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Öğe Clinical 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; Oztas, Nihan Senturk; Ucar, Gokhan; Kilickap, SaadettinIntroduction: 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.Öğe External 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) Yekeduz, Emre; Karakaya, Serdar; Erturk, Ismail; Tural, Deniz; Ucar, Gokhan; Oztas, Nihan Senturk; Arikan, RukiyeIn 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.Öğe Neutrophil-lymphocyte ratio as a prognostic factor for survival in patients with advanced renal cell carcinoma (Turkish Oncology Group Study)(Sage Publications Ltd, 2020) Hizal, Mutlu; Sendur, Mehmet A. N.; Yasar, Hatime Arzu; Bir Yucel, Kadriye; Arslan, Cagatay; Ucar, Gokhan; Karakaya, SerdarBackground To describe the prognostic value of neutrophil-lymphocyte ratio and its effect on survival in in patients with advanced renal cell carcinoma. Methods We retrospectively analyzed 331 patients. The cut-off value of neutrophil-lymphocyte ratio was specified as 3 which is mostly close-and also clinically easily applicable-to the median neutrophil-lymphocyte ratio level of our study group. High group is identified as neutrophil-lymphocyte ratio >3 (n = 160) and low group is identified as neutrophil-lymphocyte ratio <= 3 (n = 163). Results A total of 331 (with 211 male and 120 female) patients were enrolled to study. The median age of the patients was 58. The International Metastatic RCC Database Consortium risk score is calculated for the 72.8% (n = 241) of the study group and among these patients, favorable, intermediate, and poor risk rates were 22, 45.2, and 32.8%. The total usage of tyrosine kinase inhibitors reached 78% of the patients. The median overall survival was 32 months versus 11 months in the neutrophil-lymphocyte ratio low and high groups, respectively (HR: 0.49 (95% CI 0.37-0.65), p < 0.001). Conclusion In conclusion, the pre-treatment value of elevated neutrophil-lymphocyte ratio might be a predictor of poor overall survival in advanced renal cell carcinoma patients.Öğe Nivolumab as second-line treatment and beyond for metastatic renal cell carcinoma: A real-life experience from Turkish Oncology Group Kidney Cancer Consortium (TKCC) Database.(Lippincott Williams & Wilkins, 2021) Yekeduz, Emre; Erturk, Ismail; Tural, Deniz; Karadurmus, Nuri; Karakaya, Serdar; Hizal, Mutlu; Arslan, Cagatay[Abstract Not Available]Öğe Nivolumab in metastatic renal cell carcinoma: results from the Turkish Oncology Group Kidney Cancer Consortium database(Future Medicine Ltd, 2021) Yekeduz, Emre; Erturk, Ismail; Tural, Deniz; Karadurmus, Nuri; Karakaya, Serdar; Hizal, Mutlu; Arikan, RukiyeLay 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.Öğe Real-life experience of patients with sarcomatoid renal cell carcinoma: a multicenter retrospective study(Aepress Sro, 2023) Almuradova, Elvina; Basoglu, Tugba; Nayir, Erdinc; Bayram, Ertugrul; Paydas, Semra; Gokmen, Ivo; Karakaya, SerdarSarcomatoid renal cell carcinoma (sRCC) is a rare variant of renal cell carcinoma (RCC) and is associated with a poor prognosis. We reviewed the outcomes of patients from oncology centers in Turkey. Our aim is to share our real-life experi-ence and to contribute to the literature. The demographic and clinical features, treatment, and survival outcomes of 148 patients with sRCC were analyzed. The median age at the time of diagnosis was 58 years (range: 19-83 years). Most patients (62.8%) had clear-cell histology. Most patients were in the intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk group (67.6%) and were stage 4 at the time of diagnosis (63.5%). The most common sites of metastasis were the lung (60.1%), lymph nodes (47.3%), and bone (35.8%). The patients received a median of two lines (range: 0-6) of treatment. The most common side effects were fatigue, hematological side effects, hypertension, and hypothyroidism. The median follow-up was 20.9 months (range: 1-162 months). The median overall survival (OS) was 30.8 months (95% confidence interval: 24.9-36.7 months). In multivariate analysis, high MSKCC scores, sarcomatoid differentiation rates >50%, having stage 4 disease, and having lung metastasis at the time of diagnosis were independent factors for poor prognosis affecting OS. No difference was observed between patients who received tyrosine kinase inhibitor (TKI) as the first or second-line treatments. Similarly, no difference between TKI and immunotherapy as the second-line treatment. In conclusion, sRCC is a rare variant of RCC with a poor prognosis and response to treatment. Larger-scale prospective studies are needed to define an optimal treatment approach for longer survival in this aggressive variant.Öğe The relationship between pan-immune-inflammation 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) Yekeduz, Emre; Tural, Deniz; Erturk, Ismail; Karakaya, Serdar; Erol, Cihan; Ercelep, Ozlem; Arslan, CagatayBackground 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.Öğe The relationship between prognostic nutritional index and treatment response in patients with metastatic renal cell cancer(Sage Publications Ltd, 2020) Yasar, Hatime Arzu; Yucel, Kadriye Bir; Arslan, Cagatay; Ucar, Gokhan; Karakaya, Serdar; Bilgin, Burak; Taban, HakanIntroduction and aim To investigate the effect of the prognostic nutritional index on treatment response and survival in patients with metastatic renal cell cancer. Methods We retrospectively analyzed the treatment modalities; the demographic, clinical and pathological features of 396 patients with RCC and prognostic nutritional index. Based on the median value, patients were grouped as having low and high prognostic nutritional index values. Kaplan-Meier method was used for survival analysis, and Cox-regression analysis was used for multivariate analysis. Results The median overall survival was 39 months (95% CI 26.1-51.8), 28 months (95% CI 17.9-38) and 7 months (95% CI 4.7-9.2) in patients with favorable, intermediate and poor International Metastatic Renal Cell Carcinoma Database Consortium risk group, respectively. The difference between the groups was statistically significant (p < 0001). Overall survival was 11 months (95% CI 7.5-14.5) in the low-prognostic nutritional index (prognostic nutritional index <= 38.5) group, and 41 months (95% CI 30.5-51.4) in the high prognostic nutritional index (prognostic nutritional index >38.5) group (p < 0.001). In Cox regression analysis, Eastern Cooperative Oncology Group performance score (HR: 2.5), time to systemic treatment (HR: 1.7) and prognostic nutritional index (HR: 1.8) were associated with overall survival. Conclusion In patients with renal cell cancer, prognostic nutritional index is closely related to survival and has prognostic significance.Öğe The relationship between systemic immune inflammation index and survival in patients with metastatic renal cell carcinomatreated withtyrosine kinase inhibitors(Nature Portfolio, 2022) Yucel, Kadriye Bir; Yekeduz, Emre; Karakaya, Serdar; Tural, Deniz; Erturk, Ismail; Erol, Cihan; Ercelep, OzlemThis 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.Öğe Sunitinib or Pazopanib: Is There Any Difference Between Tyrosine Kinase Inhibitors in the Pre-Nivolumab Setting in Metastatic Renal Cell Carcinoma?(Springernature, 2020) Ucar, Gokhan; Acikgoz, Yusuf; Ergun, Yakup; Bal, Oznur; Yilmaz, Mesut; Karakaya, Serdar; Akdeniz, NadiyeIntroduction Treatment options for metastatic renal cell carcinoma disease have been improved in recent years. However, there is still no optimal treatment sequence or combination for metastatic disease. We aimed to investigate whether patients differed in terms of disease outcomes regarding pre-nivolumab tyrosine kinase inhibitors (TKIs). Material and methods The analysis of patients was performed after all cohorts were sub-grouped into two groups according to pre-nivolumab TKIs as following the sunitinib arm and the pazopanib arm. Result A total of 75 patients were included in this study. The median follow-up time was eight months for all cohorts. The objective response rate was statistically significantly higher in the pazopanib arm as compared to the sunitinib arm (56% vs 30%, p=0.02). Progression-free survival was significantly higher in pazopanib than sunitinib (10.3 months vs 5.3 months, p=0.02). Multivariate analysis revealed that pazopanib treatment was associated with better progression-free survival (HR: 0.44, 95 CI; 0.22-0.91, p=0.02). While the median overall survival for patients who had received sunitinib was 11.0 months, it has not been reached the median in the pazopanib arm (11.0 months vs NR, p=0.051). Discussion We demonstrated significantly better progression-free survival and a higher objective response rate with nivolumab treatment in patients who had received pazopanib as compared with patients who received sunitinib in the pre-nivolumab period.
