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    Comparison of Helical and TomoDirect Techniques with Simultaneous Integrated Boost in Early Breast Cancer Patients
    (REPORTS OF PRACTICAL ONCOLOGY AND RADIOTHERAPY, 2023) Onal, Cem; Bozca, Recep; Oymak, Ezgi; Guler, Ozan Cem
    Background: The aim of the study was to perform dosimetric comparisons of helical (H) and TomoDirect (TD) plans for whole-breast irradiation (WBI) with simultaneous integrated boost (SIB) in early-stage breast cancer patients undergoing breast conserving surgery.Materials and methods: Fifty patients, 25 with left-side and 25 with right-side tumors, were determined for a treatment planning system for a total dose of 50.4Gy in 1.8Gy per fraction to WBI, with a SIB of 2.3Gy per fraction delivered to the tumor bed. The planning target volume (PTV) doses and the conformity (CI) and homogeneity indices (HI) for PTV(breast )and PTVboost, as well as organ-at-risk (OAR) doses and treatment times, were compared between the H and TD plans.Results: All plans met the PTV coverage criteria for the H plan, except for mean V107 of PTVbreast for TD plan. The H plan yielded better homogeneity and conformity of dose distribution compared to the TD plan. The ipsilateral mean lung doses were not significantly different between the two plans. The TD plans is advantageous for mean doses to the heart, contralateral breast and lung, spinal cord, and esophagus than the H plans. In both the H and TD plans, the right-sided breast patients had lower heart dose parameters than the left-sided breast patients. The TD plan is superior to the H plan in sparing the contralateral breast and lung by decreasing low-dose volumes.Conclusions: While the OAR dose advantages of TD are appealing, shorter treatment times or improved dose homogeneity and conformity for target volume may be advantageous for H plan.
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    Retrospective Comparison of Standard and Escalated Doses of Radiotherapy in Newly Diagnosed Glioblastoma Patients Treated with Concurrent and Adjuvant Temozolomide
    (2019) Guler, Ozan Cem; Yildirim, Berna Akkus; Onal, Cem; Topkan, Erkan; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0001-6661-4185; https://orcid.org/0000-0002-2742-9021; https://orcid.org/0000-0001-8120-7123; 30950447; AAC-5654-2020; V-5717-2017; HOC-5611-2023; AAG-2213-2021
    BACKGROUND: To compare the efficacies of standard dose-(SDRT) and escalated dose radiotherapy (EDRT) in newly diagnosed glioblastoma (GBM) with concurrent and adjuvant temozolomide (TMZ). MATERIALS AND METHODS: Outcomes of 126 newly diagnosed GBM patients who received SDRT (60 Gy, 30 fractions) or EDRT (70 Gy, 30 fractions) with concurrent plus adjuvant TMZ were retrospectively analyzed. Both groups received concurrent TMZ (75 mg/m(2)) during the course of RT and at least one course of adjuvant TMZ (150-200 mg/m(2)), thereafter. Overall survival (OS) and local progression free survival (LPFS) constituted the primary and secondary endpoints, respectively. RESULTS: At median 14.2 months follow-up, 26 (20.6%) patients were alive. Median LPFS and OS were 9.2 [95% confidence interval (CI); 8.4-10.0] and 15.4 months (95% CI; 12.1-18.8), respectively, for the entire cohort. Although the median OS was numerically superior in the EDRT this difference could not reach statistical significance (22.0 vs. 14.9 months; P = 0.45), Likewise, LPFS was also (9.9 vs. 8.9 months; P = 0.89) not different between the two treatment groups. In multivariate analysis, better recursive partitioning analysis class (3-4 vs. 5; P = 0.044) and extensive surgery (gross total resection vs. subtotal resection/biopsy only; P = 0.021) were identified to associate significantly with superior OS times, irrespective of the RT protocol. CONCLUSIONS: Although the current median OS of 22 months of the EDRT group is promising, no statistically significant survival advantage for EDRT was observed even in the presence of TMZ. Randomized studies with larger population sizes and available genetic markers are warranted to conclude more reliably on the fate of EDRT plus TMZ.
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    Effect of Adjuvant Extended Temozolamide Treatment in Survival of Patients with Glioblastoma Multiforme
    (2018) Yildirim, Berna Akkus; Sumbul, Ahmet Taner; Topkan, Erkan; Ozdemir, Yurday; Besen, Ali Ayberk; Guler, Ozan Cem; Sedef, Ali Murat; Onal, Cem; https://orcid.org/0000-0001-6661-4185; https://orcid.org/0000-0002-5573-906X; https://orcid.org/0000-0001-8120-7123; https://orcid.org/0000-0002-2218-2074; https://orcid.org/0000-0002-7862-0192; V-5717-2017; D-4793-2014; AAG-2213-2021; AAG-5629-2021; AAD-6910-2021; HOC-5611-2023
    Purpose: The aim of this retrospective cohort study was to evaluate the prognostic effect extended temozolamide on survival outcomes of glioblastoma multiforme patients who were underwent surgery/biopsy followed treated with definitive chemo-radiotherapy. Materials and Methods: We retrospectively analyzed the datas of 225 patients with gliablastoma multiforme whom admitted to our clinic All patients were completed concomitant chemoradiotherapy with temozolamide and adjuvant temozolamide therapy at least for six months or more. Patients were divided into two groups as standart and extended temozolamid therapy group as using temozolamide therapy for at least 6 months or more. Results: The median follow-up of the whole patients18 (range 2-125) months, 65 patients (56%) were alive. Extended temozolamide (>6) was associated with longer survival, but was not significantly with survival outcomes in the univariate analysis (49.0 vs 68.33 months; p=0.082). However, progression free survival analysis demonstrated that the patient in extended temozolamide group had paramount extended progression free survival (14 vs 9 months) than other group in standart cycle temozolamide. Conclusion: Our study show that extended temozolamide is good tolerated and leads to a significantly increase in progression free survival and overall survival in newly diagnosed patients with glioblastoma multiforme.
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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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    Oligometastatic Bone Disease in Castration-Sensitive Prostate Cancer Patients Treated With Stereotactic Body Radiotherapy Using Ga-68-PSMA PET/CT TROD 09-004 Study
    (2021) Onal, Cem; Ozyigit, Gokhan; Akgun, Zuleyha; Atalar, Banu; Igdem, Sefik; Oymak, Ezgi; Agaoglu, Fulya; Selek, Ugur; Guler, Ozan Cem; Hurmuz, Pervin; 33661210
    Purpose To evaluate the outcomes of metastasis-directed treatment (MDT) using stereotactic body radiotherapy (SBRT) for bone-only oligometastasis (OM) detected with gallium prostate-specific membrane antigen (Ga-68-PSMA) PET/CT in castration-sensitive prostate cancer (PC) patients. Methods In this multi-institutional study, clinical data of 74 PC patients with 153 bone lesions who were undergoing MDT were retrospectively evaluated. Twenty-seven patients (36.5%) had synchronous, and 47 (63.5%) had metachronous OM. All patients had PC with 5 metastases or fewer detected by Ga-68-PSMA PET/CT and treated using SBRT with a median dose of 20 Gy. The prognostic factors for PC-specific survival (PCSS) and progression-free survival (PFS) were analyzed. Results The median follow-up was 27.3 months. Patients with synchronous OM were older and received higher rates of androgen deprivation therapy after SBRT compared with patients with metachronous OM. The 2-year PCSS and PFS rates were 92.0% and 72.0%, respectively. A prostate-specific antigen (PSA) decline was observed in 56 patients (75.7%), and 48 (64.9%) had a PSA response defined as at least 25% decrease of PSA after MDT. The 2-year local control rate per lesion was 95.4%. In multivariate analysis, single OM and PSA response after MDT were significant predictors for better PCSS and PFS. In-field recurrence was observed in 4 patients (6.5%) with 10 lesions at a median of 13.1 months after MDT completion. No serious late toxicity was observed. Conclusions We demonstrated that SBRT is an efficient and well-tolerated treatment option for PC patients with 5 bone-only oligometastases or fewer detected with Ga-68-PSMA PET/CT.
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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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    Role of vaginal brachytherapy boost following adjuvant external beam radiotherapy in cervical cancer: Turkish Society for Radiation Oncology Gynecologic Group Study (TROD 04-002)
    (2021) Gultekin, Melis; Esen, Caglayan Selenge Beduk; Balci, Beril; Alanyali, Senem; Yildirim, Berna Akkus; Guler, Ozan Cem; Sari, Sezin Yuce; Ergen, Sefika Arzu; Sahinler, Ismet; Cetin, Ilknur Alsan; Onal, Cem; Yildiz, Ferah; Ozsaran, Zeynep; 0000-0002-2742-9021; 0000-0001-6661-4185; 0000-0001-6908-3412; 32998860; D-5195-2014; V-5717-2017; AAC-5654-2020
    Objective There are a limited number of studies supporting vaginal brachytherapy boost to external beam radiotherapy in the adjuvant treatment of cervical cancer. The aim of this study was to assess the impact of the addition of vaginal brachytherapy boost to adjuvant external beam radiotherapy on oncological outcomes and toxicity in patients with cervical cancer. Methods Patients treated with post-operative external beam radiotherapy +/- chemotherapy +/- vaginal brachytherapy between January 2001 and January 2019 were retrospectively evaluated. The treatment outcomes and prognostic factors were analyzed in patients treated with external beam radiotherapy with or without vaginal brachytherapy. Results A total of 480 patients were included in the analysis. The median age was 51 years (range 42-60). At least two intermediate risk factors were observed in 51% of patients, while 49% had at least one high-risk factor. The patients in the external beam radiotherapy + vaginal brachytherapy group had worse prognostic factors than the external beam radiotherapy alone group. With a median follow-up time of 56 months (range 33-90), the 5-year overall survival rate was 82%. There was no difference in 5-year overall survival (87% vs 79%, p=0.11), recurrence-free survival (74% vs 71%, p=0.49), local recurrence-free survival (78% vs 76%, p=0.16), and distant metastasis-free survival (85% vs 76%, p=0.09) rates between treatment groups. There was no benefit of addition of vaginal brachytherapy to external beam radiotherapy in patients with positive surgical margins. In multivariate analysis, stage (overall survival and local recurrence-free survival), tumor histology (recurrence-free survival, local recurrence-free survival and distant metastasis-free survival), parametrial invasion (recurrence-free survival and distant metastasis-free survival), lymphovascular space invasion (recurrence-free survival), and lymph node metastasis (distant metastasis-free survival) were found as negative prognostic factors. Conclusion Adding vaginal brachytherapy boost to external beam radiotherapy did not provide any benefit in local control or survival in patients with cervical cancer.
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    Is there any benefit of paraaortic field irradiation in pelvic lymph node positive endometrial cancer patients? A propensity match analysis
    (2020) Onal, Cem; Yuce Sari, Sezin; Akkus Yildirim, Berna; Gultekin, Melis; Guler, Ozan Cem; Yildiz, Ferah; 0000-0002-2742-9021; 0000-0001-6908-3412; 31793400; D-5195-2014; AAC-5654-2020
    We evaluated the survival outcomes and recurrence patterns of endometrial cancer (EC) patients with pelvic lymph node metastases who received postoperative radiotherapy (RT) to the pelvis (P-RT) or to the pelvis plus paraaortic lymph nodes (PA-RT) with or without systemic chemotherapy (ChT). The data from 167 patients with stage IIIC1 EC treated with postoperative RT or RT and ChT were collected retrospectively. Those patients with pelvic lymph node metastases were treated with either P-RT (106 patients, 63%) or PA-RT (61 patients, 37%). The median follow-up time for the entire cohort was 49 (range = 5-199) months. The patients receiving adjuvant ChT and RT had significantly higher 5-year OS rates (77% vs. 33%, p < .001) and 5-year PFS rates (71% vs. 30%, p < .001) when compared to those receiving adjuvant RT alone. The patients receiving P-RT and ChT had significantly higher 5-year OS rates and 5-year PFS rates when compared to those treated with adjuvant PA-RT in the entire cohort and matched cohort. Adjuvant ChT together with RT is the strongest predictor of the OS and PFS. Prophylactic PA-RT is unnecessary, even if ChT is used together with P-RT in EC patients with pelvic lymph node metastasis.Impact statement What is already known on this subject? Local and distant recurrence risks are relatively higher in patients with stage IIIC disease, postoperative adjuvant treatment is required to reduce the recurrence risk. Adjuvant RT is a common approach for patients with locally advanced EC. Optimal target volume for RT in patients with stage IIIC EC remains controversial. We demonstrated that extended field RT is unnecessary, even if ChT is used together with pelvic RT in stage IIIC EC patients. What do the results of this study add? We demonstrated that adjuvant ChT together with RT is the strongest predictor of the OS and PFS for EC patients with pelvic lymph node metastases. Extended field RT is unnecessary, even if ChT is used together with pelvic RT in EC patients with pelvic lymph node metastases.
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    Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging
    (2020) Gultekin, Melis; Guler, Ozan Cem; Sari, Sezin Yuce; Yildirim, Berna Akkus; Onal, Cem; Celik, Husnu; Yuce, Kunter; Ayhan, Ali; Arik, Zafer; Kose, Fatih; Altundag, Ozden; Mustafayev, Teuta Zoto; Atalar, Banu; Bolukbasi, Yasemin; Yildiz, Ferah; 0000-0001-6908-3412; 0000-0002-2742-9021; 0000-0002-0156-5973; 0000-0003-0197-6622; 0000-0001-6661-4185; 32347768; AAC-5654-2020; D-5195-2014; G-4827-2016; W-9219-2019; AAJ-5802-2021
    In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, >= 50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)+/- VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statement What is already known on this subject? The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous. What do the results of this study add? This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups. What are the implications of these findings for clinical practice and/or further research? Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.
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    Stereotactic radiotherapy in patients with oligometastatic or oligoprogressive gynecological malignancies: a multi-institutional analysis
    (2020) Onal, Cem; Gultekin, Melis; Oymak, Ezgi; Guler, Ozan Cem; Yilmaz, Melek Tugce; Sari, Sezin Yuce; Yildirim, Berna Akkus; Yildiz, Ferah; 0000-0002-2742-9021; 0000-0001-6908-3412; 32273293; D-5195-2014; AAC-5654-2020
    Introduction Data supporting stereotactic body radiotherapy for oligometastatic patients are increasing; however, the outcomes for gynecological cancer patients have yet to be fully explored. Our aim is to analyze the clinical outcomes of stereotactic body radiotherapy in the treatment of patients with recurrent or oligometastatic ovarian cancer or cervical cancer. Methods The clinical data of 29 patients (35 lesions) with oligometastatic cervical cancer (21 patients, 72%) and ovarian carcinoma (8 patients, 28%) who were treated with stereotactic body radiotherapy for metastatic sites were retrospectively evaluated. All patients had <5 metastases at diagnosis or during progression, and were treated with stereotactic body radiotherapy for oligometastatic disease. Patients with >= 5 metastases or with brain metastases and those who underwent re-irradiation for primary site were excluded. Age, progression time, mean biologically effective dose, and treatment response were compared for overall survival and progression-free survival. Results A total of 29 patients were included in the study. De novo oligometastatic disease was observed in 7 patients (24%), and 22 patients (76%) had oligoprogression. The median follow-up was 15.3 months (range 1.9-95.2). The 1 and 2 year overall survival rates were 85% and 62%, respectively, and the 1 and 2 year progression-free survival rates were 27% and 18%, respectively. The 1 and 2 year local control rates for all patients were 84% and 84%, respectively. All disease progressions were observed at a median time of 7.7 months (range 1.0-16.0) after the completion of stereotactic body radiotherapy. Patients with a complete response after stereotactic body radiotherapy for oligometastasis had a significantly higher 2 year overall survival and progression-free survival compared with their counterparts. In multivariate analysis, early progression (<= 12 months) and complete response after stereotactic body radiotherapy for oligometastasis were the significant prognostic factors for improved overall survival. However, no significant factor was found for progression-free survival in the multivariable analysis. No patients experienced grade 3 or higher acute or late toxicities. Conclusions Patients with early detection of oligometastasis (<= 12 months) and with complete response observed at the stereotactic body radiotherapy site had a better survival compared with their counterparts. Stereotactic body radiotherapy at the oligometastatic site resulted in excellent local control rates with minimal toxicity, and can potentially contribute to long-term survival.