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    Are they all the same? Different effects of opioid types on survival in metastatic NSCLC receiving nivolumab
    (E-Century Publishing Corp, 2025) Balcik, Onur Yazdan; Beypinar, Ismail; Urvay, Semiha; Urun, Muslih; Ercek, Berrak; Yildiz, Canan; Araz, Murat
    The aim of this study was to evaluate the effects of concurrent opioid analgesic (OA) use and types of OA on progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC) patients receiving nivolumab. This observational, retrospective study included patients with pathologically confirmed, driver mutations negative metastatic NSCLC at five different hospitals in Turkey between 2018 and 2024. A total of 209 patients were included in this study. Of these patients, 113 (54.1%) used OA. 86 (41.1%) patients were using tramadol, and 48 (23.4%) were using fentanyl. The median survival of the group without OA was significant in the univariate analysis compared to that of the group with OA PFS (7 vs. 4 months, P = 0.006) an OS (8 vs. 14 months, P = 0.003). The group with bone metastases had worse OS than the group without bone metastases [7 vs. 15 months, HR (95% CI) = 1.810 (1.064-3.079), (P = 0.029)]. In the group without bone metastases, patients on tramadol had worse PFS than patients not on tramadol [5 vs. 8 months, HR (95% CI) = 2.260 (1.097-4.655), (P = 0.027)]. In conclusion, OA use was associated with poor PFS and OS. Fentanyl use led to worse OS in the group with bone metastases, whereas tramadol use led to worse PFS in the group without bone metastases. The prognostic impact of OA may differ according to the site of metastasis; therefore, prospective studies that include the type of OA are needed.
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    CEA and CA 19-9 combined tumor marker index as a prognostic tool for metastatic pancreatic cancer: is two better than one?
    (E-Century Publishing Corp, 2025) Demir, Bilgin; Alemdar, Merve Biyikli; Balcik, Onur Yazdan
    Metastatic pancreatic cancer (PC) is one of the cancers with the worst prognosis, and prognostic tests are lacking in this population. If an effective prognostic indicator can be identified, the patient population can be monitored more closely. This retrospective study aimed to investigate the prognostic impact of tumor marker index (TMI) in patients with metastatic PC. Patients diagnosed with metastatic PC at Ayd & imath;n Adnan Menderes University between 2019 and 2024 were included in the study. Demographic data, tumor marker levels, and treatment received were recorded. The prognostic value of TMI was determined as 3.15 using the receiver operating characteristic (ROC) method. Progression-free survival (PFS) and overall survival (OS) were recorded. 218 metastatic PC patients with a median follow-up duration of 10.81 months were included in the study. The median PFS was 7.26 months for the High TMI group, while it was 10.76 months for the Low TMI group (P=0.003). The median OS of patients with high TMI was 9.3 months, which was significantly lower than the 17.9 months observed in the low TMI group (P<0.001). TMI is a simple and, cost-effective prognostic tool for metastatic PC, and a higher TMI is associated with poorer survival outcomes.
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    Efficacy and safety of omitting 5-fluorouracil bolus in combination chemotherapy regimens for gastrointestinal cancers: a systematic review and meta-analysis
    (Taylor & Francis Ltd, 2025) Ilhan, Yusuf; Balcik, Onur Yazdan; Sahin, Elif; Merc Cetinkaya, Aysegul; Almuradova, Elvina; Bardakci, Murat; Dinckal, Cigdem
    IntroductionThis meta-analysis aimed to evaluate the impact of omitting the 5-FU bolus in chemotherapy regimens for gastrointestinal cancers on treatment efficacy and toxicity.MethodsWe searched major databases and congress proceedings until 25 October 2024 to identify studies comparing 5-FU bolus and non-5-FU bolus regimens in patients with gastrointestinal cancers. The studies included those reporting on progression-free survival (PFS), overall survival (OS), and adverse events in metastatic gastrointestinal cancer patients.ResultsThe analysis included 7 studies with 12,698 patients. No significant differences in PFS (HR: 0.94, 95% CI: 0.83-1.07) or OS (HR: 0.96, 95% CI: 0.89-1.03) were found between the 5-FU bolus and non-bolus groups. However, significantly higher rates of grade 3-4 neutropenia (OR: 0.46, 95% CI: 0.37-0.57) and any grade thrombocytopenia (OR: 0.53, 95% CI: 0.35-0.80) were observed in the 5-FU bolus group. No significant differences were found for other toxicities like febrile neutropenia, diarrhea, or nausea.ConclusionsThis meta-analysis demonstrates that the omission of 5-FU bolus from the commonly used 5-FU-based chemotherapy regimens in gastrointestinal cancers, with the use of only 5-FU infusion, may reduce the risk of hematologic toxicities such as neutropenia and thrombocytopenia without affecting survival outcomes in metastatic gastrointestinal cancers.Protocol registrationwww.crd.york.ac.uk/prospero identifier is CRD42024602968.
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    FOXP3/TLS; a prognostic marker in patients with bladder carcinoma without muscle invasion
    (Elsevier Science Inc, 2025) Balcik, Onur Yazdan; Yilmaz, Fatih
    Objective: Bladder carcinoma (BC) is a common type of cancer. Approximately 20% of BC patients have non-muscle invasive bladder cancer (NMIBC). Despite adequate BCG treatment, recurrence occurs in approximately 40% of the patients. There is no adequate prognostic marker for recurrence in a group of patients. Forkhead box P3 (FOXP3) is a regulatory T cell marker that sometimes exhibits anti- tumoral effects and can be used as a tumor marker. T-cell immunoglobulin and mucin domain 3 (TIM-3) is an immune checkpoint inhibitor of T cells. Tertiary lymphoid structures (TLS) increase malignancy and inflammation in non-lymphoid organs. Therefore, we aimed to evaluate the prognostic value of FOXP3, TIM-3, and TLS in patients with NMIBC. Methods: Patients with pathologically confirmed NMIBC were included in this study. Stromal and intraepithelial cells were evaluated separately using immunohistochemistry, and FOXP3, TIM-3, TLS, FOXP3/TLS, and TIM-3/TLS were calculated and noted. The cutoff value was determined using ROC analysis. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using univariate and multivariate Cox proportional hazard analyses. Results: The study included ninety-six patients. FOXP3/TLS high group had a better RFS than FOXP3/TLS low group (P = 0.001; HR, 0.079; 95% CI, 0.019-0.337). This was also significant in the multivariate analysis (P = 0.018; HR, 0.125; 95% CI, 0.022-0.705). In the group receiving BCG, FOXP3/TLS, FOXP3-TLS, TIM-3-TLS and TIM-3/TLS elevation were lower in patients with relapse than in patients without relapse and were statistically significant. Combined TIM-3 and FOXP3 elevation was found to be good prognostic regardless of whether it was found in intraepithelial, stromal or TLS. Conclusion: FOXP3/TLS elevation is a good prognostic and predictive marker in all non-muscle invasive bladder cancer cases and in the subgroup receiving BCG. Elevation of FOXP3-TLS, TIM-3-TLS, and TIM-3/TLS is associated with longer RFS in patients receiving BCG. Combined TIM-3 and FOXP3 elevation is indicative of a low recurrence rate in NMIBC. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
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    Novel tumor marker index combining carcinoembryonic antigen and carbohydrate antigen 19-9: New prognostic factor for metastatic colorectal cancer
    (Baishideng Publishing Group Inc, 2025) Ilhan, Yusuf; Balcik, Onur Yazdan; Guzel, Halil Goksel; Onder, Arif Hakan; Demir, Bilgin; Baser, Mehmet Nuri; Karadag, Ibrahim
    BACKGROUND Metastatic colorectal cancer (mCRC) is a global health challenge with a poor prognosis. Prognostic markers are critical for survival prediction. AIM To evaluate a novel tumor marker index (TMI) combining carcinoembryonic antigen and carbohydrate antigen 19-9. METHODS This multicenter, retrospective study measured baseline carcinoembryonic antigen and carbohydrate antigen 19-9 levels to calculate a TMI as the geometric mean of values normalized to their upper limits of normal. Receiver operating characteristic curve analysis assessed TMI's prognostic accuracy, and patients were stratified into high-TMI (>= 1.39) and low-TMI (< 1.39) groups. The primary endpoint was overall survival (OS), with progression-free survival and treatment response as secondary endpoints. RESULTS The study included 305 mCRC patients with a median follow-up of 22.9 months. The median OS for high-TMI patients was 29.5 months, significantly lower than the 45.6 months observed in the low-TMI group (P = 0.02). The 2-year OS rates for the high- and low-TMI groups were 59.4% and 72.9%, respectively. Median progression-free survival was also shorter for the high-TMI group (14.0 vs 16.0 months, P = 0.84). High TMI is an independent prognostic factor for worse OS. CONCLUSION TMI is a simple, cost-effective prognostic tool for mCRC, with high TMI associated with poorer survival outcomes.
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    Reshaping the landscape of ovarian cancer: implications from the surgery for ovarian cancer FIGO 4 study
    (Mosby-Elsevier, 2025) Guzel, Halil Goksel; Balcik, Onur Yazdan; Ilhan, Yusuf
    [Abstract Not Available]
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    Rethinking Neoadjuvant Therapy: A Critical Evaluation of Exclusion Criteria in Gastric Cancer Surgery Studies
    (Korean Gastric Cancer Assoc, 2025) Ilhan, Yusuf; Guzel, Halil Goksel; Balcik, Onur Yazdan
    [Abstract Not Available]
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    The ascendancy of eosinophil counts in non-small cell lung cancer: a potential marker for predicting response and survival under nivolumab treatment
    (E-Century Publishing Corp, 2024) Ozbay, Mehmet Fatih; Cetinkaya, Aysegul Merc; Balcik, Onur Yazdan; Ilhan, Yusuf; Genc, Tugrul Burak; Goksu, Sema Sezgin
    Lung cancer is the leading cause of cancer-related death globally and is often diagnosed at an advanced stage. Nivolumab represents a significant advancement for treating advanced non-small cell lung cancer (NSCLC). However, the absence of reliable biomarkers predicting treatment response hinders personalized therapy. Eosinophils play a notable role in cancer biology, particularly when treated with immune checkpoint inhibitors. Eosinophils can infiltrate tumor tissues, directly interacting with tumor cells or modifying the tumor microenvironment. This study aims to assess the potential of PD-L1 expression and peripheral blood eosinophil count in predicting treatment response and patient survival. This retrospective cohort study was conducted in three major cancer centers in Turkey, including 174 advanced NSCLC patients who had progressed after chemotherapy between July 2019 and November 2023. Demographic and clinical data, PD-L1 levels, and eosinophil counts were analyzed using SPSS 27.0. Survival analyses were performed with Kaplan-Meier and Cox regression models. Increased peripheral blood eosinophil count was positively associated with response to Nivolumab treatment and overall survival. Among treatment responders, 54.1% had eosinophil levels between 100-499 cells/mm3 before treatment, increasing to 70.8% post-treatment. In patients with high PD-L1 positivity (>50%), eosinophil levels averaged 266.0 cells/mm3, with improved survival outcomes (mean survival: 24.06 months, median: 20.0 months). Non-responders had a mean survival of 19.05 months and a median survival of 15.2 months. Peripheral eosinophil count appears to be a potential biomarker for predicting response to Nivolumab treatment and survival in NSCLC patients. Combined evaluation of eosinophil count and PD-L1 expression may enhance personalized treatment strategies. Further validation in prospective, randomized studies is necessary.