Browsing by Author "Akyol, Fadil"

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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.
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; 31283600
Purpose 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.
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-5717-2017
Role of 68-Ga-PSMA-PET/CT in pelvic radiotherapy field definitions for lymph node coverage in prostate cancer patients
(2020) Onal, Cem; Ozyigit, Gokhan; Guler, Ozan Cem; Hurmuz, Pervin; Torun, Nese; Tuncel, Murat; Dolek, Yemliha; Yedekci, Yagiz; Oymak, Ezgi; Tilki, Burak; Akyol, Fadil; 0000-0002-2742-9021; 0000-0001-6908-3412; 32861704; AAE-2718-2021; D-5195-2014; AAC-5654-2020
Purpose: To evaluate the distribution of metastatic lymph nodes (LN) detected on Ga-68-PSMA-positron emission tomography/computed tomography (PET/CT) in treatment-naive prostate cancer (PC) patients and to analyze the LN coverage rates of the pelvic fields defined in the GETUG trial and RTOG guidelines and a pelvic field extending superiorly from the L4/L5 interspace. Materials and methods: Ga-68-PSMA-PET/CT images obtained at diagnosis of 138 PC patients were retro-spectively analyzed. The number and locations of Ga-68-PSMA-positive LNs were co-registered with one single-planning CT. The numbers, locations, and sizes of LNs located outside the three pelvic volumes were investigated for the entire cohort and for patients with LN metastasis in the pelvic area only. Results: A total of 441 PSMA-PET-positive LN metastases were identified. The most frequent metastatic LNs were internal iliac LNs (25.2%). Para-aortic and presacral LNs outside the three pelvic fields were present in 20 (14.5%) and 22 patients (15.9%), respectively. The LN coverage rates according to the GETUG trial, the RTOG guidelines, and the pelvic field extending superiorly from L4/L5 were 44.2%, 52.2%, and 71, respectively, in the entire cohort and 51.7%, 61 and 83.1%, respectively, in patients with only pelvic LN metastasis. The number of metastatic LNs was a predictive factor for LNs located outside the three pelvic fields. Conclusions: Extending the cranial margin of the pelvic field from L5/S1 to L4/L5 increases the accuracy of pelvic field irradiation in approximately 20% of patients, highlighting the importance of proximal common iliac irradiation, particularly in patients with multiple LN metastasis. (C) 2020 Elsevier B.V. All rights reserved.
Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration-resistant prostate cancer patients during abiraterone/enzalutamide treatment
(2021) Onal, Cem; Kose, Fatih; Ozyigit, Gokhan; Aksoy, Sercan; Oymak, Ezgi; Muallaoglu, Sadik; Guler, Ozan C.; Tilki, Burak; Hurmuz, Pervin; Akyol, Fadil; 0000-0002-2742-9021; 33905131; D-5195-2014
Background Metastasis-directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor-targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer-specific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST-free survival (NEST-FS) were also assessed. Materials and Methods The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1-5) were treated with MDT. The primary endpoints were PCSS and PFS. The secondary endpoints were time to switch to NEST and NEST-FS. Results The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the prostate-specific antigen (PSA) response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than 6 months after the beginning of ARTA and higher PSA levels after MDT were significant predictors of worse PCSS and PFS. The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower radiation doses for MDT were independent predictors of NEST-FS in multivariate analysis. Conclusions MDT for oligoprogressive lesions is effective and may provide several benefits compared to switching from ARTA treatment to NEST. Patients with early progression while on ARTAs and inadequate PSA responses after MDT have a greater risk of rapid disease progression and poor survival, which necessitates intensified treatment.
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-5195-2014
Purpose 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.
Three Dimensional Conformal Radiotherapy and Androgen Deprivation Therapy in Patients with Clinically Localized Prostate Cancer; Hacettepe University Experience
(2015) Ozdemir, Yurday; Akyol, Fadil; Ozyiğit, Gokhan; Hurmuz, Pervin; Onal, Cem; Selek, Ugur; Karabulut, Erdem
The aim of this study into evaluate the treatment results of three dimensional conformal radiotherapy (3DCRT) and androgen deprivation therapy (ADT) in patients with clinically localized prostate cancer (CLPC). Between June 1998 and December 2011, 577 patients with the diagnosis of CLPC were treated. ADT was started 3 months prior to radiotherapy (RT). 3DCRT was delivered to prostate and the seminal vesicles (SV) to a total dose of 70Gy. Additionally, patients with lymph node (LN) positivity received 50.4Gy RT to pelvic LN's. Median follow up time was 65 months. Five-ten years overall survival (OS), cause specific survival (CSS), PSA relapse-free survival (PSA-RFS) and distant metastasis-free survival (DMFS) rates were 92-74%, 97-91%, 77-55% and 94-88%, respectively. OS was negatively affected from LN positivity (p < 0.001). In the subgroup of patients With GS 8, there was no significant difference between < 1 years and 1 years of ADT in terms of CSS, PSA-RFS and DMFS. OS was better in patients with < 1 years of ADT (p = 0.01). Five year OS (p = 0.02), CSS (p = 0.05), PSA-RFS (p = 0.01) and DMFS (p = 0.07) rates were inferior in the high risk group patients that used ADT 1 year. Acute and late RTOG grade III/IV gastrointestinal system toxicity rates were 1.7% and 5% and acute and chronic RTOG grade III/IV genitourinary system toxicity rates were 1.4% and 5%, respectively. 3DCRT and ADT combination is an effective treatment modality with acceptable toxicities in patients with clinically localized prostate cancer.
Treatment outcomes of metastasis-directed treatment using(68)Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002)
(2020) Hurmuz, Pervin; Onal, Cem; Ozyigit, Gokhan; Igdem, Sefik; Atalar, Banu; Sayan, Haluk; Akgun, Zuleyha; Kurt, Meral; Ozkok, Hale Basak; Selek, Ugur; Oymak, Ezgi; Tilki, Burak; Guler, Ozan Cem; Mustafayev, Teuto Zoto; Saricanbaz, Irem; Rzazade, Rashad; Akyol, Fadil; 0000-0001-6908-3412; 0000-0002-2742-9021; 32617620; AAC-5654-2020; D-5195-2014
Purpose The aim of this study was to evaluate the outcomes of(68)Ga prostate-specific membrane antigen (Ga-68-PSMA) positron-emission tomography (PET)/CT-based metastasis-directed treatment (MDT) for oligometastatic prostate cancer (PC). Methods In this multi-institutional study, clinical data of 176 PC patients with 353 lesions receiving MDT between 2014 and 2019 were retrospectively evaluated. All patients had biopsy proven PC with <= 5 metastases detected with(68)Ga-PSMA-PET/CT. MDT was delivered with conventional fractionation or stereotactic body radiotherapy (SBRT) techniques. CTCAE v4.0 was used for acute and RTOG/EORTC Late Radiation Morbidity Scoring Schema was used for late toxicity evaluation. Results At the time of MDT, 59 patients (33.5%) had synchronous and 117 patients (66.5%) had metachronous metastases. Median number of metastases was one and the MDT technique was SBRT in 73.3% patients. The 2-year overall survival (OS) and progression-free survival (PFS) rates were 87.6% and 63.1%, respectively. With a median follow-up of 22.9 months, 9 patients had local recurrence at the irradiated site. The 2-year local control rate at the treated oligometastatic site per patient was 93.2%. In multivariate analysis, an increased number of oligometastases and untreated primary PC were negative predictors for OS; advanced clinical tumor stage, untreated primary PC, BED3 value of <= 108Gy, and MDT with conventional fractionation were negative predictors for PFS. No patient experienced grade >= 3 acute toxicity, but one patient had a late grade 3 toxicity of compression fracture after spinal SBRT. Conclusion Ga-68-PSMA-PET/CT-based MDT is an efficient and safe treatment for oligometastatic PC patients. Proper patient selection might improve treatment outcomes.
Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy
(2019) Ozyigit, Gokhan; Onal, Cem; Igdem, Sefik; Alicikus, Zumre Arican; Iribas, Ayca; Akin, Mustafa; Yalman, Deniz; Cetin, Ilknur; Aksu, Melek Gamze; Atalar, Banu; Dincbas, Fazilet; Hurmuz, Pervin; Guler, Ozan Cem; Aydin, Barbaros; Sert, Fatma; Yildirim, Cumhur; Gorken, Ilknur Birkay; Agaoglu, Fulya Yaman; Korcum, Aylin Fidan; Yüce, Deniz; Ozkok, Serdar; Darendeliler, Emin; Akyol, Fadil; 31143994
Purpose To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT)+ androgen deprivation therapy (ADT) in the modern era. Methods Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70Gy total irradiation dose to prostate +/- seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT. Results The median follow-up time was 5.9 years (range 0.4-18.2 years); 5-year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (>= 78Gy) and longer ADT duration (>= 2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10. Conclusions Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78Gy and ADT period <2 years) had the worst treatment outcomes.