic therapy. Conclusions: In this real-world cohort, no statistically significant differences in OS or PFS were detected between Mono-IO and IO + ChT; however, the wide confidence intervals do not exclude clinically meaningful differences, and equivalence cannot be inferred from these data. PD-L1 TPS ≥ 90% may potentially serve as a biomarker to identify patients who derive benefit from monotherapy, although this exploratory finding requires validation in larger cohorts. Given that the majority of patients did not transition to subsequent therapy in routine practice, likely reflecting multifactorial host frailty and rapid disease evolution, first-line therapeutic optimization warrants careful individualized consideration.

Objective: To evaluate clinical outcomes of whole-brain radiotherapy (WBRT) and identify prognostic factors associated withoverall survival (OS) in non-small cell lung cancer (NSCLC) patients with brain metastases who were not candidates for stereotacticradiotherapy (SRT).Patients and Methods: In this retrospective study, 71 NSCLC patients with brain metastases who underwent WBRT were included.Clinical and treatment data were collected, and survival outcomes and prognostic factors were evaluated.Results: The median age was 65 years, and 78.9% of patients were male. Adenocarcinoma was the most common histological subtype(54.9%). A Karnofsky Performance Status (KPS) ≥80 was observed in 74.6% of patients. Brain metastases were synchronous in 64.8%of cases, and 32.4% of patients had isolated intracranial disease. The median OS and intracranial progression-free survival (iPFS)following WBRT were both 3 months (95% CI: 1.0–5.0 and 1.7–4.3, respectively). In multivariate analysis, independent predictors ofimproved OS included KPS ≥80 (HR=5.72), early radiologic response (HR=4.10), the use of immunotherapy or targeted agents as firstlinesystemic therapy (HR=5.26), and the presence of isolated brain metastasis (HR=4.53).Conclusion: These findings highlight key predictors of improved survival after WBRT and underscore its continued clinical relevancein carefully selected NSCLC patients ineligible for SRT.

Background and Objectives: Fibroblast growth factor receptor (FGFR) alterations are therapeutic targets in urothelial carcinoma, but their prognostic significance in muscle-invasive bladder cancer (MIBC) is uncertain. We evaluated the frequency of FGFR1–3 alterations and their association with overall survival (OS) in Turkish patients with MIBC. Materials and Methods: Formalin-fixed, paraffin-embedded tumour samples from 194 patients with non-metastatic muscle-invasive (n = 154) or metastatic (n = 40) urothelial carcinoma of the bladder were analysed by targeted next-generation sequencing of FGFR1–3. Variants were classified according to ACMG/AMP tiers. OS was assessed with Kaplan–Meier and Cox regression analyses in the overall cohort and in both subgroups. Results: At least one FGFR alteration was detected in 131 patients (67.5%): FGFR3 in 42.8%, FGFR1 in 24.7% and FGFR2 in 20.6%. Most FGFR1 (91.7%) and FGFR2 (87.5%) alterations were Tier III variants, whereas Tier I FGFR3 hotspot mutations were found in 17.5% of the cohort. Median OS was shorter in FGFR-altered than in FGFR-unaltered patients (14 vs. 18 months; p = 0.024), with a similar difference in the non-metastatic subgroup (19 vs. 24 months; p = 0.047) but not in the metastatic subgroup (8 vs. 7 months; p = 0.653). After adjustment for metastatic status, ECOG performance status and age, overall FGFR alteration status was not an independent prognostic factor (HR 1.31, 95% CI 0.87–1.97; p = 0.200), whereas FGFR1 alteration was independently associated with worse OS (HR 1.62, 95% CI 1.07–2.44; p = 0.023). FGFR3 alterations were not prognostic. Conclusions: FGFR alterations, predominantly in FGFR3, are frequent in MIBC and are associated with shorter OS, but not independently of metastatic status and performance status. FGFR1 alteration was associated with poor prognosis, but this finding requires validation in larger cohorts.

Evaluation of the Relationship Between Prognostic Nutritional Index and Survival in Operated Stage II and III Colorectal Cancer Patients Receiving Adjuvant Chemotherapy - International Journal of Gastrointestinal Cancer Research

Background and Objectives: During the 2016–2022 period, tyrosine kinase inhibitor (TKI) monotherapy was the standard first-line option at our center before combination protocols became available. This study evaluates patients experiencing initial TKI failure who subsequently received second- or later-line nivolumab. Because clinical practice lacks low-cost, accessible tools to prognosticate outcomes in this setting, we evaluated whether baseline psoas muscle index (PMI), early on-treatment C-reactive protein (CRP) kinetics, and a specific panel of blood-derived inflammatory/nutritional ratios offer reliable prognostic value. Materials and methods: We retrospectively reviewed data from 49 consecutive mRCC patients who progressed on a TKI and received second- or later-line nivolumab monotherapy. Primary endpoints were overall survival (OS; N = 49) and time-to-treatment failure (TTF; N = 48). We utilized Kaplan–Meier and Cox regression models for analysis. Benjamini–Hochberg false discovery rate (FDR) correction (q < 0.05) controlled false positive inflation across two separate testing frameworks: seven log-rank assessments for TTF and the core Cox models. Adjusted models accounted for clinical covariates including International Metastatic RCC Database Consortium (IMDC) risk category, Eastern Cooperative Oncology Group performance status (ECOG PS), and de novo metastatic presentation. We calculated the intraclass correlation coefficient (ICC) to evaluate measurement reproducibility. Results: Median follow-up reached 48.4 months (reverse Kaplan–Meier; maximum: 87.8 months), with a cohort-wide median OS of 13.9 months (IQR: 5.8–36.2). A low baseline C-reactive protein-to-albumin ratio (CAR) mapped to a distinct survival benefit, showing a median OS of 32.6 months versus 5.8 months in the high-CAR group (log-rank p < 0.001; BH q = 0.003). In adjusted multivariable Cox hazards modeling, both CAR (HR: 1.029; p = 0.002) and the prognostic nutritional index (PNI; HR: 0.893; p < 0.001) maintained independent prognostic significance. When evaluating the 43 patients with complete 3-month CRP records, we found a significantly higher objective response rate (ORR) in those at or below the cohort-median ratio threshold of 1.16 compared to patients above it (54.5% vs. 23.8%; p = 0.039). The overall ITT population registered an ORR of 36.7% (18/49). Conclusions: Low pretreatment CAR and elevated PNI identify mRCC patients showing improved survival profiles in this post-TKI nivolumab subgroup. Additionally, an elevated 3-month CRP ratio correlates with compromised objective response rates and a trend toward shorter TTF, though the TTF endpoint did not clear strict FDR parameters (BH q = 0.098). These retrospective, single-center data serve strictly for signal generation and require independent prospective multi-institutional confirmation before translating to oncology practice.

Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor, has demonstrated efficacy in pivotal trials in both pretreated and treatment-naïve patients with ALK-positive non-small-cell lung cancer (NSCLC). However, real-world evidence from large multicenter cohorts remains limited. We conducted a retrospective multicenter study including 114 patients with advanced ALK-positive NSCLC treated with brigatinib across 28 centers in Turkey between May 2020 and December 2024. Objective response rate (ORR) was assessed by RECIST v1.1. Median progression-free survival (mPFS) and overall survival (mOS) were estimated by the Kaplan-Meier method, and prognostic factors were analyzed using Cox regression. The median age was 55 years. Brigatinib was administered as first-line therapy in 68.4% of cases. In the overall cohort, the mPFS and OS were 24.2 and 44.2 months. The ORR was 70.2%. In the first-line setting, the ORR was 79.5%, with an mPFS of 28.6 months and an mOS of 50.3 months. In contrast, those treated in the second-line or later setting had less-favorable outcomes, which independently correlated with worse OS in multivariate analysis. Patients with baseline brain metastases achieved favorable outcomes, with an mPFS of 26.2 months, an mOS of 46.3 months, and an ORR of 76.5%. Adverse events were reported in 83.3% of patients, most commonly gastrointestinal toxicities, creatine phosphokinase elevation, and liver enzyme abnormalities. This nationwide multicenter study offers comprehensive real-world evidence confirming the effectiveness and tolerability of brigatinib in ALK-positive NSCLC, with especially favorable outcomes in the first-line setting and in patients with brain metastases.

Background and Objectives: Clinically meaningful drug–drug interactions may be overlooked in oncology. Proton pump inhibitors (PPIs) may modulate outcomes with immune checkpoint inhibitors (ICIs) by altering the gut microbiome, altering the immune milieu, and affecting transporter interactions. We evaluated whether concomitant PPI use affects survival among patients with metastatic non-small cell lung cancer (NSCLC) treated with nivolumab. Materials and Methods: We retrospectively included patients with metastatic NSCLC who received second-line nivolumab across five oncology centers (January 2020–June 2023). Patients were grouped as concomitant PPI users vs. non-users. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method and compared with the log-rank test; multivariable Cox models assessed independent associations. Results: A total of 194 patients were screened, of whom 30 were excluded according to predefined criteria. The final analysis included 164 patients—85 PPI users and 79 non-users. Median OS was 26.1 months (95% CI 15.5–36.7) in PPI users and 29.3 months (22.2–36.4) in non-users; this difference was not statistically significant (p = 0.54). Median PFS was 6.2 months (3.7–8.6) in PPI users vs. 10.2 months (7.1–13.2) in non-users (p = 0.04). In multivariable analysis, absence of concomitant PPI use (No vs. Yes) was independently associated with longer PFS (HR = 0.52, 95% CI 0.24–0.89, p = 0.03), whereas PPI use was not associated with OS (HR = 0.96, 95% CI 0.67–1.61, p = 0.83). Conclusions: Concomitant PPI use during nivolumab therapy was associated with significantly shorter PFS and a numerical reduction in OS in real-world metastatic NSCLC. Where clinically feasible, the need for PPIs should be re-evaluated before and during ICI therapy.

Background Artificial intelligence is increasingly being used for analyzing image data in medicine. Objectives We aimed to develop a computer vision artificial intelligence (AI) application using limited training material to aid in the multi-label, multi-disease diagnosis of chest X-rays. Methods We trained an EfficientNetB0 pre-trained model, leveraging transfer learning and deep learning techniques. Six thoracic disease categories were defined, and the model was initially trained on images sourced online and chest X-rays from a hospital database for training and internal validation. Subsequently, the model underwent external validation. Results In constructing and validating Deep Chest, we utilized 453 images, achieving an area under curve (AUC) of 0.98, sensitivity of 0.98, specificity of 0.80, and accuracy of 0.83. Notably, for diagnosing masses or nodules, the sensitivity, specificity, and accuracy were 0.97, 0.81, and 0.83, respectively. We deployed Deep Chest as a free experimental web application. Conclusions This tool demonstrated high accuracy in diagnosing both single and coexisting pulmonary pathologies, including pulmonary masses or nodules. Deep Chest thus represents a promising AI-based solution for enhancing diagnostic capabilities in thoracic radiology, with the potential to be utilized across various medical disciplines, especially in scenarios where expert support is limited.

Objective: This study aimed to assess the efficacy and safety of FOLFIRI and paclitaxel in patients with advanced gastric cancer (AGC) who were previously treated with first-line modified docetaxel, cisplatin, 5-fluorouracil (mDCF) or 5-Fluorouracil, oxaliplatin, docetaxel (FLOT).Methods: Patients, who received a triplet regimen in the first line setting and were treated with FOLFIRI or paclitaxel in the second-line treatment were included.Results: The study included 198 patients, with 115 receiving FOLFIRI and 83 receiving paclitaxel. The median age was 58 (range: 24-69). The median progression-free survival (mPFS) was 5.2 [95% confidence interval (CI), 4.4-5.5] months in the FOLFIRI arm, and 4.1 (95% CI, 3.3-4.6) months in the paclitaxel arm (p = 0.007). The median overall survival (mOS) was 9.4 (95% CI, 7.4-10.5) months in the FOLFIRI arm and 7.2 (95% CI, 5.6-8.3) months in the paclitaxel arm (p= 0.008). Grade 3-4 neuropathy was higher in patients receiving paclitaxel compared to those receiving FOLFIRI (p = 0.04). Grade 3-4 diarrhea was 8% in the FOLFIRI arm and 2.4% in the paclitaxel arm (p= 0.02).Conclusion: Beyond progression with docetaxel-based triplet chemotherapy, FOLFIRI may be preferred as a second-line treatment over paclitaxel due to its longer mPFS and mOS.

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