Aim: Adult granulosa cell tumors (AGCTs) are rare estrogen-producing ovarian neoplasms that typically exhibit a prolonged clinical course and late recurrences. Investigating dry eye disease (DED) in this patient population is essential, as AGCT-related hormonal alterations and therapeutic interventions may affect ocular health. This study aimed to determine the prevalence of DED among patients with AGCT and to assess its associations with age, menopausal status, clinicopathological features, comorbidities, and oncologic treatments.Materials and Methods: This retrospective, single-center study evaluated 55 patients with histopathologically confirmed AGCT diagnosed between 2012 and 2024. DED was identified based on ophthalmology consultation records, documented ocular symptoms, and objective testing, including Schirmer test results (≤5 mm/5 min). Associations among clinicopathological parameters, menopausal status, adjuvant treatments, comorbidities, and DED were assessed using univariate and multivariate logistic regression analyses, conducted with SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA).Results: DED was detected in 23.6% (n=13) of patients. Patients with DED were older at diagnosis in unadjusted comparisons (mean 55.2 vs. 48.6 years); however, age was not independently associated with DED in logistic regression analyses. In univariate analyses, no statistically significant associations were observed between DED and menopausal status, ER or inhibin expression, FIGO stage, endometrial pathology, recurrence, or type of adjuvant therapy. In the multivariable logistic regression model, comorbidity (OR 1.696; 95% CI, 0.809–3.554; p=0.162) and tumor size >10 cm (OR 2.375; 95% CI, 0.648–8.708; p=0.192) showed non-significant trends toward higher odds of DED. In descriptive comparisons, patients who received paclitaxel-based therapy had a numerically higher prevalence of DED, although this difference was not statistically significant.Conclusions: Dry eye disease should be actively considered in patients with adult granulosa cell tumors, especially among older adults, individuals with comorbidities, and those receiving taxane-based therapy. Integrating brief ocular surface screening into standard oncologic follow-up could facilitate the identification of underrecognized symptoms and enhance patient comfort and quality of life.

Background and Objectives: Neoadjuvant dual HER2 blockade combined with chemotherapy is the standard treatment approach for patients with high-risk early-stage or locally advanced HER2-positive breast cancer. However, the optimal chemotherapy backbone and the predictive value of systemic inflammatory biomarkers remain subjects of ongoing investigation. This study aimed to compare pathologic complete response (pCR) rates between neoadjuvant dose-dense doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab and pertuzumab (ddAC+THP) and docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), and to evaluate the predictive performance of pretreatment inflammatory biomarkers. Materials and Methods: In this multicenter retrospective study, patients with HER2-positive breast cancer treated with neoadjuvant ddAC+THP or TCHP between 2019 and 2025 at three tertiary centers were evaluated. Pretreatment inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, were calculated from baseline laboratory parameters. Receiver operating characteristic analyses were performed to determine optimal cutoff values, and logistic regression analyses were used to identify predictors of pCR. Results: A total of 197 patients were included, of whom 138 received ddAC+THP and 59 received TCHP. Overall, 125 patients (63.5%) achieved pCR. The pCR rate was numerically higher in the ddAC+THP group than in the TCHP group (65.2% vs. 59.3%), although the difference was not statistically significant (p = 0.431). Among the evaluated biomarkers, SIRI demonstrated the highest discriminatory performance for predicting pCR (AUC: 0.725, 95% CI: 0.652–0.797), followed by NLR (AUC: 0.673, 95% CI: 0.595–0.750). In multivariable analysis, hormone receptor positivity (OR: 0.291, 95% CI: 0.131–0.645; p = 0.002) and elevated SIRI (>0.845) (OR: 0.088, 95% CI: 0.036–0.216; p < 0.001) were independently associated with lower odds of achieving pCR. No significant difference in pCR was observed between treatment regimens across predefined subgroup analyses. Conclusions: Neoadjuvant ddAC+THP and TCHP achieved comparable pCR outcomes in patients with HER2-positive breast cancer. SIRI was independently associated with a lower likelihood of achieving pCR and showed acceptable discriminatory performance. These findings suggest that SIRI may represent an exploratory, readily available inflammatory biomarker for pCR risk stratification; however, prospective validation is required before clinical application.

Background/Objectives: Histologic regression in primary cutaneous melanoma has shown inconsistent prognostic associations, and its relevance to immune checkpoint inhibitor (ICI) outcomes in patients who later develop recurrent or metastatic disease remains unclear. Methods: This retrospective single-center cohort included 81 patients with resected stage I–III cutaneous melanoma who later developed recurrent or metastatic disease and received ICIs. Histologic regression was classified as present or absent based on primary pathology reports. Objective response rate (ORR) and disease control rate (DCR) were assessed according to RECIST v1.1. Progression-free survival (PFS) and overall survival (OS) from ICI initiation were estimated using Kaplan–Meier analysis and evaluated with prespecified multivariable Cox models. Results: Histologic regression was identified in 24 patients (29.6%). Baseline characteristics were largely comparable between groups, although regression was more frequent in male patients (83.3% vs 59.6%; p = 0.039). ORR was numerically higher in the regression-present group (58.3% vs 43.9%; p = 0.330), and DCR was also higher (87.5% vs 66.7%; p = 0.061). Median PFS was significantly longer in patients with regression (39.3 vs 17.8 months; log-rank p = 0.044). In multivariable analysis, regression remained independently associated with longer PFS (adjusted HR, 0.43; 95% CI, 0.19–0.94; p = 0.035), whereas no independent association with OS was observed (adjusted HR, 0.54; 95% CI, 0.28–1.06; p = 0.071). Conclusions: In patients with recurrent or metastatic melanoma treated with ICIs, primary tumor histologic regression was independently associated with prolonged PFS but not OS. These findings suggest a potential link between regression and early immune-mediated disease control, while its impact on long-term survival remains uncertain.

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.