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    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.
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    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, Suayib
    Dynamic 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.
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    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, Sercan
    Background: 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.
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    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, Saadettin
    Objective: 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.
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    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, Saadettin
    Background: 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.