Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item Prevention of Radiation-Induced Retinopathy with Amifostine in Wistar Albino Rats(2015) Yildirim, Berna Akkus; Cetin, Eren; Topkan, Erkan; Ozyigit, Gokhan; Cengiz, Mustafa; Surucu, Selcuk; Usubutun, Alp; Akyol, Fadil; 0000-0001-6661-4185; 25768249; V-5717-2017Item Stereotactic Body Radiotherapy and Tyrosine Kinase Inhibitors in Patients with Oligometastatic Renal Cell Carcinoma: A Multi-Institutional Study(2023) Onal, Cem; Oymak, Ezgi; Guler, Ozan Cem; Tilki, Burak; Yavas, Guler; Hurmuz, Pervin; Yavas, Cagdas; Ozyigit, Gokhan; https://orcid.org/0000-0002-2742-9021; 36450836; HOC-5611-2023Purpose Few studies have determined the viability of stereotactic body radiotherapy (SBRT) and tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell carcinoma (mRCC). We examined the results of RCC patients who had five or fewer lesions and were treated with TKI and SBRT.Methods The clinical data of 42 patients with 96 metastases treated between 2011 and 2020 were retrospectively evaluated. The prognostic factors predicting overall survival (OS) and progression-free survival (PFS) were assessed in uni-and multivariable analyses.Results Median follow-up and time between TKI therapy and SBRT were 62.3 and 3.7 months, respectively. The 2-year OS and PFS rates were 58.0% and 51.3%, respectively, and 2-year local control rate was 94.1% per SBRT-treated lesion. In univariable analysis, the time between TKI therapy and SBRT and treatment response were significant prognostic factors for OS and PFS. In multivariable analysis, a time between TKI therapy and SBRT of less than 3 months and complete response were significant predictors of better OS and PFS. Only 12 patients (28.6%) had a systemic treatment change at a median of 18.2 months after SBRT, mostly in patients with a non-complete treatment response after this therapy. Two patients (4.8%) experienced grade III toxicity, and all side effects observed during metastasis-directed therapy subsided over time.Conclusion We demonstrated that SBRT in combination with TKIs is an effective and safe treatment option for RCC patients with <= 5 metastases. However, distant metastasis was observed in 60% of the patients, indicating that distant disease control still has room for improvement.Item 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-5195-2014Introduction: 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.Item 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-5195-2014Purpose 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.Item The Promise of Metastasis-Directed Therapy for Oligometastatic Prostate Cancer: Going Beneath the Surface with Molecular Imaging(2022) Sutera, Philip; Phillips, Ryan M.; Deek, Matthew; Ozyigit, Gokhan; Onal, Cem; Tran, Phuoc T.; 35058322Item 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-5195-2014Background 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.Item Prostate-specific membrane antigen PET response associates with radiographic progression-free survival following stereotactic ablative radiation therapy in oligometastatic castration-sensitive prostate cancer.(2022) Sutera, Philip; Deek, Matthew; Guler, Ozan Cem; Hurmuz, Pervin; Reyhan, Mehmet; Rowe, Steven P.; Hrinivich, William; Ren, Lei; Kiess, Ana Ponce; Song, Daniel Y.; Oymak, Ezgi; Pienta, Kenneth J.; Pomper, Martin; Feng, Felix Y.; Ozyigit, Gokhan; Tran, Phuoc T.; Phillips, Ryan; Onal, Huseyin CemItem 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-5195-2014Background 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.Item 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; 33661210Purpose 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.Item Stereotactic radiotherapy to oligoprogressive lesions detected with Ga-68-PSMA-PET/CT in castration-resistant prostate cancer patients(2021) Onal, Cem; Ozyigit, Gokhan; Oymak, Ezgi; Guler, Ozan Cem; Tilki, Burak; Hurmuz, Pervin; Akyol, Fadil; 0000-0002-2742-9021; 33693965; D-5195-2014Purpose We assessed the outcomes of stereotactic body radiotherapy (SBRT) to treat oligoprogressive castration-resistant prostate cancer (CRPC) patients with <= 5 lesions using gallium prostate-specific membrane antigen-positron emission tomography (Ga-68-PSMA-PET/CT). Methods The clinical data of 67 CRPC patients with 133 lesions treated with Ga-68-PSMA-PET/CT-based SBRT were retrospectively analyzed. All of the patients had oligoprogressive disease during androgen-deprivation therapy (ADT). The prognostic factors for overall- (OS) and progression-free survival (PFS) and the predictive factors for switching to next-line systemic treatment (NEST) and NEST-free survival (NEST-FS) were analyzed. Results With a median follow-up of 17.5 months, the 2-year overall survival (OS) and PFS rates were 86.9% and 34.4%, respectively. The PSA response was observed in 49 patients (73.1%). Progression was observed in 37 patients (55.2%) at a median of 11.0 months following SBRT. A total of 45 patients (67.2%) remained on ADT after SBRT, and 22 patients (32.8%) had a NEST change at a median of 16.4 months after metastasis-directed treatment (MDT). Patients with a NEST change had higher post-SBRT PSA values and fewer PSA nadirs after MDT than their counterparts. In multivariate analysis, higher pre-SBRT PSA values were the only significant predictor for worse OS and NEST-FS, and no significant factor was found for PFS. No serious acute or late toxicities were observed. Conclusion This study demonstrated the feasibility of MDT using SBRT to treat oligoprogressive lesions by Ga-68-PSMA-PET/CT in CRPC patients is efficient and well-tolerated, prolonging the effectiveness of ADT by delaying NEST.
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