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Öğe The association between antibiotic use and survival in renal cell carcinoma patients treated with immunotherapy: a multi-center study(Mosby Inc., 2021) Güven, Deniz Can; Acar, Ramazan; Yekedüz, Emre; Bilgetekin, İrem; Baytemur, Naziyet Kose; Erol, Cihan; Ceylan, Furkan Sacit; Kılıçkap, SaadettinBackground: Immunotherapy improves overall survival (OS) in the second and later lines of renal cell carcinoma (RCC) treatment. Recent studies have suggested that antibiotic (ATB) use either shortly before or after the start of immunotherapy could lead to decreased OS. Herein, we evaluate the impact of ATB use on OS in RCC patients treated with nivolumab in a multi-center cohort from Turkey. Methods: The data of 93 metastatic RCC patients treated with nivolumab in the second line or later were retrospectively collected from 6 oncology centers. Previous treatments, sites of metastases, International Metastatic RCC Database Consortium risk classification, and ATB use in the three months before (-3) or three months after (+3) the start of immunotherapy were recorded together with survival data. The association of clinical factors with OS and progression-free survival (PFS) was analyzed with univariate and multivariable analyses. Results: The median age was 61 (interquartile range 54-67), and 76.3% of the patients were male. The median OS of the cohort was 23.75 ± 4.41, and the PFS was 8.44 ± 1.61 months. Thirty-one (33.3%) patients used ATBs in the 3 months before (-3) or 3 months after (+3) nivolumab initiation. In the multivariable analyses, ATB exposure (HR: 2.306, 95% confidence interval [CI]: 1.155-4.601, P = 0.018) and the presence of brain metastases at the baseline (HR: 2.608, 95% CI: 1.200-5.666, P = 0.015) had a statistically significant association with OS, while ATB exposure was the only statistically significant parameter associated with PFS (HR: 2.238, 95% CI: 1.284-3.900, P = 0.004). Conclusion: In our study, patients with ATB exposure in the 3 months before or 3 months after the start of immunotherapy had shorter OS. Our findings further support meticulous risk–benefit assessments of prescribing ATBs for patients who are either receiving or are expected to receive immunotherapy.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 Clinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: a multicenter study(SPRINGER, 2022) Yekedüz, Emre; Özbay, Mehmet Fatih; Çaglayan, Dilek; Yıldırım, Atila; Erol, CihanAim To compare survival outcomes, response rates, and adverse events (AEs) in proton pump inhibitor (PPI) user and nonuser patients with metastatic colorectal cancer (mCRC) treated with regorafenib. Methods We included 272 patients with mCRC treated with regorafenib in this study. Patients were divided into two categories according to their status of PPI use. The primary endpoint was overall survival (OS). The secondary endpoints were time to treatment failure (TTF), response rates, and safety. To exclude immortal time bias in survival analyses, we compared PPI non-user patients and all patients. Results There were 141 and 131 patients in the PPI non-user and user groups. Baseline characteristics were similar in each group. Pantoprazole was the most used PPI. At the median 35.2 (95% confidence interval (CI): 32.6-37.9) months follow-up, the median OS was similar in PPI non-user and all patients (6.9 months (95% CI: 5.3-8.5) and 7.7 months (95% CI:6.6-8.8), p = 0.913). TTF was also similar in PPI non-user and all patients (3.3 months (95% CI: 2.7-3.9) and 3.5 months (95% CI: 3.0-4.0), p = 0.661). In multivariable analysis, no statistically significant difference was observed between PPI user and nonuser groups in OS and TTF (hazard ratio (HR), 0.99; 95% CI, 0.77-1.28; p = 0.963 for OS; HR, 0.93; 0.77-1.20, p = 0.598 for TTF). The objective response rates (ORR) were similar in the PPI non-user and user groups (19.8% and 16.8%, p = 0.455). The rates of any grade AEs were also similar in each group. Conclusion This study found no worse outcome in the combined use of PPI and regorafenib among patients with mCRC.Öğe Clinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: A multicenter study(LIPPINCOTT WILLIAMS & WILKINS, 2022) Yekedüz, Emre; Özbay, Mehmet Fatih; Çağlayan, Dilek; Yıldırım, Atila; Erol, Cihan; Yıldırım, Hasan Çağrı; Tunç, Sezai; Özyurt, Neslihan; Özdemir, Feyyaz; Şendur, Mehmet Ali Nahit; Kılıçkap, SaadettinClinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: A multicenter studyÖğe First-line treatment of patients with HER2-positive metastatic gastric and gastroesophageal junction cancer(Association of Basic Medical Sciences of FBIH, 2022) Aktürk Esen, Selin; Ergün, Yakup; Erol, Cihan; Arıkan, Rukiye; Er, Muhammed MuhiddinFluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which plati-num-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received f luorouracil, oxaliplatin, and leucovo-rin (mFOLFOX)+trastuzumab or cisplatin and f luorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLF-OX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (p = 0.495). About 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (p = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, p = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, p = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, mFOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens.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) Tural, Deniz; Yekedüz, Emre; Ertürk, İsmail; Karakaya, Serdar; Erol, Cihan; Ercelep, Özlem; Arslan, Çağatay; Sever, Özlem Nuray; Şentürk Öztaş, Nihan; Küçükarda, Ahmet; Can, Orçun; Öksüzoğlu, Berna; Şendur, Mehmet Ali; Karadurmuş, Nuri; Urun, Yüksel; Kılıçkap, SaadettinBackground Pan-immune-infammation 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 (103 /mm3 ) x monocyte (103 /mm3 ) x platelet (103 /mm3 )/lymphocyte (103 /mm3 ). Results A total of 152 patients with mRCC were included in this study. According to cut-of 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 systemic immune inflammation index and survival in patients with metastatic renal cell carcinomatreated withtyrosine kinase inhibitors(Nature Research, 2022) Yücel, Kadriye Bir; Yekedüz, Emre; Karakaya, Serdar; Tural, Deniz; Ertürk, İsmail; Erol, Cihan; Ercelep, Özlem; Öztaş Şentürk, Nihan; Arslan, Çağatay; Uçar, Gökhan; Küçükarda, Ahmet; Sever, Özlem Nuray; Kılıçkap, Saadettin; Can, Orçun; Yazgan, Satı Çoskun; Öksüzoğlu, Berna; Karadurmuş, Nuri; Şendur, Mehmet Ali; 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 (cellsx109/L) x platelet (cellsx109/L)] / lymphocyte (cellsx109/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.