Browsing by Author "Dirican A."
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Item Enhanced cytotoxicity and apoptosis by thymoquinone in combination with zoledronic acid in hormone- and drugresistant prostate cancer cell lines(Zerbinis Publications, 2014) Dirican A.; Erten C.; Atmaca H.; Bozkurt E.; Kucukzeybek Y.; Varol U.; Tarhan M.O.; Karaca B.; Uslu R.Purpose: Thymoquinone (TQ), an active ingredient of black seed oil (Nigella Sativa), has been shown to possess cytotoxic activity against a variety of cancer cell lines. Our purpose was to investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the TQ in hormone- and drug-refractory prostate cancer cells PC-3 and DU-145. Methods: XTT cell proliferation assay was used to assess cytotoxicity; DNA fragmentation and caspase 3/7 activity were also measured. Results: The combination of TQ and ZA resulted in a significant synergistic cytotoxic activity and DN A fragmentation when compared to any single agent alone, in a dose- and time-dependent manner. In addition, TQ and ZA combination increased the caspase 3/7 activity in PC-3 cell line, while this activity could not be demonstrated in DU-145 cell line. Conclusion: TQ and ZA had minimal hematological and non-hematological toxicity profile compared to cytotoxic agents. So, this combination may be an alternative approach for patients who are unable to be treated by conventional treatments because of poor performance status.Item Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K–AKT pathway(Springer-Verlag Italia s.r.l., 2015) Dirican A.; Atmaca H.; Bozkurt E.; Erten C.; Karaca B.; Uslu R.Background: The treatment of castrate-resistant prostate cancer (CRPC) still remains as an important challenge of daily oncology practice. Docetaxel significantly prolongs overall survival in men with CRPC. Thymoquinone (TQ), one of the flavonoid compounds isolated from Nigealla sativa, has been shown to possess cytotoxic activity against a variety of cancer cell lines. Materials and Methods: The aim of the study was to investigate the possible synergistic cytotoxic/apoptotic effects of a novel combination, docetaxel and TQ in DU-145 hormone- and drug-refractory prostate cancer cells and their effects on PI3K and ERK signaling pathways Results: We observed that the combination of docetaxel and TQ resulted in a significant synergistic cytotoxicy and apoptosis as compared to any single agent alone, in a dose-dependent manner. It was found that viability of the combination treated cells was not significantly changed in the presence of LY294002 as compared to inhibitor treated cells. However, in the presence of FR180204, viability of combination treated cells was significantly decreased as compared to inhibitor treated cells. In conclusion, cytotoxic effect of the docetaxel and TQ combination is correlated with the block of the PI3K/Akt signaling pathway in DU-145 cells. Conclusion: Therefore, this combination strategy may be an alternative approach for the challenging era of daily oncologic practice. Also, the combination of docetaxel and TQ might allow a reduction in docetaxel doses and diminish adverse effects of docetaxel while maintaining the therapeutic effect in patients with CRPC. © 2014, Federación de Sociedades Españolas de Oncología (FESEO).Item A New Inflammatory Prognostic Index, Based on C-reactive Protein, the Neutrophil to Lymphocyte Ratio and Serum Albumin is Useful for Predicting Prognosis in Non-Small Cell Lung Cancer Cases(Asian Pacific Organization for Cancer Prevention, 2016) Dirican N.; Dirican A.; Anar C.; Atalay S.; Ozturk O.; Bircan A.; Akkaya A.; Cakir M.Purpose: We aimed to establish an inflammatory prognostic index (IPI) in early and advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze its predictive value for NSCLC survival. Materials and Methods: A retrospective review of 685 patients with early and advanced NSCLC diagnosed between 2009 and 2014 was conducted with collection of clinical, and laboratory data. The IPI was calculated as C-reactive protein × NLR (neutrophil/ lymphocyte ratio)/serum albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. Results: The optimal cut-off value of IPI for overall survival (OS) stratification was determined to be 15. Totals of 334 (48.8%) and 351 (51.2%) patients were assigned to high and low IPI groups, respectively. Compared with low IPI, high IPI was associated with older age, greater tumor size, high lymph node involvement, distant metastases, advanced stage and poor performance status. Median OS was worse in the high IPI group (low vs high, 8.0 vs 34.0 months; HR, 3.5; p<0.001). Progression free survival values of the patients who had high vs low IPI were determined 6 months (95% CI:5.3-6.6) and 14 months (95% CI:12.1-15.8), respectively (HR; 2.4, P<0.001). On multivariate analysis, stage, performance status, lactate dehydrogenase and IPI were independent prognostic factors for OS. Subgroup analysis showed IPI was generally a significant prognostic factor in all clinical variables. Conclusion: The described IPI may be an inexpensive, easily accessible and independent prognostic index for NSCLC patients, useful for clinical practice. © 2016, Asian Pacific Journal of Cancer Prevention. All Rights Reserved.Item A new inflammatory prognostic index, based on C-reactive protein, the neutrophil to lymphocyte ratio and serum albumin is useful for predicting prognosis in non-small cell lung cancer cases(Asian Pacific Organization for Cancer Prevention, 2016) Dirican N.; Dirican A.; Anar C.; Atalay S.; Ozturk O.; Bircan A.; Akkaya A.; Cakir M.Purpose: We aimed to establish an inflammatory prognostic index (IPI) in early and advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze its predictive value for NSCLC survival. Materials and Methods: A retrospective review of 685 patients with early and advanced NSCLC diagnosed between 2009 and 2014 was conducted with collection of clinical, and laboratory data. The IPI was calculated as C-reactive protein × NLR (neutrophil/ lymphocyte ratio)/serum albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. Results: The optimal cut-off value of IPI for overall survival (OS) stratification was determined to be 15. Totals of 334 (48.8%) and 351 (51.2%) patients were assigned to high and low IPI groups, respectively. Compared with low IPI, high IPI was associated with older age, greater tumor size, high lymph node involvement, distant metastases, advanced stage and poor performance status. Median OS was worse in the high IPI group (low vs high, 8.0 vs 34.0 months; HR, 3.5; p < 0.001). Progression free survival values of the patients who had high vs low IPI were determined 6 months (95% CI:5.3-6.6) and 14 months (95% CI:12.1-15.8), respectively (HR; 2.4, P < 0.001). On multivariate analysis, stage, performance status, lactate dehydrogenase and IPI were independent prognostic factors for OS. Subgroup analysis showed IPI was generally a significant prognostic factor in all clinical variables. Conclusion: The described IPI may be an inexpensive, easily accessible and independent prognostic index for NSCLC patients, useful for clinical practice.Item Evaluation of heterozygous deletion of TP53 gene in pleural fluid samples: A case series of 11 patients; [Plevral Sıvı Örneklerinde TP53 Geni Heterozigot Delesyonunun Değerlendirilmesi: 11 Hastalık Bir Seri](Derman Medical Publishing, 2016) Dirican N.; Bagci Ö.; Uz E.; Öztürk Ö.; Bircan H.; Dirican A.We described heterozygous deletion of tumor protein 53 (TP53) gene in 11 patients including 2 patients with non-malignant diseases (pneumonia) and 9 patients with malignant diseases [including small cell lung cancer (n = 3), non-small cell lung carcinoma (n = 4), non-Hodgkin’s lymphoma (n=1), and gastric carcinoma (n=1)]. Chromosomal aberrant status was analyzed by fluorescence in situ hybridization with centromere specific and 17p13.1 locus specific probes. In 3 of 9 cancer patients we did not find malignant pleural effusion with histological examination and/or closed pleural biopsy. Heterozygous deletion of TP53 gene was found to be significantly higher in patients with malignant disease when compared to the patients with benign pleural fluid. As a result, we suggest that heterozygous deletion of TP53 may have indicator value for malignancy; however further studies are warranted to confirm this suggestion in large patient cohorts. © 2016, Journal of Clinical and Analytical Medicine. All Rights Reserved.Item Association of intra-tumoral tumour-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio is an independent prognostic factor in non-small cell lung cancer(Blackwell Publishing Ltd, 2017) Dirican N.; Karakaya Y.A.; Gunes S.; Daloglu F.T.; Dirican A.Background: Studies suggest that tumour-infiltrating lymphocytes (TILs) and inflammation markers have independent roles in non-small cell lung cancer (NSCLC), but the relationship between the two pronostic factors remains unclear. In this study, we investigated TILs and inflammation markers in with patients advanced stage NSCLC and assessed the association of their levels with prognosis. Materials and Methods: TILs were evaluated by immunohistochemical staining for cluster of differentiation 3 (CD3) and cluster of differentiation 5 (CD5) and by hematoxylin and eosin staining for non-specific lymphocyte. We investigated the localisation pattern of TILs in advanced stage NSCLC. We divided all cases into two groups: TILs-high and TILs-low groups, by 75th percentile of the population of. In our study, inflammation markers were assessed by C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR). Results: The results showed that the presence of intra-tumoral high CD3+ and low CD5+ were an independent prognostic factor for overall survival (respectively, P = 0.022 and P = 0.025). Moreover, the high NLR and serum high CRP levels were associated with poor survival (respectively, P = 0.008; P = 0.027). In multi-variate survival analysis, the high CD3+, low CD5+, high NLR, tumour node metastasis (TNM) stage, depth of tumour invasion and lymph node metastasis remained independent prognostic factors (respectively, P = 0.018, P = 0.020, P = 0.024, P = 0.038, P = 0.020 and P = 0.047).The high NLR was detected negative correlation with intra-tumoral CD3+ and positive correlation with intra-tumoral CD5+ (respectively, r = −0.623, P = 0.012; r = 0.628, P = 0.028). Conclusions: This study is first report demonstrating the prognostic value of intra-tumoral low CD5+ with NSCLC. Increased CD3+ and low CD5+ was observed in patients with poor prognosis; the two molecules were correlated with NLR, suggesting that inflammation might be used as improve therapeutic efficacy to immunotherapy for advanced NSCLC. © 2015 John Wiley & Sons LtdItem A rare parasitic infection: visceral leishmaniasis case after gastric cancer treatment(Springer-Verlag Wien, 2018) Yolcu A.; Dirican A.; Ozturk G.G.; Cetin C.B.; Aydogdu I.We present a case of Visceral Leishmaniasis (VL) in a patient with gastric cancer treated with chemoradiotherapy. A 69-year-old man with gastric carcinoma had been treated with total gastrectomy, lymphadenectomy and postoperative radiotherapy with chemotherapy. Then 3 years after treatment, due to pancytopenia with progressive trombocytopenia and splenomegaly, bone marrow examination was performed and Leishmania spp. amastigotes were diagnosed. When antibiotherapy was completed, splenomegaly was eliminated and the laboratory results became normal. VL should be kept in mind in the differential diagnosis of patients, even adults, with splenomegaly, trombocytopenia and a history of contact with dogs in endemic countries such as Turkey. © 2018, Springer-Verlag GmbH Austria, part of Springer Nature.Item Programmed cell death ligand-1 expression in gastroenteropancreatic neuroendocrine tumors(Zerbinis Publications, 2019) Oktay E.; Yalcin G.D.; Ekmekci S.; Kahraman D.S.; Yalcin A.; Degirmenci M.; Dirican A.; Altin Z.; Ozdemir O.; Surmeli Z.; Diniz G.; Ayhan S.; Bulut G.; Erdogan A.; Uslu R.Purpose: Gastroenteropancreatic tumors (GEPNETs) is a heterogeneous disease with variable clinical course. While promising therapeutic options exist for other adult cancers, there are no new molecular-based treatments developed for GEPNETs. One of the main targets of cancer immunotherapy is the Programmed Cell Death Ligand-1 (PD-L1) pathway. Our purpose was to investigate the profile of PD-L1 expression in different organs of GEPNETs and compare the conventional immunohistochemistry (IHC) with the RNA expression analysis via real time polymerase chain reaction (RT-PCR) in order to determine which patients might be appropriate for immune check point-targeted therapy. Methods: A total of 59 surgically or endoscopically resected GEPNET tissues were retrospectively collected. The expression of PD-L1 and mRNA was evaluated with IHC. Results: The expression of PD-L1 was significantly associated with the high-grade classification (p=0.012). PD-L1 mRNA expression in tumor samples appeared to be higher compared to the corresponding normal tissues. In appendix, stomach and small intestine, the expression of PD-L1 mRNA was higher in the tumor tissues compared to the respective controls. In pancreas and colon, control tissues tend to have a higher PD-L1 mRNA expression compared to tumor tissues. PD-L1 mRNA expression was higher in GEP carcinomas (p=0.0031). Conclusion: RT-PCR was found to be more sensitive in detecting PD-L1 expression than conventional IHC. This study may provide an important starting point and useful background information for future research about immunotherapy for appendix, stomach and small intestine neuroendocrine carcinomas. © 2019 Zerbinis Publications. All rights reserved.Item Estimating Chemotherapy Side Effect in Histopathologically Diagnosed Patients over 65 with Metastatic Breast Cancer Using Deep Learning; [Derin Öǧrenme ile Histopatolojik Olarak Tani Konmuş 65 Yaş Üstö Metastatik Meme Kanseri Hastalarinda Kemoterapi Yan Etkisini Öngörme](Institute of Electrical and Electronics Engineers Inc., 2019) Beduk H.; Beduk M.S.; Dirican A.; Tuglu M.I.Breast cancer has become one of the increasing social health problems. Breast cancer cases are increasing every year in Turkey, one in 8 women develops breast cancer and every year, 25,000 new breast cancer cases are diagnosed. Increased obesity and menopausal age, decreased fertility, environmental and genetic factors also increase the rate of breast cancer. Diagnosis and treatment of breast cancer is of great importance.Deep learning is a part of machine learning that began to be used in the early 2010s. It is a method that provides more effective inferences by using machine learning methods with the help of multiple layers. With deep learning, very realistic results were obtained in estimations based on historical data. As in many other fields, deep learning methods have been used in the field of medicine.In this study, it is aimed to make an analysis study to predict side effects in patients who are given chemotherapy by using deep learning methods in breast cancer patients diagnosed over 65 years. As a result of this study, it was aimed to give an idea to physicians whether or not to apply chemotherapy to breast cancer patients over 65 years. In this study, a two-class problem, positive and negative, was discussed and as a result 74% accuracy was obtained. This is the first study on this subject, there is no previous study on whether breast cancer should be given with deep learning in the elderly with breast cancer. © 2019 IEEE.Item Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab(Springer Japan, 2021) Tural D.; Ölmez Ö.F.; Sümbül A.T.; Özhan N.; Çakar B.; Köstek O.; Ekenel M.; Erman M.; Coşkun H.Ş.; Selçukbiricik F.; Keskin Ö.; Türköz F.P.; Oruç K.; Bayram S.; Bilgetekin İ.; Yıldız B.; Şendur M.A.N.; Paksoy N.; Dirican A.; Erdem D.; Selam M.; Tanrıverdi Ö.; Paydaş S.; Urakçı Z.; Atağ E.; Güncan S.; Ürün Y.; Alkan A.; Kaya A.O.; Özyükseler D.T.; Taşkaynatan H.; Yıldırım M.; Sönmez M.; Başoğlu T.; Gündüz Ş.; Kılıçkap S.; Artaç M.Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. Patients and methods: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. Results: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37–86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673–5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120–4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558–4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031–4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1–3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. Conclusions: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer. © 2021, Japan Society of Clinical Oncology.Item Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences(Elsevier B.V., 2021) Tural D.; Ölmez Ö.F.; Sümbül A.T.; Artaç M.; Özhan N.; Akar E.; Çakar B.; Köstek O.; Ekenel M.; Erman M.; Coşkun H.Ş.; Selçukbiricik F.; Keskin Ö.; Türköz F.P.; Oruç K.; Bayram S.; Yılmaz U.; Bilgetekin İ.; Yıldız B.; Şendur M.A.N.; Paksoy N.; Dirican A.; Erdem D.; Selam M.; Tanrıverdi Ö.; Paydaş S.; Urakçı Z.; Atağ E.; Güncan S.; Ürün Y.; Alkan A.; Kaya A.O.; Özyükseler D.T.; Taşkaynatan H.; Yıldırım M.; Sönmez M.; Başoğlu T.; Gündüz Ş.; Kılıçkap S.Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. Objective: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. Design, setting, and participants: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. Outcome measurements and statistical analysis: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. Results and limitations: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47–28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25–5.49) and 9.8 mo (95% CI, 6.7–12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3–4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies. Conclusions: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. Patient summary: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting. © 2020 European Association of UrologyItem Can Albumin Bilirubin Ratio and Inflammatory Prognostic Index Be A New Marker Determining Survival in Metastatic Pancreatic Cancer?(NLM (Medline), 2021) Ekinci F.; Sarı D.; Çelik C.; Dirican A.; Erdoğan A.P.; Gökse G.OBJECTIVE: The main purpose of our study is to analyze the predictive and prognostic value of inflammatory prognostic index (IPI (using albumin, CRP, neutrophils and lymphocytes) and albumin / bilirubin ratio in metastatic pancreatic cancer patients in addition to other markers currently used. MATERIALS AND METHODS: Medical records of patients with pancreatic cancer treated in Celal Bayar University Medical Faculty Hospital Medical Oncology Clinic between February 2012 and April 2020 were retrospectively reviewed. Clinicopathologic variables such as age, gender, performance status (PS), treatments, histopathology type, localization of metastasis, comorbidity were recorded by an electronic medical record system. Patients performance status were recorded according to the Eastern Cooperative Oncology Group (ECOG). A total of 110 pancreatic cancer patients were reviewed. The IPI was calculated as C-reactive protein × NLR (neutrophil/lymphocyte ratio)/serum albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. RESULTS: Median OS of all patients was 6 months. The NLR cut off value we calculated was 3,47. The median OS of 47 (49,4%) patients was 8 months (95 % cl. 8,673- 15,383) with NLR < 3,47 and median OS of 48 (50,6%) patients was 4 months (95 % cl. 4,221-7,523) with NLR ≥ 3,47 (P: 0,001). The cut off value calculated for the IPI was 0,79. The median OS of 24 (25,8 %) patients was 8 months (95 % cl. 7,475-18,814) with IPI < 0,79 andmedian OS of 69 (74,2 %) patients was 5 months (95 % cl. 5,774-9,580) with IPI ≥ 0,79 (P: 0,047). The ABR cut off value we calculated was 5,23. The median OS of 45 (47,3 %) patients was 4 months (95 % cl. 8,879- 15,174) with ABR ≥ 5,23 and median OS of 50 (42,7 %) patients was 9 months (95 % cl. 4,015-7,585) with ABR < 5,23 (p< 0.001) (Figure 1). According to this analyses, presenting with jaundice, peritoneum metastasis, CA19.9 and LDH values higher than cut off, high NLR, high IPI and high ABR were also significantly associated with OS. In multivariate analyses, ABR was an independent prognostic factor in PC. Patients with high ABR (> 5,23) had increases in the risk of death compared with those with low ABR (< 5,23) (HR, 0,305; 95 % CI, 0,176-0,531; p: 0.000). Alongside ABR, CA-19.9 (HR, 2,300; 95 % CI, 1,111-4,764; p: 0,025) and LDH (HR, 3,348; 95 % CI, 1,792-6,253; p: 0.000) were an independent prognostic factor in PC. CONCLUSION: In this study, we demonstrated that both IPI and ABR, which were not evaluated in PC before, are non-invasive, cheap, accessible, and easily formulated parameters in determining the prognosis. Especially the fact that ABR is an independent prognostic indicator in multivariate analysis makes it stronger. Although we are aware that our study is retrospective, we hope that the reliability of these scores will increase if it is done with more patient series and if it is done multicenter.Item Could the Inflammatory Prognostic Index Predict the Efficacy of Regorafenib in Patients with Metastatic Colorectal Cancer?(Springer, 2022) Erdoğan A.P.; Ekinci F.; Karabaş A.; Balçık O.Y.; Barutça S.; Dirican A.Purpose: To investigate the clinical importance of the inflammatory prognostic index (IPI) in patients with metastatic colorectal cancer treated with regorafenib. Methods: A retrospective analysis of 65 metastatic CRC patients treated with regorafenib between 2015 and 2020 was performed. The association between NLR, PNLR, IPI, and overall survival (OS) and progression-free survival (PFS) was evaluated. Results: According to the cut-off points, patients were divided into two groups. The patients in the high IPI group showed poorer OS compared to patients in the low IPI groups. The PFS was better in patients with low neutrophil-lymphocyte ratio (NLR) and platelet-neutrophil to lymphocyte ratio (PNLR), and the OS was better in patients with low IPI. Conclusion: Among the immune inflammation scores analyzed in mCRC patients receiving regorafenib, NLR and PNLR were the best predictor of recurrence, whereas IPI was the best predictor of long-term survival. After being confirmed by better designed controlled trials, IPI can be used to identify the group of patients who will benefit more from regorafenib treatment. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.Item Vinorelbine Induced Serpentine Supravenous Hyperpigmentation(Turkiye Klinikleri, 2022) Yetut A.D.; Taş S.; Ekinci F.; Çelik C.; Erdoğan A.P.; Dirican A.Serpentine supravenous hyperpigmentation (SSH) is a rare complexity arising from antineoplastic therapy. Vinorelbine, a chemotherapeutic drug that is frequently used for the treatment of breast and lung cancer, contributes to the etiology of SSH. A 54 years old male patient was being treated for lung adenocarcinoma. An intravenous (IV) infusion of vinorelbine was administered in the distal dorsal vein of the left forearm. Erythematous hyperpigmentation at the infusion area was observed a week after the administration of the chemotherapeutic drug. The initial symptoms of SSH usually appear between 1 to 15 days post IV administration of a cytotoxic drug, and it spontaneously be-comes hyperpigmented within 1-3 weeks. However, these local reactions can be prevented by applying IV infusion for a short period (15-30 min) along with adequate venous irrigation (75-124 mL) instead of bolus administration. The termination of the drug can also be considered. © 2022 by Turkish Society of Medical Oncology.Item A multicentre, multinational study of clinical characteristics and prognosis of hepatocellular carcinoma; [Étude multicentrique et multinationale des caractéristiques cliniques et du pronostic du carcinome hépatocellulaire](World Health Organization, 2023) Dirican A.; Uncu D.; Sekacheva M.; Artaç M.; Aladashvil A.; Erdogan A.; Kaplan M.; Alacacıoğlu A.; Boukovinas I.; Turhal N.Background: Hepatocellular carcinoma (HCC) is a significant health problem, and the associated mortality rate is increasing. Aim: We aimed to determine the clinical characteristics and prognosis for HCC in member countries of the OncoBridge Study Group. Methods: We recruited 630 patients diagnosed with HCC between 2013 and 2019 from 4 countries (Türkiye, Russia, Georgia, and Greece). Univariate and multivariate analyses were conducted to investigate clinical and laboratory prognostic factors. Receiver operating characteristic (ROC) analysis was used to determine the prognostic value of the neutrophil to lymphocyte ratio (NLR) and alpha-fetoprotein (AFP) value. Results: The 3 most common etiological factors were hepatitis B infection (39.7%), hepatitis C virus infection (17.0%) and non-alcoholic fatty liver disease (9.0%). Median overall survival for the whole group was 25 [95% confidence interval (CI): 15.7–34.2] months. Cut-off values for AFP and NLR were accepted as 200 ng/mL and 3.45, respectively. The area under the ROC curve values for AFP, NLR and NLR+AFP were 0.625 (95% CI: 0.547–0.704), 0.589 (95% CI: 0.512–0.667) and 0.657 (95% CI: 0.583–0.731). From the multivariate analysis, advanced tumour size, lymph node involvement and metastasis (TNM) stage, presence of cirrhosis, high AFP, and high NLR values were associated with poor survival. Conclusion: AFP, NLR, advanced TNM, and presence of cirrhosis may predict prognosis in patients with HCC. Studies involving more countries are needed to corroborate these findings. © Authors 2023; Licensee: World Health Organization.Item The Confusion Caused by the Fear of COVID 19 in the Future of Cancer Patients(Ibn Sina Trust, 2023) Ekinci F.; Ateş G.A.; Erdoğan A.P.; Çelik C.; Dirican A.; Göksel G.Objective: The “centrality of events scale” (CES) was formed to determine to what extent this localisation of a traumatic memory is formed. The CES was used in this study to determine how overshadowed the cancer disease was by fear of COVID-19 in cancer patients or how centralised the cognitive trauma was in this patient group.Materials and Methods: In the first paragraph of the short 7-item CES, it was written, “Please think about the most stressful or traumatic event in your life”, then 3 options were given. These alternatives were: A) I am currently being treated here for my disease., B) I am likely to catch COVID-19 and C) Other. After marking one of these options, the subjects were instructed to mark their level of agreement with the 7 items as stated by Berntsen and Rubin, and thus this section was the same as the original questionnaire. To be able to evaluate the questionnaire results taking the disease characteristics into account, a record was made of age, gender, treatment history (chemotherapy and radiotherapy), current treatment (chemotherapy, hoemone therapy, immunotherapy, monoclonal antibodies, tyrosine kinase inhibitors) treatment aim (adjuvant, neoadjuvant, palliative), disease status on presentation (no spread, local, metastatic).The questionnaires were administered to all the cancer patients who presented at the oncology clinic between 1 April and 1 October 2020. Results:This study was conducted to seek an answer to this question, and it was seen that of a total of 523 patients diagnosed with cancer, the vast majority (n:368, 70.4%) saw the most traumatic and stressful event of their life as cancer, with the response to option A on the questionnaire. The possibility of contracting COVID-19 was selected by 83 (15.9%) patients as the most stressful or traumatic event in their life. The option of C was marked by 72 (13.8%) patients. This showed that neither cancer nor fear of coronavirus infection was strong enough to replace the traumatic event experienced and centred in the identity of these 72 patients. These traumas of the patients were analyzed with the mean CES points. The highest points were obtained by those who marked option A, at 3.71, which was statistically significantly higher than the 3.29 points for B and 3.29 points for C (p:0.004).Conclusion:A trauma left in the past actually lives on in the cognitive memory and may even be established at the centre of the self and personal identity. Thus, by modifying the short 7-item CES, developed by Berntsen and Rubin to be an objective, measurable format, the results of this study demonstratated both the extent to which the possibility of contracting COVID-19 has started to be established in cancer patients and the unshakable but declining centrality of cancer in the traumatic past. © 2023, Ibn Sina Trust. All rights reserved.Item Can Cytoreductive Nephrectomy Improve Outcomes of Nivolumab Treatment in Patients with Metastatic Clear-Cell Renal Carcinoma?(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Ocak B.; Sahin A.B.; Ertürk I.; Korkmaz M.; Erdem D.; Cakıroglu U.; Karaca M.; Dirican A.; Olmez O.F.; Goktas Aydın S.; Gökyer A.; Kücükarda A.; Gülmez A.; Yumuk P.F.; Demircan N.C.; Oyman A.; Sakalar T.; Karatas F.; Demir H.; Yasin A.I.; Deligonul A.; Dakiki B.; Goktug M.R.; Avcı O.; Tacar S.Y.; Turhal N.S.; Deniz G.I.; Kacan T.; Cubukcu E.; Evrensel T.Background: This study aimed to investigate the effect of cytoreductive nephrectomy (CN) on the survival outcomes of nivolumab used as a subsequent therapy after the failure of at least one anti-vascular endothelial growth factor (VEGF) agent in patients with metastatic clear-cell renal-cell carcinoma (ccRCC). Methods: We included 106 de novo metastatic ccRCC patients who received nivolumab after progression on at least one anti-VEGF agent. Multivariate Cox regression analysis was performed to investigate the factors affecting survival in patients receiving nivolumab. Results: Of the 106 de novo metastatic ccRCC patients, 83 (78.3%) underwent CN. There were no statistical differences between the two groups in terms of age, gender, Eastern Cooperative Oncology Group (ECOG) score, tumor size, International Metastatic RCC Database Consortium (IMDC) risk group, number of previous treatment lines, first-line anti-VEGF therapy, or metastasis sites (p = 0.137, p = 0.608, p = 0.100, p = 0.376, p = 0.185, p = 0.776, p = 0.350, and p = 0.608, respectively). The patients who received nivolumab with CN had a longer time to treatment discontinuation (TTD) [14.5 months, 95% confidence interval (CI): 8.6–20.3] than did those without CN 6.7 months (95% CI: 3.9–9.5) (p = 0.001). The median overall survival (OS) was 22.7 months (95% CI: 16.1–29.4). The patients with CN had a median OS of 22.9 months (95% CI: 16.3–29.4), while those without CN had a median OS of 8.1 months (95% CI: 5.6–10.5) (p = 0.104). In the multivariate analysis, CN [hazard ratio (HR): 0.521; 95% CI: 0.297–0.916; p = 0.024] and the IMDC risk score (p = 0.011) were statistically significant factors affecting TTD; however, the IMDC risk score (p = 0.006) was the only significant factor for overall survival. Conclusions: Our study showed that the TTD of nivolumab was longer in metastatic ccRCC patients who underwent cytoreductive nephrectomy. © 2024 by the authors.