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    Prognostic Significance Of Albumin And Globulin Levels In Cervical Cancer Patients Treated With Chemoradiotherapy
    (2023) Oymak, Ezgi; Guler, Ozan Cem; Onal, Cem; https://orcid.org/0000-0002-2742-9021; 36356983; D-5195-2014
    ObjectiveAlbumin-globulin ratio or albumin-globulin score predict survival in many cancers, but there are few data on cervical cancer patients. This study examined whether pre-treatment albumin and globulin levels, as well as the albumin-globulin ratio and albumin-globulin score, can predict treatment outcomes in cervical cancer patients undergoing definitive chemoradiotherapy. MethodsA retrospective analysis of cervical cancer patients treated between January 2006 and July 2014 was performed. Receiver operating characteristic curves for serum albumin and globulin levels, as well as albumin-globulin ratio values, were generated in order to determine the cut-off values for these parameters and to predict their sensitivity and specificity for predicting recurrence and survival. Univariate and multivariate analyses were used to identify prognostic factors for overall survival and progression-free survival. ResultsA total of 139 patients were included. The median follow-up time was 11.5 years. The 5- and 10-year overall survival rates were 54.7% and 39.3%, while the 5- and 10-year progression-free survival rates were 48.9% and 36.4%, respectively. The optimal cut-off points were 3.79 g/dL for albumin, 3.27 g/dL for globulin, and 1.56 for albumin-globulin ratio. In the univariate analysis, significant prognostic factors for overall survival and progression-free survival were albumin-globulin ratio, albumin-globulin score, patient age, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, lymph node metastasis, and treatment response. Older age, advanced stage, low albumin-globulin ratio, albumin-globulin score of 2, and inadequate treatment response had poor overall survival and progression-free survival in multivariable analysis. However, serum albumin and globulin levels were not found to be a significantly predictive factor for survival. There was a significant correlation between albumin levels, globulin levels, tumor size, stage, lymph node metastasis, and treatment response. ConclusionsPre-treatment albumin-globulin ratio and albumin-globulin score are useful prognostic factors in patients with cervical squamous cell cancer treated with definitive chemoradiotherapy, and may be suitable biomarkers for predicting treatment outcomes.
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    Treatment Outcomes of Stereotactic Body Radiotherapy in Patients with Synchronous and Metachronous Oligometastatic Renal Cell Carcinoma
    (2023) Guler, Ozan Cem; Oymak, Ezgi; Hurmuz, Pervin; Yavas, Guler; Tilki, Burak; Yavas, Cagdas; Ozyigit, Gokhan; Onal, Cem; 0000-0002-2742-9021; 36455527; D-5195-2014
    Introduction: The aim of this study was to investigate the clinical outcomes of metastasis-directed therapy (MDT) using stereotactic body radiotherapy (SBRT) in patients with synchronous or metachronous oligometastatic renal cell carcinoma (RCC). Methods: The clinical data of 87 patients with 138 lesions who received MDT between February 2008 and January 2019 were retrospectively analyzed. All patients had <= 5 metastasis at diagnosis (synchronous) or during progression (metachronous) and were treated with SBRT for their metastasis. The primary endpoints were local control (LC) and progression-free survival (PFS). The secondary endpoint was overall survival (OS). Results: Median follow-up was 20.4 months for entire cohort and 27.2 months for survivors. Synchronous oligometastatic disease was observed in 35 patients (40.2%), and 52 patients (59.8%) had metachronous disease. Seventy-two patients (82.8%) received systemic treatment synchronously or after MDT, while 15 patients (17.2%) did not receive any systemic treatment. The 1- and 2-year OS rates were 79.4% and 58.1%, respectively, and the 1- and 2-year PFS rates were 58.6% and 15.1%, respectively. The 1- and 2-year LC rates per lesion were 96.6% and 91.4%, respectively. There were no significant differences in survival between patients with synchronous oligometastasis and those with metachronous oligometastasis. All disease progressions were observed at a median time of 31.6 months (range: 1.9-196.9 months) after the completion of SBRT. Patients with solitary oligometastasis had significantly better OS compared to patients with >1 metastasis (p = 0.04). No patients experienced grade 3 or higher acute or late toxicities. Conclusion: SBRT is a successful treatment for oligometastatic RCC patients due to its excellent LC and minimal toxicity profile. There were no statistically significant survival differences between patients with synchronous and metachronous oligometastasis. Patients with solitary oligometastasis outlived their counterparts.
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    The prognostic value of mean apparent diffusion coefficient measured with diffusion-weighted magnetic resonance image in patients with prostate cancer treated with definitive radiotherapy
    (2022) Onal, Cem; Erbay, Gurcan; Guler, Ozan Cem; Oymak, Ezgi; 35753556
    Purpose: To assess the correlation between initial tumor apparent diffusion coefficient (ADC) values and clinicopathological parameters in prostate cancer (PCa) patients treated with definitive radiotherapy (RT). Additionally, the prognostic factors for freedom from biochemical failure (FFBF) and progressionfree survival (PFS) in this patient cohort were analyzed. Materials and methods: The clinical data of 503 patients with biopsy-confirmed PCa were evaluated retrospectively. All patients had clearly evident tumors on diffusion-weighted magnetic resonance imaging (DW-MRI) for ADC values. Univariable and multivariable analyses were used to determine prognostic factors for FFBF and PFS. Results: The median follow-up was 72.9 months. The 5-year FFBF and PFS rates were 93.2% and 86.2%, respectively. Significantly lower ADC values were found in patients with a high PSA level; advanced clinical stage; higher ISUP score, and higher risk group than their counterparts. Receiver operating characteristic (ROC) curve analysis revealed an ADC cut-off value of 0.737 x 10-3 mm2/sec for tumor recurrence. Patients who progressed had a lower mean ADC value than those who did not (0.712 +/- 0.158 vs. 1.365 +/- 0. 227 x 10-3 mm2/sec; p < 0.001). There was a significant difference in 5-year FFBF (96.3% vs. 90%; p < 0.001) and PFS rates (83.8% vs. 73.5%; p = 0.002) between patients with higher and lower mean ADC values. The FFBF and PFS were found to be correlated with tumor ADC value and ISUP grades in multivariable analysis. Additionally, older age was found to be a significant predictor of worse PFS. Conclusions: Lower ADC values were found in patients with high-risk characteristics such as a high serum PSA level, stage or grade of tumor, or high-risk disease, implying that ADC values could be used to predict prognosis. Lower ADC values and higher ISUP grades were associated with an increased risk of BF and progression, implying that treatment intensification may be required in these patients. (c) 2022 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 173 (2022) 285-291
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    Bone Only Oligometastatic Renal Cell Carcinoma Patients Treated with Stereotactic Body Radiotherapy: A Multi Institutional Study
    (2022) Onal, Cem; Guler, Ozan Cem; Hurmuz, Pervin; Yavas, Guler; Tilki, Burak; Oymak, Ezgi; Yavas, Cagdas; Ozyigit, Gokhan; 0000-0002-2742-9021; 35695908; D-5195-2014
    Purpose This study aimed to analyze the prognostic factors associated with overall survival (OS) and progression-free survival (PFS) in patients with bone-only metastatic renal cell carcinoma (RCC) who have five or fewer lesions treated with stereotactic body radiotherapy (SBRT). Methods The clinical data of 54 patients with 70 bone metastases undergoing SBRT treated between 2013 and 2020 with a dose of at least 5 Gy per fraction and a biologically effective dose (BED) of at least 90 Gy were retrospectively evaluated. Results The majority of lesions were located in the spine (57.4%) and had only one metastasis (64.8%). After a median follow-up of 22.4 months, the 1- and 2-year OS rates were 84.6% and 67.3%, respectively, and median OS was 43.1 months. The 1- and 2-year PFS rates and median PFS were 63.0%, 38.9%, and 15.3 months, respectively. In SBRT-treated lesions, the 1-year local control (LC) rate was 94.9%. Age, metastasis localization, and number of fractions of SBRT were significant prognostic factors for OS in univariate analysis. In multivariate analysis, patients with spinal metastasis had better OS compared to their counterparts, and patients who received single-fraction SBRT had better PFS than those who did not. No patient experienced acute or late toxicities of grade 3 or greater. Conclusion Despite excellent LC at the oligometastatic site treated with SBRT, disease progression was observed in nearly half of patients 13 months after metastasis-directed local therapy, particularly as distant disease progression other than the treated lesion, necessitating an effective systemic treatment to improve treatment outcomes.
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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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    The Role Of Stereotactic Body Radiotherapy In Switching Systemic Therapy For Patients With Extracranial Oligometastatic Renal Cell Carcinoma
    (2022) Onal, Cem; Hurmuz, Pervin; Guler, Ozan Cem; Yavas, Guler; Tilki, Burak; Oymak, Ezgi; Yavas, Cagdas; Ozyigit, Gokhan; https://orcid.org/0000-0002-2742-9021; 35119653; D-5195-2014
    Background Targeting oligometastatic lesions with metastasis-directed therapy (MDT) using stereotactic-body radiotherapy (SBRT) may improve treatment outcomes and postpone the need for second-line systemic therapy (NEST). We looked at the results of oligometastatic renal cell carcinoma (RCC) patients who had five or fewer lesions and were treated with SBRT. Methods We examined the treatment outcomes of 70 extracranial metastatic RCC (mRCC) patients treated at two oncology centers between 2011 and 2020. The clinical parameters of patients with and without NEST changes were compared. The prognostic factors for overall survival (OS), progression-free survival (PFS), and NEST-free survival were evaluated. Results Median age was 67 years (range 31-83 years). Lung and bone metastasis were found in 78.4% and 12.6% of patients, respectively. With a median follow-up of 21.1 months, median OS was 49.1 months and the median PFS was 18.3 months. Histology was a prognostic factor for OS, BED, and treatment switch for PFS in univariate analysis. In multivariate analysis, the significant predictor of poor OS was clear cell histology, and a lower BED for PFS. Following SBRT for oligometastatic lesions, 19 patients (27.2%) had a median NEST change of 15.2 months after MDT completion. There were no significant differences in median OS or PFS between patients who had NEST changes and those who did not. No patient experienced grade >= 3 acute and late toxicities. Conclusions The SBRT to oligometastatic sites is an effective and safe treatment option for <= 5 metastases in RCC patients by providing favorable survival and delaying NEST change.
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    National Multi-Center Observational Retrospective Study to Understand Treatment Patterns and Outcomes for Stage III Non-Small Cell Lung Cancer Patients in Turkey: Turkish Society for Radiation Oncology Study, STONE Trial
    (2022) Onal, Cem; Demiral, Ayse Nur; Atalar, Banu; Yalman, Deniz; Dagoglu, Nergiz; Hurmuz, Pervin; Erpolat, Petek; Akyurek, Serap; Gul, Sute Karabulut; Berber, Tanju; Guler, Ozan Cem; Umay, Cenk; Sert, Fatma; Karahacioglu, Eray; Birgi, Sumerya Duru; Yaprak, Gokhan; Saglam, Esra Kaytan
    This study investigated treatment patterns and outcomes in patients with inoperable stage III non-small cell lung cancer (NSCLC) treated with radiotherapy (RT) in Turkey. We included 492 patients with stage III NSCLC in this multi-center retrospective study. Pa-tient demographics, clinical characteristics, and clinical treatment patterns from the time of the initial diagnosis to disease progression were recorded. Additionally, the prognostic factors predicting overall survival (OS) and progression-free survival (PFS) were analyzed. For the initial treatment, 429 patients (89.2%) received chemotherapy and RT, whereas 53 patients (10.8%) were treated only with RT. The first disease progression occurred in 288 patients (58.4%) at 9.3 months (median) after the initial treatment, and 64.6% re-ceived treatment after first progression. The second disease progression occurred in 30 patients, and 20 patients (66.7%) received treatment. Median OS and PFS were 27.0 months and 13.4 months, respectively. Age (p< 0.001), stage (p= 0.04), poor performance score (PS) (p= 0.03) and RT doses (p= 0.002) were independent predictors for OS and PFS in our multivariate analysis. Additional significant predictors for OS in the multivariate analysis were gender (p= 0.004), treatment period (0.02), and irradiation technique (p= 0.02). Disease progression occurred in nearly 58% of the patients, and one-third of these patients remained untreated during the disease progression. These findings indicate a need for additional treatment options in patients with unresectable stage III NSCLC with high-risk features, namely older age, stage IIIB disease, poor PS, and lower RT doses.
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    Clinical parameters and nomograms for predicting lymph node metastasis detected with Ga-68-PSMA-PET/CT in prostate cancer patients candidate to definitive radiotherapy
    (2021) Onal, Cem; Ozyigit, Gokhan; Oymak, Ezgi; Guler, Ozan Cem; Hurmuz, Pervin; Tilki, Burak; Reyhan, Mehmet; Tuncel, Murat; Akyol, Fadil; 0000-0002-2742-9021; 33949694; D-5195-2014
    Background Defining the extent of disease spread with imaging modalities is crucial for therapeutic decision-making and definition of treatment. This study aimed to investigate whether clinical parameters and nomograms predict prostate-specific membrane antigen (PSMA)-positive lymph nodes in treatment-naive nonmetastatic prostate cancer (PC) patients. Materials and Methods The clinical data of 443 PC patients (83.3% high-risk and 16.7% intermediate-risk) were retrospectively analyzed. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were generated to evaluate the accuracy of clinical parameters (prostate-specific antigen [PSA], T stage, Gleason score [GS], International Society of Urological Pathology [ISUP] grade) and nomograms (Roach formula [RF], Yale formula [YF], and a new formula [NF]) in predicting lymph node metastasis. The AUCs of the various parameters and clinical nomograms were compared using ROC and precision-recall (PR) curves. Results A total of 288 lymph node metastases were identified in 121 patients (27.3%) using Ga-68-PSMA-11-positron emission tomography (PET)/computed tomography (CT). Most PSMA-avid lymph node metastases occurred in external or internal iliac lymph nodes (142; 49.3%). Clinical T stage, PSA, GS, and ISUP grade were significantly associated with PSMA-positive lymph nodes according to univariate logistic regression analysis. The PSMA-positive lymph nodes were more frequently detected in patients with PSA >20 ng/ml, GS >= 7 or high risk disease compared to their counterparts. The clinical T stage, serum PSA level, GS, and ISUP grade showed similar accuracy in predicting PSMA-positive metastasis, with AUC values ranging from 0.675 to 0.704. The median risks for PSMA-positive lymph nodes according to the RF, YF, and NF were 31.3% (range: 12.3%-100%), 22.3% (range: 4.7%-100%), and 40.5% (range: 12.3%-100%), respectively. The AUC values generated from ROC and PR curve analyses were similar for all clinical nomograms, although the RF and YF had higher accuracy compared to NF. Conclusion The clinical T stage, PSA, GS, and ISUP grade are independent predictors of PSMA-positive lymph nodes. The RF and YF can be used to identify patients who can benefit from Ga-68-PSMA-11 PET/CT for the detection of lymph node metastasis. Together with nomograms, Ga-68-PSMA-11 PET/CT images help to localize PSMA-positive lymph node metastases and can thus assist in surgery and radiotherapy planning.
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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.