Objective: CDK4/6 inhibitors are the standard first-line treatment for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). However, treatment response shows heterogeneity among patients. The objective of this multicentre, retrospective study is to investigate real-world parameters affecting overall survival (OS) in patients receiving CDK4/6 inhibitor therapy, particularly the effect of high oestrogen receptor (ER) expression (≥90%). Methods: A total of 603 HR-positive/HER2-negative MMK patients treated with a CDK4/6 inhibitor (ribociclib or palbociclib) from five centres were retrospectively reviewed. Age, menopausal status, metastatic status, metastatic sites, pathological subtype, HER2 status (low/negative), ER expression level (< 90% vs ≥90%), progesterone receptor (PR) status, and prior endocrine therapy (ET) or chemotherapy (CT) before CDK4/6 inhibitor were evaluated for their impact on OS using univariate and multivariate Cox regression analyses. Results: In the univariate analysis, OS was significantly longer in patients who did not receive ET prior to CDK4/6 inhibitor treatment (median OS: 51.0 months vs. 33.3 months; p< 0.01). OS was also better in patients without liver metastases (50.0 months vs. 34.0 months; p=0.019), those with bone metastases only (57.7 months vs. 40.5 months; p=0.022), and PR-positive patients (50.0 months vs. 36.0 months; p=0.037) also had better OS. OS was numerically longer in patients with ER expression ≥90% compared to those with < 90% (49.0 months vs. 41.0 months; p=0.072). In multivariate analysis, not having received ET prior to CDK4/6 inhibitor therapy (p=0.045) and high ER expression (≥90%) (p=0.031) were independently associated with better OS. Conclusion: Our study demonstrates that HR-positive/HER2-negative MBC patients who are naive to endocrine therapy prior to CDK4/6 inhibitor treatment and have high ER expression (≥90%) in their tumours derive greater OS benefit from this treatment. The ER expression level threshold of ≥90% may be proposed as a potential biomarker for predicting response to CDK4/6 inhibitor therapy. These findings necessitate further prospective studies to improve patient selection.

Background/Objectives: Claudin-18.2 (CLDN18.2) has recently emerged as a therapeutic target in gastric cancer; however, its prognostic relevance in the neoadjuvant setting remains insufficiently defined. We evaluated the clinical significance of CLDN18.2 and fibroblast growth factor receptor 2b (FGFR2b) expression in patients with locally advanced gastric cancer treated with neoadjuvant therapy. Methods: This retrospective single-center study included 64 patients with locally advanced gastric cancer who received neoadjuvant chemotherapy followed by curative surgery. Pretreatment endoscopic biopsy specimens were analyzed using immunohistochemistry to assess CLDN18.2 and FGFR2b expression. Survival outcomes were evaluated using Kaplan–Meier analysis and Cox proportional hazards regression models. Results: CLDN18.2 positivity was detected in 29.7% of patients and was not associated with baseline clinicopathological characteristics or pathological treatment response. However, CLDN18.2-positive tumors demonstrated significantly shorter relapse-free survival (median 19.0 vs. 36.6 months, p = 0.038) and overall survival (median 28.9 vs. 53.4 months, p = 0.005). In multivariable analysis, CLDN18.2 positivity remained an independent predictor of relapse-free survival. FGFR2b positivity was observed in 14.1% of patients and was evaluated descriptively due to limited case numbers. Conclusions: CLDN18.2 expression may represent a clinically relevant prognostic biomarker reflecting aggressive tumor biology in locally advanced gastric cancer treated with neoadjuvant therapy.

Tiroid Kanserlerinde Epidemiyoloji Emine Bihter ENİSELER Tiroid Kanserlerinde Patoloji Zübeyde YILDIRIM Tiroid Kanserlerinde Radyolojik Tanı Yontemleri Bartu ÇETİN Tiroid Nodullerine Klinik Yaklaşım Mustafa DEMİRPENCE Tiroid Kanserlerinde Cerrahi Seda BAŞTÜRK Diferansiye Tiroid Karsinomlarında Radyoaktif İyot Tedavisi Selda YILMAZ TATAR Tiroid Kanserlerine Genel Bakış Mehmet Alper YILMAZ Papiller Tiroid Kanseri Emir Gökhan KAHRAMAN Folikuler Tiroid Kanseri Emir Gökhan KAHRAMAN Tiroid Onkositik Karsinomu Gürkan GÜL Meduller Tiroid Kanseri Gürkan GÜL Anaplastik Tiroid Kanseri Kıvanç MERCAN Herediter Non-Meduller Tiroid Kanserleri Kıvanç MERCAN Tiroid Kanserlerinde Radyoterapi Endikasyonları Fatma SERT Tiroid Kanserlerinde İzlem Selda YILMAZ TATAR

Background: Platinum resistance remains a major therapeutic challenge in epithelial ovarian cancer (EOC). The tumour–stroma ratio (TSR) has emerged as a potential histopathological marker of tumour biology, but its clinical significance in different clinical settings remains unclear. We evaluated the association between stromal proportion, assessed using the TSR methodology, platinum resistance, and survival outcomes in patients undergoing primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT+IDS). Methods: This retrospective study included 83 patients with epithelial ovarian cancer (EOC) who underwent either primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT+IDS) between 2017 and 2024. Patients were analysed separately according to treatment strategy. Stromal proportion was assessed on primary surgical specimens in the PDS cohort and on pretreatment diagnostic biopsy specimens in the NACT+IDS cohort. For this retrospective analysis, platinum resistance was operationally defined as recurrence within six months after completion of first-line platinum-based chemotherapy. Survival outcomes were analysed using the Kaplan–Meier method, and univariable binary logistic regression was performed separately within the PDS and NACT+IDS cohorts to explore the association between stromal category and platinum resistance. Results: Platinum resistance occurred in 25.3% of patients. In the PDS cohort, stromal category was not associated with clinicopathological characteristics, platinum resistance, disease-free survival (DFS), or overall survival (OS). In the NACT+IDS cohort, patients in the stroma-high group had a numerically higher rate of platinum resistance than those in the stroma-low group (57.9% vs. 22.2%; Fisher’s exact p = 0.114). Based on univariable logistic regression analysis, the stroma-high group had higher estimated odds of platinum resistance (OR 4.81, 95% CI 0.78–29.40), although this finding did not reach statistical significance (p = 0.090). No significant association was observed between stromal category and survival outcomes in either cohort. Conclusions: In the NACT+IDS cohort, patients in the stroma-high group had a numerically higher rate of platinum resistance than those in the stroma-low group; however, this difference did not reach statistical significance. These results should be interpreted with caution due to the retrospective study design and limited sample size; however, they nonetheless support further investigation of pretreatment TSR as a simple and easily applicable histopathological parameter in EOC. Larger prospective multicentre studies are required to determine whether this exploratory signal is reproducible and clinically relevant.

Background: HR (hormone receptor)-positive, HER2 (Human Epidermal Growth Factor Receptor 2)-negative metastatic breast cancer represents the majority of advanced breast cancer cases. Although CDK4/6 (cyclin-dependent kinase) inhibitors combined with endocrine therapy have become the standard first-line approach, the optimal treatment strategy after disease progression remains unclear. Methods: We conducted a multicenter retrospective study of 218 patients treated across five tertiary oncology centers in Turkey who progressed on CDK4/6 inhibitors and subsequently received either endocrine therapy (ET) or chemotherapy (CT). Results: Endocrine therapy, administered in 65 patients—most commonly with everolimus-based combinations—was associated with a significantly longer overall survival (OS) compared with CT (18.0 vs 10.0 months, p = 0.011). While progression-free survival (PFS) showed a numerical advantage for ET (6.0 vs 4.9 months), the difference did not reach statistical significance. Multivariate analysis confirmed both treatment type and de novo metastatic presentation as independent predictors of survival. Conclusion: These findings demonstrate that, in real-world clinical practice, continued endocrine therapy beyond CDK4/6 inhibitors progression yields superior survival compared to chemotherapy, particularly in patients with de novo metastatic disease. Our results support the prioritization of endocrine-based approaches over chemotherapy in this setting and underscore the urgent need for prospective trials to refine treatment sequencing strategies for this large patient population. Plain Language Summary: Hormone receptor-positive, HER2-negative metastatic breast cancer is the most common subtype of advanced breast cancer, yet the best treatment strategy after progression on CDK4/6 inhibitors remains uncertain. Many patients are switched directly to chemotherapy, which is often associated with limited benefit and significant toxicity. In this large multicenter study from Turkey, we compared endocrine therapy with chemotherapy in women whose disease progressed after CDK4/6 inhibitors. We found that patients who continued endocrine therapy, particularly with mTOR-based combinations, lived significantly longer than those who received chemotherapy. Importantly, patients who presented with de novo metastatic disease also had better survival. These findings highlight that chemotherapy may not always be the best option after CDK4/6 inhibitor failure and support the continued use of endocrine-based strategies. Our results provide real-world evidence that could influence clinical decision-making and guide the design of future prospective trials.

Background/Objectives: Pathological response after neoadjuvant chemotherapy is an established prognostic factor in locally advanced gastric cancer, but it does not fully reflect the biological heterogeneity of residual disease. The immune microenvironment may provide additional prognostic information. We therefore investigated the relationship between post-neoadjuvant Immunoscore, pathological findings, and disease-free survival in patients with microsatellite-stable locally advanced gastric cancer. Methods: This retrospective, single-center study included patients with locally advanced gastric adenocarcinoma who received four cycles of neoadjuvant FLOT followed by curative-intent gastrectomy between November 2023 and May 2025. Immunoscore was determined in post-neoadjuvant resection specimens based on CD3⁺ and CD8⁺ T-cell infiltration in the tumor center and invasive margin. Immunoscore assessments were performed by two pathologists blinded to clinical and outcome data, with final evaluations established through consensus review. Associations between Immunoscore and clinicopathological features were examined, including exploratory multivariable analyses adjusting for baseline clinical T stage and histological subtype. Disease-free survival was analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results: The final analysis included 48 patients. Compared with the low-Immunoscore group, the high-Immunoscore group had lower rates of ypT4 disease (37.5% vs. 75.0%; p = 0.014), ypN3 disease (21.9% vs. 68.8%; p = 0.002), and perineural invasion (43.8% vs. 75.0%; p = 0.041). The association between low Immunoscore and ypN3 disease persisted after adjustment for baseline clinical T stage and histological subtype (adjusted OR 5.89, 95% CI 1.32–26.23; p = 0.020). Tumor regression grade did not differ significantly between the groups (p = 0.211). During a median follow-up of 18.0 months, 17 patients developed recurrence. Disease-free survival was numerically longer in the high-Immunoscore group. The difference was not significant by the log-rank test (p = 0.100), whereas an exploratory Breslow analysis showed a difference between the survival distributions (p = 0.025). However, Cox regression did not demonstrate a statistically significant association with disease-free survival (HR 0.47, 95% CI 0.18–1.21; p = 0.117). Conclusions: A higher post-neoadjuvant Immunoscore was associated with less advanced residual tumor and nodal disease and less frequent perineural invasion, without a statistically significant association with tumor regression grade or disease-free survival in the primary analyses. Immunoscore may therefore complement conventional pathological assessment after neoadjuvant FLOT. These findings require validation in larger prospective cohorts.