Browsing by Author "Ürün, Yüksel"
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Review Citation - WoS: 10Citation - Scopus: 9Advancements in Platinum Chemotherapy for Metastatic Castration-Resistant Prostate Cancer: Insights and Perspectives(ELSEVIER SCI LTD, 2024-11) Akkuş, Erman; Arslan, Çağatay; Ürün, YükselDespite improvements in survival, metastatic castration-resistant prostate cancer (mCRPC) remains a significant clinical challenge. While taxanes, new hormonal agents, radiopharmaceuticals, and PARP inhibitors offer valuable treatment options, this review explores the potential of platinum chemotherapies (carboplatin, cisplatin, and oxaliplatin) as alternative choices. Existing research demonstrates promising preliminary results for platinum-based therapies in mCRPC showing PSA response rates (7.7-95 %) and improved overall survival (8-26.6 months). However, chemotherapy-related cytopenias are a frequent side effect. Further research is underway to evaluate the efficacy of platinum regimens against specific mCRPC histopathological variants, particularly aggressive subtypes where the carboplatin and cabazitaxel combination is already recommended. The unique DNA-targeting action of platinum therapy holds promise for patients with deficient DNA repair (dDDR), especially those with BRCA mutations. This potential is supported by both preclinical and ongoing clinical research. Given the limited success of immunotherapy in mCRPC, researchers are exploring the potential for platinum therapies to enhance its efficacy. Additionally, trials are investigating the synergy of combining platinum therapy with both immunotherapy and PARP inhibitors. Further exploration into the effectiveness of platinum therapies in specific mCRPC subpopulations, particularly those with dDDR, is crucial for optimizing their future use. In conclusion, this review highlights the promising potential of platinum-based chemotherapy as a valuable treatment option for mCRPC. While current evidence is encouraging, ongoing research is essential to further optimize its efficacy, identify optimal combinations with other therapies, and better understand its impact on specific mCRPC subpopulations.Article Citation - WoS: 3Citation - Scopus: 3Clinical Features and Prognostic Factors of Metastatic Non-Clear Cell Renal Cell Carcinoma: a Multicenter Study From the Turkish Oncology Group Kidney Cancer Consortium(Karger, 2023) Erol, Cihan; Yekeduz, Emre; Tural, Deniz; Karakaya, Serdar; Şentürk Öztaş, Nihan; Uçcar, Gökhan; Kılıçkap, Saadettin; Arslan, Çağatay; Ürün, Yüksel; Uçar, Gökhan; Oztas, Nihan SenturkIntroduction: We aimed to evaluate clinical features, prognostic factors, and treatment preferences in patients with non-clear cell renal cell carcinoma (nccRCC). Methods: Patients with metastatic nccRCC were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. Clinical features, prognostic factors, and overall survival (OS) outcomes were investigated. Results: A total of 118 patients diagnosed with nccRCC were included in this study. The median age at diagnosis was 62 years (interquartile range: 56-69). Papillary (57.6%) and chromophobe tumors (12.7%) are common histologic subtypes. Sarcomatoid differentiation was present in 19.5% of all patients. When the patients were categorized according to the International Metastatic RCC Database Consortium (IMDC) risk scores, 66.9% of the patients were found to be in the intermediate or poor risk group. Approximately half of the patients (55.9%) received interferon in the first line. At the median follow-up of 53.2 months (95% confidence interval [CI]: 34.7-71.8), the median OS was 19.3 months (95% CI: 14.1-24.5). In multivariate analysis, lung metastasis (hazard ratio [HR]:2.22, 95% CI: 1.23-3.99) and IMDC risk score (HR: 2.35, 95% CI: 1.01-5.44 for intermediate risk; HR: 8.86, 95% CI: 3.47-22.61 for poor risk) were found to be independent prognostic factors. Conclusion: In this study, survival outcomes are consistent with previous studies. The IMDC risk score and lung metastasis are the independent prognostic factors for OS. This is an area that needs research to better treat this group of patients and create new treatment options.Article Citation - WoS: 6Citation - Scopus: 6External Validation of a Novel Risk Model in Patients With Favorable Risk Renal Cell Carcinoma Defined by International Metastatic Renal Cell Carcinoma Database Consortium (imdc): Results From the Turkish Oncology Group Kidney Cancer Consortium (tkcc) Database(Cig Media Group, Lp, 2023-02) Yekeduz, Emre; Karakaya, Serdar; Erturk, Ismail; Tural, Deniz; Ucar, Gokhan; Oztas, Nihan Senturk; Arikan, Rukiye; Arslan, Çağatay; Ürün, Yüksel; Şentürk Öztaş, NihanIn this report, we validated a novel prognostic model structured by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) for patients with metastatic renal cell carcinoma. The former favor-able risk group was divided into 2 new categories: very favorable and favorable. Patients with very favorable risk had better survival than those with the novel favorable risk. Further studies are needed to evaluate whether less intensive therapies could be as effective as current combinations of therapies in the very favorable risk group. Background: A novel prognostic model was recommended for patients with metastatic RCC (mRCC) by the Interna-tional mRCC Database Consortium (IMDC). In this study, we aimed to externally validate a novel risk model for the IMDC-favorable risk group in patients with mRCC. Methods: The Turkish Oncology Group Kidney Cancer Consortium (TKCC) is a multicenter registry that includes 13 cancer centers in Turkey. As described by Schmidt et al., 3 parameters (ie, time from diagnosis to systemic therapy < 3 vs. >3 years, Kar nofsky Perfor mance Status [KPS] 80 vs. > 80, and the presence of brain, liver, or bone metastasis) were used to divide the IMDC favorable risk group into 2 new categories: very favorable and favorable risk groups. The primary endpoint was overall survival (OS). Time to treatment failure (TTF) and objective response rate (ORR) in the very favorable and favorable risk groups were the secondary endpoints. Results: A total of 545 patients with mRCC from all IMDC risk groups and 112 patients from the favorable risk group were included in this study. According to the novel classification model, 44 (39.3%) and 68 (60.7%) patients with former favorable risk were categorized into very favorable and favorable risk groups, respectively. The median OS (55.8 months vs. 34.2 months, P = .025) and TTF (25.5 months vs. 15.5 months, P = .010) were longer in the very favorable risk group than in the favorable risk group. The concordance index of the new IMDC model in all patients was 0.65 for OS. Despite the higher ORR in the very favorable risk group than in the favorable risk group, the difference between the groups was not statistically significant (52.4% vs. 44.7, P = .573). Conclusions: This was the first study to externally validate the novel IMDC risk model presented in the American Society of Clinical Oncology Genitourinary Cancers Symposium 2021.Article Citation - WoS: 6Citation - Scopus: 5Nivolumab in Metastatic Renal Cell Carcinoma: Results From the Turkish Oncology Group Kidney Cancer Consortium Database(Future Medicine Ltd, 2021-11-02) Yekeduz, Emre; Erturk, Ismail; Tural, Deniz; Karadurmus, Nuri; Karakaya, Serdar; Hizal, Mutlu; Arikan, Rukiye; Arslan, Cagatay; Hlzal, Mutlu; Ürün, YükselLay abstract Nivolumab is an immune checkpoint inhibitor (ICI) that blocks the communication between T cells and cancer cells and instead activates T cells to fight against cancer. Metastatic renal cell carcinoma (mRCC) is one of the most susceptible tumors to ICIs. The Checkmate 025 trial showed the efficacy of nivolumab in patients with previously treated mRCC. In this real-world study, 173 patients with mRCC were treated with nivolumab in the second line and beyond. Nivolumab was effective in the real-world setting without additional safety concerns. Aim: The authors present real-world data on the efficacy and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Methods: The Turkish Oncology Group Kidney Cancer Consortium (TKCC) database includes patients with mRCC from 13 cancer centers in Turkey. Patients with mRCC treated with nivolumab in the second line and beyond were extracted from the TKCC database. Results: A total of 173 patients were included. The rates of patients treated with nivolumab in the second, third, fourth and fifth lines were 47.4%, 32.4%, 14.5% and 5.7%, respectively. The median overall survival and progression-free survival were 24.2 months and 9.6 months, respectively. Nivolumab was discontinued owing to adverse events in 11 (6.4%) patients. Conclusion: Nivolumab was effective in patients with mRCC and no new safety signal was observed.Article Citation - WoS: 1Citation - Scopus: 1Objective Response Rate Is a Surrogate Marker for Long-Term Overall Survival in Metastatic Urothelial Carcinoma Patients Treated With Immune Checkpoint Inhibitors(Cig media group, lp, 2024-10) Tural, Deniz; Arslan, Çagatay; Selçukbiricik, Fatih; Ölmez, Ömer Fatih; Erman, Mustafa; Ürün, Yüksel; Erdem, Dilek; Kilickap, SaadettinBackground: This study aimed to evaluate the utility of RECIST criteria-based objective response rate (ORR) as a potential surrogate endpoint for long-term overall survival (OS) in patients with metastatic urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs). Methods: The primary endpoint was overall ORR and OS, duration of treatment (DoR) with ICIs. ORR was analyzed using Fisher's exact test. Median follow-up and OS were estimated by using the Kaplan-Meier method. Results: The median follow-up was 58 (1.15-71) months. Progression developed in 94 (47%) patients during the first 3 months of ICIs therapy. The treatment response to ICIs included complete response (CR), partial response (PR) and stable disease in 10% (n = 20), 23% (n = 46), and 20% (n = 41) of patients, respectively. The responder and nonresponder groups differed in terms of certain baseline characteristics, such as Bellmunt risk factors, and neutrophil-to-lymphocyte ratio (NLR). The 5-year OS rates for patients with CR and PR were 73% and 23%, respectively. The median DoR for CR, PR, and SD were 51.8 months (44.5-59.1), 20.7 months (16.7-24.6), and 8.8 months (5.5-12.1), respectively. Overall, 16(80%) patients with CR and 14(30%) patients with PR had an ongoing response at the time of the analysis. In the univariate analysis, NLR > 3, liver metastases, ECOG PS >= 1, and hemoglobin levels < 10 mg/dl, as well as the PR and CR, were all significantly associated with OS. In multivariate analysis, presence of liver metastases (HR 2.3; 95% CI, 1.3-4.2; P < .004) was found to be an independent determinant of short OS, while PR (HR 0.3; 95% CI, 0.15-0.5; P < .001) and CR (HR 0.06; 95% CI, 0.014-0.27; P < .001) were associated with improved OS. Conclusions: In conclusion, this 5-year analysis of real-world data in the setting of metastatic urothelial cancer indicated a significant correlation between ORR, especially CR, and OS in patients who received ICIs. Therefore, identifying a potential surrogate marker for survival in patients treated with ICIs would represent an important advance in the early identification of patients' response or resistance to ICIs.Article Citation - WoS: 3Citation - Scopus: 3Perceptions and Expectations: a Study on Prognostic Perception and Quality of Life in Patients With Metastatic Renal and Bladder Cancer(LIPPINCOTT WILLIAMS & WILKINS, 2024-08) Bölek, Hatice; Arslan, Çagatay; Başaran, Mert; Cicin, Irfan; Ozguroglu, Mustafa; Tural, Deniz; Ürün, YükselPURPOSEDurable complete response rates for metastatic renal cell carcinoma (mRCC) and metastatic bladder cancer (mBC) are low despite new therapy. Palliative care focuses on life extension and quality of life (QoL), not cure. This study aims to investigate patients' perceptions of treatment outcomes in mRCC and mBC and to assess the influence of QoL and optimism levels on these perceptions.METHODSFrom March 15, 2023, to January 15, 2024, a multicenter, cross-sectional online survey was carried out, targeting patients diagnosed with mRCC and mBC. The survey comprised structured questions aimed at evaluating perceptions concerning disease cure, symptom improvement, daily activity performance, and life extension due to treatment. Additionally, to evaluate optimism and QoL, the European Organization for Research and Treatment of Cancer 30.3 QoL questionnaire and life orientation test were implemented. Study on patients' perceptions of treatment outcomes in metastatic kidney and bladder cancer shows high optimism, inaccurate cure beliefs.RESULTSIn total, 169 patients participated in the survey; the majority of the patients stated their general health status as good (72.2%) and excellent (13.6%). Patients who rated their overall health status as good-excellent had a higher median general QoL and optimism score compared with those who rated it as fair-poor. In all, 85.2% of patients considered the possibility of a cure very likely or likely. Most participants believed treatment could provide symptom relief (30.2% very likely, 49.1% likely), enhanced ability to perform daily activities (28.4% very likely, 55.6% likely), and life extension (32.5% very likely, 53.3% likely). Patients responding very likely and likely to these questions regarding treatment outcomes had higher QoL and optimism scores than those responding a little likely and not possible.CONCLUSIONThe majority of patients with mRCC and mBC held inaccurate beliefs about treatment outcomes. Better QoL and optimism were associated with increased inaccuracy.Conference Object Perceptions and Expectations: a Study on Prognostic Perception and Quality of Life in Patients With Metastatic Renal and Bladder Cancer.(Lippincott williams & wilkins, 2024-08) Bolek, Hatice; Arslan, Cagatay; Başaran, Mert; Cicin, İrfan; Ozguroglu, Mustafa; Tural, Deniz; Ürün, YükselArticle Citation - WoS: 24Citation - Scopus: 24The Relationship Between Pan-Immune Value and Survival Outcomes in Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab in the Second Line and Beyond: a Turkish Oncology Group Kidney Cancer Consortium (tkcc) Study(Springer, 2022-05-26) Yekeduz, Emre; Tural, Deniz; Erturk, Ismail; Karakaya, Serdar; Erol, Cihan; Ercelep, Ozlem; Arslan, Cagatay; Ürün, YükselBackground Pan-immune-inflammation value (PIV) is an easily accessible immune marker based on peripheral blood to estimate prognosis in patients with cancer. This study evaluates the prognostic value of PIV in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab. Methods In this retrospective cohort study, patients with mRCC treated with nivolumab in the second line and beyond were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. PIV was calculated using the following formula: neutrophil -(10(3)/mm(3)) x monocyte -(10(3)/mm(3)) x platelet-(10(3)/mm(3))/lymphocyte -(103/mm(3)). Results A total of 152 patients with mRCC were included in this study. According to cut-off value for PIV, 77 (50.7%) and 75 (49.3%) patients fell into PIV-low (<= 372) and PIV-high (> 372) groups, respectively. In multivariate analysis, PIV-high (HR: 1.64, 95% CI 1.04-2.58, p = 0.033 for overall survival (OS); HR: 1.55, 95% CI 1.02-2.38, p = 0.042 for progression-free survival (PFS)) was independent risk factor for OS and PFS after adjusting for confounding variables, such as performance score, the International mRCC Database Consortium (IMDC) risk score, and liver metastasis. Conclusion This study established that pre-treatment PIV might be a prognostic biomarker in patients with mRCC treated with nivolumab in the second line and beyond.Article Citation - WoS: 15Citation - Scopus: 15The Relationship Between Systemic Immune Inflammation Index and Survival in Patients With Metastatic Renal Cell Carcinomatreated Withtyrosine Kinase Inhibitors(Nature Portfolio, 2022-10-03) Yucel, Kadriye Bir; Yekeduz, Emre; Karakaya, Serdar; Tural, Deniz; Erturk, Ismail; Erol, Cihan; Ercelep, Ozlem; Arslan, Cagatay; Ürün, YükselThis study aims to investigate the prognostic value of the systemic immune-inflammation index (SII)and its impact on survival in patients with metastatic renal cell carcinoma (mRCC). A total of 706patients with mRCC treated with tyrosine kinase inhibitors (TKIs)between January 2007 and June 2020 (i.e., sunitinib, pazopanib) were included in this study. SII was calculated in 621 patients with the following formula:[neutrophil (cellsx10(9)/L) x platelet (cellsx10(9)/L)] / lymphocyte (cellsx10(9)/L).All patients were classified into SII-high and SII-low groups based on the cut-off value of SII at 756, which was the median SII level of our study group. The minimal follow-up duration was 10 months in all cohorts. The median age of patients was 60 (interquartile range (IQR):53-67) years. Three out of four patients were male. The majority of patients (85.7%) had clear cell histology, and sarcomatoid differentiation was observed in 16.9% of all patients. There were 311 and 310 patients in the SII-low and SII-high groups, respectively. In general, baseline characteristics were similar in each group. However, the rate of patients treated with sunitinib (63.3% vs. 49.0%, p < 0.001) and those who underwent nephrectomy (83.6% vs. 64.2%, p < 0.001) was higher in the SII-low group than in the SII-high group. On the other hand, patients with the IMDC poorrisk (31.6% vs. 8.0%, p < 0.001), those with bone (51.8% vs. 32.2%, p < 0.001) or central nervous system (12.9% vs. 5.8%, p = 0.026) metastasis, and those with Eastern Cooperative Oncology Group(ECOG) 2-4 performance score (28.1% vs.17.7%, p = 0.002) were more common in the SII-high group than in the SII-low group. The median overall survival (OS) was longer in the SII-low group than in the SII-high group (34.6 months vs. 14.5 months, p < 0.001). Similarly, the median progression-free survival (PFS) was longer in the SII-low group than in the SII-high group (18.0 months vs. 7.7 months, p < 0.001).In multivariableanalysis, SII was an independent prognostic factor for OS (hazard ratio (HR):1.39, 95% confidence interval (CI):1.05-1.85, p = 0.01) and PFS (HR:1.60, 95% CI:1.24-2.05, p < 0.001).Pre-treatment level of high SII might be considered a predictor of poor prognosisin patients with mRCC treated with TKIs.

