Publications by authors named "Burak Tilki"

6 Publications

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Clinical parameters and nomograms for predicting lymph node metastasis detected with Ga-PSMA-PET/CT in prostate cancer patients candidate to definitive radiotherapy.

Prostate 2021 May 5. Epub 2021 May 5.

Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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-naïve 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-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-PSMA-11 PET/CT for the detection of lymph node metastasis. Together with nomograms, Ga-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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http://dx.doi.org/10.1002/pros.24142DOI Listing
May 2021

Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration-resistant prostate cancer patients during abiraterone/enzalutamide treatment.

Prostate 2021 Apr 27. Epub 2021 Apr 27.

Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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.
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http://dx.doi.org/10.1002/pros.24132DOI Listing
April 2021

Stereotactic radiotherapy to oligoprogressive lesions detected with Ga-PSMA-PET/CT in castration-resistant prostate cancer patients.

Eur J Nucl Med Mol Imaging 2021 Mar 10. Epub 2021 Mar 10.

Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

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-PSMA-PET/CT).

Methods: The clinical data of 67 CRPC patients with 133 lesions treated with Ga-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-PSMA-PET/CT in CRPC patients is efficient and well-tolerated, prolonging the effectiveness of ADT by delaying NEST.
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http://dx.doi.org/10.1007/s00259-021-05298-zDOI Listing
March 2021

Role of 68-Ga-PSMA-PET/CT in pelvic radiotherapy field definitions for lymph node coverage in prostate cancer patients.

Radiother Oncol 2020 10 28;151:222-227. Epub 2020 Aug 28.

Department of Radiation Oncology, Hacettepe University, Faculty of Medicine, Ankara, Turkey.

Purpose: To evaluate the distribution of metastatic lymph nodes (LN) detected on Ga-PSMA-positron emission tomography/computed tomography (PET/CT) in treatment-naïve 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-PSMA-PET/CT images obtained at diagnosis of 138 PC patients were retrospectively analyzed. The number and locations of Ga-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.
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http://dx.doi.org/10.1016/j.radonc.2020.08.021DOI Listing
October 2020

Treatment outcomes of metastasis-directed treatment using Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002).

Strahlenther Onkol 2020 Nov 2;196(11):1034-1043. Epub 2020 Jul 2.

Faculty of Medicine, Department of Radiation Oncology, Hacettepe University, Ankara, Turkey.

Purpose: The aim of this study was to evaluate the outcomes of Ga prostate-specific membrane antigen (Ga-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 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 ≤108 Gy, 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-PSMA-PET/CT-based MDT is an efficient and safe treatment for oligometastatic PC patients. Proper patient selection might improve treatment outcomes.
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http://dx.doi.org/10.1007/s00066-020-01660-6DOI Listing
November 2020

In Regard to Fernando et al.: Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial.

Radiother Oncol 2020 06 19;147:232. Epub 2020 Feb 19.

Hacettepe University, Faculty of Medicine, Department of Radiation Oncology, Turkey.

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http://dx.doi.org/10.1016/j.radonc.2020.01.015DOI Listing
June 2020