Bahattin Engin Kaya

Background and Objectives: Metastatic renal cell carcinoma (mRCC) remains a lethal disease despite advances with immune checkpoint inhibitors such as nivolumab. However, a substantial proportion of patients exhibit primary resistance or early progression, highlighting the need for reliable and easily accessible prognostic biomarkers. The C-reactive protein–albumin–lymphocyte (CALLY) index is a novel immunonutritional biomarker integrating systemic inflammation, nutritional status, and immune competence. Materials and Methods: In this retrospective single-center study, 91 patients with mRCC treated with nivolumab were analyzed. Patients were stratified into low and high CALLY index groups based on a receiver operating characteristic-derived cut-off (0.322). Survival outcomes were assessed using Kaplan–Meier analysis and Cox regression models. Results: Patients with a low CALLY index demonstrated significantly shorter progression-free survival (4.5 vs. 13.5 months, p < 0.001) and overall survival (9.1 vs. 25.5 months, p = 0.003). Multivariate analysis confirmed the CALLY index as an independent prognostic factor for both progression-free survival (HR: 2.63, p = 0.002) and overall survival (HR: 1.88, p = 0.035). Conclusions: The CALLY index is a simple, cost-effective, and reproducible biomarker that independently predicts survival in nivolumab-treated mRCC. It may serve as a practical tool for risk stratification and personalized treatment planning in the immunotherapy era.

Background/Objectives: The prognostic significance of the uric acid-to-albumin ratio (UAR) in patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has not been adequately investigated. This study aimed to investigate the association between baseline UAR and survival outcomes in this patient population. Methods: This retrospective study included HR-positive/HER2-negative metastatic breast cancer patients treated with ribociclib or palbociclib at Necmettin Erbakan University between May 2020 and April 2025. UAR was calculated by dividing the serum uric acid level (mg/dL) by the serum albumin level (g/dL). Based on receiver operating characteristic (ROC) analysis, the optimal cut-off value for UAR was identified as 1.0 (AUC = 0.67; sensitivity 68%; specificity 58%). Patients were subsequently classified into two groups as UAR < 1 and UAR ≥ 1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared with the log-rank test. Independent prognostic factors were evaluated using Cox regression analyses. Results: A total of 118 eligible patients were included in the analysis, including 34 (28.8%) in the UAR < 1 group and 84 (71.2%) in the UAR ≥ 1 group. The proportion of postmenopausal patients was significantly higher in the UAR ≥ 1 group (p = 0.01). Kaplan–Meier analysis showed that median PFS was not reached in the UAR < 1 group, whereas it was 33.05 months in the UAR ≥ 1 group (log-rank p = 0.06). Median OS was not reached in the UAR < 1 group and was 50.7 months in the UAR ≥ 1 group (p = 0.017). Multivariate Cox regression analysis demonstrated that UAR < 1 was associated with improved PFS (HR = 0.65; 95% CI: 0.34–0.89; p = 0.04). Postmenopausal status emerged as an independent adverse prognostic factor for PFS (HR = 1.92; 95% CI: 1.10–4.05; p = 0.04). In addition, UAR < 1 was associated with a reduced risk of mortality in the OS analysis (HR = 0.61; 95% CI: 0.26–0.87; p = 0.01). Conclusions: Lower baseline UAR was associated with more favorable survival outcomes in HR-positive/HER2-negative metastatic breast cancer patients treated with CDK4/6 inhibitors. As an inexpensive and easily accessible biomarker derived from routine laboratory parameters, UAR may provide additional prognostic information for clinical risk stratification.

Background and Objectives: Gastric cancer is an aggressive malignancy characterized by high recurrence rates, even following curative resection. The Albumin–Bilirubin (ALBI) score was originally established to assess hepatic functional reserve in patients with hepatocellular carcinoma (HCC). By reflecting both systemic inflammation and nutritional status, the ALBI score has demonstrated significant prognostic utility across a spectrum of solid malignancies. The present study aimed to evaluate the prognostic significance of the ALBI score in gastric cancer patients receiving adjuvant therapy after curative-intent resection. Materials and Methods: This retrospective study included 168 patients with gastric cancer who underwent curative-intent resection followed by adjuvant therapy between November 2008 and January 2021. ALBI scores were calculated from pre-treatment serum albumin and bilirubin levels. Patients were dichotomized into ALBI Grade 1 and ALBI Grade 2 based on an optimal ROC-derived cut-off value of −2.60. Survival outcomes, including overall survival (OS) and recurrence-free survival (RFS), were estimated using the Kaplan–Meier method and compared via the log-rank test. Independent prognostic factors were identified using univariate and multivariate Cox proportional hazards regression models. Results: Of the 168 patients, 56.5% were classified as ALBI Grade 1 and 43.5% as ALBI Grade 2. ALBI Grade 2 was associated with significantly shorter median RFS (18.7 vs. 72.2 months; p = 0.001) and OS (40.7 vs. 104.3 months; p = 0.003). Multivariable analysis identified ALBI Grade 2 as an independent predictor for both poor OS (HR: 1.699, p = 0.010) and RFS (HR: 1.767, p = 0.004). Pathological stage III disease was also a significant independent prognostic factor for OS (HR: 3.024) and RFS (HR: 3.049) (all p = 0.010). Additionally, elevated CEA correlated with shorter RFS (p = 0.023). Conclusions: The ALBI score is a prognostic marker for both overall and recurrence-free survival in gastric cancer patients receiving adjuvant therapy. A lower ALBI score is associated with longer survival outcomes. The ALBI score may support postoperative risk stratification and individualized follow-up planning.

Background and Objectives: Overweight and obesity is defined as a Body Mass Index (BMI) of 25.0–29.9 kg/m² and ≥30.0 kg/m². The prognostic significance of obesity in metastatic prostate cancer is still unclear, especially between the castration-sensitive (CSPC) and castration-resistant (CRPC) disease states. New evidence suggests that obese patients who get androgen receptor–targeted therapies may have an unexpected survival advantage. This study examined the correlation between body mass index (BMI) and survival outcomes in patients administered androgen receptor pathway inhibitors. Materials and Methods: A retrospective analysis was conducted on a cohort of 167 patients with metastatic prostate cancer treated between 2015 and 2024. BMI was analyzed as both a continuous variable and a categorical variable, which was classified as normal weight, overweight or obese. The primary goal of this study is to compare PFS and OS among BMI groups. We employed Kaplan–Meier survival analysis and Cox regression modeling to evaluate prognostic indicators. The CSPC and CRPC groups were evaluated separately. Results: PFSs for normal, overweight and obese CSPC patients were 11.3, 15.1, 19.5 months, respectively; p = 0.03 but the OS did not differ significantly between BMI groups. OS for normal, overweight and obese CRPC patients were 32.8, 47.6 and 43.4 months, respectively; p = 0.01. There was also a trend toward better PFS, but it was not statistically significant. Multivariate analysis found that obesity (BMI ≥ 30) was a separate protective factor for PFS in CSPC, while high-volume disease was a bad prognostic factor for OS in CRPC. A high Gleason score and ECOG-PS 2 were consistently associated with poor outcomes. Conclusions: Obesity has a phase-dependent prognostic influence in metastatic prostate cancer, providing a PFS advantage in CSPC and an OS benefit in CRPC. These results suggest that there may be an obesity paradox in people who are getting androgen receptor–targeted therapy. Further prospective studies are required to gain a better understanding of the biological reasons for this association.

Aim: This study aimed to evaluate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab monotherapy. Methods: We retrospectively analyzed 80 patients with mRCC who received at least one cycle of nivolumab between February 2016 and March 2024 at a single academic center. Patients were categorized into three groups according to pre-treatment mGPS (0, 1, or 2). Survival outcomes were assessed using the Kaplan–Meier method. Results: The median progression-free survival (mPFS) was 31.3, 6.8, and 4.4 months in patients with mGPS 0, 1, and 2, respectively (p = 0.001). The median overall survival (mOS) was 33.4 months for mGPS 0, 14.1 months for mGPS 1, and 6.7 months for mGPS 2 (p = 0.001). mGPS was significantly associated with both PFS and OS. Notably, patients with mGPS 0 had substantially better survival outcomes. These findings suggest a potential association between higher systemic inflammation (as reflected by mGPS) and adverse prognostic features. mGPS demonstrated partial overlap with the IMDC (International Metastatic RCC Database Consortium) classification but offered additional prognostic stratification due to its incorporation of inflammatory markers. Conclusion: mGPS is a simple, objective, and clinically applicable biomarker that may support survival prediction and patient selection in the context of ICI therapy for mRCC. Its integration into routine clinical decision-making could enhance personalized treatment strategies. Prospective studies in larger cohorts are needed to validate these findings.

Background and Objectives: Erlotinib, a tyrosine kinase inhibitor (TKI), is an established therapy for patients with metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Preclinical and clinical evidence suggests that chronic stress, mediated through β-adrenergic signaling, promotes tumor progression, angiogenesis, and therapy resistance. Furthermore, interactions between β-adrenergic signaling and EGFR pathways have been hypothesized to negatively influence treatment responses. Based on this rationale, we investigated whether concomitant beta-blocker use may improve survival outcomes in EGFR-mutant NSCLC patients treated with erlotinib. Materials and Methods: This retrospective analysis included 103 patients with metastatic EGFR-mutant NSCLC who received erlotinib. Patients were classified according to concurrent beta-blocker use, defined as continuous therapy for at least six months prior to erlotinib initiation, prescribed for cardiovascular indications. Progression-free survival (PFS) and overall survival (OS) were compared between beta-blocker users and non-users. Results: Patients receiving erlotinib with concomitant beta-blocker therapy achieved a median PFS (mPFS) of 21.4 months (95% CI, 13.1–29.7), compared with 9.7 months (95% CI, 6.7–12.7) in non-users (p = 0.003). Median OS (mOS) was 32.4 months (95% CI, 14.8–50.0) in the beta-blocker group versus 19.9 months (95% CI, 14.8–25.0) in the non-beta-blocker group (p = 0.010). Multivariate Cox regression confirmed beta-blocker use as an independent prognostic factor for both PFS (p = 0.004) and OS (p = 0.014). Conclusions: Concomitant beta-blocker use was associated with significantly prolonged survival in patients with EGFR-mutant metastatic NSCLC receiving erlotinib. These findings support the hypothesis that β-adrenergic inhibition enhances the efficacy of EGFR-targeted therapy. Prospective studies are warranted to validate these results and to further elucidate the underlying biological mechanisms.

Introduction In the treatment of metastatic non-small cell lung cancer (mNSCLC), targeted therapies are utilized in the presence of driver mutations. Tyrosine kinase inhibitors (TKIs) have contributed positively to survival outcomes in this patient group. In driver mutant mNSCLC patients, caution is warranted for the development of small cell lung cancer (SCLC) differentiation following progression under TKI therapy. SCLC is associated with an aggressive course and shorter survival. The cornerstone of SCLC treatment is conventional chemotherapy. In this study, we aimed to present the development of SCLC differentiation in driver mutant mNSCLC patients who received at least one line of TKI therapy as a single-center experience. Patients and methods Between April 2013 and January 2024, the medical records of 144 patients diagnosed with mNSCLC and found to harbor driver mutations were retrospectively reviewed at Necmettin Erbakan University Faculty of Medicine Hospital, Oncology Clinic. All patients had received at least one line of TKI. The analysis included evaluation of driver mutations, treatments administered, and the rate of SCLC differentiation in this patient population. Results A total of 144 patients were included in the study. Among them, 122 patients (84.9%) had an EGFR mutation, 21 patients (15.1%) had an ALK mutation, and 1 patient had a ROS1 mutation. TKI therapy was administered as first-line treatment in 50% of the patients, as second-line in 40.3%, and as third-line in 6.3%. Biopsies were performed in 22 out of 144 patients after disease progression. Of these, 21 biopsies were from patients with EGFR mutations, and 1 was from a patient with an ALK mutation. Biopsies were conducted after first-line therapy in 8 cases, after second-line therapy in 11 cases, and after third-line therapy in 3 cases. SCLC differentiation was observed in 3 out of 22 patients (13.6%), all of whom had EGFR mutations. Additionally, 2 of these 3 patients developed SCLC differentiation following first-line TKI therapy, while 1 developed it after second-line TKI therapy. Discussion The rate of SCLC differentiation in NSCLC is generally low and is considered rare. It is estimated that the rate of SCLC differentiation in NSCLC ranges between 1% and 3%. In our clinic, when evaluating driver mutant mNSCLC patients who received at least one line of TKI therapy, SCLC differentiation was observed in 3 patients (13.6%). The limitations of our study include its retrospective nature and the small sample size. However, the findings suggest that SCLC differentiation is a potential occurrence in driver mutant mNSCLC patients treated with TKIs. Therefore, careful monitoring and the detection of possible differentiation are essential in the follow-up of these patients.

Background/Aims: Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative diseases. Along with the increase in myeloproliferative cell lines, they can cause various clinical outcomes such as arterial and venous thrombosis, pulmonary hypertension, and myocardial infarction. This study was designed to evaluate the cardiac effects of these diseases via electrocardiography and echocardiography. Methods: A total of 50 patients with a diagnosis of PV, 50 patients with a diagnosis of ET, and 50 healthy individuals as a control group were included in this study. Data on patient demographics were recorded in all subjects. All patients and control subjects had electrocardiography (ECG) recordings and routine transthoracic echocardiographic examination. Pulse wave velocity (PWV) was assessed with a Holter blood pressure device. Results: In total, 50 PV patients, 50 ET patients, and 50 control group were included in the study. The demographic characteristics of the PV, ET and control groups were similar. The PR interval was significantly shorter in control subjects than in PV and ET patients (p:0.007, p:0.024). Although the measured values were within normal limits, diastolic posterior wall thickness was significantly lower in the control group compared to PV and ET patients (p:0.019, p:0.009). PWV was significantly higher in ET patients compared to the control group (p:0.012). Conclusion: In this study, evaluating the effects of PV and ET on electrocardiography and transthoracic echocardiography; ECG parameters used to predict ventricular arrhythmias (QT, QTc, Tp-Te, Tp-Te/QT) and Pulmonary Artery Pressure showed no significant change, in opposition to existing literature. Nonetheless, similar to previous publications, PV and ET were found to negatively affect the diastolic function parameters on transthoracic echocardiography. While the aortic stiffness was significantly higher in ET patients compared to the control group, no significant difference was noted between PV patients and control subjects in terms of aortic stiffness.