Background: Metastatic gastric cancer (GC) and gastroesophageal junction (GEJ) cancer are associated with a poor prognosis. Recent advancements in treatment have incorporated trastuzumab, anti-PD-1 agents, and anti-claudin therapies alongside chemotherapy (ChT), significantly improving outcomes. Contemporary studies predominantly employ doublet ChT as the backbone for these regimens, although historically triplet ChT regimens have been favored, particularly in younger patients requiring rapid tumor shrinkage. Objective: The aim of this study was to compare the efficacy of mFOLFOX-6 and mDCF regimens in the treatment of advanced GC and GEJ adenocarcinoma. Design: This was a retrospective multicenter study. Methods: Patient data were obtained from the databases of 25 hospitals across Turkey. Demographic and clinicopathological characteristics were documented. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan–Meier method, and group discrepancies were assessed with log-rank test. Results: A total of 493 patients were included in the analysis, with similar baseline characteristics between the two groups. The objective response rate was 36.3% in the mDCF group and 38% in the mFOLFOX-6 group ( p = 0.7). The median PFS was 6 months for mDCF and 7 months for mFOLFOX-6 ( p = 0.2), while the median OS was 12 months for mDCF and 11 months for mFOLFOX-6 ( p = 0.4). Grade 3–4 neutropenia occurred in 27.6% of patients treated with mDCF versus 17.8% with mFOLFOX-6 ( p = 0.01). Likewise, grade 3–4 anemia was more frequent in the mDCF group (9.5%) compared to the mFOLFOX-6 group (4.8%; p = 0.04). Conclusion: Modified FOLFOX-6 demonstrated comparable efficacy to mDCF in the treatment of advanced GC and GEJ adenocarcinoma. Moreover, mFOLFOX-6 was associated with a lower incidence of hematological adverse effects.

The pivotal prognostic determinant for recurrence and survival in surgically treated gastric cancer (GC) patients remains the lymph node status. Despite the adoption of D2 lymph node dissection as the standard approach in recent years, its association with increased morbidity in elderly patients raises concerns. This study aims to explore the prognostic significance of the Positive Lymph Node Ratio (PLNR) score in the context of recurrence and survival among elderly patients with surgically treated GC. A retrospective review of files about surgically treated patients with GC was conducted. The prognostic impact of the PLNR score on overall survival (OS) was assessed through Receiver Operating Characteristic (ROC) analysis. The cut-off value for the PLNR, determined through ROC analysis, was identified as 0.138. This value serves as a crucial threshold, as it distinguishes patients with a higher risk of poor outcomes. Patients with a PLNR score of 0.138 or below exhibited a median OS of 111 months, whereas those with a PLNR score above 0.138 had a significantly lower median OS of 22 months (p = 0.004). Our findings revealed that the PLNR emerged as an independent predictor of survival and recurrence in patients undergoing GC resection.However, it's important to note that while valuable, the PLNR system has limitations. It does not encompass the T stage, a key factor in cancer staging. Therefore, it cannot be a direct substitute for the comprehensive information TNM staging provides. It should be used as a supplementary tool in predicting prognosis, particularly in elderly patients unsuitable for standard lymph node dissection.

Background and Objectives: HER-2 expression plays a critical role in the biological behavior and treatment of gastric cancer. With the emergence of HER-2-targeted therapies, classification into negative, low, and positive groups has gained clinical importance. The present study focused on assessing the link between HER-2 status and clinical–pathological variables, metastatic involvement, and overall survival (OS) among advanced gastric cancer patients. Materials and Methods: A total of 300 patients with advanced gastric adenocarcinoma were retrospectively analyzed. The mean age of the 300 patients included in the study was 61.8 years, and 70% of them were male. Based on immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), patients were classified as HER-2-negative (IHC 0), HER-2-low (IHC 1+ or 2+/FISH-negative), or HER-2-positive (IHC 3+ or 2+/FISH-positive). Clinicopathological variables, metastatic sites, and OS were compared among groups using Pearson’s Chi-square, Fisher’s exact test, ANOVA, and Kaplan–Meier survival analysis. Results: Significant differences were observed among HER-2 subgroups in pathological subtype (p = 0.006), liver metastasis (p = 0.009), lung metastasis (p = 0.006), and other metastatic sites (p = 0.001). HER-2-positive patients demonstrated higher rates of adenocarcinoma histology and increased liver and lung metastases. In female patients, HER-2 status was significantly associated with lung (p = 0.001) and other metastases (p < 0.001). Median OS for the entire cohort was 9.83 months (95% CI: 8.29–11.36). HER-2-positive patients had a significantly longer OS (15.06 months) compared with HER-2-negative patients (8.73 months; p = 0.039). Conclusions: HER-2 status is an important predictor of metastatic behavior and survival in advanced gastric cancer. HER-2-positive patients display distinct metastatic patterns and improved outcomes, supporting the value of HER-2-targeted therapies. The HER-2-low group may represent a biologically and clinically relevant intermediate subtype requiring further investigation.

Background: Clinical trials in metastatic hormone receptor-positive (HR+) human epidermal growth factor receptor-2 (HER2)-negative patients have shown that cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors both increase response rates and provide survival benefits. The efficacy of these therapies needs to be supported by real-life data. In this study, we aimed to evaluate treatment response, survival and affecting factors in patients with HR+/HER2− metastatic breast cancer (MBC) who were followed up with CDK 4/6 inhibitors in our center. Materials and methods: A retrospective analysis of 120 patients with HR+/HER2− MBC treated with ribociclib or palbociclib in combination with letrozole or fulvestrant was performed. Results: Median progression-free survival (mPFS) was 24 months in the general population, 27 months in the ribociclib arm and 20 months in the palbociclib arm, with no significant difference in progression-free survival (PFS) in both arms (p = 0.25). The mPFS was longer in the ribociclib + letrozole arm compared to palbociclib + letrozole (27 vs. 20 months, respectively). PFS was also longer in patients receiving ribociclib + fulvestrant compared to palbociclib + fulvestrant but not statistically significant (33 vs. 21 months, respectively). Median overall survival (mOS) was not reached, but 3-year overall survival (OS) was statistically significantly longer in the ribociclib arm (87% vs. 55.5%, respectively, p = 0.03). Conclusion: Palbociclib and ribociclib are first-line treatment options for metastatic HR+/HER2− disease and have similar efficacy. In our study, while the mPFS was not statistically significant in both arms, the 3-year OS rate was higher in the ribociclib arm and statistically significant. Our findings were confirmed in randomized studies comparing both agents head-to-head.

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have become a cornerstone in the treatment of HR+/HER2- advanced breast cancer. While their efficacy is well-established, emerging reports of nephrotoxicity warrant further investigation into its incidence, risk factors, and potential impact on survival outcomes. Objectives: This study aimed to evaluate the incidence and risk factors for nephrotoxicity in patients receiving CDK4/6 inhibitors (palbociclib or ribociclib) and to analyze its association with progression-free survival (PFS) and overall survival (OS). Design: This was a single-center, retrospective cohort study. Methods: We reviewed the medical records of 120 patients with advanced breast cancer treated with palbociclib or ribociclib between October 2018 and July 2024. Nephrotoxicity was defined as a ⩾20% decline in creatinine clearance (CKD-EPI 2021) from baseline. Statistical analyses included descriptive statistics, chi-square tests, t-tests, Kaplan–Meier survival analysis, and Cox regression models. Results: Nephrotoxicity occurred in 28 patients (23.3%). Older age (⩾65 years) and higher baseline urea and creatinine levels were significant risk factors ( p < 0.001). Paradoxically, patients who developed nephrotoxicity showed a trend toward better survival outcomes: median PFS was 30 months versus 20 months ( p = 0.188), and the 3-year OS rate was 77.9% versus 63.8% ( p = 0.801), though these differences were not statistically significant. In multivariate Cox analysis, the development of nephrotoxicity showed a trend toward a 71% reduction in mortality risk (HR = 0.293, p = 0.078), but it was not statistically significant. Conclusion: Nephrotoxicity is relatively common in patients treated with CDK4/6 inhibitors, particularly in older individuals and those with elevated baseline renal parameters. Contrary to conventional expectations, its occurrence may be associated with a trend toward improved survival, possibly reflecting higher drug exposure or effective target inhibition. These findings highlight the need for careful renal monitoring and suggest that nephrotoxicity could serve as a potential surrogate marker for treatment efficacy, warranting validation in larger prospective studies.

Background and Objectives: The Advanced Lung Cancer Inflammation Index (ALI), a composite marker integrating body mass index (BMI), serum albumin, and neutrophil-to-lymphocyte ratio (NLR), has demonstrated prognostic value in various cancers. However, its role in metastatic gastric cancer (mGC) remains unexplored. This study aimed to investigate the prognostic significance of the ALI in patients with mGC. Materials and Methods: This retrospective study included 206 patients with de novo or recurrent metastatic gastric cancer treated at Manisa Celal Bayar University between September 2009 and 2024. The ALI was calculated as “BMI × serum albumin (g/dL)/NLR”. A cut-off value of 20.8 was determined using Receiver Operating Characteristic (ROC) curve analysis. Patients were stratified into high (ALI > 20.8) and low (ALI ≤ 20.8) groups. Survival outcomes were evaluated using Kaplan–Meier analysis, and prognostic factors were examined with Cox regression models. Results: The median overall survival (OS) was significantly longer in the high-ALI group compared to the low-ALI group (11.4 months vs. 5.2 months, p < 0.001). The 1-year and 2-year OS rates were 42.9% and 11.3% for the high-ALI group, versus 11.6% and 2.1% for the low-ALI group, respectively. Multivariate Cox regression analysis confirmed that a low ALI was an independent predictor of poorer survival (HR: 2.07, 95% CI: 1.47–2.92, p < 0.001). The low-ALI group also had a higher prevalence of peritoneal metastases and a lower likelihood of receiving first- and second-line chemotherapy. Conclusions: The ALI is a strong and independent prognostic factor for survival in patients with metastatic gastric cancer. As an easily calculable and cost-effective index derived from routine parameters, it shows significant potential for risk stratification and treatment planning in clinical practice. Prospective, multi-centre studies are warranted to validate these findings.