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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 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 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 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 The frequency and determinants of metabolic syndrome in operated patients with stage ı-ııı breast cancer(Akad Doktorlar Yayinevi, 2020) Sarıcı, Saim Furkan; Sunar, Veli; Aksoy, SercanMetabolic syndrome is a clinical condition with a combination of multiple cardiac risk factors including obesity, insulin resistance, hypertriglyceridemia, low HDL, and hypertension. There is serious evidence that metabolic syndrome increases the risk of breast cancer. In this study, we aimed to define the frequency and determinants of metabolic syndrome in operated patients with stage I-III breast cancer. Operated patients with stage I-III breast cancer who admitted to our clinic between April 2009 and April 2018 were examined cross-sectionally. Metabolic syndrome was defined according to NCEP criteria. Metabolic syndrome criteria, demographic data, tumor size, grade, lymph node, estrogen-progesterone, HER2 status, and chemotherapy / endocrine treatment histories were obtained from patients and hospital records. 700 patients with a median age of 50.6 were analyzed. Tamoxifen was given to 194 patients and aromatase inhibitors were given to 240 patients. Any hormonal therapy was not given to 266 patients (new diagnosis and/ or triple-negative patients). Metabolic syndrome was observed in 43.1% of patients according to NCEP criteria Metabolic syndrome was found to be more frequent in the group receiving aromatase inhibitor than the group receiving tamoxifen (53.4% vs. 24.7%, p< 0.001). The frequency of metabolic syndrome was 48.2% in the group not receiving any hormonal treatment. Metabolic syndrome was more common in the postmenopausal patient group than the premenopausal group (49.0% vs. 26.1% p< 0.001). The incidence of metabolic syndrome was lower in patients with HER2 positive and a history of oral contraceptive use. (33.9% vs. 44.0% HER2, 0.11 and 37.7% vs. 40.8% oral contraceptive use history, p= 0.25). 75.1% of the patients had received adjuvant chemotherapy. There was no difference in the frequency of metabolic syndrome between the groups receiving and not receiving adjuvant chemotherapy. There was no statistically significant correlation between the presence of metabolic syndrome and estrogen/progesterone receptor status, tumor size, lymph node, stage, grade, hormone replacement therapy, chemotherapy, and smoking history. 43.1% of operated patients with stage I-III breast cancer had metabolic syndrome. Metabolic syndrome was more common in patients receiving adjuvant aromatase inhibitors, whereas less common in patients using oral contraceptives and having HER2 positive. These findings suggest that aromatase inhibitors may contribute to the development of the metabolic syndrome. Prospective studies are needed to explain this relationship.Öğe Impact of opioid analgesics on survival in cancer patients receiving immune checkpoint inhibitors(Springer, 2024) Kavgacı, Gözde; Güven, Deniz Can; Kaygusuz, Yunus; Karaca, Ece; Dizdar, Ömer; Kılıçkap, Saadettin; Aksoy, Sercan; Erman, Mustafa; Yalçın, SuayibPurpose This study aimed to assess the effects of concurrent opioid analgesic (OA) use with immune checkpoint inhibitors (ICIs) on progression-free survival (PFS) and overall survival (OS). Methods In this observational retrospective study, we included advanced cancer patients who received ICIs at Hacettepe University Hospital's Department of Medical Oncology between June 2018 and January 2023. Results Our study included 375 recurrent or metastatic cancer patients treated with ICIs in the first, second line, or beyond. There were no significant differences between the OA-treated and OA-untreated groups regarding median age, age group, gender, primary tumor location, ICI type, or the presence of baseline liver and lung metastases. However, the OA-treated group exhibited a significantly higher proportion of patients who had received three or more prior treatments before initiating ICIs (p = 0.015). OA-Untreatment was significantly correlated with prolonged mPFS (6.83 vs. 4.30 months, HR 0.59, 95% CI 0.44-0.79, p < 0.001) and mOS (17.05 vs. 7.68 months, HR 0.60, 95% CI 0.45-0.80, p < 0.001). Conclusions Our study demonstrates an association between the concurrent use of OAs and reduced OS and PFS in patients treated with ICIs. While OA treatment serves as a surrogate marker for higher disease burden, it may also suggest a potential biological relationship between opioids and immunotherapy efficacy.
