MCBÜ Açıkerişim Sistemi :: Browsing by Author "Erdogan A.P."

Browsing by Author "Erdogan A.P."

Now showing 1 - 13 of 13

Octreotide in combination with AT-101 induces cytotoxicity and apoptosis through up-regulation of somatostatin receptors 2 and 5 in DU-145 prostate cancer cells
(Springer Science and Business Media B.V., 2016) Degirmenci M.; Erdogan A.P.; Bulut G.; Atmaca H.; Uzunoglu S.; Karaca B.; Karabulut B.; Uslu R.
Prostate cancer (PCa) is the most common type of cancer among males. Although survival rate of early-stage PCa is high, treatment options are very limited for recurrent disease. In this study, the possible synergistic cytotoxic and apoptotic effect of octreotide in combination with AT-101 was investigated in DU-145 hormone and drug refractory prostate cancer cell line. To enlighten the action mechanisms of the combination treatment, expression levels of somatostatin receptors 2 and 5 (SSTR2 and SSTR5) were also investigated. Cell viability was measured by XTT assay. Apoptosis was assessed through DNA fragmentation analysis and caspase 3/7 assay. mRNA and protein levels of SSTR2 and SSTR5 were evaluated by qRT-PCR and western blot analysis, respectively. Octreotide in combination with AT-101 inhibited cell viability and induced apoptosis synergistically in DU-145 cells as compared to any agent alone. Combination treatment increased both SSTR2 and SSTR5 mRNA and protein levels in DU-145 cells. The data suggest that this combination therapy may be a good candidate for patients with advanced metastatic PCa do not respond to androgen deprivation. © 2015, International Society of Oncology and BioMarkers (ISOBM).
Combination of zoledronic acid and serine/threonine phosphatase inhibitors induces synergistic cytotoxicity and apoptosis in human breast cancer cells via inhibition of PI3K/Akt pathway
(Springer Science and Business Media B.V., 2016) Surmeli Z.; Gursoy P.; Erdogan A.P.; Bozkurt E.; Atmaca H.; Uzunoglu S.; Sezgin C.; Şanlı U.A.; Uslu R.; Karaca B.
The aim of this study was to investigate the cytotoxic and apoptotic effects of zoledronic acid (ZA) in combination with serine/threonine protein phosphatase inhibitors, calyculin-A (CA) and okadaic acid (OA), in human MCF-7 and MDA-MB-231 breast cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. DNA fragmentation and caspase-3/7 activity assays were performed to evaluate apoptosis. Activities of phosphatase 1 (PP1) and phosphatase 2A (PP2A) were measured by serine/threonine phosphatase ELISA kit. Expression levels of PI3K, p-PI3K, Akt, p-Akt, Bcl-2, p-Bcl-2, Bad, and p-Bad proteins were evaluated by Western blot analysis. Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis as compared to any agent alone in both MCF-7 and MDA-MB-231 breast cancer cells. Combination treatment also resulted in inhibition of both PP1 and PP2A activities. Both agents used alone or in combination did not induce significant changes in total PI3K, Akt, Bcl-2, and Bad expressions, while p-PI3K, p-Akt, p-Bcl-2, and p-Bad levels were reduced by the combination treatment as compared to agents alone. Moreover, apoptotic effect of combination treatment was significantly inhibited in the presence of LY294002, a specific PI3K inhibitor, in both breast cancer cell lines. In conclusion, synergistic apoptotic effect of the combination treatment is correlated with the block of the PI3K/Akt signal pathway in breast cancer cells. © 2015, International Society of Oncology and BioMarkers (ISOBM).
Inflammatory Prognostic Index in Metastatic Renal Carcinoma Treated with Nivolumab
(College of Physicians and Surgeons Pakistan, 2022) Ekinci F.; Erdogan A.P.; Yildirim S.; Bulut G.; Yilmaz C.; Barutca S.
Objective: To evaluate the utility of inflammatory prognostic index (IPI), albumin, c-reactive protein (CRP), and lactate dehydrogenase (LDH) as predictive biomarkers of oncologic outcome in metastatic renal cell cancer (mRCC) patients treated with nivolumab. Study Design: Descriptive study. Place and Duration of Study: Manisa Celal Bayar University, Aydın Adnan Menderes University, Bitlis Tatvan State Hospital and Private Hatay Defne Hospital Medical Oncology Clinics, Turkey, from January 2017 to June 2020. Methodology: Seventy-five mRCC patients treated with nivolumab between January 2017 and June 2020 were enrolled. Several factors were retrospectively investigated, including IPI, CRP, LDH, and albumin level, for their association with progression-free survival (PFS) and overall survival (OS). The IPI was calculated as CRP × NLR/albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. Results: When analysed according to the calculated IPI score, it is seen that the group with <2.153 has an OS duration of 96.3 months, while the group with ≥2.153 has a shorter time of 42.9 months (p=0.02). In the analysis performed according to albumin level, it was reported that those with low levels (22.8 months) had worse median OS than those with high levels (92.8 months) (p=0.004). According to the cox regression analysis results, it was determined that those with a high IPI score significantly increased the risk of death compared to those with a low score (HR:2.4, p=0.023). However, this significance could not be confirmed in the multivariate analysis. It was analysed that those with low albumin levels significantly increased the risk of death compared to both univariate analysis (HR:3.3, p=0.007) and multivariate analysis (HR:4.4, p=0.003). Conclusion: Those with high IPI scores and low albumin levels were associated with worse median OS. However, only the multivariate analysis analysed albumin level as an independent prognostic variable. Prospective and more extensive research is needed to consolidate the potential prognostic power of these markers. © 2022 College of Physicians and Surgeons Pakistan. All rights reserved.
HALP Score as a New Prognostic Index in Metastatic Renal Cell Cancer
(College of Physicians and Surgeons Pakistan, 2022) Ekinci F.; Balcik O.Y.; Oktay E.; Erdogan A.P.
Objective: To evaluate prognostic significance of the new index, designed by formulating hemoglobin, albumin, lymphocyte, and platelet (HALP) counts in patients with metastatic renal cell carcinoma (RCC). Study Design: Descriptive study. Place and Duration of Study: Department of Medical Oncology, Celal Bayar University, Manisa, Turkey and Adnan Menderes University, Aydin, Turkey, from January 2014 to April 2020. Methodology: Patients with metastatic RCC and sufficient follow-up data were included in the study as a retrospective cohort. HALP score was calculated as hemoglobin (g/L) × albumin (g/L) levels × lymphocyte count (/L)/platelet count (/L). The cut-off value was determined by examining the area under the ROC curve for the HALP value. The endpoints of this study included overall survival (OS) and progression-free survival (PFS). Results: The mean overall survival (OS) of the patients with low HALP score was 17.7 months (95% CI, 2.21 - 33.18), while the OS of the patients with high HALP score was 89.7 months (95% CI, 55.62 - 123.77) and reached statistical significance (p=0.001). The results of univariate (p = 0.009) and multivariate (p=0.012) analyses were statistically significant as well. Conclusion: The HALP score in metastatic RCC patients was closely related to the prognosis. Worse OS was found in patients with a low HALP score. © 2022 College of Physicians and Surgeons Pakistan. All rights reserved.
Systemic Immune Inflammation Index as a Key Marker of Survival and Immune-related Adverse Events in Immune Checkpoint Inhibitor Therapy
(College of Physicians and Surgeons Pakistan, 2022) Ekinci F.; Balcik O.Y.; Demir B.; Gursoy P.; Ozveren A.; Erdogan A.P.
Objective: To evaluate the prognostic significance of the new index designed by formulating neutrophil, lymphocyte, and platelet counts in patients with metastatic disease receiving immune checkpoint inhibitors (ICI) and its effect on the immune-related adverse events (irAEs). Study Design: Cohort study. Place and Duration of Study: Department of Medical Oncology, University of Manisa Celal Bayar, University of Aydin Adnan Menderes, and University of Ege, and Izmir Kent Hospital, Turkey, from January 2016 to April 2020. Methodology: Patients with metastatic disease receiving ICI sufficient follow-up data were included. Patients, who had received treatment for a minimum of 3 months, were evaluated for the response. Systemic immune-inflammation index (SII) was calculated as neutrophil (/L) × (lymphocyte (/L) / platelet (/L). The cut-off value was determined by examining the area under the receiver operating characteristic (ROC) curve for the SII value. The endpoints of this study included overall survival (OS) and progression-free survival (PFS). Results: A total of 168, patients who received ICI in the metastatic stage, were evaluated. The OS of the patients with low SII scores was 110.8 months (95% CI, 88.2-133.5), while patients with high SII scores were 36.0 months (95% CI, 28.4-43.6) and reached statistical significance (p <0.001). The results of univariate (HR=3.376, 95% CI, 1.986-5.739, p<0.001 and multivariate (HR=2.792, 95% CI, 1.495-5.215, p=0.011) analyses were statistically significant as well. Conclusion: The SII score in patients with metastatic disease receiving ICI was closely related to the prognosis. Patients with a high SII score are associated with a worse prognosis, these patients develop fewer irAEs. © 2022 College of Physicians and Surgeons Pakistan. All rights reserved.
Efficacy and safety of folfiri plus aflibercept in second-line treatment of metastatic colorectal cancer: Real-life data from Turkish oncology group
(Wolters Kluwer Medknow Publications, 2022) Erol C.; Sendur M.A.N.; Bilgetekin I.; Garbioglu D.B.; Hamdard J.; Akbas S.; Hizal M.; Arslan C.; Sevinc A.; Kucukarda A.; Erdem D.; Kahraman S.; Cakir E.; Demirkiran A.; On S.; Dogan I.; Erdogan A.P.; Koca S.; Kubilay P.; Eren O.O.; Cilbir E.; Celik E.; Araz M.; Ozyukseler D.T.; Yildirim M.E.; Bahceci A.; Taskaynatan H.; Oyman A.; Deniz G.I.; Menekse S.; Kut E.; Gulmez A.; Sakin A.; Nayir E.; Acar R.; Sen E.; Inal A.; Turhal S.; Kaya A.O.; Paydas S.; Tastekin D.; Hacibekiroglu I.; Cincin I.; Bilici A.; Mandel N.M.; Dede D.S.; Akinci M.B.; Oksuzoglu B.; Uncu D.; Yalcin B.; Artac1 M.
Aims: The addition of aflibercept to the fluorouracil and irinotecan (FOLFIRI) regimen significantly improved clinical outcomes in patients with metastatic colorectal cancer (CRC) previously treated with oxaliplatin. We aimed to investigate the efficacy and safety of second-line FOLFIRI and aflibercept combination in patients with metastatic CRC in real-life experience. Materials and Methods: Four hundred and thirty-three patients who treated with FOLFIRI and aflibercept in the second-line were included in the study. The clinical and pathological features of the patients were recorded retrospectively. Survival (overall and progression-free survival [PFS]), response rates, and safety data were analyzed. Results: The median age was 61. Majority of patients (87.5%) received first-line bevacizumab and 10.1% of patients received anti-epidermal growth factor receptor agents. About 80% of patients had KRAS, 18.6% of patients had NRAS, and 6.4% of patients had BRAF mutations. The median OS was 11.6 months (95% confidence interval [CI], 10.6-12.6) and the median PFS was 6 months (95% CI, 5.5-6.5). About 4.6% of patients had complete response and 30.6% of patients had partial response as best tumor response. Grade 1-2 toxicities were seen in 33.4% of patients, while grade 3-4 toxicities were recorded in 27% of patients. Eight patients (2%) died due to treatment toxicity. Conclusions: Overall and PFS were similar in routine clinical practice compared to phase III pivotal VELOUR trial. However, response rates were found to be higher. It was observed that there were fewer adverse events compared to the VELOUR trial. © 2022 Authors. All rights reserved.
Factors Predicting Response in Breast Cancer Receiving Neoadjuvant Therapy and the Role of Ki67 Labeling Index
(College of Physicians and Surgeons Pakistan, 2023) Ekinci F.; Uzun M.; Demir B.; Unek I.T.; Erdogan A.P.
Objective: To determine the predictive value of Ki67 on pathological complete response (pCR) of breast and axilla regions in breast cancer (BC) patients receiving neoadjuvant therapy (NAT). Study Design: Descriptive study. Place and Duration of the Study: Departments of Medical Oncology, Sirnak State Hospital, Aydin State Hospital, Manisa Celal Bayar University, and Dokuz Eylul University, from November 2010 to July 2022. Methodology: PCR and various histopathological parameters were evaluated for BC patients receiving NAT. The Youden Index method was used to find the cut-off value for the Ki67 variable according to the receiver operating characteristic (ROC) curve. This value was obtained as 77.5. Breast and axillary responses were individually evaluated to assess response to NAT. Univariate and multivariate logistic regression analysis were used to predict both breast and axillary pCR. Results: A total number of 280 females receiving NAT for BC were included in the study. Multivariate analysis for breast pCR to NAT showed that Ki67 index (>77.5 vs <77.5, p=0.047) was statistically significant marker. While Ki67 index was significant for breast pCR in both univariate and multivariate analyses, the same was not observed on axillary response (p=0.387). Conclusion: High Ki67 level was significantly associated with breast pCR in BC patients receiving NAT, but a similar effect was not observed on axillary pCR. These findings suggest that breast and axilla tissues have a biological differences in treatment responses. © 2023 College of Physicians and Surgeons Pakistan. All rights reserved.
The inflammatory prognostic index as a potential predictor of prognosis in metastatic gastric cancer
(Nature Research, 2023) Ozveren A.; Erdogan A.P.; Ekinci F.
Clinical studies aimed at identifying effective and simple prognostic markers for gastric cancer are still being carried out. Inflammatory prognostic index (IPI) is being recognized as a promising prognostic marker in patients with Non-Small Cell Lung Cancer. To evaluate the prognostic utility of IPI in stage 4 gastric cancer. A total of 152 patients with stage 4 gastric cancer, whose laboratory parameters, progression-free survival (PFS) and overall survival (OS) data could be accessed, were evaluated. Kaplan Meier analysis was used for survival analyses. Hazard ratios were expressed with 95% CI values. All methods were performed in accordance with the relevant guidelines and regulations. Study was approved by the Manisa Celal Bayar University’s Non-Invasive Clinical Research Ethics Committee (approval No. E-85252386-050.04.04-49119, date: 22.03.2021). We confirm that all methods were performed in accordance with relevant named guidelines and regulations. Median age at diagnosis was 63 years (range: 32–88). The number of patients who received first-line chemotherapy was 129 (84.9%). Median PFS with first-line treatment was 5.3 months, while it was 3.3 months with second-line treatment. Median OS was 9.4 months. Median IPI score was 22.2. We evaluated IPI score for its value in detecting survival status with ROC analysis and identified an IPI cut-off score of 14.6. Low IPI score was significantly associated with longer PFS and OS compared to high IPI (PFS in high vs. low IPI, 3.6 vs. 7 months; p < 0.001) (OS in high vs. low IPI, 6.6 vs. 14.2 months; p < 0.001). IPI score can be an independent prognostic index that is inexpensive, easy to access and evaluate for patients with metastatic gastric cancer, and may be useful in predicting survival in daily practice. © 2023, The Author(s).
Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer
(Newlands Press Ltd, 2023) Kahraman S.; Erul E.; Seyyar M.; Gumusay O.; Bayram E.; Demirel B.C.; Acar O.; Aksoy S.; Baytemur N.K.; Sahin E.; Cabuk D.; Basaran G.; Paydas S.; Yaren A.; Guven D.C.; Erdogan A.P.; Demirci U.; Yasar A.; Bayoglu İ.V.; Hizal M.; Gulbagci B.; Paksoy N.; Davarci S.E.; Yilmaz F.; Dogan O.; Orhan S.O.; Kayikcioglu E.; Aytac A.; Keskinkilic M.; Mocan E.E.; Unal O.U.; Aydin E.; Yucel H.; Isik D.; Eren O.; Uluc B.O.; Ozcelik M.; Hacibekiroglu I.; Aydiner A.; Demir H.; Oksuzoglu B.; Cilbir E.; Cubukcu E.; Cetin B.; Oktay E.; Erol C.; Okutur S.K.; Yildirim N.; Alkan A.; Selcukbiricik F.; Aksoy A.; Karakas Y.; Ozkanli G.; Duman B.B.; Aydin D.; Dulgar O.; Er M.M.; Teker F.; Yavuzsen T.; Aykan M.B.; Inal A.; Iriagac Y.; Kalkan N.O.; Keser M.; Sakalar T.; Menekse S.; Kut E.; Bilgin B.; Karaoglanoglu M.; Sunar V.; Ozdemir O.; Turhal N.S.; Karadurmus N.; Yalcin B.; Nahit Sendur M.A.
Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference. © 2023 Future Medicine Ltd.
HALP Score as a New Prognostic Factor for Patients with Metastatic Bladder Cancer
(College of Physicians and Surgeons Pakistan, 2023) Acar O.; Ayhan M.; Demir B.; Ekinci F.; Aytac A.; Erdogan A.P.
Objective: To investigate the effect of the haemoglobin, albumin, lymphocyte, and platelet (HALP) score (Haemoglobin, Albumin, Lymphocyte, Platelet count) on survival as a new prognostic factor in metastatic bladder cancer. Study Design: Descriptive study. Place and Duration of the Study: Department of Medical Oncology, Celal Bayar University, Manisa, Turkey, and Adnan Menderes University, Aydin, Turkey, from 2010 to 2020. Methodology: The medical charts of patients with metastatic bladder cancer were reviewed retrospectively. Prognostic value of the HALP score as a marker of overall survival was examined through a receiver operating characteristic (ROC) curve analysis. Results: The cut-off value for the HALP score in the ROC curve analysis was 29. The median overall survival (OS) was 19 months when the HALP score was less than 29, and the median OS was 40 months when the HALP score was 29 or greater, and this finding was statistically significant (p = 0.003). Conclusion: The HALP score is closely related to prognosis in metastatic bladder cancer. A high HALP score is associated with better survival outcomes. © 2023 College of Physicians and Surgeons Pakistan. All rights reserved.
Positive Lymph Node Ratio as a new prognostic score in Geriatric patients with operated gastric cancer
(Elsevier Ltd, 2024) Acar O.; Balcik O.Y.; Urun M.; Avci T.; Sahbazlar M.; Erdogan A.P.
Objective: The pivotal prognostic determinant for recurrence and survival in surgically treated gastric cancer (GC) patients remains the lymph node status. Despite the adoption of D2 lymph node dissection as the standard approach in recent years, its association with increased morbidity in elderly patients raises concerns. This study aims to explore the prognostic significance of the Positive Lymph Node Ratio (PLNR) score in the context of recurrence and survival among elderly patients with surgically treated GC. Material and method: A retrospective review of files about surgically treated patients with GC was conducted. The prognostic impact of the PLNR score on overall survival (OS) was assessed through Receiver Operating Characteristic (ROC) analysis. Results: The cut-off value for the PLNR, determined through ROC analysis, was identified as 0.138. This value serves as a crucial threshold, as it distinguishes patients with a higher risk of poor outcomes. Patients with a PLNR score of 0.138 or below exhibited a median OS of 111 months, whereas those with a PLNR score above 0.138 had a significantly lower median OS of 22 months (p = 0.004). Conclusion: Our findings revealed that the PLNR emerged as an independent predictor of survival and recurrence in patients undergoing GC resection.However, it's important to note that while valuable, the PLNR system has limitations. It does not encompass the T stage, a key factor in cancer staging. Therefore, it cannot be a direct substitute for the comprehensive information TNM staging provides. It should be used as a supplementary tool in predicting prognosis, particularly in elderly patients unsuitable for standard lymph node dissection. © 2024 The Authors
Comparison of the efficacy of sunitinib and pazopanib in patients with advanced non-clear renal cell carcinoma
(Taylor and Francis Ltd., 2024) Yildirim H.C.; Bayram E.; Chalabiyev E.; Majidova N.; Avci T.; Güzel H.G.; Kapar C.; Uzun M.; Perkin P.; Akgül F.; Yildirim S.S.; Sali S.; Yildiz A.; Kazaz S.N.; Hendem E.; Arcagok M.; Tufan G.; Yildirim U.; Akgul O.F.; Arslan Ç.; Taban H.; Sahin E.; Caglayan M.; Esen R.; Öksüzoğlu B.; Guven D.C.; Kaplan M.A.; Araz M.; Basaran M.; Cubukcu E.; Gokmen E.; Cicin I.; Algin E.; Semiz H.S.; Tural D.; Ozturk B.; Erdogan A.P.; Sari M.; Kara O.; Erman M.
Non-clear cell renal cell carcinoma (non-ccRCC) is a highly heterogeneous disease group, accounting for approximately 25% of all RCC cases. Due to its rarity and especially heterogeneity, phase III trial data is limited and treatment options generally follow those of clear cell RCC. In the literature, there exists a number of studies with sunitinib, cabozantinib, and everolimus, but data on the efficacy of pazopanib are limited. Our aim in this study was to compare the efficacy of pazopanib and sunitinib, in a multicenter retrospective cohort of non-ccRCC patients. Our study included patients diagnosed with non-ccRCC who received pazopanib or sunitinib treatment as first-line therapy from 22 tertiary hospitals. We compared the progression-free survival (PFS), overall survival (OS), and response rates of pazopanib and sunitinib treatments. Additionally, we investigated prognostic factors in non-ccRCC. PFS and response rates of sunitinib and pazopanib were found to be similar, while a numerical difference was observed in OS. Being 65 years and older, being in the intermediate or poor risk group according to the International Metastatic Renal Cell Carcinoma Database Consortium, having liver metastases, presence of a sarcomatoid component, and having de novo metastatic disease were found to be significantly associated with shorter PFS. Pazopanib treatment appears to have similar efficacy in the treatment of non-ccRCC compared to sunitinib. Though randomized controlled trials are lacking and will probably be never be available, we suggest that pazopanib could be a preferred agent like sunitinib and cabozantinib. © 2024 Edizioni Scientifiche per l’Informazione su Farmaci e Terapia (Italian Society of Chemotherapy).
Real-Life Efficacy of Palbociclib and Ribociclib in Advanced Breast Cancer
(Multidisciplinary Digital Publishing Institute (MDPI), 2025) Avci T.; Sahbazlar M.; Ekinci F.; Erdogan A.P.
Background: Clinical trials in metastatic hormone receptor-positive (HR+) human epidermal growth factor receptor-2 (HER2)-negative patients have shown that cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors both increase response rates and provide survival benefits. The efficacy of these therapies needs to be supported by real-life data. In this study, we aimed to evaluate treatment response, survival and affecting factors in patients with HR+/HER2− metastatic breast cancer (MBC) who were followed up with CDK 4/6 inhibitors in our center. Materials and methods: A retrospective analysis of 120 patients with HR+/HER2− MBC treated with ribociclib or palbociclib in combination with letrozole or fulvestrant was performed. Results: Median progression-free survival (mPFS) was 24 months in the general population, 27 months in the ribociclib arm and 20 months in the palbociclib arm, with no significant difference in progression-free survival (PFS) in both arms (p = 0.25). The mPFS was longer in the ribociclib + letrozole arm compared to palbociclib + letrozole (27 vs. 20 months, respectively). PFS was also longer in patients receiving ribociclib + fulvestrant compared to palbociclib + fulvestrant but not statistically significant (33 vs. 21 months, respectively). Median overall survival (mOS) was not reached, but 3-year overall survival (OS) was statistically significantly longer in the ribociclib arm (87% vs. 55.5%, respectively, p = 0.03). Conclusion: Palbociclib and ribociclib are first-line treatment options for metastatic HR+/HER2− disease and have similar efficacy. In our study, while the mPFS was not statistically significant in both arms, the 3-year OS rate was higher in the ribociclib arm and statistically significant. Our findings were confirmed in randomized studies comparing both agents head-to-head. © 2025 by the authors.

Browsing by Author "Erdogan A.P."

Results Per Page

Sort Options