Mustafa Ersoy

Background: Prognostic biomarkers for risk stratification remain limited in de novo metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen receptor pathway inhibitors (ARPIs). We evaluated baseline serum 25-hydroxyvitamin D [25(OH)D] and developed and externally validated a progression-free survival (PFS) model. Methods: This multicenter retrospective study included 273 patients initiating ARPI-based therapy between January 2021 and April 2026. Etlik City Hospital formed the training cohort (n = 192; 85 PFS events), and Gazi University and Kütahya City Hospital formed the external validation cohort (n = 81; 27 PFS events). LASSO-penalized Cox regression retained age, ISUP grade group, CHAARTED disease volume, log-transformed PSA, and hemoglobin. Model B added continuous 25(OH)D. Internal validation used 1000 bootstrap resamples. Performance was assessed by the Harrell C-index, time-dependent AUC, and calibration at 1 and 2 years. PFS was the primary endpoint; overall survival analyses were exploratory. The study was not prospectively registered. Results: Higher baseline 25(OH)D was associated with longer PFS in Model B (HR per 10-ng/mL increase, 0.64; 95% CI, 0.49-0.83; P < .001). Adding 25(OH)D improved model fit (likelihood-ratio χ² = 12.71; P < .001) and increased apparent C-index from 0.712 to 0.740. In external validation, C-indices were 0.71 (95% CI, 0.64-0.78) and 0.76 (95% CI, 0.69-0.83), respectively (Δ = 0.05; 95% CI, 0.01-0.10). Conclusions: Baseline 25(OH)D added modest prognostic information beyond clinical factors, with supportive external validation. These findings do not establish treatment-predictive utility or benefit from vitamin D supplementation. Prospective validation is needed before clinical implementation.

Nivolumab is currently widely used in the treatment of lung cancer. Studies have been conducted using flat doses of 240 mg and 3 mg/kg. In fact, studies involving a small number of patients have begun to explore low-dose immunotherapies. The literature on the optimal dose of immunotherapy, the use of weight based, or fixed doses is very recent and has become a one of the subject of ongoing research. This multicenter study included 716 patients with NSCLC. Patients receiving standard doses of 3 mg/kg and 240 mg of nivolumab were divided into subgroups based on their weight. Patients weighing 80 kg have already received a flat dose. However, patients weighing < 80 kg who received a flat dose were considered to be receiving high-dose therapy. Conversely, patients weighing more than 80 kg who received a flat dose were maintained on a low dose. Therefore, overall survival, progression-free survival, and toxicity were examined according to weight-based usage. The median progression free survival (PFS) for those receiving a 3 mg/kg dose was 6 months, whereas it was 9.8 months for those receiving a flat dose (p < 0.001). The median (metastatic overall survival) OS for those receiving a 3 mg/kg dose was 12 months, whereas it was 14 months for those receiving a 240 mg dose (p = 0.03). This study was based on real-world data. Therefore, our results may be instructive regarding the nivolumab dose, which is a commonly used treatment for NSCLC patients. Our results suggest that a flat dose may be preferred in all groups and as a subgroup, especially in patients weighing < 80 kg.

Immune checkpoint inhibitors such as nivolumab have brought meaningful benefits to patients with advanced non-small cell lung cancer (NSCLC), yet many patients still experience limited responses. Vitamin D is a key modulator of immune function, and deficiency is common in individuals with cancer. Given its potential role in shaping immunotherapy response, we retrospectively assessed whether baseline vitamin D levels were associated with clinical outcomes in advanced NSCLC patients treated with nivolumab. We retrospectively analyzed patients with stage IV NSCLC treated with nivolumab across multiple centers, predominantly as second-line therapy. Prior to nivolumab initiation, all patients were confirmed to be negative for common driver mutations, including EGFR, ALK, ROS1, and other actionable genomic alterations. Baseline serum 25-hydroxyvitamin D levels were measured prior to nivolumab initiation, and patients were categorized as having severe deficiency (< 10 ng/mL), deficiency (10–20 ng/mL), or sufficient levels (≥ 20 ng/mL). The presence of liver metastases was recorded at baseline. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards models adjusted for age, sex, ECOG performance status, liver metastasis, and other metastatic sites were used to evaluate the independent prognostic value of vitamin D status. Objective response rates (ORR) were assessed in patients with available radiologic data. A total of 890 patients were screened, and after excluding those with missing baseline vitamin D data, 305 patients were included in the analysis. The median age was 64 years (range 34–85), and 68% of patients were male. Vitamin D levels were < 10 ng/mL in 30%, 10–20 ng/mL in 44%, and ≥ 20 ng/mL in 26% of patients. Patients with severe vitamin D deficiency were numerically older (median age 65 vs. 63 years) and had higher rates of ECOG PS ≥ 2 (15.1% vs. 7.5%) and squamous histology (37.6% vs. 27.5%), though these differences were not statistically significant (p > 0.05 for all). Liver metastases were present in 54 patients (17.7%), and the distribution was similar across vitamin D groups (p = 0.92). Median PFS was shortest in patients with severe vitamin D deficiency (3.4 months), intermediate in the 10–20 ng/mL group (5.2 months), and longest in patients with sufficient levels (8.1 months). Median OS ranged from 8.6 months in the < 10 ng/mL group to 15.8 months in the ≥ 20 ng/mL group. Patients with liver metastases had significantly shorter OS compared to those without (median OS 9.8 vs. 13.6 months, HR 1.48, p = 0.006). Vitamin D deficiency was associated with significantly worse PFS and OS on univariate analysis. In multivariable analysis, vitamin D levels < 20 ng/mL remained independently associated with poorer OS. ORR was numerically higher in patients with sufficient vitamin D levels (30% vs. 14%). Lower baseline vitamin D levels were associated with inferior clinical outcomes in advanced NSCLC patients treated with nivolumab. Patients with vitamin D levels ≥ 20 ng/mL demonstrated longer PFS and OS and a trend toward higher response rates. These findings support a prognostic role for vitamin D status in immunotherapy-treated NSCLC; however, prospective studies are required to determine whether vitamin D optimization can causally enhance immunotherapy efficacy.

Background: Immune checkpoint inhibitors (ICIs) such as nivolumab have transformed the treatment landscape of metastatic non-small cell lung cancer (NSCLC). We aimed to evaluate survival outcomes of patients who developed immune-related adverse events (irAEs) that required permanent treatment discontinuation. Methods: This national, multicenter study included 25 patients with metastatic NSCLC from four tertiary oncology centers in Turkey. All patients received nivolumab monotherapy and discontinued treatment because of irAEs. Long-term survival was analyzed using Kaplan–Meier methods and compared indirectly with historical benchmarks. Results: The median overall survival (OS) was 35.73 months (95% CI: 30.06–41.40). The 2-year and 5-year OS rates were 78.9% and 27.0%, respectively. Median progression-free survival (PFS) was 16.23 months. Pneumonitis was the most frequent irAE (48%). Liver metastases significantly reduced OS (23.93 vs. 38.50 months, p = 0.005). In univariate analysis, ECOG 2 status (HR:22.07), bone metastases (HR:3.52), and subsequent systemic therapy (HR:30.19) weresignificant predictors of progression. Conclusions: Patients with metastatic NSCLC who discontinue nivolumab due to irAEs achieve notable survival outcomes, suggesting that treatment-limiting toxicity may signal a robust and durable antitumor immune response. These findings, though limited by a small cohort, highlight a distinct responder phenotype in real-world clinical practice.

This study aims to evaluate the effectiveness and real-world applicability of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC), focusing on pathological complete response (pCR) and disease-free survival (DFS) across different chemotherapy regimens. In this multicenter retrospective study, patients treated between January 2019 and January 2023, 437 patients with locally advanced rectal cancer who underwent total neoadjuvant therapy followed by surgery were analyzed. Standard fluoropyrimidine-based chemotherapy regimens (CAPOX, FOLFOX, or FOLFIRINOX) were used according to institutional practice, and long-course chemoradiotherapy constituted the predominant radiotherapy approach. Patients were grouped based on chemotherapy sequencing as induction, consolidation, or sandwich regimens. Outcomes were evaluated using multivariable logistic regression for pathological complete response and Kaplan–Meier analysis with Cox proportional-hazards modeling for disease-free survival. The median follow-up duration was 66 months. The overall pCR rate was 26.3% (n = 115). pCR rates did not differ significantly between induction, sandwich, and consolidation chemotherapy regimens. A longer interval (> 8 weeks) between radiotherapy and surgery was associated with a higher likelihood of achieving pCR. In contrast, cT4 disease and baseline CEA levels > 3 ng/mL were associated with lower pCR rates.The estimated 3-year disease-free survival (DFS) rate was 83.8%. Recurrence rates within 3 years were numerically higher in patients receiving induction and sandwich regimens compared with consolidation chemotherapy, although these differences did not reach statistical significance. In multivariable analysis, poor tumor regression grade, ypT4 stage, ypN + disease, and post-TNT CEA ≥ 3 ng/mL were independently associated with an increased risk of recurrence. TNT is effective and feasible in real-world settings, achieving pCR and DFS outcomes comparable to clinical trials. No statistically significant differences were observed in pCR or recurrence rates between induction, consolidation, and sandwich chemotherapy regimens. Prospective phase III trials are needed to compare DFS and OS outcomes across these treatment strategies. The online version contains supplementary material available at 10.1007/s12672-026-04842-3.

Hormone receptor-positive, HER2-negative breast cancer represents a significant subset of patients who often exhibit suboptimal responses to neoadjuvant chemotherapy (NACT). Identifying strategies to enhance chemosensitivity in this population is a clinical priority. In this study, we investigated the potential contribution of statin therapy to the efficacy of NACT. We retrospectively analyzed 60 patients treated between 2014 and 2025, comprising 22 statin users and 38 non-users. While the overall cohort analysis did not demonstrate a statistically significant difference in pCR rates, an exploratory postmenopausal subgroup analysis (performed because all statin users were postmenopausal) showed a higher pCR rate among statin users; this finding is hypothesis-generating and should be interpreted cautiously (31.8 vs. 5.0%, p = 0.047). In an exploratory multivariable logistic regression analysis limited by sparse events in the postmenopausal subgroup, statin use was associated with pCR after adjustment for Ki-67 proliferation index and clinical T stage; however, the estimate was imprecise and should be interpreted cautiously. Although pCR is not a validated surrogate for long-term survival in this specific subtype, our findings suggest that statins may biologically enhance short-term chemosensitivity, potentially through mevalonate pathway inhibition and modulation of the tumor microenvironment. These preliminary results support the need for larger prospective studies to further elucidate the role of statins as adjunctive agents in breast cancer management.

Aims: The aim of this study was to compare treatment adherence in cancer patients who received infusional 5-fluorouracil or capecitabine and did not experience grade 2 or higher adverse events, demonstrating that, in addition to factors such as efficacy and toxicity profile evaluated in oncology studies, adherence is also an important consideration for clinicians regarding patient outcomes.Methods: This was a retrospective cohort study conducted at a single center. The study enrolled 61 cancer patients who received either intravenous 5-fluorouracil or oral capecitabine at the Kütahya Health Sciences University Evliya Çelebi Education and Research Hospital and Kütahya City Hospital between 2021 and 2025. Treatment adherence was compared by evaluating whether patients received the intended dose of capecitabine or 5-fluorouracil.Results: Our study found that 14 out of 30 patients receiving capecitabine were non-adherent to treatment, while 7 out of 31 patients in the 5-fluorouracil group were non-adherent. A statistically significant degree of non-adherence was observed in the capecitabine group.Conclusion: Capecitabine is an effective and well-tolerated treatment, but its oral administration at home means that patient adherence is of utmost importance. Clinicians must pay the highest level of attention to patient adherence to ensure the efficacy of capecitabine treatment.

PURPOSE: Early-onset gastrointestinal cancers are concerning entities globally, yet early-onset biliary tract cancers (EOBTCs) are understudied. Early-stage disease is crucial for young patients' survival. METHODS: TOG/GI-SAFRADJU (ClinicalTrials.gov identifier: NCT06975917 ) is a multicenter, hospital-based, registry initiative of the Turkish Oncology Group, including patients with resected BTCs. Early-onset was defined as a diagnosis at age v 25.7%, P = .038). Adjuvant treatments did not differ between EOBTC and non-EOBTC. Among patients who received adjuvant chemotherapy, RFS (13.9 months [95% CI, 11.4 to 22.1] v 15.9 months [95% CI, 13.6 to 18.9], P = .947) and OS (35.6 months [95% CI, 28.0 to 81.4] v 31.3 months [95% CI, 27.8 to 44.3], P = .670) were similar between EOBTC and non-EOBTC groups. Among patients with EOBTC, R1-resection and high CA19-9 levels were associated with shorter RFS, and gallbladder localization and high CA19-9 were associated with shorter OS in adjusted analyses. Using these factors, risk scores early-stage EOBTC RFS score (EOB-RS) for RFS and early-stage EOBTC OS score (EOB-OS) for OS were formed, each including three ranks. Both scores significantly ordered the prognosis of patients with EOBTC (EOB-RS, [0 points]: 22.7 months, [1 or 2]: 10.3 months, [3]: 5.7 months, P < .001, EOB-OS: [0]: 110.9 months, [1 or 2]: 29.6 months, [3]: 10.1 months, P < .001). CONCLUSION: Resected EOBTC patients showed survival comparable to older counterparts receiving surgery/adjuvant therapy. This study suggests a potential risk scoring system for early-stage EOBTC, pending validation.

Aims: This study aimed to investigate whether the efficacy of neoadjuvant chemotherapy differs between HER2-low and HER2-zero subgroups in hormone receptor–positive, HER2-negative breast cancer. Materials and Methods: A total of 61 patients who received neoadjuvant chemotherapy between 2015 and 2025 were retrospectively analyzed. HER2 status was determined from pre-treatment core biopsy specimens and classified as HER2-low (IHC 1 + or 2 + and FISH-negative) or HER2-zero (IHC 0). The pathological complete response (pCR) rates were compared between the two groups. Results: Among 61 patients, 28 had HER2-low and 33 had HER2-zero tumors. The pCR rate was 7.1% in the HER2-low group and 27.3% in the HER2-zero group (p = 0.042). A post-hoc power analysis based on these results showed a moderate power (0.59) to detect the observed difference. Conclusions: HER2-low expression may negatively influence chemosensitivity in hormone receptor–positive breast cancer treated with neoadjuvant chemotherapy. Further studies are warranted to evaluate the potential role of trastuzumab deruxtecan (T-DXd) and other antibody–drug conjugates in this newly defined subgroup.