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    Bevacuzimab May Be Less Effective in Obese Metastatic Colorectal Cancer Patients
    (Springer, 2019) Artac, Mehmet; Korkmaz, Levent; Coskun, Hasan Senol; Dane, Faysal; Karabulut, Bulent; Karaagac, Mustafa; Cabuk, Devrim
    PurposeThe purpose of this study was to investigate whether obesity affects survival in metastatic colorectal cancer (mCRC) patients treated with bevacizumab combined with chemotherapy.MethodsA total of 563 patients with mCRC who had received first-line chemotherapy in combination with bevacizumab were studied. Patients were grouped as obese (BMI levels >30) or non-obese (BMI levels <30). Progression-free survival (PFS) and overall survival (OS) were analyzed. Primary tumor location was also investigated in terms of PFS and OS.ResultsThe median age of the patients was 59years. The non-obese group had longer PFS than the obese group (P=0.030). The 2-year survival rate of the non-obese group was also significantly higher (P=0.036). The median PFS of non-obese patients was significantly longer in Kras wild-type patients (10.1 vs. 8.1months, P=0.010). Among patients with left-sided primary tumor location, median PFS and OS were significantly higher in the non-obese group (PFS non-obese, 11.5months; obese, 8.8months; P=0.002) (OS non-obese, 29.4months; obese, 21.4months; P=0.026).ConclusionsEfficacy of bevacizumab may be lower in obese patients. Among patients with Kras wild-type left-sided tumors treated with bevacizumab-based regimens, the prognosis could be worse for obese patients than that for non-obese patients. There is a need for prospectively designed studies of obese patients to prove the efficacy and dosages of bevacizumab in treatment of mCRC.
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    Irinotecan and Ifosfamide Combination is an Effective and Safe Option in Patients with Refractory Small Cell Lung Cancer: A Retrospective Cross-Sectional Study
    (Kare Publ, 2020) Karaagac, Mustafa; Artac, Mehmet; Goksu, Sema Sezgin; Eryilmaz, Melek Karakurt; Coskun, Hasan Senol; Bozcuk, Hakan
    Objectives: Recurrent and progressive small cell lung cancer (SCLC) has a very poor prognosis, and treatment options are limited. Combination of irinotecan with ifosfamide ( I-I regimen) in SCLC has limited preliminary data. In this study, we aimed to evaluate the efficacy and toxicity of I-I regimen in patients with previously treated SCLC. Methods: A total of 25 patients were retrospectively reviewed. Ifosfamide dose was 1500 mg/m2/ per day, days 1-3, irinotecan 80 mg/m2 per day days 1.8 and 15 every four weeks. Results: Median age of patients was 55 years (range 42-80). Median chemotherapy cycles were 3 (range 1-7). The frequency of the second, third and fourth line treatments were 68%, 24%, and 8% respectively. Partial remission was obtained in 15 patients (60%) and complete remission in one patient (4%). Median progression free survival (PFS) and overall survival (OS) figures were 7.8 and 11.1 months, respectively. Granulocyte colony stimulating factor (G-CSF) was used in 40% of patients. Grade 3-4 anemia, leukopenia, and thrombocytopenia were seen in 20%, 36% and 12% of these cases, respectively. Conclusion: Ifosfamide and irinotecan combination is an effective and a tolerable treatment option for patients with platinum refractory SCLC.
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    Irinotecan and Ifosfamide Combination is an Effective and Safe Option in Patients with Refractory Small Cell Lung Cancer: A Retrospective Cross-Sectional Study
    (Kare Publ, 2020) Karaagac, Mustafa; Artac, Mehmet; Goksu, Sema Sezgin; Eryilmaz, Melek Karakurt; Coskun, Hasan Senol; Bozcuk, Hakan
    Objectives: Recurrent and progressive small cell lung cancer (SCLC) has a very poor prognosis, and treatment options are limited. Combination of irinotecan with ifosfamide ( I-I regimen) in SCLC has limited preliminary data. In this study, we aimed to evaluate the efficacy and toxicity of I-I regimen in patients with previously treated SCLC. Methods: A total of 25 patients were retrospectively reviewed. Ifosfamide dose was 1500 mg/m2/ per day, days 1-3, irinotecan 80 mg/m2 per day days 1.8 and 15 every four weeks. Results: Median age of patients was 55 years (range 42-80). Median chemotherapy cycles were 3 (range 1-7). The frequency of the second, third and fourth line treatments were 68%, 24%, and 8% respectively. Partial remission was obtained in 15 patients (60%) and complete remission in one patient (4%). Median progression free survival (PFS) and overall survival (OS) figures were 7.8 and 11.1 months, respectively. Granulocyte colony stimulating factor (G-CSF) was used in 40% of patients. Grade 3-4 anemia, leukopenia, and thrombocytopenia were seen in 20%, 36% and 12% of these cases, respectively. Conclusion: Ifosfamide and irinotecan combination is an effective and a tolerable treatment option for patients with platinum refractory SCLC.
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    Prospective external validation of an updated algorithm to quantify risk of febrile neutropenia in cancer patients after a cycle of chemotherapy
    (Springer, 2022) Bozcuk, Hakan; Coskun, Hasan Senol; Ilhan, Yusuf; Goksu, Sema Sezgin; Yildiz, Mustafa; Bayram, Selami; Yerlikaya, Tahir
    Purpose Febrile neutropenia resulting from chemotherapy is a significant cause of morbidity and mortality in cancer patients. We had previously published the associates of the risk of febrile neutropenia, and this study now extends and modifies the previous model as well as tests its external validity. Methods We have recruited documented febrile neutropenia cases with solid tumors, in addition to a selected control group of cancer patients from one institution treated between 2015 and 2019. We then united our sample with our previously published original derivation group, to modify and update our previous model by logistic regression analysis. Additionally, consecutive cancer patients from 5 institutions were recruited in 2020 to test external validity of the resultant algorithm. Results A total of 4075 cycles of chemotherapy in 1282 cases were recruited in the updated, new model derivation group, and a total of 8 variables were selected for the updated algorithm. In the new external validation group, 653 cycles of chemotherapy in 624 patients were analyzed, to indicate that after cycles without prophylactic granulocyte colony-stimulating factor (GCSF) usage, the algorithm yielded a sensitivity value of 91%, specificity of 40%, and an area under curve (AUC) figure of 0.78, when a risk cutoff threshold value of >= 0.20 is chosen. This algorithm is now embedded in a web application for free clinical use. Conclusion Our algorithm identifies and quantifies the risk of febrile neutropenia in cancer patients. Further studies are required to improve this model with additional predictors.
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    The Relationship Between Plexin C1 Overexpression and Survival in Hepatocellular Carcinoma: a Turkish Oncology Group (TOG) Study
    (Springer, 2022) NazimTurhal, Serdar; Dogan, Mutlu; Esendagli, Guldal; Artac, Mehmet; Korkmaz, Levent; Coskun, Hasan Senol; Goker, Erdem
    Purpose Plexin C1 is a transmembrane receptor and plexin C1 overexpression might have role in carcinogenesis. Hepatocellular carcinoma (HCC) has poor prognosis because of its aggressive behavior and limited treatment options, especially in advanced stage. We recently documented that Plexin C1 was overexpressed in HCC. We aimed to evaluate the prognostic significance of Plexin C1 overexpression in HCC in the present study. Methods Plexin C1 overexpression was evaluated immunohistochemically on paraffin-embedded blocks of the HCC patients. Plexin C1 immunohistochemical staining was scored. Plexin C1 overexpression staining intensity and prevalence were used for plexin scale staining evaluation and plexin scores were estimated according this staining scale. Plexin C1 score and its association with survival and clinicopathological features was assessed. Results Sixty-seven HCC patients with adequate tissue for pathological evaluation were included. Median age was 63 years with male predominance (male to female ratio was 4.75 (n 57/12). Well-differentiated HCC (53.7%) patients had higher plexin C1 overexpression (p < 0.05). Median OS was 22.1 months. Patients with lower plexin C1 score (< 12) had shorter OS (17.5 vs 30.1 months, p = 0.036). Neutrophil count, GGT, and PNR (platelet/neutrophil ratio) had prognostic significance (p = 0.047, p = 0.018, and p = 0.045). Conclusion Plexin C1 overexpression is inversely correlated with grade in HCC. The patients with lower rate of Plexin C1 overexpression have worse survival outcome. It might be a prognostic factor in HCC.
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    Response to first-line chemotherapy regimen is associated with efficacy of immune checkpoint blockade therapies in patients with metastatic urothelial carcinoma
    (Springer Japan Kk, 2022) Tural, Deniz; Selcukbiricik, Fatih; Olmez, Omer Fatih; Sumbul, Ahmet Taner; Erman, Mustafa; Coskun, Hasan Senol; Artac, Mehmet
    Background Atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important. Patients and methods In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher's exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method. Results The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio [HR] = 1.9; p = 0.04}, ECOG PS >= 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p < 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39; p < 0.001) maintained a significant association with OS in multivariate analysis. Conclusions Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients' use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.
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    Using Interferon Alfa Before Tyrosine Kinase Inhibitors May Increase Survival in Patients With Metastatic Renal Cell Carcinoma: A Turkish Oncology Group (TOG) Study
    (Cig Media Group, Lp, 2016) Artac, Mehmet; Coskun, Hasan Senol; Korkmaz, Levent; Kocer, Murat; Turhal, Nazim Serdar; Engin, Huseyin; Dede, Isa
    Survival outcomes of interferon-alfa and tyrosine kinase inhibitors for 104 cases of metastatic renal cell carcinoma were included in this study. First-line interferon-alfa treatment before tyrosine kinase inhibitors had an additive survival affect. Background: We aimed to investigate the outcomes of interferon alfa and sequencing tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma. Patients and Methods: This multicenter study assessing the efficacy of TKIs after interferon alfa therapy in the first-line setting in patients with metastatic renal cell carcinoma. Patients (n = 104) from 8 centers in Turkey, who had been treated with interferon alfa in the first-line setting, were included in the study. Prognostic factors were evaluated for progression-free survival (PFS). Results: The median age of the patients was 57 years. The median PFS of the patients treated with interferon alfa in the first-line was 3.6 months. A total of 61 patients received TKIs (sunitinib, n = 58; sorafenib, n = 3) after progression while on interferon alfa. The median PFS among the TKI-treated patients was 13.2 months. In the univariate analysis for interferon alfa treatment, neutrophil and hemoglobin level, platelet count, and Karnofsky performance status were the significant factors associated with PFS. In the univariate analysis for TKI treatment, neutrophil and hemoglobin levels were the significant factors for PFS. The median total PFS of the patients who had been treated with first-line interferon alfa and second-line TKIs was 24.9 months. Conclusion: This study showed that first-line interferon alfa treatment before TKIs may improve the total PFS in patients with metastatic renal cell carcinoma. (C) 2016 Elsevier Inc. All rights reserved.