Fakülteler / Faculties
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Item Oncofertility for Gynecologic and Non-Gynecologic Cancers: Fertility Sparing in Young Women of Reproductive Age(2014) Dursun, Polat; Dogan, N. Utku; Ayhan, Ali; 25090914; AAJ-5802-2021About ten percent of all female cancer survivors is younger than 40 years of age. For these young women the primary goal is to ensure the highest possibility of cure and to maintain the reproductive functions as well. Oncofertility is a new concept including both oncology and reproductive medicine. By this recently defined concept young women will have maximal chance to make an optimal decision without any significant impact and delay in oncologic outcome. Oncofertility concept could be applied for genital cancer as well as non-genital cancer of reproductive age. Currently sperm and embryo banking are the standard methods used for young patients with cancer whose future fertility is under risk. In contrary oocyte banking, ovarian tissue cryopreservation are all controversial procedures and still accepted as experimental by many authors although American Society of Reproductive Medicine (ASRM) consideres oocyte cryopreservation "no longer experimental". For genital cancers procedures for oncofertility depends on the type of the cancer and the treatment of choice. In this review the current data and concepts regarding oncofertility concept including the gynecologic oncologic perspective is reviewed. (C) 2014 Elsevier Ireland Ltd. All rights reserved.Item The Preoperative Albumin Level Is an Independent Prognostic Factor for Optimally Debulked Epithelial Ovarian Cancer(2017) Ayhan, Ali; Gunakan, Emre; Alyazici, Irem; Haberal, Nihan; Altundag, Ozden; Dursun, Polat; https://orcid.org/0000-0003-0197-6622; 28875365; AAJ-5802-2021; W-9219-2019Purpose A low albumin level has been reported to be a prognostic factor for various cancers. The aim of this study was to determine the association between preoperative serum albumin level and survival in patients with epithelial ovarian cancer (EOC). Methods Records of 337 patients with EOC that underwent optimal cytoreductive surgery were retrospectively reviewed. Threshold albumin level was planned as 32.5 g L-1 due to the statistical analyses. Results Mean overall survival was 51.5 months. Area under the ROC curve was found statistically significant for the discriminative role of albumin for survival outcome (AUC = 0.857, 95% CI 0.813-0.90, P < 0.001). The best cut-off point for albumin was determined as 32.5 g L-1. The sensitivity rate, specificity rate, positive and negative predictive values, and accuracy rate for this cut-off level were found 67.2, 91.2, 81.2, 83.1, and 82.5%, respectively. Preoperative hypoalbuminemia was noted in 101 (30.0%) of the patients, of which 6.2% had an albumin level < 25 g L-1. The albumin level was independently and significantly associated with overall survival (HR 2.6; 95% CI 2.1-3.1; P < 0.001). Subgroup analysis showed that patients with an albumin level < 32.5 and >= 32.5 g L-1 had mean estimated overall survival of 40.6 and 96.0 months, respectively. Age, stage, and presence of ascites were the other independent significant factors. Conclusions The preoperative albumin level is an independent prognostic factor for overall survival in optimally debulked EOC patients. Further investigations about preoperative albumin level in prognostic models will contribute to the literature.Item Importance of Laparoscopy in Predicting Complete Cytoreduction at Advanced Stage Ovarian Cancer(2022) Durdag, Gulsen Dogan; Alemdaroglu, Songul; Baran, Safak Yilmaz; Serbetcioglu, Gonca Coban; Ozmete, Ozlem; Ezer, Ali; Celik, Husnu; https://orcid.org/0000-0003-4335-6659Purpose Laparoscopy has been used in evaluation of ovarian cancer to assess the extent and surgical resectability of the disease, and to avoid futile laparotomy, where primary cytoreduction is not suitable. Aim of this study is to investigate the contribution of laparoscopy in predicting 'no gross residue' in advanced stage ovarian cancer. Methods Data of advanced stage ovarian cancer patients, who underwent diagnostic laparoscopy for prediction of complete cytoreduction due to an alternative model, are analyzed retrospectively. Accordingly, in the absence of obvious mesenteric retraction or extensive tumoral implants on small intestine in laparoscopic assessment, cases were deemed surgically resectable, and the operation was continued with laparotomy to achieve complete cytoreduction. Clinical features of the patients, surgical details, complete and optimal cytoreduction rates, and perioperative complications were evaluated. Results Out of 243 patients with advanced stage ovarian/tubal/peritoneal cancer, laparoscopy was performed at 93 patients, 77 of whom underwent primary cytoreduction subsequently. Complete cytoreduction (no gross residue) and optimal cytoreduction (< 1 cm residual tumor) rates were 75.3 and 100%, respectively. None of the patients had suboptimal surgery. Morbidity and mortality rates were acceptable. Conclusion Laparoscopic evaluation prior to cytoreductive surgery can highly contribute to prediction of complete or optimal cytoreduction in suitable patients. However, experience and skills of the surgeon, as well as technical equipment of the center, may affect surgery; therefore, the model to predict residual tumor should be individualized according to the set up and the surgical team of each center.Item Survival In Recurrent Ovarian Cancer Patients Before And After The Bevacizumab Era: An Observational Single-Centre Study(2022) Akilli, Huseyin; Rahatli, Samed; Aliyeva, Khayala; Altundag, Ozden; Kuscu, Ulku Esra; Ayhan, Ali; https://orcid.org/0000-0002-5240-8441; https://orcid.org/0000-0003-0197-6622; 35260031; AAX-3230-2020; W-9219-2019A retrospective observational study was carried out in Baskent University School of Medicine, Ankara, Turkey. Recurrent ovarian cancer patients treated between 2007 and 2017 were divided into two groups according to their bevacizumab status. The primary endpoints were overall survival (OS) and safety. Three hundred and ninety-six patients enrolled in this study, 200 (50.5%) received bevacizumab while 196 (49.5%) patients never received bevacizumab. The median follow-up time was 48.2 and 47.6 months, respectively. The 5-year OS was 61% and 46%, respectively (p=.007). In multivariate analysis, only platinum-sensitivity (HR: 3.75, 95% CI: 3.0-5.32; p<.001) was identified as independent prognostic factors. In subgroup analyses according to platinum status, bevacizumab did not affect the 5 year OS in platinum sensitive patients (64% versus 68% p=.28) but increased survival in platinum resistant patients (36% versus 44%, p=.00). The rate of grade III-IV haematologic toxicities was 13.7% in the bevacizumab group and 11% in the other group (p=.6).Impact Statement What is already known on this subject? Bevacizumab increases the progression-free survival in platinum-sensitive and resistant recurrent ovarian cancer patients without changing overall survival. What do the results of this study add? Bevacizumab did not affect OS in platinum sensitive recurrent ovarian cancer patients however improved OS in platinum resistant patients with mild toxicity. What are the implications of these findings for clinical practice and/or further research? This study emphasised the crucial role of bevacizumab in the treatment of recurrent ovarian cancer patients.Item The utility of 1.5 tesla MR-guided adaptive stereotactic body radiotherapy for recurrent ovarian tumor - Case reports and review of the literature(2022) Yavas, Guler; Kuscu, Ulku Esra; Ayhan, Ali; Yavas, Cagdas; Onal, Cem; 36261943Introduction: Although epithelioid ovarian cancer (EOC) is a radiosensitive tumor and radiotherapy (RT) played a significant role in adjuvant treatment management in the past, the role of RT has evolved with the advent of platinum-based chemotherapy regimens. Nonetheless, modern RT techniques may be useful in certain patients particularly those with recurrent disease.Presentation of case: After surgery and chemotherapy, two patients, aged 57 and 70, presented with recurrent lesions in the parailiac region. The recurrent lesions were treated with high field 1.5-Tesla MR-Linac treatment in 5 fractions at a dose of 30 Gy. The patients tolerated the treatment well and were disease free after 12 and 20 months of magnetic resonance guided radiotherapy (MRgRT), respectively.Discussion: MRgRT is a novel and rapidly evolving technology that allows for the highly precise treatment of even mobile targets through direct visualization of the tumor. The majority of patients with EOC frequently present with abdominal-pelvic recurrences. It has been demonstrated that EOC requires high radiation doses for curative treatment. MR-Linac enables monitoring of organ motion during treatment, which is necessary for delivering higher doses to target volumes while sparing surrounding organs.Conclusion: To reduce radiation doses to nearby normal tissues, MRgRT allows for the delivery of hypofractio-nated RT with tight safety margins. Regardless of initial resistance or gradual development of intolerance to standard chemotherapy regimens, the role of RT in patients with persistent or recurrent EOC should be reconsidered.Item The clinical outcomes of ovarian cancer in patients with brain metastasis(2021) Simsek, Seda Yuksel; Guler, Ozan Cem; Durdag, Gulsen Dogan; Sari, Sezin Yuce; Gultekin, Melis; Yildiz, Ferah; Celik, Husnu; Erbay, Gurcan; Onal, Huseyin Cem; 0000-0003-3191-9776; AAK-7016-2021Objective: To present the clinical characteristics and treatment outcomes of patients with ovarian cancer with brain metastasis. Methods: This study was designed as a retrospective observational study. Patients' data were obtained from hospital records. Patients who were diagnosed with brain metastatic ovarian cancer in two tertiary referral centers between 2012 and 2020 were included in the study. Results: In total, there were 56 patients diagnosed as having brain metastatic ovarian cancer. The median age was 56 years, 91% of patients were at an advanced stage at initial diagnosis. The median time from the initial diagnosis to brain metastasis was 34.0 months. Sixty-seven percent of patients were determined as having multiple brain metastatic lesions. Whole brain radiotherapy (WBRT) , stereotactic radiosurgery (SRS) and combined approach were utilized as primary treatment. The 1 and 2-year survival rates were 38% and 17%, respectively. Patient age and tumor histology were found to be significant prognostic factors that impact the survival in univariate analyses. The 1-year survival of patients aged younger than 55 years was 49.2%, and 28.2% for patients aged over 55 years (p = 0.04). Patients with nonserous histology had significantly longer one year overall survival compared to serous histology (61.4% vs 29.8%) (p= 0.01). Conclusion: The brain is one of the rarest locations for ovarian cancer metastasis. Radiotherapeutic approaches are the mainstay of treatment but survival rates are low. Age and tumor histology were determined as significant parameters that affected survival rates.Item RAB25 confers resistance to chemotherapy by altering mitochondrial apoptosis signaling in ovarian cancer cells(2020) Temel, Sehime Gulsun; Giray, Asli; Karaka, Bahriye; Gul, Ozgur; Kozanoglu, Ilknur; Celik, Husnu; Basaga, Huveyda; Acikbas, Ufuk; Sucularli, Ceren; Oztop, Sidika; Aka, Yeliz; Kutuk, Ozgur; 0000-0001-5653-6080; 0000-0001-9854-7220; 0000-0002-5268-1210; 32901335; AAJ-7911-2020; AAH-1671-2019; AAE-1241-2021Ovarian cancer remains one of the most frequent causes of cancer-related death in women. Many patients with ovarian cancer suffer from de novo or acquired resistance to chemotherapy. Here, we report that RAB25 suppresses chemotherapy-induced mitochondrial apoptosis signaling in ovarian cancer cell lines and primary ovarian cancer cells. RAB25 blocks chemotherapy-induced apoptosis upstream of mitochondrial outer membrane permeabilization by either increasing antiapoptotic BCL-2 proteins or decreasing proapoptotic BCL-2 proteins. In particular, BAX expression negatively correlates with RAB25 expression in ovarian cancer cells. BH3 profiling assays corroborated that RAB25 decreases mitochondrial cell death priming. Suppressing RAB25 by means of RNAi or RFP14 inhibitory hydrocarbon-stapled peptide sensitizes ovarian cancer cells to chemotherapy as well as RAB25-mediated proliferation, invasion and migration. Our data suggest that RAB25 is a potential therapeutic target for ovarian cancer.Item Clinical characteristics of relapsed ovarian cancer patients with striking response to the bevacizumab at first relapse(2020) Kose, Fatih; Alemdaroglu, Songul; Mertsoylu, Huseyin; Besen, Ali Ayberk; Guler, Ozan Cem; Simsek, Seda Yuksel; Erbay, Gurcan; Onal, Cem; Celik, Husnu; 0000-0002-2742-9021; 0000-0003-4335-6659; 0000-0001-6908-3412; 0000-0002-0156-5973; 0000-0002-7862-0192; 0000-0002-1932-9784; D-5195-2014; AAI-8400-2021; AAC-5654-2020; G-4827-2016; AAD-6910-2021; M-9530-2014Background: Ovarian cancer is fifth leading cause of the cancer related death in women. Platin based doublet regimen plus bevacizumab is standard treatment in relapse. The primary aim of this study is to define clinicopathological characteristics of the relapsed ovarian cancer who derived unexpectedly long benefit from bevacizumab treatment. Methods: Total number of 106 patients with relapsed ovarian cancer and treated with bevacizumab (bevacizumab is not reimbursed as a part of adjuvant treatment in Turkey) on their first relapse were included. For the purpose of the study, the patients were placed into two groups, Group A and B, selected on the basis of the rate of PFS 1 (time between first day of adjuvant chemotherapy and first radiological progression) to PFS 2 (time between first day of second line treatment and second radiological progression). The patients included into Group A if PFS 1 greater than PFS 2 and Group B vice versa. Results: Group A and B were consisted of 67 (63%) and 39 (37%) patients. At a median follow-up of 32.1 months (5.3-110.8), 56 (52.8%) patients were died. Significant number of patients (78.4%) treated with primary surgery without neoadjuvant treatment and 59 (57.8%) out of the 102 patients had debulking surgery when their cancer relapsed. PFS 1 and 2 were estimated as 16.5 mo (14.1-18.9) vs. 13.7 mo (9.9-17.5) and 13.4 mo (8.0-18.6) vs. 29.7 mo (21.5-38.0) in group A and B, respectively (p < 0.001 and p < 0.001). Only parameter that show significant difference between groups was the rate of platin resistant patients; Group A: 13 (19.4%) out of 67 patients vs. Group B: 15 (38.6%) out of 39 patients with ap value of 0.041. Binary logistic regression indicates PFS1 is significant inverse predictor (shorter PFS-1 means greater chance of being in group B) of entering Group B [Chi-Square = 16.5, df = 6 and p = 0.011 (< 0.05)]. PFS1 is significant at the 5% level [ PFS1 wald = 4.33,p = 0.038 (p < 0.05)]. In multivariate analysis, cox-regression proportional hazard, cytoreductive surgery at second relapse (yes or no) (p: 0.028; HR: 0.3, 0.02-0.7, 95% CI) showed significant effect on PFS-2. On the other hand, platin resistance (< 6 mos; yes or no) (p: 0.04; HR: 4.0, 1.1-14.4, 95% CI) and secondary surgery outcome (no visible vs. visible) (p: 0.003; HR: 0.2, 0.07-0.58, 95% CI) showed significant effect on OS. Bevacizumab related adverse effects with greater than grad 3 detected in 13 (15%) and 10 (25%) in group A and B (p: 0.77). Conclusions: Our findings indicate that bevacizumab produced strikingly high PFS (over 24 months) in significant portion of relapsed ovarian cancer patients whom were mostly platin resistant cases with short PFS-1. This gain specifically achieved in patients who had aggressive secondary surgery with no-visible surgical outcome.Item Oncologic outcomes in patients undergoing maximal or optimal cytoreductive surgery for Stage 3C serous ovarian, tubal or peritoneal carcinomas(2019) Gurkan, Damla; Akin, Aylin Ceren; Sahin, Hanifi; Tohma, Yusuf Aytac; Sahin, Eda Adeviye; Gunakan, Emre; Iflazoglu, Nidal; Haberal, Asuman Nihan; Ayhan, Ali; 0000-0001-9418-4733; 31482736The aim of this study was to evaluate overall survival (OS) and disease-free survival (DFS) of patients with Stage 3C serous ovarian, tubal and peritoneal carcinomas. A retrospective analysis of 111 patients who underwent maximal or optimal cytoreductive surgery was performed. Patients were divided into three groups as ovarian cancer (n = 47), tubal cancer (n = 24) and peritoneal cancer (n = 40). Median follow-up was 30 months. There was no significant difference in DFS and OS among the groups. Complete cytoreduction was an independent prognostic factor for DFS in all groups (HR 2.3, 95% CI 1.14-4.93; p=.020). Positive peritoneal cytology (HR 2.2, 95% CI 1.02-4.78; p=.044), and retroperitoneal lymph node involvement (HR 2.3, 95% CI1.11-4.89; p=.025) were independent risk factors for decreased OS, and extended cytoreduction (HR 2.7, 95% CI 1.05-6.99; p=.039) were independent risk factors for increased OS. In conclusion, these malignancies should be considered a single entity during treatment.IMPACT STATEMENT What is already known on this subject? Epithelial ovarian cancer is the second most common gynaecological cancer in women worldwide. There are different histological types including ovarian, tubal and peritoneal carcinomas in which malignant cells form in the tissue covering the ovary or lining the fallopian tube of peritoneum. Recent data have supported the view that these malignancies should be considered a single entity and should be treated the same way. What the results of this study add? In the present study, we evaluated overall survival and disease-free survival of patients with Stage 3C ovarian, tubal and peritoneal cancer undergoing maximal or optimal cytoreductive surgery. We found similar oncologic outcomes in all patient groups. To the best of our knowledge, this is the first study to compare oncologic outcomes of these similar and often confused malignancies in the literature. We, therefore, believe that the present study provides additional information to the body of knowledge on this topic. s are of these findings for clinical practice and/or further research? This study is important, as it indicates similar oncologic outcomes in patients undergoing maximal or optimal cytoreductive surgery for Stage 3C ovarian, tubal and peritoneal cancer. Based on these findings, clinicians should keep in mind that these malignancies should be considered a single clinical entity and be treated the same way. We believe that our study would pave the way for further studies regarding this subject.Item Prognostic Factors Affecting Survival in Patients with Ovarian Cancer: A 5-Year Experience in an University Hospital(2017) Ayhan, Ali; Pinar, Guel; Pinar, Tevfik; Durukan, Ayse; AAJ-5802-2021The aim if this study is to explore the impact of the various prognostic factors on overall survival in women with ovarian cancer (00). Patients diagnosed with gynecologic malignancy in Gynecology Clinic of Baskent University Medicine Faculty between 2010 and 2015 included to study. Patients with ovarian (n= 112) cancers examined retrospectively. Kaplan-Meier, Univariate and Multivariate Cox regression model were performed to estimate for associations of potential variables with survival factors. The mean patient age was 56.4 y, range 20-80. The overall survival was 94.3%, 83.4%, 66.4%, 54.7% and 42.8% at 1, 2 3, 4 and 5 years respectively (60.5 months, range 43-68). 3-year disease-free survival was 25.3% (18.3 months, range 17-20). Multivariate analysis of patients indicated that stage, histology, grade, age at diagnosis, comorbidity, recurrence, BMI, menopausal status and regional distance were independent prognostic factors on survival (p< 0.05). In conclusion, these results will presents a framework to identify fundamental causes in survival for OC.