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Item Treatment Outcomes of Breast Cancer Liver Metastasis Treated with Stereotactic Body Radiotherapy(2018) Onal, Cem; Guler, Ozan Cem; Yildirim, Berna Akkus; https://orcid.org/0000-0002-2742-9021; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0001-6661-4185; 30296648; HOC-5611-2023; AAC-5654-2020; V-5717-2017Background: To assess the outcomes of breast cancer liver metastasis (BCLM) treated with stereotactic body radiotherapy (SBRT) and systemic treatment. Materials and methods: Patients with oligometastasis at the time of liver metastasis (LM) or who became oligometastatic (<= 5 metastases) after systemic treatment were assessed. Twenty-nine liver metastatic lesions were treated with a total of 54 Gy delivered in 3 fractions. The local control (LC), overall survival (OS), and progression-free survival (PFS) rates were calculated using Kaplan-Meier analyses. Results: A total of 22 patients with 29 liver metastatic lesions treated with liver SBRT between April 2013 and September 2017 were retrospectively analyzed. After a median follow-up time of 16.0 months (range 4.4-59.4 months), 18 patients (82%) had disease recurrence, median of 7.4 months (range 1.0-27.9 months) after completion of liver SBRT. The 1- and 2-year OS rates were 85% and 57%, and the 1- and 2-year PFS rates were 38% and 8%, respectively. The 1- and 2-year LC rates were 100% and 88%, respectively. No significant prognostic factors, including disease extension, size of metastasis, number of liver metastasis and timing of liver metastasis, hormonal status affecting OS, PFS and LC were found. No patients experienced Grade 4 or 5 toxicity; furthermore, only one patient experienced rib fracture 6 months after completion of treatment, and one patient had a duodenal ulcer. Conclusion: This study is the first to evaluate the feasibility of SBRT to BCLM patients. Liver SBRT is a conservative approach with excellent LC and limited toxicities. (C) 2018 Elsevier Ltd. All rights reserved.Item Prognostic values of ADC(mean) and SUVmax of the primary tumour in cervical cancer patients treated with definitive chemoradiotherapy(2019) Yildirim, Berna Akkus; Onal, Cem; Erbay, Gurcan; Guler, Ozan Cem; Karadeli, Elif; Reyhan, Mehmet; Koc, Zafer; 0000-0002-2742-9021; 0000-0003-0987-1980; 30354907; D-5195-2014; S-8384-2016We analysed the correlation of F-18-fluorodeoxyglucose uptake into primary tumours using the maximum standardised uptake value (SUVmax) and the mean apparent diffusion coefficient (ADC(mean)) values in magnetic resonance imaging (MRI) with the clinical and pathological factors in patients with cervical cancer who were treated with concurrent chemoradiotherapy. The patients were stratified according to the primary tumour pre-treatment ADC(mean) and SUVmax cut-off values. There were significant correlations between the SUVmax of the primary tumour and tumour size, and the treatment response. The correlation between the ADC(mean) and FIGO stage, tumour size, and the lymph node metastasis was significant. The SUVmax was significantly and inversely correlated with the ADC(mean) for cervical cancer (r = -0.44, p <.001). In the multivariate analysis, the primary tumour ADC(mean), treatment response and the lymph node metastasis emerged as significant independent predictors of both OS and DFS, and of the primary tumour SUVmax for DFS. Tumour size has a borderline significance for OS. High SUVmax and low ADC(mean) of the primary tumour are important predictive factors for identifying high-risk patients with cervical cancer who are treated with definitive chemoradiotherapy. These results point to a future role for the diffusion-weighted MRI and for F-18-fluorodeoxyglucose positron emission tomography, not only in the staging of cervical cancer but as an aid in the selection of an adjuvant treatment regimen after chemoradiotherapy for individual patients.Item Treatment outcomes of endometrial cancer patients with paraaortic lymph node metastasis: a multi-institutional analysis(2019) Onal, Cem; Yildirim, Berna Akkus; Sari, Sezin Yuce; Yavas, Guler; Gultekin, Melis; Guler, Ozan Cem; Yildiz, Ferah; Akyurek, Serap; 0000-0002-2742-9021; 0000-0001-6908-3412; 30640689; D-5195-2014; AAC-5654-2020Objective To analyze the prognostic factors and treatment outcomes in endometrial cancer patients with paraaortic lymph node metastasis. Methods Data from four centers were collected retrospectively for 92 patients with endometrial cancer treated with combined radiotherapy and chemotherapy or adjuvant radiotherapy alone postoperatively, delivered by either the sandwich or sequential method. Prognostic factors affecting overall survival and progression-free survival were analyzed. Results The 5-year overall survival and progression-free survival rates were 35 % and 33 %, respectively, after a median follow-up time of 33 months. The 5-year overall survival and progression-free survival rates were significantly higher in patients receiving radiotherapy and chemotherapy postoperatively compared with patients treated with adjuvant radiotherapy alone (P < 0.001and P < 0.001, respectively). In a subgroup analysis of patients treated with adjuvant combined chemotherapy and radiotherapy, the 5-year overall survival and progression-free survival rates were significantly higher in patients receiving chemotherapy and radiotherapy via the sandwich method compared with patients treated with sequential chemotherapy and radiotherapy (P = 0.02and P = 0.03, respectively). In the univariate analysis, in addition to treatment strategy, pathology, depth of myometrial invasion, and tumor grade were significant prognostic factors for both overall survival and progression-free survival. In the multivariate analysis, grade III disease, myometrial invasion greater than or equal to 50%, and adjuvant radiotherapy alone were negative predictors for both overall survival and progression-free survival. Conclusion We demonstrated that adjuvant combined treatment including radiotherapyand chemotherapy significantly increases overall survival and progression-free survival rates compared with postoperative pelvic and paraaortic radiotherapy.Item Primary extranodal lymphoma of the glands. Literature review and options for best practice in 2019(2019) Belkacemi, Yazid; Sio, Torence T.; Colson-Durand, Laurianne; Onal, Cem; Villa, Salvador; Anacak, Yavuz; Krengli, Marco; Thariat, Juliette; Ugurluer, Gamze; Miller, Robert C.; Mirimanoft, Rene-Olivier; Ozsahin, Mahmut; To, Nhu Hanh; 0000-0002-2742-9021; 30819450; D-5195-2014Primary extranodal non-Hodgkin's lymphomas (EN-NHL) are a heterogeneous group of malignancies that involve numerous entities with significant difference in terms of tumor site locations, prognostic factors, biology expression, and therapeutic options. In the literature, many EN-NHL types were reported from limited series which only allowed narrow views for elucidating prognostic factors and defining the role of loco-regional therapies in the era of new systemic and biologically targeted therapies. The Rare Cancer Network (RCN), an international multidisciplinary consortium, has published a number of reports on several EN-NHL sites which included many gland locations. In this review, we will focus on the recent literature for a selected number of EN-NHL types in both exocrine and endocrine gland locations. We aim to provide renewed and clear messages for the best practice in 2019 for diagnosis, histopathology, treatments, and also their prognostic implications. We believe that better understanding of molecular and genetic characteristics of these particular diseases is crucial for an appropriate management in the era of personalized treatment developments.Item A multi-institutional analysis of sequential versus 'sandwich' adjuvant chemotherapy and radiotherapy for stage IIIC endometrial carcinoma(2019) Onal, Cem; Sari, Sezin Yuce; Yildirim, Berna Akkus; Yavas, Guler; Gultekin, Melis; Guler, Ozan Cem; Akyurek, Serap; Yildiz, Ferah; 0000-0002-2742-9021; 30887753; D-5195-2014Objective: To analyze the outcomes of sequential or sandwich chemotherapy (ChT) and radiotherapy (RT) in patients with node-positive endometrial cancer (EC). Methods: Data from 4 centers were collected retrospectively for 179 patients with stage IIIC EC treated with postoperative RT and ChT (paclitaxel and carboplatin). Patients were either treated with 6 cycles of ChT followed by RT (sequential arm; 96 patients) or with 3 cycles of ChT, RT, and an additional 3 cycles of ChT (sandwich arm; 83 patients). Prognostic factors affecting overall survival (OS) and progression-free survival (PFS) were analyzed. Results: The 5-year OS and PFS rates were 64% and 59%, respectively, with a median followup of 41 months (range, 5-167 months). The 5-year OS rates were significantly higher in the sandwich than sequential arms (74% vs. 56%; p=0.03) and the difference for 5-year PFS rates was nearly significant (65% vs. 54%; p=0.05). In univariate analysis, treatment strategy, age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology, rate of myometrial invasion, and grade were prognostic factors for OS and PFS. In multivariate analysis, non-endometrioid histology, advanced FIGO stage, and adjuvant sequential ChT and RT were negative predictors for OS, whereas only non-endometrioid histology was a prognostic factor for PFS. Conclusion: Postoperative adjuvant ChT and RT for stage IIIC EC patients, either given sequentially or sandwiched, offers excellent clinical efficacy and acceptably low toxicity. Our data support the superiority of the sandwich regimen compared to the sequential strategy in stage IIIC EC patients for OS.Item The prognostic value of haematologic parameter changes during treatment in cervical cancer patients treated with definitive chemoradiotherapy(2019) Yildirim, Berna A.; Guler, Ozan Cem; Kose, Fatih; Onal, Cem; 0000-0001-6908-3412; 0000-0002-0156-5973; 31023114; AAC-5654-2020We retrospectively analysed the prognostic significance of changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) during treatment with definitive chemoradiotherapy (CRT) in 104 cervical cancer patients. The absolute white blood cell, ANC and ALC decrease during treatment, NLR increased throughout treatment and reached to a plateau at fifth week. The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in low-haematological risk (LHR) group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. In multivariate analysis, high-haematological risk (HHR) group and lymph node metastasis were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients.IMPACT STATEMENTWhat is already known on this subject? The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in LHR group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. Lymph node metastasis and HHR and were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients.What the results of this study add? Weekly changes in ANC, ALC, and NLR, especially after 3rd week of treatment are predictive factors of disease progression, not the high-risk features of disease. Furthermore, in HHR group more patients with extensive stage disease, larger tumour and lymph node metastasis were observed compared to LHR group.What the implications are of these findings for clinical practice and/or further research? The patients may be stratified according to risk factors. The treatment intensification maybe required for HHR patients compared to LHR patients. Since our findings are preliminary, further studies are required to support these findings.Item Integration of 68Ga-PSMA-PET/CT in Radiotherapy Planning for Prostate Cancer Patients(2019) Onal, Cem; Torun, Nese; Akyol, Fadil; Guler, Ozan Cem; Hurmuz, Pervin; Yildirim, Berna Akkus; Caglar, Meltem; Reyhan, Mehmet; Ozyigit, Gokhan; 0000-0001-6908-3412; 31283600Purpose To assess the role of (68)Gallium-labeled-prostate-specific membrane antigen PET/CT (Ga-68-PSMA-PET/CT) in risk group definition and radiotherapy planning in the initially planned definitive radiotherapy (RT) for prostate cancer patients. Methods The clinical data of 191 prostate cancer patients treated with definitive intensity-modulated RT were retrospectively analyzed. All patients were initially staged with thoracoabdominal CT and bone scintigraphy, and the second staging was performed using Ga-68-PSMA-PET/CT. Both stages were evaluated for the decision making of RT and any change in RT target volumes. Results After staging with Ga-68-PSMA-PET/CT, 26 patients (13.6%) had risk group changes, 16 patients (8.4%) had an increase in risk group, and 10 patients (5.2%) had a decrease in risk group. Down-staging occurred in 22 patients (11.5%), and upstaging was observed in 30 patients (15.7%). A total of 26 patients (13.6%) had nodal stage changes. After the Ga-68-PSMA-PET/CT scans, the number of metastatic patient increased to 17 (8.9%), with 4 of them moving from oligo- to polymetastatic disease. An additional irradiation of pelvic lymphatics and metastatic site was performed in 13 patients (6.8%) and 6 patients (3.2%), respectively. The RT was aborted in 4 patients (2.1%) because of parenchymal or distant site metastasis observed in the Ga-68-PSMA-PET/CT. Conclusions We found that Ga-68-PSMA-PET/CT causes considerable migration in stage, risk group, and RT field arrangements, especially in high-risk patients regardless of the GS and baseline prostate-specific antigen values alone. Ga-68-PSMA-PET/CT seems to have a great influence on RT decision making in prostate cancer patients.Item The Comparision of Breast Cancer in the Young and Elderly Patients(2019) Petek Erpolat, Ozge; Yuce Sari, Sezin; Ergen, Sefika Arzu; Aydin, Barbaros; Akkus, Berna; Gultekin, Melis; Copan Oksuz, Didem; Arican, Zumre; Onal, Cem; Gursel, Bilge; Akmansu, Muge; Ozyigit, Gokhan; Bilkay Gorken, Ilknur; Yildiz, FerahOBJECTIVE To compare the tumor characteristics, treatment approaches, recurrence patterns and survival results rates of young and elderly patients with breast cancer. METHODS In this study, Between between 2000-2013, a total of 779 patients were treated for breast cancer at nine radiation oncology departments were evaluated retrospectively. Three-hundred eight four of these patients were young (<= 35 years), and 395 of those the patients were elderly (>= 70 years). RESULTS Young patients were more likely to present with aggressive tumor features. They were more often received comprehensive lymphatic irradiation, tumor bed boost and intense chemotherapy. No difference was found for 5 and 10-year loco-regional recurrence- free survival rates were (96% and 93% for young, 97% and 97% for elderly). The 5 and 10-year distant recurrence- free survival rates were lower in the young patients (77% and 67% for young, 85% and 85% for elderly, p<0.0001). No difference was found in 5 and 10-year breast cancer- specific survival (91% and 79% for young, 92% and 87% for elderly). The 5 and 10-year overall survival rates were higher in the young patients (92% and 78% for young, 78% and 63% for elderly, p<0.0001). CONCLUSION The reason for the similarity between the age groups in terms ofregarding loco-regional recurrence- free survival can be more comprehensive lymphatic irradiation and tumor bed boost, the young patients received. The distant recurrence- free survival rates rates were significantly lower in the young patients even though they received more intensive chemotherapy. Future studies aimed at more effective systemic regimens to decrease distant recurrence in young patients are warranted.Item Definitive Brachytherapy in Inoperable Endometrial Cancer(2019) Onal, CemIn elderly patients with medical comorbidities that increase perioperative risks, surgery cannot be performed, and definitive radiotherapy (RT) is a therapeutic option. Although staging for endometrial cancer is based on surgical findings, clinical and radiological imaging has not been standardized yet. For a radiological evaluation of inoperable endometrial cancer, magnetic resonance imaging (MRI) is preferred for local tumor infiltration, and positron emission tomography is accepted as the most accurate modality for assessing lymph node and distant metastases. External RT alone is inadequate, and intracavitary brachytherapy with or without external RT is recommended depending on the disease stage in patients with inoperable endometrial cancer. However, there is currently no standard treatment approach for patients with inoperable endometrial cancer. For patients with inoperable endometrial cancer treated with definitive RT, there are some problems including the RT technique, treatment volumes, and systemic treatment. Based on clinical practice, image-based brachytherapy using computed tomography and magnetic resonance imaging is highly recommended.Item Radiotherapy After Skin-Sparing Mastectomy and Implant-Based Breast Reconstruction(2019) Sari, Sezin Yuce; Guler, Ozan Cem; Gultekin, Melis; Yildirim, Berna Akkus; Onal, Cem; Ozyigit, Gokhan; Yildiz, Ferah; 0000-0001-6908-3412; 31255547; AAC-5654-2020We aimed to evaluate the cosmetic results of radiotherapy in 170 breast cancer patients after implant-based reconstruction. Cosmetic results were excellent or fair in most patients after radiotherapy. However, bolus use, lymphatic irradiation, and the volume receiving at least 110% of the prescribed dose being >1% significantly deteriorated the outcomes. Introduction: We evaluated the cosmetic results of radiotherapy (RT) after implant-based reconstruction (IBR). Patients and Methods: We retrospectively evaluated 170 patients with 171 breast cancers treated between December 2004 and January 2016 in 2 university hospitals. RT fields were reconstructed breast (RB) only in 24 (14%), and RB and regional lymphatics in 147 (86%) breasts, respectively. All but 1 patient received a total 50 Gy with conventional fractionation. All patients received systemic chemotherapy. One hundred thirty-eight (81%) patients received hormonal therapy; 118 tamoxifen and 20 aromatase inhibitor. Results: Median follow-up time was 46.8 months (range, 1-163 months). The 5-year disease-free and overall survival rate was 83% and 93%, respectively. Cosmetic results were considered excellent in 111 (65%), fair in 46 (27%), and bad in 14 (8%) RB by patients. Thirty-four (20%) RB had restorative surgery; because of surgeons' preference because of implant natural life time span in 5, and contracture, fibrosis, deformation, or dislocation of the implant, or cellulitis in the remaining. Statistically significant adverse factors in univariate analysis for impaired cosmetic outcome were bolus use on the RB, lymphatic irradiation, and volume that received at least 110% of the prescribed dose being >1%. The use of bolus material was the only prognostic factor for deterioration of the cosmetic result in multivariate analysis. Conclusion: RT after IBR yields acceptable cosmetic results. Although only 111 (65%) of RBs were considered to have excellent cosmetic results, only a small percentage of patients needed reoperation because of bad cosmetic outcome. (C) 2019 Elsevier Inc. All rights reserved.
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