Objectives: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening hyperinflammatory syndrome increasingly reported with immune checkpoint inhibitors (ICIs). However, comparative real-world data across different ICI classes and treatment strategies are limited. This study aimed to characterize HLH reporting patterns associated with ICIs and to compare disproportionality signals among PD-1 inhibitors, PD-L1 inhibitors, and combination regimens using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: A retrospective pharmacovigilance analysis was performed using FAERS reports submitted between 2013 and 2025. HLH-related cases were identified using core Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms. Reporting odds ratios (RORs) with 95% confidence intervals (Cis) were calculated to assess disproportionality across ICI treatment strategies, with ICI monotherapy as the reference. Restricted analyses compared PD-1 inhibitors, PD-L1 inhibitors, and ICI plus CTLA-4 inhibitor therapy. Results: A total of 733 HLH-related reports associated with ICIs were identified. The median age was 65 years (range 1–92), and 54.9% of patients were male. Lung cancer (34.4%) and melanoma (16.0%) were the most frequently reported malignancies. ICI monotherapy accounted for 34.7% of cases, while combination regimens included ICI plus chemotherapy (31.6%), ICI plus targeted therapy (17.8%), and ICI plus CTLA-4 inhibitors (15.9%). All cases were classified as serious adverse events; hospitalization occurred in 69.2% and death in 25.1%. Compared with monotherapy, combination regimens showed higher reporting odds of HLH, with the strongest signal for ICI plus targeted therapy (ROR 2.17, 95% CI 1.72–2.73). PD-1 inhibitors demonstrated higher reporting odds than PD-L1 inhibitors (ROR 1.86, 95% CI 1.41–2.46). Conclusions: This large real-world pharmacovigilance analysis demonstrates differential HLH reporting patterns across ICI classes and treatment strategies. Higher reporting odds with combination regimens and PD-1 inhibitors highlight the need for heightened clinical vigilance, particularly in combination treatment settings.

Background/Objectives: Neoadjuvant chemotherapy is the standard of care for patients with locally advanced gastric cancer. Inflammatory and nutritional indices have been proposed as potential prognostic biomarkers in this setting. This study aimed to evaluate their association with pathological response and relapse-free survival (RFS) in patients with locally advanced gastric cancer treated with the perioperative FLOT regimen. Methods: This multicenter retrospective study included 120 patients treated with perioperative FLOT between 2018 and 2022. Pathological response was assessed using the Becker regression grading system. Pretreatment inflammatory and nutritional biomarkers were calculated from baseline data. Association with pathological responses and RFS were analyzed using logistic regression, Kaplan–Meier estimates, and Cox models. Results: Pathological response was strongly associated with higher radiologic and R0 resection rates and lower recurrence (all p < 0.001). None of the biomarkers correlated significantly with pathological response. Pathological response was the strongest prognostic factor for RFS (p < 0.001), while age (p = 0.011) and histologic subtype (p = 0.004) were also independent predictors. The CEA/albumin ratio showed a trend toward significance (HR 1.805; 95% CI 0.918–3.551; p = 0.087), and patients with lower ratios had longer RFS (median not reached vs. 15.8 months, p = 0.014). Conclusions: Pathological response remains the most powerful prognostic factor in locally advanced gastric cancer treated with perioperative FLOT. Although inflammatory and nutritional indices alone may not predict treatment response, the CEA/albumin ratio demonstrates potential prognostic value for RFS. Larger prospective studies with standardized cut-off values are warranted to validate these findings and to further explore the dynamic prognostic role of immunonutritional markers.

Thrombotic Microangiopathy Associated with Etoposide in Metastatic Lung Cancer: Diagnostic and Therapeutic Challenges - Journal of Oncological Sciences

Objective: Advanced thyroid carcinoma includes biologically distinct subtypes with variable clinical behavior, and the outcomes of targeted therapy in routine practice may differ from those reported in clinical trials. This study evaluated the effectiveness and tolerability of tyrosine kinase inhibitor–based treatments in patients with advanced thyroid carcinoma treated at a single tertiary oncology center. Methods: In this retrospective single-center study, patients with advanced thyroid carcinoma who received tyrosine kinase inhibitor therapy between 2016 and 2025 were reviewed. Clinical and pathological characteristics, treatment regimens, tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events were analyzed. Survival outcomes were estimated using the Kaplan–Meier method. Results: A total of 39 patients were included: 24 with radioactive iodine-refractory (RAI) differentiated thyroid carcinoma, 10 with medullary thyroid carcinoma, and 5 with anaplastic thyroid carcinoma. Objective response rates were 62.4%, 70%, and 40%, respectively. Median progression-free survival was 24.4 months (95% CI, 18.1-30.8), 19.3 months (95% CI, 16.0-22.6), and 5.7 months (95% CI, 4.5-6.9), respectively. Median overall survival was 51.7 months (95% CI, 33.4-70.1) in differentiated carcinoma, not reached in medullary carcinoma, and 7.7 months (95% CI, 4.4-10.9) in anaplastic carcinoma. Treatment-related adverse events were observed in 79.1%, 90%, and 60% of patients, respectively. Dose reductions were required in 62.5% of patients with differentiated carcinoma and 40% of those with medullary carcinoma. Conclusion: This real-world single-center study suggests favorable disease control outcomes with tyrosine kinase inhibitor–based therapies in advanced differentiated and medullary thyroid carcinoma, whereas outcomes remained poor in anaplastic thyroid carcinoma despite targeted treatment. Although adverse events were common, they were generally manageable in routine clinical practice. Cite this article as: Evinç SJ, Birsin Z, Cebeci S, et al. Real-world outcomes of tyrosine kinase inhibitor–based therapy in advanced thyroid carcinoma: a single-center retrospective study. Cerrahpaşa Med J. 2026, 50, 0046, doi: 10.5152/cjm.2026.26046.

ObjectiveRenal adverse events associated with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have gained increasing attention in clinical practice. However, comparative real-world data regarding renal safety profiles among individual CDK4/6 inhibitors remain limited. This study aimed to characterize renal adverse event reporting associated with abemaciclib, palbociclib, and ribociclib and compare disproportionality signals among these agents using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsA retrospective pharmacovigilance analysis was conducted using FAERS reports submitted between January 2014 and March 2026. Renal adverse events were identified using Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms within the Renal and Urinary Disorders System Organ Class. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated to evaluate disproportionality signals for selected renal and electrolyte adverse events.ResultsFollowing deduplication, 14,193 reports associated with abemaciclib, 91,359 with palbociclib, and 29,488 with ribociclib were identified. Renal adverse events were reported in 898, 2,636, and 1,826 reports, respectively. Acute kidney injury was more frequently reported with abemaciclib (35.7%) and ribociclib (19.7%) than with palbociclib (12.4%) (p < 0.001). Renal impairment/failure was the most commonly reported grouped renal adverse event category. Abemaciclib demonstrated the highest reporting odds for acute kidney injury (ROR 4.06, 95% CI 3.53–4.67), followed by ribociclib (ROR 1.94, 95% CI 1.69–2.22), whereas ribociclib showed the strongest disproportionality signals for decreased glomerular filtration rate, hypocalcemia, creatinine increased, hyponatremia, and hypokalemia. Overall, 65.6% of reports were serious and hospitalization occurred in 32.5% of cases.ConclusionThis large-scale pharmacovigilance analysis identified substantial differences in renal adverse event reporting patterns among CDK4/6 inhibitors. Abemaciclib was more frequently associated with acute kidney injury and adverse events suggestive of intrinsic renal injury, whereas ribociclib demonstrated stronger signals for laboratory indicators of renal dysfunction and electrolyte abnormalities. Although spontaneous reporting data cannot establish causality or estimate incidence, these findings suggest heterogeneous renal adverse event profiles among CDK4/6 inhibitors and support careful renal monitoring during treatment.

Background/Objectives: Outcomes after perioperative FLOT for gastric and gastroesophageal junction adenocarcinoma remain variable, even among patients treated with curative intent. Although postoperative pathological findings are central to risk assessment, they do not fully capture patient-related factors that may influence recovery, treatment completion, and survival. This multicenter study evaluated routinely available clinical, laboratory, and pathological variables and assessed whether integrating these variables could improve postoperative prognostic stratification. Methods: We retrospectively analyzed 173 patients with locally advanced gastric or gastroesophageal junction adenocarcinoma treated with perioperative FLOT across seven oncology centers in Türkiye. Overall survival (OS) was the primary endpoint. Baseline inflammatory/nutritional status, pretreatment carcinoembryonic antigen (CEA), postoperative nodal status, and comorbidity burden were assessed. An exploratory modified FLOT Prognostic Score (mFPS) was constructed by assigning one point each for high inflammatory/nutritional risk, elevated CEA, ypN-positive disease, and age-adjusted Charlson Comorbidity Index ≥ 5. Results: At a median follow-up of 39.7 months, median OS was 41.4 months, with estimated 2-year and 5-year OS rates of 69% and 44%, respectively. Surgery was performed in 164 patients, and 83 patients completed planned adjuvant chemotherapy. In multivariable analysis, ypN-positive disease, higher comorbidity burden, and high inflammatory/nutritional risk were independently associated with shorter OS. Among the 126 patients with complete data available for all score components, the mFPS stratified patients into groups with significantly different outcomes: median overall survival was not reached in the low-risk group, compared with 56.1 months in the intermediate-risk group and 18.7 months in the high-risk group. Conclusions: Survival after perioperative FLOT was not determined by residual disease burden alone. Integrating postoperative nodal status with baseline host-related factors may help identify patients at increased risk of adverse outcomes following curative-intent treatment. The proposed score should be considered exploratory and requires external validation before clinical application.