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    Uterine Perforation During 3-Dimensional Image-Guided Brachytherapy in Patients With Cervical Cancer Baskent University Experience
    (2014) Onal, Cem; Guler, Ozan Cem; Dolek, Yemliha; Erbay, Gurcan; https://orcid.org/0000-0002-2742-9021; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0002-1706-8680; 24407583; HOC-5611-2023; AAC-5654-2020; AAK-5370-2021
    Objectives This study aimed to determine the incidence and characteristics of uterine perforation at our department using 3-dimensional computed tomography (CT)-based brachytherapy (BRT). The characteristics of the patients presenting with perforation and impact of the perforation on the treatment course were also analyzed. Materials and Methods The clinical and radiologic data of 200 patients with biopsy-proven cervical cancer treated using CT-based BRT were retrospectively evaluated. All patients had undergone tandem-based intracavitary BRT, and 67 patients had undergone magnetic resonance imaging (MRI) before BRT. Results Of the 200 patients, 17 (8.5%) had uterine perforation. Of the 626 applications with CT images, 30 (4.8%) resulted in uterine perforation. The median age of patients with perforation was higher (68 years; range, 44-89 years) than that of the patients without perforation (59 years; range, 21-87 years), and the mean (SD) tumor size at diagnosis was larger in patients with perforation (7.0 [1.5] cm) than in patients without perforation (5.0 [1.5] cm). The most frequent perforation site was the posterior uterine wall (8 patients), followed by the fundus (5 patients) and anterior wall (4 patients). Of the 7 patients with a retroverted uterus, 4 had uterine perforation during BRT. In 67 patients with MRI delivered before BRT, only 3 (4%) had uterine perforation, and 2 of the 3 patients with uterine perforation had a retroverted uterus. However, of the 133 patients with no MRI evaluation before BRT, 14 (11%) had uterine perforation. No life-threatening complications or signs of intraperitoneal tumor cell seeding were observed. Conclusions Older age, larger tumors, a retroverted uterus, and a stenotic cervical os were all predisposing factors for uterine perforation during BRT. Preoperative MRI is a feasible and safe method to decrease the risks of uterine perforation and could be used preoperatively in centers where intraoperative ultrasonography is not used in routine practice.
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    Prognostic Value of 18F-Fluorodeoxyglucose Uptake in Pelvic Lymph Nodes in Patients with Cervical Cancer Treated with Definitive Chemoradiotherapy
    (2015) Onal, Cem; Guler, Ozan C.; Reyhan, Mehmet; Yapar, Ali Fuat; 0000-0001-6908-3412; 0000-0003-1715-4180; 0000-0002-2742-9021; 0000-0001-8550-3368; 25641567; AAC-5654-2020; AAI-8973-2021; D-5195-2014; AAJ-5242-2021; HOC-5611-2023
    Purpose. To evaluate the prognostic significance of the maximum standardized uptake (SUVmax) value for pelvic lymph nodes in patients with cervical cancer and its impact on treatment response, disease control, and survival. Methods. Ninety-three patients with pelvic or para-aortic metastasis detected by PET/CT and treated with definitive chemoradiotherapy were evaluated. The impact of pelvic lymph node SUVmax on prognostic factors and treatment outcomes was assessed. Results. The size and SUVmax of pelvic lymph nodes were significantly correlated (r = 0.859; p < 0.001). Patients with pelvic and para-aortic lymph node metastases had significantly higher SUVmax values for both primary tumor (23.4 +/- 9.2 vs. 18.5 +/- 73; p = 0.01) and pelvic lymph nodes (11.4 +/- 4.6 vs. 7.4 +/- 3.8; p = 0.001). Patients with pelvic lymph node SUVmax >= 7.5 had significantly higher primary tumor SUVmax, larger pelvic lymph nodes, higher rates of para-aortic lymph node metastasis, and lower post-therapy complete response rates. Overall survival (OS) and disease-free survival (DFS) rates were significantly higher in patients with SUVmax < 7.5 compared to patients with SUVmax >= 7.5. In a multivariate analysis, pelvic lymph node SUVmax and post-therapy metabolic response were significant prognostic factors for both OS and DFS for all patients, but no significant prognostic factors were found in pelvic lymph node metastasis only. Conclusions. Patients with highly FDG-avid pelvic lymph nodes have a higher risk of disease recurrence with worse survival. Identification of these patients may assist in the evaluation of the clinical benefits of additional treatments. (C) 2015 Elsevier Inc. All rights reserved.
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    Treatment Outcomes of Patients with Cervical Cancer with Complete Metabolic Responses After Definitive Chemoradiotherapy
    (2014) Onal, Cem; Reyhan, Mehmet; Guler, Ozan C.; Yapar, Ali Fuat; https://orcid.org/0000-0002-2742-9021; https://orcid.org/0000-0001-8550-3368; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0003-1715-4180; 24562649; HOC-5611-2023; AAJ-5242-2021; AAC-5654-2020; AAI-8973-2021
    Purpose We sought to evaluate failure patterns and prognostic factors predictive of recurrences and survival in cervical cancer patients who are treated with definitive chemoradiotherapy (ChRT), who have a subsequent complete metabolic response (CMR) with (18) F-fluorodeoxyglucose positron-emission tomography (FDG-PET) after treatment. Methods The records of 152 cervical cancer patients who were treated with definitive chemoradiotherapy were evaluated. All patients underwent pre-treatment positron emission tomography (PET-CT), and post-treatment PET-CT was performed within a median of 3.9 months (range, 3.0-9.8 months) after the completion of ChRT. The prognoses of partial response/progressive disease (PR/PD) cases (30 patients, 18 %) and CMR cases (122 patients, %82) were evaluated. Univariate and multivariate analysis effecting the treatment outcome was performed in CMR cases. Results The median follow-ups for all patients and surviving patients were 28.7 (range, 3.3-78.7 months) and 33.2 months (range, 6.23-78.7 months), respectively. Four-year overall survival (OS) rate was significantly better in patients with CMR compared to patients with PR/PD (66.9 % vs. 12.4 %, p < 0.001, respectively). Patients with PR/PD had higher maximum standardized uptake value (SUVmax) of primary cervical tumor (26.4 +/- 10.1 vs. 15.9 +/- 6.3; p < 0.001) and larger tumor (6.4 cm +/- 2.3 cm vs. 5.0 cm +/- 1.4 cm; p < 0.001) compared to patients with CMR. Of the 122 patients with post-treatment CMRs, 25 (21 %) developed local, locoregional, or distant failure. In univariate analysis, tumor size a parts per thousand yen 5 cm, 'International Federation of Obstetricians and Gynecologists' (FIGO) stage a parts per thousand yenaEuro parts per thousand IIB, and pelvic and/or para-aortic lymph node metastasis were predictive of both overall survival (OS) and disease-free survival (DFS), while histology was predictive of only OS. In multivariate analysis, tumor size, stage and lymph node metastasis were predictive of OS and DFS. Conclusion Although CMR is associated with better outcomes, relapses remain problematic, especially in patients with bulky tumors (a parts per thousand yen 5 cm), extensive stage (a parts per thousand yen IIB) or pelvic and/or para-aortic lymph node metastasis. These findings could support the need for more aggressive treatment or adjuvant chemotherapy regimens.
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    Papanicolaou Smear Findings in Solid-Organ Transplant Recipients Compared With Normal Subjects According to the Bethesda 2001 System
    (2015) Atilgan, Alev Ok; Tepeoglu, Merih; Haberal, A. Nihan; Durukan, Elif; Kuscu, Esra; Haberal, Mehmet; 0000-0002-9894-8005; 0000-0002-3462-7632; 0000-0001-9852-9911; 0000-0001-8595-8880; 0000-0002-0992-6980; 0000-0002-8579-5564; 25894158; AAK-5222-2021; AAJ-8097-2021; AAK-4587-2021; AAK-3333-2021; AAI-8792-2021; AAJ-8621-2021
    Objectives: Solid-organ transplant recipients are at increased risk of developing cancer including cervical cancer compared with woman in the general population, mostly due to long-term immunosuppressive therapy. The Papanicolaou smear remains the primary method of screening cervical pathology including preinvasive and invasive lesions. The objective of this study was to evaluate Pap smear findings in solid-organ transplant recipients, determine the prevalence of abnormal smears, and compare these patients with the general population. Materials and Methods: We retrospectively examined 111 women patients who received liver or kidney transplant between January 1990 to December 2012 at Baskent University Ankara Hospital. Pap smear findings were compared with normal control patients matched for same age and technical procedure of cervical cytology. To selection of control patients, propensity score matching program was performed. All Pap smears were re-examined according to Bethesda 2001 criteria. Results: In 111 transplant patients, 2 patients (1.8%) had atypical squamous cells of undetermined significance, 8 patients (7.2%) had low-grade squamous intraepithelial lesion, 15 patients (13.5%) had Candida infection, 2 patients (1.8%) had Trichomonas vaginalis, 1 patient (0.9%) had herpes simplex infection, 13 patients (11.7%) had bacterial vaginosis, 15 patients (13.5%) had reactive changes due to inflammation, and 18 patients (16.2%) had atrophy. When we compared our results with the control group, there were statistically significant differences (P <= .05) between the 2 groups in epithelial cell abnormalities (low-grade squamous intraepithelial lesion), Candida infection, bacterial vaginosis, and atrophy. Conclusions: Pap smear screening potentially may help recognize cervical preinvasive and invasive lesions. The risk of developing cervical intraepithelial neoplasia is greater in transplant recipients because of immunosuppressive therapy. The incidence of low-grade squamous intraepithelial lesion was significantly greater in transplant recipients than the general population. Intensive follow-up with Pap smear in transplant recipients is important in the early detection of these lesions.
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    Is Colposcopic Evaluation Necessary in All Women with Postcoital Bleeding?
    (2015) Gulumser, Cagri; Tuncer, Aykut; Kuscu, Esra; Ayhan, Ali; 0000-0002-5434-1025; 0000-0002-0992-6980; 26254856; K-1760-2018; AAJ-5802-2021; AAI-8792-2021
    Objective: To evaluate what extent postcoital bleeding (PCB) is an indicator of cervical cancer (CIN2 (+)). Methods: This is a retrospective cohort study. Between 2007 and 2013, amongst all referred patients, a total of 1491 consecutive women who had both conventional cytology and cervical biopsy were enrolled in the study. Of those 237 women have PCB, according to biopsy results, subjects were divided into two groups: CIN1 (-) and CIN2 (+). Multiple logistic regressions was used to construct a model to predict the occurrence of CIN 2 (+) based on age, menopause, marriage status, smoking, PCB, HPV and cytology. Results: Among the all women with CIN 2 (+) colposcopy guided biopsy result, PCB was 13.1% (53/406). The relationship between biopsy results and age, parity, menopausal status, marital status, smoking, presence of PCB, HPV DNA, and cytology is statistically significant (p = 0.012, p = 0.001, p = 0.023, 0.013, p > 0.001, p = 0.038, p < 0.001, p < 0.001, respectively). According to regression analysis only smoking, HPV (+) and abnormal cytology increase the probability of CIN2 (+); 1.687 times (p = 0.018), 4.065 times (p < 0.001), 5.787 times (p = 0.001) respectively. Having PCB only does not indicate an increased risk of CIN2 (+). Conclusion: Colposcopic examination and biopsy should be performed only in the situation where women have PCB and any of the following: smoking, positive HPV, or abnormal cytology. (C) 2015 Published by Elsevier Ireland Ltd.
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    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-5802-2021
    About 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.
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    Risk Factors for Residual Disease After Cervical Conization in Patients with Cervical Intraepithelial Neoplasia Grades 2 and 3 and Positive Surgical Margins
    (2016) Ayhan, Ali; Tuncer, Hasan Aykut; Reyhan, Nihan Haberal; Kuscu, Esra; Dursun, Polat; 0000-0001-9852-9911; 0000-0002-5434-1025; 0000-0002-0992-6980; 27038228; AAK-4587-2021; K-1760-2018; AAJ-5802-2021; AAI-8792-2021
    Objective: To evaluate risk factors for the persistence of cervical intraepithelial neoplasia (CIN) grade >= 2 following repeat surgical procedures in patients with CIN grades 2 and 3 and positive surgical margins. Study design: This study included patients with CIN grades 2 and 3 and positive surgical margins following loop electrosurgical excision procedures (LEEP), who had undergone additional surgery between 2007 and 2014. Factors associated with CIN grade >= 2 on biopsy results after the second operation were assessed by multiple logistic regression analysis. Factors considered included patient age, parity, menopausal status, smoking, referral cytology, initial LEEP pathology, time interval between LEEP and surgical procedures, presence of disease on endocervical sampling, endocervical surgical margins, glands, disease surrounding >= 50% of the cervical circumference and requirement for multiple sweeps on initial LEEP to excise a lesion. The forward likelihood ratio method was used and significance was set at p < 0.05. Results: Repeat surgical procedures were performed in 104 patients, 75 with CIN 2 and 29 with CIN 3, with 43 (41.3%) reported as normal or CIN 1. However, 57 (54.8%) patients had CIN >= 2 lesions and four (3.8%) had previously undiagnosed cervical cancer. Factors associated with CIN >= 2 lesions included requirement for multiple sweeps (vs. a single sweep; odds ratio [OR] 5.967; 95% confidence interval [CI] 2.183-16.311, p < 0.001) and involvement of >= 50% of the cervical circumference (vs. <50%; OR 5.073; 95% CI 1.501-17.146, p = 0.009). Conclusion: As lesions requiring multiple sweeps for excision and/or surrounding >= 50% of the cervical circumference during initial conization are associated with recurrent CIN >= 2 lesions, attention should be paid during resection to prevent margin positivity. If surgical margins are positive, however, repeat surgical procedures should be considered in patients with CIN 2 and CIN 3 lesions and these risk factors. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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    Prognostic Use of Pretreatment Hematologic Parameters in Patients Receiving Definitive Chemoradiotherapy for Cervical Cancer
    (2016) Onal, Cem; Guler, Ozan C.; Yildirim, Berna A.; 0000-0002-2742-9021; 0000-0001-6661-4185; 0000-0001-6908-3412; 27206286; D-5195-2014; V-5717-2017; AAC-5654-2020
    Objectives: The aim of this work was to evaluate the prognostic role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in recipients of definitive chemoradiotherapy (ChRT) for cervical cancer. Methods: In 235 patients given definitive ChRT for histologically confirmed cervical cancer, clinical data and pretreatment complete blood cell counts were analyzed. Prognostic and therapeutic ramifications of NLR and PLR were assessed. Results: Median pretreatment NLR and PLR were 3.03 (range, 1.04-13.03) and 133.02 (range, 36.3-518.16), respectively. Both NLR and PLR correlated significantly with tumor size, lymph node metastasis, and treatment response. In addition to NLR and PLR, tumor stage, size, and nodal metastasis were identified by univariate analysis as significant predictors of overall survival (OS) and progression-free survival (PFS). By multivariate analysis, independent predictors of OS and PFS were NLR (OS: hazard ratio [HR], 3.322; 95% confidence interval [CI], 1.905-5.790; PFS: HR, 3.579; 95% CI, 2.106-6.082; both P < 0.001) and lymph node metastasis (OS: HR, 2.620; 95% CI, 1.706-4.023; PFS: HR, 2.989; 95% CI, 1.918-4.378; both P < 0.001), although patients' age (HR, 1.019; 95% CI, 1.003-1.035; P = 0.02) was also significantly predictive of OS. Conclusions: Pretreatment NLR and PLR were associated with larger tumors, lymph node metastasis, and poorer therapeutic responses to definitive ChRT. By multivariate analysis, pretreatment NLR and lymph node metastasis were found independently predictive of OS and PFS, whereas patients' age was significantly predictive of OS only. In patients with advanced cervical cancer, NLR is a potential biomarker, serving to guide systemic therapy and predict treatment outcomes.
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    Predicting Tumor Recurrence in Patients with Cervical Carcinoma Treated with Definitive Chemoradiotherapy: Value Of Quantitative Histogram Analysis On Diffusion-Weighted MR Images
    (2017) Erbay, Gurcan; Onal, Cem; Karadeli, Elif; Guler, Ozan C.; Arica, Sami; Koc, Zafer; https://orcid.org/0000-0002-1706-8680; https://orcid.org/0000-0002-0352-8818; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0003-0987-1980; 27445314; AAK-5370-2021; HOC-5611-2023; AAK-5399-2021; AAC-5654-2020; S-8384-2016
    Background: Further research is required for evaluating the use of ADC histogram analysis in more advanced stages of cervical cancer treated with definitive chemoradiotherapy (CRT). Purpose: To investigate the utility of apparent diffusion coefficient (ADC) histogram derived from diffusion-weighted magnetic resonance images in cervical cancer patients treated with definitive CRT. Material and Methods: The clinical and radiological data of 50 patients with histologically proven cervical squamous cell carcinoma treated with definitive CRT were retrospectively analyzed. The impact of clinicopathological factors and ADC histogram parameters on prognostic factors and treatment outcomes was assessed. Results: The mean and median ADC values for the cohort were 1.043 +/- 0.135 x 10(-3) mm(2)/s and 1.018 x 10(-3) mm(2)/s (range, 0.787-1.443 x 10(-3) mm(2)/s). The mean ADC was significantly lower for patients with advanced stage (>= IIB) or lymph node metastasis compared with patients with stage < IIB or no lymph node metastasis. The mean ADC, 75th percentile ADC (ADC75), 90th percentile ADC (ADC90), and 95th percentile ADC (ADC95) were significantly lower in patients with tumor recurrence compared with patients without recurrence. In multivariate analysis, tumor size, ADC75 and ADC95 were independent prognostic factors for both overall survival and disease-free survival. Conclusion: ADC histogram parameters could be markers for disease recurrence and for predicting survival outcomes. ADC75, ADC90, and ADC95 of the primary tumor were significant predictors of disease recurrence in cervical cancer patients treated with definitive CRT.
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    Definitive Chemoradiotherapy in Elderly Cervical Cancer Patients: A Multiinstitutional Analysis
    (2017) Guler, Ozan Cem; Sari, Sezin Yuce; Birgi, Sumerya Duru; Gultekin, Melis; Yildiz, Ferah; Onal, Cem; https://orcid.org/0000-0002-2742-9021; 28604459; D-5195-2014
    Objective The aim of the study was to investigate the prognostic factors for survival and treatment-related toxicities in older (65 years) cervical cancer patients treated with definitive chemoradiotherapy. In addition, we sought to compare the outcomes between the older elderly (75 years) and their younger old counterparts (age, 65-74 years). Materials and Methods We retrospectively reviewed medical records from 269 biopsy-proven nonmetastatic cervical cancer patients treated with external radiotherapy and intracavitary brachytherapy at the departments of radiation oncology in 2 different universities. The prognostic factors for survival, local control, and distant metastasis (DM) were analyzed. Results The median follow-up time was 38.8 months (range, 1.5-175.5 months) for the entire cohort and 70.0 months (range, 6.1-175.7 months) for survivors. The 2- and 5-year overall survival (OS), disease-free survival (DFS), and cause-specific survival rates were 66% and 42%, 63% and 39%, and 72% and 55%, respectively. Patients 75 years or older showed significantly worse OS compared with patients aged 65 to 74 years but showed no significant difference in DFS. The 2- and 5-year local control rates were 86% and 71%, respectively. The incidences of DMs at 2 and 5 years were 22% and 30%, respectively. In multivariate analysis, vaginal infiltration and lymph node metastasis were predictive of OS, DFS, local recurrence, and DM. Concomitant chemotherapy was predictive of OS, DFS, and local recurrence, and larger tumor (>4 cm) was a significant prognostic factor for local recurrence. None of the patients had toxicity that necessitated the discontinuation of radiotherapy. All patients were evaluable for acute toxicity, and no grade higher than 3 adverse events occurred during external beam radiation therapy or brachytherapy. Conclusions Although age limited the delivery of aggressive treatment, concurrent chemoradiotherapy in elderly patients associated with improved outcomes similar as in younger counterparts without increasing serious acute and late toxicities.