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    Checkpoint inhibitors in advanced nonsmall-cell lung cancer; a Bayesian network meta-analysis
    (Wolters Kluwer Medknow Publications, 2020) Bozcuk, Hakan; Yildirim, Mustafa; Sever, Ozlem; Mutlu, Hasan; Artac, Mehmet
    Background: Checkpoint inhibitors (CPIs) have improved survival compared to chemotherapy alone in advanced nonsmall-cell lung cancer (NSCLC). This article aims to compare indirect evidence and rank the effect of different CPIs in this setting. Materials and Methods: In this network meta-analysis, we searched for trials comparing CPIs in advanced NSCLC. Figures for survival endpoints were extracted. In addition, a network meta-regression analysis was carried out. Results: A total of 9220 patients from 16 trials were included in the analysis. In the first-line setting, for the overall survival endpoint, the chemotherapy + Pembrolizumab combination had the highest effectivity rank probability as compared to chemotherapy (hazard ratio = 0.788, 95% credential interval = 0.728-0.855). For the second-line setting, and also for the efficacy in terms of progression-free survival, various CPIs and their combinations were ranked. Conclusion: Some degree of differences in terms of efficacy exists between different types, dosages, settings, and combinations of CPI. We quantify these differences to guide clinical practice.
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    Do high-risk features support the use of adjuvant chemotherapy in stage II colon cancer? A Turkish Oncology Group study
    (Sage Publications Ltd, 2014) Artac, Mehmet; Turha, Nazim Serdar; Kocer, Murat; Karabulut, Bulent; Bozcuk, Hakan; Yalcin, Suayip; Karaagac, Mustafa
    Background. A high-risk group of patients with stage II colon cancer has been identified by the results of studies in Western populations. The aim of this study was to investigate the prognostic factors of adjuvant chemotherapy in Turkish patients with stage II colon cancer. Methods. A total of 554 stage II colon cancer patients were retrospectively enrolled in the study. Three hundred fifty-three patients had received adjuvant chemotherapy (5-FU-LV, FOLFOX or FLOX) and 201 had received no adjuvant chemotherapy. T4 tumor stage, lymphovascular invasion, perineural invasion, bowel obstruction and/or perforation, <12 harvested lymph nodes, and poor differentiation were defined as high-risk factors. Results. The median age of the patients was 62 years (range 26-88). The median disease-free survival (DFS) was 58.1 months (95% CI, 47.6 months to 68.5 months) in the non-treatment group and has not been reached in the treatment group (P <0.01). In univariate analysis, patient age >60 years and T4 tumor stage were statistically significant factors that affected DFS as poor prognostic factors. Adjuvant chemotherapy reduced the risk of recurrence with statistical significance (P <0.01). In multivariate analysis, patient age >60 years and T4 tumor stage were independent risk factors affecting DFS. In addition, adjuvant chemotherapy was an independent favorable prognostic factor for DFS (P <0.01). Conclusions. Clinical and pathological risk factors in patients with stage II colon cancer may be different in the Turkish population compared to other populations. Further prospective studies in colon cancer are needed to understand the differences in biology and risk factors between races.
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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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    Programmed death-1 or programmed death ligand-1 inhibitors? A meta-analysis of differential efficacy as compared to chemotherapy in advanced non-small cell lung cancer
    (Sage Publications Ltd, 2021) Bozcuk, Hakan; Artac, Mehmet; Mutlu, Hasan; Sever, Ozlem; Yildirim, Mustafa
    Background Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PDL-1) inhibitors have improved survival over chemotherapy in advanced Non- Small Cell Lung Cancer (NSCLC). However, it is unclear if there are class specific differences in the efficacy of Checkpoint Inhibitors (CPIs) in NSCLC, and this paper is designed to answer these clinical questions. Methods For this Meta-analysis, we searched PubMed, Science of Web, Clinicaltrials.gov and online sources for trials comparing PD-1 and PDL-1 CPIs in advanced NSCLC. The data for Hazard Ratio (HR) and their Confidence Intervals (CI) for Overall Survival (OS) was extracted. Results A sum of 9739 patients from 16 trials were included in the efficacy evaluation. For the OS endpoint, both PD-1 inhibitors (HR = 0.76, 95%CI = 0.69-0.83, P < 0.001) and PDL-1 inhibitors (HR = 0.84, 95%CI = 0.74-0.95, P < 0.001) were superior to chemotherapy in treatment naive (upfront) patients, the results were similar in treatment refractory patients (PD-1 inhibitors (HR = 0.67, 95%CI = 0.60-0.75, P < 0.001) and PDL-1 inhibitors (HR = 0.78, 95%CI = 0.69-0.88, P < 0.001) were superior to chemotherapy). There was no difference in the effect of PD-1 and PDL-1 classes of CPIs over chemotherapy in treatment naive and treatment refractory settings (Q = 1.88, df = 1, P = 0.017, and, Q = 3.27, df = 1, P = 0.070, respectively). Conclusion Efficacy of PD-1 and PDL-1 class of CPIs was not different, although differences among individual CPIs or their combinations cannot be excluded. We were also able to compute pooled efficacy data, as compared to chemotherapy alone, for trials where these groups of CPIs were utilized.
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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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    Serum leptin level and waist-to-hip ratio (WHR) predict the overall survival of metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs)
    (Springer Japan Kk, 2013) Artac, Mehmet; Bozcuk, Hakan; Kiyici, Aysel; Eren, Orhan Onder; Boruban, Melih Cem; Ozdogan, Mustafa
    Our objective was to determine whether serum leptin levels and obesity-related factors could affect outcome for metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs). Sixty MBC patients treated with first line hormonal therapy were enrolled in this study. Median age was 51 years (range 28-75). Median leptin level was 19400 pg/ml (1970-91900) and estradiol level 29.6 pg/ml (4.0-181.9). Factors associated with overall survival in univariate analysis were age and waist-to-hip ratio (WHR), whereas only WHR retained significance in the multivariate analysis. However, no factor was associated with progression-free survival. However, WHR was found to be a significant prognostic marker only if the leptin level was a parts per thousand yen19400 pg/ml (HR = 0.38; 95% CI: 0.16-0.91). This study suggests that serum leptin levels and WHR together may serve as potential prognostic markers in MBC patients treated with AIs.
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    Survivin Expression May Affect The Neoadjuvantchemotherapy Response İn Breast Cancer Patients
    (2017) Er, Zehra; Peştereli, Hatice Elif; Tavlı, Lema; Bozcuk, Hakan; Erdoğan, Gülgün; Esen, Hacı Hasan; Artaç, Mehmet; Korkmaz, Levent; Gündüz, Şeyda; Karaağaç, Mustafa; Demircioğlu, Sinan
    To investigate whether there is a predictive effect of NF-kappaB, survivin, and Ki-67 expressions on pathological response and disease relapse in breast cancer (BC) patients. Ki-67, survivin and NF-kappaB expressions were analyzed in the pathology specimens of breast biopsy before and after neoadjuvant chemotherapy (NeoCT) in BC patients (n52). Event -free survival (EFS) (defined as recurrence or metastasis free) analyze was performed. The median overall survival was 43.5 months and the median EFS was 51 months (95% CI: 33.3-68.9) in all patients. The expression percentages of NF-kappaB, survivin, and Ki-67 significantly decreased after NeoCT (p>0.001). Survivin expression level before NeoCT was significantly higher in patients who did not respond to NeoCT than both partial-responders and complete-responders (p0.038, p0.010, respectively). Type of NeoCT was the only independent factor on pathological response status (p0.007). Addition of taxanes to NeoCT improved pathological complete response rates about six times. However, no predictor was found to be a prognostic factor for EFS in multivariate analyze. Higher survivin expression level before NeoCT may be associated with poor pathological response to NeoCT. These findings must be tested with prospective clinical trials.