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    Assessing the Quality of Life in Patients with Endometrial Cancer Treated with Adjuvant Radiotherapy
    (2015) Karabuga, Havva; Gultekin, Melis; Tulunay, Gokhan; Yuce, Kunter; Ayhan, Ali; Yuce, Deniz; Yildiz, Ferah; 0000-0003-0440-0725; 26207785; AAJ-5802-2021
    Objective The current study evaluates long-term quality of life (QOL) and sexual function of patients with endometrial cancer who received adjuvant pelvic external beam radiotherapy (EBRT) and/or vaginal brachytherapy (BRT). Materials and Methods One hundred forty-four endometrial cancer survivors who were treated between January 2000 and December 2009 in our department were included in this study. Median follow-up was 79 months (range, 31-138 months). Fifty-two patients were treated with 45 to 50.4 Gy EBRT, 76 were with BRT, and 16 were with both EBRT and BRT. Brachytherapy was in the form of vaginal cuff BRT with 5 x 550 cGy high dose rate BRT, prescribed to the first 4 cm and whole wall thickness of vagina. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and subscales from the supplemental 24-item Cervical Cancer Module. Results Vaginal BRT patients reported better physical functioning (P = 0.01), role functioning (P = 0.03), and sexual enjoyment (P = 0.01) compared to EBRT group. Symptom score (P = 0.01), lymphedema (P = 0.03), pain (P = 0.02), and diarrhea (P = 0.009) scores were also higher with EBRT. Vaginal BRT did not worsen symptom scores or sexual functions when added to EBRT. Obese patients experienced higher rates of lymphedema (P = 0.008). Cognitive and role functioning scores were significantly higher in patients with normal body mass index. Conclusions External beam radiotherapy negatively affects long-term QOL and sexual functions in endometrial cancer survivors. Vaginal BRT provides higher QOL. Patients with body mass index within normal limits have improved QOL.
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    Restaging of Cervical Cancer Patients Treated with Adjuvant Radiotherapy According to FIGO 2018 and Suggestions for the Next Staging: Turkish Society for Radiation Oncology Gynecologic Group Study (TROD 04-004)
    (2022) Alanyali, Senem; Balci, Beril; Esen, Caglayan Selenge Beduk; Gultekin, Melis; Yildirim, Berna Akkus; Ozkurt, Selnur; Ergen, Sefika Arzu; Gursel, Sukriye Bilge; Cetin, Ilknur Alsan; Sert, Fatma; Sari, Sezin Yuce; Ibis, Kamuran; Onal, Cem; Sahinler, Ismet; Yildiz, Ferah; Ozsaran, Zeynep
    OBJECTIVE The objective of this study was to compare Federation of Gynecology and Obstetrics (FIGO) 2009 and 2018 staging systems in patients with uterine cervical cancer. METHODS Medical records of 571 patients who were treated with adjuvant radiotherapy or radiochemotherapy between 2001 and 2018 were retrospectively reviewed. Differences in overall survival (OS) and progression-free survival (PFS) rates according to FIGO 2009 and FIGO 2018 staging systems were compared using the log-rank test. Cox regression model was used to identify independent prognostic factors for survival. RESULTS The median follow-up was 59 months. Five-year OS and PFS rates were 81.1% and 77.7%, respectively. Stage migration was recorded in 401 patients (70.2%) and the most remarkable stage migration was detected in stage I patients (60%). A total of 157 (27.5%) patients upstaged to stage IIIC disease. According to FIGO 2009, 5-year OS rates were 87.3%, 80.5% (p=0.076), and PFS rates were 82.8%, 77.5% (p=0.036) for stage IB1 and IB2, respectively. According to FIGO 2018, the 5-year OS rates for stage IB1, IB2, and IB3 were 89.8%, 87.1%, and 81.4% (p=0.310), and PFS rates were 90.2%, 80.5%, and 80.1% (p=0.189), respectively. Patients with >= 2 pelvic lymph node (LN) metastases had worse 5-year OS and PFS rates than patients with one metastasis (p=0.015 and p=0.006). Number of para-aortic LN metastasis and metastatic LN ratio (MLNR) were also correlated with 5-year OS and PFS. CONCLUSION Current FIGO staging system better discriminates patients with cervical cancer. However, integration of metastatic LN number and/or MLNR to the upcoming FIGO staging system may improve the prognostic value of the staging.
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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.
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    Local Recurrence Outcomes After Breast Conserving Surgery and Adjuvant Radiotherapy in Ductal Carcinoma in Situ of The Breast And A Comparison With Ecog E5194 Study
    (2018) Akagunduz, Ozlem Ozkaya; Ergen, Arzu; Erpolat, Petek; Gultekin, Melis; Yildirim, Berna Akkus; Parvizi, Murteza; Ikiz, Didem; Oksuz, Didem Colpan; Onal, Cem; Yildiz, Ferah; Ozsaran, Zeynep; https://orcid.org/0000-0001-6661-4185; https://orcid.org/0000-0002-2742-9021; 30121548; V-5717-2017; D-5195-2014
    Purpose: Turkish Radiation Oncology Study Group investigated local recurrence rates and prognostic factors in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast conservative surgery (BCS) followed by radiotherapy (RT) and Eastern Cooperative Oncology Group (ECOG) Study E5194 were compared with the original study. Patients and methods: Totally 252 patients were evaluated retrospectively. Prognostic factors that might influence local control (age, nuclear grade, comedo necrosis, surgical margins, tumor size, hormone receptor status) were compared. The eligibility criteria of ECOG 5194 were stratified into two groups as in the original study and were compared for local control. Results: The median follow-up time was 59 (21-220) months. Local recurrence was observed in 9 patients (3.6%) who had invasive carcinoma (3 patients) and DCIS (6 patients). Ten years local control rates was 91.8% respectively. We found that the risk of ipsilateral breast recurrence was significantly higher in women younger than 50 years old (p = 0.016). In addition, a statistically significant trend was found in patients with tumor larger than 1 cm and HER2 positive tumors (p = 0.051, p = 0.068 respectively). When 12-year results were compared with the ECOG 5194, adjuvant RT produced an absolute difference of 11% in low-intermediate and 20% in high grade in local control. Conclusion: In our study, the 10-year local control rate was 92% and younger than 50 years old was the most important unfavorable prognostic factor for local recurrence. There was provided 20% absolute local control with adjuvant radiotherapy which eligibility criteria of ECOG 5194 high grade group. (C) 2018 Elsevier Ltd. All rights reserved.
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    The Impact Of Serum Albumin-To-Alkaline Phosphatase Ratio In Cervical Cancer Patients Treated With Definitive Chemoradiotherapy
    (2022) Onal, Cem; Gultekin, Melis; Yavas, Guler; Oymak, Ezgi; Sari, Sezin Yuce; Guler, Ozan Cem; Yigit, Ecem; Yildiz, Ferah; 35653776
    We retrospectively analysed the prognostic significance of serum albumin, alkaline phosphatase (ALP) and albumin to ALP ratio (AAPR) and other prognostic factors affecting the overall survival (OS) and progression-free survival (PFS) in 200 cervical cancer patients treated with definitive chemoradiotherapy (CRT). The prognostic factors for OS and DFS, in addition to the predictive factors of albumin, ALP and AAPR, were investigated. Older age, lymph node metastasis, non-complete response (CR) to treatment and low serum albumin levels emerged as predictors of poor OS and PFS in multivariate analysis. However, with a cut-off value of 0.51, AAPR was not a significant prognostic factor of survival in multivariable analysis. There were no significant differences in clinicopathological factors between patients with low and high AAPR, except for lymph node metastasis, where lymph node metastasis rate was significantly higher in patients with a low AAPR compared to those with a high AAPR. Patients with CR had a significantly higher serum albumin level and AAPR compared to patients without CR. The pre-treatment serum albumin level was independent predictive for survival; therefore, it could be a suitable biomarker to guide systemic therapy and predict patient outcomes. Impact Statement What is already known on this subject? Two major determinants of tumour progression are nutritional status and inflammation. The albumin-to-alkaline phosphatase ratio (AAPR), which was originally proposed as a marker for nutritional status and immune response, was recently discovered to be a prognostic factor for various cancer types. However, its utility in the treatment of cervical cancer has not been established. What do the results of this study add? Low serum albumin levels were associated with a significantly shorter OS and PFS in cervical cancer patients treated definitively with CRT. AAPR, on the other hand, was not a significant prognostic factor for survival with a cut-off value of 0.51. Regional lymph node metastasis was significantly more common in patients with a low AAPR than in those with a high AAPR. What are the implications of these findings for clinical practice and/or further research? Patients with multiple clinicopathological risk factors and low serum albumin levels had an increased risk of disease recurrence and a poorer prognosis, highlighting the importance of additional adjuvant treatment strategies in these patients. Due to the preliminary nature of our findings, additional research is required to corroborate them.
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    Uterine papillary serous and clear cell carcinomas: Comparison of characteristics and clinical outcomes
    (2022) Sari, Sezin Yuce; Guler, Ozan Cem; Oymak, Ezgi; Gultekin, Melis; Yigit, Ecem; Kahvecioglu, Alper; Yuce, Kunter; Celik, Husnu; Usubutun, Alp; Bolat, Filiz; Onal, Cem; Yildiz, Ferah; 0000-0003-1185-9227; 35385171
    Introduction To assess the rate of disease control and survival after adjuvant treatment in patients with uterine papillary serous (PSC) and clear cell carcinoma (CCC) and compare the results between these two subtypes. Methods The medical charts of 199 patients with de novo uterine PSC or CCC who underwent radiotherapy (RT) following surgery between 2001 and 2019 in three radiation oncology departments were retrospectively evaluated. Adjuvant treatment was decided by a multidisciplinary tumor board. All patients were planned to undergo adjuvant 4-6 cycles of chemotherapy with external beam RT (EBRT) and/or vaginal brachytherapy (VBT). Results Median age was 63 years for all, 64 years for PSC, and 59 years for CCC, respectively. Complete surgical staging was applied in 98% of patients. Histopathologic subtype was PSC in 142 (71%) and pure CCC in 57 (29%) patients, respectively. FIGO stage was I in 107 (54%), II in 35 (18%), and III in 57 (28%) patients, respectively. Lympho-vascular space invasion and positive peritoneal cytology (PPC) were present in 42% and 10% of patients, respectively. All patients but 23 (12%) underwent adjuvant chemotherapy. Median follow-up was 49.5 months for all patients, 43.9 months for patients with PSC, and 90.4 months for patients with CCC, respectively. During follow-up, 20 (10%) patients developed pelvic recurrence (PR) and 37 (19%) developed distant metastasis (DM). PSC subtype increased the PR and DM rates, although the latter not statistically significant. The 5-year overall survival and disease-free survival rate was 73% and 69% for all patients, 71% and 66% for patients with PSC, and 77% and 75% for patients with CCC, respectively. The difference was more prominent in patients with stage >= IB disease. In multivariate analysis, advanced age and PPC significantly decreased all survival rates. Conclusion PSC has a worse prognosis than CCC with regard to pelvic and distant recurrence with a trend for decreased survival rates. Therefore, a more aggressive therapy is needed for patients with uterine PSC, particularly in patients with stage >= IB disease.
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    Vaginal cuff brachytherapy practice in endometrial cancer patients: a report from the Turkish Oncology Group
    (2021) Bolukbasi, Yasemin; Onal, Cem; Ozsaran, Zeynep; Senyurek, Sukran; Akdemir, Eyub Yasar; Selek, Ugur; Yildiz, Ferah; 33897788
    Purpose: The American Brachytherapy Association is attempting to develop standards for delivering brachytherapy, although differences in practice have been reported in the literature. This study evaluated vaginal cuff brachytherapy (VBT) practice and quality of life-related recommendations among Turkish radiation oncologists. Material and methods: A nationwide web-based 17-item survey was distributed to the members of the Turkish Society for Radiation Oncology. These members received e-mail notifications, and a link was posted on the Turkish Society for Radiation Oncology internet site to solicit voluntary responses The survey addressed the simulation processes, target volume, prescribed dose, delivery schedules, and recommendations related to vaginal side effects. Results: Fifty-seven radiation oncologists responded to the survey. The most used dose fraction schemes for adjuvant VBT were 7 Gy x 3 fractions (30%), 5.5 Gy x 5 fractions (26%), and 6 Gy x 5 fractions (28%). The preferred VBT scheme was 5 Gy x 3 fractions (50%) when the external beam radiotherapy (EBRT) dose was 45 Gy external radiotherapy, while the preferred schemes were 6 Gy x 3 fractions (30%) or 5 Gy x 3 fractions (32%) when the external radiotherapy dose was increased to 50.4 Gy. One-half of the respondents delivered VBT twice a week, and the dose was prescribed to 0.5 cm from vaginal mucosa by 86% of the respondents. There was no common definition for the dose prescription length, which was defined as 3 cm from the vaginal cuff in 33% of responses and as 4 cm in 35% of responses. For serous and clear cell histological types, 38% of the respondents targeted "full cylinder length". To prevent vaginal side effects, 78% of the respondents recommended using a vaginal dilator and/or sexual intercourse after VBT. Conclusions: This survey revealed variations in the clinical practice of VBT among Turkish radiation oncologists, which suggests that standardization is necessary.
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    Outcome and Safety Analysis of Endometrial Cancer Patients Treated with Postoperative 3D-Conformal Radiotherapy or Intensity Modulated Radiotherapy
    (2021) Onal, Cem; Sari, Sezin Yuce; Yavas, Guler; Oymak, Ezgi; Birgi, Sumerya Duru; Yigit, Ecem; Guler, Ozan Cem; Gultekin, Melis; Akyurek, Serap; Yildiz, Ferah; 33999750
    Background We sought to analyze the toxicity rates and the treatment outcomes in endometrial cancer (EC) patients treated with postoperative three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). Material and methods The clinical data of 646 EC patients treated with postoperative adjuvant 3DCRT (265 patients, 41%) or with IMRT (381 patients, 59%) between April 2007 and August 2019 were retrospectively analyzed. The primary endpoints were treatment-related acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. The secondary endpoints were LC and overall survival (OS) and disease-free survival (DFS). Results Median follow-up time was 37 months. The rates for acute GI and GU toxicities of any grade for the entire group were 55.6% and 46.8%, respectively. Acute grade >= 2 GI toxicity was significantly less in patients treated with IMRT compared to those treated with 3DCRT (11.0% vs. 19.2%, p=.004). However, no significant difference grade >= 2 GU toxicities was observed between the 3DCRT and IMRT groups (15.1% vs. 11.0%; p=.15). Acute grade >= 2 GI and GU toxicities were higher in patients receiving systemic chemotherapy, while paraaortic field irradiation increases only the risk of acute grade >= 2 GI toxicity. Estimated 3-year late grade >= 3 GI toxicity rates in the 3DCRT- and IMRT-treated patients were 4.6% and 1.9% (p= .03), respectively. The patients treated with adjuvant ChT had higher rates of late serious GI complications than those without adjuvant ChT. No significant difference in terms of survival and disease control was observed between the 3DCRT and IMRT treatment groups. No significant factor for LC was found in the multivariate analysis. Conclusion In this multicentric study involving one of largest patient population, we found that IMRT-treated EC patients showed comparable clinical outcomes but with a lower incidence of GI toxicities compared with those treated with 3DCRT.
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    Impact of lymph node ratio in patients with stage IIIC endometrial carcinoma treated with postoperative radiotherapy
    (2021) Onal, Cem; Sari, Sezin Yuce; Yavas, Guler; Guler, Ozan Cem; Yiğit, Ecem; Oymak, Ezgi; Gultekin, Melis; Yildiz, Ferah; 0000-0002-2742-9021; 34355983; D-5195-2014
    Aim: To evaluate the prognostic value of the lymph node ratio (LNR) and other clinicopathological factors in patients with stage IIIC endometrial cancer. Methods: Factors affecting overall survival (OS) and progression-free survival (PFS) were assessed in 397 patients with stage IIIC endometrial cancer treated with postoperative radiotherapy. Patients undergoing the removal of at least ten lymph nodes were included in the study. Results: The 5-year OS and PFS rates were 58% and 52%, respectively, with a median follow-up time of 35.7 months. The LNR cutoff value was 9.6%. In the multivariate analysis, advanced age (>= 60 years), grade III tumor, presence of cervical stromal invasion, higher LNR and lack of adjuvant chemotherapy were independent predictors for worse OS and PFS. Conclusion: The LNR is an independent predictor for OS and PFS in patients with stage IIIC endometrial cancer treated with postoperative radiotherapy.
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    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-7016-2021
    Objective: 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.