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Öğe Antibody responses to COVID-19 vaccination in cancer: a systematic review(Frontiers Media SA, 2021) Güven, Deniz Can; Şahin, Taha Koray; Kılıçkap, Saadettin; Uçkun, Fatih M.Introduction: After the results of phase III vaccine studies became available, the leading oncology societies recommended two doses of COVID-19 vaccination to all patients with cancer with no specific recommendation for tumor type and active treatments. However, the data on the COVID-19 vaccine efficacy in cancer patients is limited due to exclusion of cancer patients from most vaccine clinical trials. Therefore, we systemically reviewed the available evidence evaluating the antibody responses in cancer patients. Methods: We conducted a systematic search from the Pubmed database and calculated risk differences (RD) and 95% confidence intervals (CI) to compare seroconversion rates between cancer patients and controls using the Review Manager software, version 5.3. Results: Our systematic search retrieved a total 27 studies and we included 17 studies with control arms in the analyses. Cancer patients had significantly lower seroconversion rates (37.3%) than controls (74.1%) (RD: -0.44, 95% CI: -0.52, -0.35, p<0.001) with first vaccine dose. After two doses, the seroconversion rates were 99.6% in control arm and 78.3% in cancer patients (RD: -0.19, 95% CI: -0.28, -0.10, p<0.001). The difference in seroconversion rates was more pronounced patients with hematologic malignancies (72.6%) (RD: -0.25, 95% CI: -0.27, -0.22, p<0.001) than patients with solid tumors (91.6%) (RD: -0.09, 95% CI: -0.13, -0.04, p<0.003) and patients in remission (RD: -0.10, 95% CI: -0.14, -0.06, p<0.001). Conclusion: In conclusion, COVID-19 vaccine seroconversion rates were significantly lower in patients with hematological malignancies and patients under active treatment. Further research focusing on the approaches to improve vaccine efficacy and exploration of novel treatment options is urgently needed for these patients.Öğe The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors(IOS Press, 2022) Güven, Deniz Can; Aktepe, Oktay Halit; Aksun, Melek Seren; Şahin , Taha Koray; Kavgacı, Gözde; Üçgül, Enes; Çakır, İbrahim Yahya; Yıldırım, Hasan Çağrı; Güner, Gürkan; Akın, Serkan; Kertmen, Neyran; Dizdar, Ömer; Aksoy, Sercan; Erman, Mustafa; Suayib, Yalçın; Kılıçkap, SaadettinBACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.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 The association between early changes in neutrophil-lymphocyte ratio and survival in patients treated with immunotherapy(MDPI, 2022) Güven, Deniz Can; Şahin, Taha Koray; Erul, Enes; Çakır, İbrahim Yahya; Üçgül, Enes; Yıldırım, Hasan Çağrı; Aktepe, Oktay Halit; Erman, Mustafa; Kılıçkap, Saadettin; Aksoy, Sercan; Yalçın, SuayibDynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data are limited. We evaluated the association between the neutrophil-lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. We retrospectively evaluated the data of 231 patients with advanced-stage cancer. We recorded baseline clinical characteristics, baseline NLR and fourth-week NLR changes, and survival data. A compound prognostic score, the NLR2-CEL score, was developed with the following parameters: baseline NLR (<5 vs. ?5), ECOG status (0 vs. ?1), Charlson Comorbidity Index (CCI, <9 vs. ?9), LDH (N vs. ?ULN), and fourth-week NLR change (10% or over NLR increase). In the multivariable analyses, higher NLR (HR: 1.743, p = 0.002), 10% or over NLR increase in the fourth week of treatment (HR: 1.807, p = 0.001), higher ECOG performance score (HR: 1.552, p = 0.006), higher LDH levels (HR: 1.454, p = 0.017), and higher CCI (HR: 1.400, p = 0.041) were associated with decreased OS. Compared to patients with the lowest scores, patients in the highest score group had significantly lower OS (HR: 7.967, 95% CI: 3.531-17.979, p < 0.001) and PFS. The composite score had moderate success for survival prediction, with an AUC of 0.702 (95% CI: 0.626-0.779, p < 0.001). We observed significantly lower survival in patients with higher baseline NLR values and increased NLR values under treatment.Öğe The Association between the Pan-Immune-Inflammation Value and Cancer Prognosis: A systematic review and meta-analysis(PMC, 2022) Güven, Deniz Can; Şahin, Taha Koray; Erul, Enes; Kılıçkap, Saadettin; Gambichler, Thilo; Aksoy, SercanBackground: Prognostic scores derived from the blood count have garnered significant interest as an indirect measure of the inflammatory pressure in cancer. The recently developed pan-immune-inflammation value (PIV), an equation including the neutrophil, platelet, monocyte, and lymphocyte levels, has been evaluated in several cohorts, although with variations in the tumor types, disease stages, cut-offs, and treatments. Therefore, we evaluated the association between survival and PIV in cancer, performing a systematic review and meta-analysis. Methods: We conducted a systematic review from the Pubmed, Medline, and Embase databases to filter the published studies until 17 May 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model. Results: Fifteen studies encompassing 4942 patients were included. In the pooled analysis of fifteen studies, the patients with higher PIV levels had significantly increased risk of death than those with lower PIV levels (HR: 2.00, 95% CI: 1.51–2.64, p < 0.001) and increased risk of progression or death (HR: 1.80, 95% CI: 1.39–2.32, p < 0.001). Analyses were consistent across several clinical scenarios, including non-metastatic or metastatic disease, different cut-offs (500, 400, and 300), and treatment with targeted therapy or immunotherapy (p < 0.001 for each). Conclusion: The available evidence demonstrates that PIV could be a prognostic biomarker in cancer. However, further research is needed to explore the promise of PIV as a prognostic biomarker in patients with non-metastatic disease or patients treated without immunotherapy or targeted therapy.Öğe The association of BMI and sarcopenia with survival in patients with glioblastoma multiforme(2021) Güven, Deniz Can; Aksun, Melek Seren; Çakır, İbrahim Yahya; Kılıçkap, Saadettin; Kertmen, NeyranBackground: The association between obesity and sarcopenia (via temporal muscle thickness) with overall survival (OS) has been evaluated in several glioblastoma multiforme studies, however, the data are inconclusive. Methods: The authors conducted meta-analyses via the generic inverse-variance method with a random-effects model. Results: In the pooled analysis of five studies, including 973 patients, patients with lower temporal muscle thickness had significantly decreased OS (HR: 1.62, 95% CI: 1.16-2.28, p = 0.005). The pooled analysis of five studies, including 2131 patients, demonstrated decreased OS in patients with lower BMI compared with patients with obesity (HR: 1.45, 95% CI: 1.12-1.88, p = 0.005). Conclusion: Readily available body composition parameters could be used for prognosis prediction and to aid in treatment decisions in patients with glioblastoma multiforme.Öğe The benefit of treatment beyond progression with immune checkpoint inhibitors: A multi-center retrospective cohort study(Springer, 2022) Güven, Deniz Can; Yekedüz, Emre; Erul, Enes; Coşkun Yazgan, Sati; Şahin, Taha Koray; Karataş, Göktürk; Aksoy, Sercan; Erman, Mustafa; Yalçın, Suayib; Urun, Yüksel; Kılıçkap, SaadettinObjective: Treatment beyond progression (TBP) with immune checkpoint inhibitors (ICIs) is an evolving field due to the limitations of conventional imaging in response evaluation. However, real-life data on the benefit of TBP is scarce, especially from the limited resource settings and patients treated in the later lines. Therefore, we aimed to investigate the survival benefit of TBP with ICIs in patients with advanced tumors from a limited resource setting. Methods: For this multi-center retrospective cohort study, we included 282 patients treated with ICIs and had radiological progression according to RECIST 1.1 criteria. We evaluated post-progression survival according to the use of TBP (TBP and non-TBP groups) with univariate and multivariate analyses. Results: The cohort's median age was 61, and 84.4% were treated in the second or later lines. 82 (29.1%) of 282 patients continued on ICIs following the initial progression. In multivariate analyses, patients in the TBP group had improved post-progression survival compared to non-TBP (13.18 vs. 4.63 months, HR: 0.500, 95% CI: 0.349-0.717, p < 0.001). The benefit of the TBP was independent of the tumor type, treatment line, and age. Furthermore, TBP with ICIs remained associated with improved post-progression survival (HR: 0.600, 95% CI: 0.380-0.947, p = 0.028) after excluding the patients with no further treatment after progression in the non-TBP arm. Conclusions: In this study, we observed that patients receiving ICIs beyond progression had considerably longer survival. Continuation of ICIs after progression should be considered a reasonable management option for patients with advanced cancer, specifically for patients with limited alternative options.Öğe Blood based biomarkers as predictive factors for hyperprogressive disease(MDPI, 2022) Yıldırım, Hasan Çağrı; Güven, Deniz Can; Aktepe, Oktay Halit; Taban, Hakan; Yılmaz, Feride; Yasar, Serkan; Aksoy, Sercan; Erman, Mustafa; Kılıçkap, Saadettin; Yalçın, SuayibPurpose: With the widespread use of immunotherapy agents, we encounter treatment responses such as hyperprogression disease (HPD) that we have not seen with previous standard chemotherapy and targeted therapies. It is known that survival in patients with HPD is shorter than in patients without HPD. Therefore, it is important to know the factors that will predict HPD. We aimed to identify HPD-related factors in patients treated with immunotherapy. Methods: A total of 121 adult metastatic cancer patients treated with immunotherapy for any cancer were included. Baseline demographics, the ECOG performance status, type of tumors and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. Results: The median age was 62.28 (interquartile range (IQR) 54.02-67.63) years, and the median follow-up was 12.26 (IQR 5.6-24.36) months. Renal cell carcinoma (33%) and melanoma (33.8%) were the most common diagnoses. Twenty patients (16.5%) had HPD. A high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007) were found to be associated with hyperprogression. Sex (female vs. male, p: 0.114), age (>65 vs. <65, p: 0.772), ECOG (0 vs. 1-4, p: 0.480) and the line of treatment (1-5, p: 0.112) were not found to be associated with hyperprogression. Conclusions: In this study, we observed HPD in 16.5% of immunotherapy-treated patients and increased HPD risk in patients with a high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007).Öğe Crizotinib efficacy after progression with entrectinib in ROS1-Positive lung cancer: a case report(CUREUS INC, 2022) Taban, Hakan; Güven, Deniz Can; Kılıçkap, SaadettinCrizotinib and entrectinib are approved tyrosine kinase inhibitors by the FDA to treat advanced-stage ROS1-positive non-small cell lung cancer (NSCLC). Although, entrectinib could be used after crizotinib, it is unknown whether crizotinib is effective after entrectinib. We report a case of NSCLC with ROS1 rearrangement that achieved a nearly complete response with crizotinib in the second-line treatment after progression with entrectinib. A 22-year-old Caucasian non-smoker female patient was diagnosed with stage IV non-squamous lung cancer with ROS1 positivity. We started on entrectinib as first-line therapy. Due to progression in the 10th month of treatment, entrectinib was stopped and crizotinib was started as a second -line treatment. At the end of the third month of the treatment, a nearly complete response was obtained in the follow-up imaging. The patient is still being followed up with crizotinib and is in the 15th month of treatment. Based on our experience, crizotinib can be an option as second-line therapy in patients who are treated with entrectinib in the first line, especially in patients without brain metastasis.Öğe Differences between hyperprogressive disease and progressive disease in patients receiving immunotherapy(Kare Publishing, 2022) Yıldırım, Hasan Çağrı; Güven, Deniz Can; Aktepe, Oktay Halit; Taban, Hakan; Yılmaz, Feride; Yaşar, Serkan; Aktaş, Burak Yasin; Güner, Gürkan; Dizdar, Ömer; Aksoy, Sercan; Erman, Mustafa; Yalçın, Suayib; Kılıçkap, SaadettinObjectives: Although immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment. In this group, a few of the patients with a hyperprogressive disease (HPD) have shorter overall survival (OS) compared with those having a progressive disease (PD). Therefore, biomarkers are needed to differentiate HPD and PD. Methods: Ninety-five patients treated with ICIs with progression according to response evaluation criteria ın solid tumors criteria in the first control imaging were included. HPD was defined according to Russo's work. The PILE scoring system, which includes pan-immune-inflammation value, lactate dehydrogenase, and Eastern Cooperative Oncology Group PS, was followed. The relationship between PILE score and HPD was analyzed. Results: The median OS of all cohorts was 11.18 months. The patients in the HPD group had decreased OS (4.77 vs. 13.94 months, p<0.001) and progression-free survival (PFS) (1.89 vs. 3.16 months, p<0.001) compared with those in the PD group. The risk of HPD was higher than the risk of PD in patients with a high PILE score (p=0.001). Conclusion: In this study, we showed that patients treated with ICI with a higher PILE score are at greater risk for HPD. The PILE score may be a biomarker to differentiate HPD from PD. © 2022 by Eurasian Journal of Medicine and Oncology.Öğe Newly diagnosed cancer and the COVID-19 pandemic: tumour stage migration and higher early mortality(BMJ, 2021) Güven, Deniz Can; Şahin, Taha Koray; Yıldırım, Hasan Çağrı; Çeşmeci, Engin; Gülbahçe İncesu, Fatıma Gül; Kılıçkap, SaadettinBackground: We compared the new outpatient clinic referrals during the first 10 months of the COVID-19 pandemic with the year before. Methods: We compared baseline characteristics of the 2208 new referrals in 2020 (n=922) and 2019 (n=1286) with ?2 and Mann-Whitney U tests and calculated ORs with binary logistic regression. To evaluate the expected changes in the cancer survival secondary to stage migration, we used the 5-year survival data of Survival, Epidemiology and End Results (SEER) Program 2010-2016. Results: The percentage of patients with inoperable or metastatic disease was significantly increased during the pandemic (49.8% vs 39%, OR: 1.553, 95% CI: 1.309 to 1.843, p<0.001). We observed a significant decrease in the percentage of patients diagnosed via the screening methods (18.8% vs 28.7%, OR: 1.698, 95% CI: 1.240 to 2.325, p=0.001). The 90-day mortality after the cancer diagnosis was significantly higher during the pandemic (10.5% vs 6.6%, OR: 1.661, 95% CI: 1.225 to 2.252, p=0.001). Due to the increased advanced-stage disease rate at first referral, significant decreases in 5-year survival rates were expected for breast cancer (-8.9%), colorectal cancer (-11.1%), cervix cancer (-10.3%) and melanoma (-7%). Conclusion: We think that collaborative efforts are paramount to prevent the pandemic of late cancer diagnoses and ensure patient safety during the pandemic.