Publications by authors named "Gökhan Özyiğit"

84 Publications

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 Jun 27;81(9):543-552. 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
June 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

Oligometastatic Bone Disease in Castration-Sensitive Prostate Cancer Patients Treated With Stereotactic Body Radiotherapy Using 68Ga-PSMA PET/CT: TROD 09-004 Study.

Clin Nucl Med 2021 06;46(6):465-470

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

Purpose: 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 (68Ga-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 68Ga-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 68Ga-PSMA PET/CT.
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http://dx.doi.org/10.1097/RLU.0000000000003558DOI Listing
June 2021

A novel inverse optimization based three-dimensional conformal radiotherapy technique in craniospinal irradiation.

Phys Eng Sci Med 2021 Mar 8;44(1):265-275. Epub 2021 Feb 8.

Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, 06100, Ankara, Turkey.

Our aim was to develop a novel inverse optimization-based three-dimensional conformal radiotherapy (i3DCRT) technique for craniospinal irradiation. The imaging data of 20 patients with medulloblastoma were used retrospectively. The first group included 10 pediatric patients with supine position treated under anesthesia/sedation, and the second group included 10 young adult/adult patients treated with prone position. Three different treatment plans were created for each patient via i3DCRT, forward-planned three-dimensional conformal radiotherapy (f3DCRT) and intensity-modulated radiotherapy (IMRT) techniques. A total dose of 36 Gy was prescribed in 20 fractions for all plans. The comparative evaluation was conducted by using the parameters of conformity-index, homogeneity-index, and doses to the target volumes and organs at risk (OARs). The plans created with i3DCRT technique achieved better conformity and homogeneity compared to f3DCRT. In terms of OARs sparing, we found pronounced dose reductions in esophagus and heart in i3DCRT compared to f3DCRT plans. i3DCRT technique also provided a well-conformed dose distribution not superior, but comparable, to IMRT without increase in the total monitor unit per fraction (MU/fx) with respect to f3DCRT. The average monitor unit per fraction (MU/fx) for i3DCRT, f3DCRT and IMRT plans were found as 379.3, 378.0 and 1051.7 MU for the first group and 577.4, 563.5 and 1368.7 MU for the second group, respectively. Novel i3DCRT technique solves the problems associated with field junctions and beam edge matching encountered in f3DCRT plans. Additionally, i3DCRT technique can create almost similar plans as with IMRT with lower total MU/fx.
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http://dx.doi.org/10.1007/s13246-021-00976-6DOI Listing
March 2021

Does Internal Mammary Node Irradiation for Breast Cancer Make a Significant Difference to the Diameter of the Internal Mammary Artery? Correlation with Computed Tomography.

Breast Care (Basel) 2020 Dec 22;15(6):635-641. Epub 2020 Jun 22.

Department of Radiology, Hacettepe University Medical School, Ankara, Turkey.

Objective: Lymphatic irradiation in breast cancer improves locoregional control and has been shown to decrease distant metastasis. However, irradiation also accelerates the formation of atherosclerosis and can cause stenosis, not only in the coronary arteries but also in the internal mammary artery (IMA). The aim of this study was to investigate the effects of radiation on IMAs via computed tomography (CT).

Methods: We reviewed the data of 3,612 patients with breast cancer treated with radiotherapy (RT) between January 2010 and December 2016. We included 239 patients with appropriate imaging and nodal irradiation in the study. All patients were treated with lymphatic irradiation of 46-50 Gy, and a boost dose (6-10 Gy) to the involved internal mammary nodes (IMNs) when imaging studies demonstrated pathological enlargement. Bilateral IMA diameter and the presence of calcification were assessed via thin contrast-enhanced CT and those of ipsilateral irradiated IMAs were compared with those of contralateral nonirradiated IMAs.

Results: The mean diameter of irradiated IMAs was significantly shorter than that of nonirradiated IMAs, regardless of laterality. All vascular calcifications were determined on the irradiated side. A boost dose of radiation to the IMNs and radiation technique did not significantly affect the IMA diameter or the presence of calcification.

Conclusions: The diameter of the IMA is decreased due to RT regardless of laterality, radiation technique, and administration of a boost dose. Evaluation of vessels on CT before coronary artery bypass graft or flap reconstruction can help the surgeon select the most appropriate vessel.
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http://dx.doi.org/10.1159/000508244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768163PMC
December 2020

A hesitated approach: primary radiotherapy for keloids-a case series.

Strahlenther Onkol 2021 Jan 4. Epub 2021 Jan 4.

Department of Radiation Oncology, Hacettepe University Medical School, 06100, Ankara, Turkey.

Purpose: To assess the efficacy and toxicity of hypofractionated radiotherapy (RT) alone in treatment-resistant symptomatic keloids.

Methods: Six patients with a total of 13 inoperable large keloid lesions and no response to previous treatments were admitted to our department between 2017 and 2019. All patients were examined for detailed wound localization, size, contour, and color assessment, and for objective and subjective symptoms. Response to treatment was graded as "complete remission" in case of full symptomatic relief and >75% decrease in lesion size, as "partial remission" in case of partial symptomatic relief and 25-75% decrease in lesion size, and as "stable disease" in case of no symptomatic relief or <25% decrease in lesion size. Patients were followed up monthly for the first 3 months and every 3 months thereafter by physical examination.

Results: A total dose of 37.5 Gy external RT in five fractions was prescribed by 6‑MeV electrons in 4 patients and 6‑MV photons in 2 patients. Complete response was obtained in all patients at the 6‑month control. All patients were satisfied with cosmetic results at their last control. Grade 2 dermatitis developed in all patients during the second week of RT but resolved completely in all after 6 months following the end of RT.

Conclusion: In keloids that are unresponsive to standard treatment, hypofractionated RT using a total dose of 37.5 Gy in five fractions is feasible.
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http://dx.doi.org/10.1007/s00066-020-01736-3DOI Listing
January 2021

Parotid gland stem cells: Mini yet mighty.

Head Neck 2021 Apr 27;43(4):1122-1127. Epub 2020 Nov 27.

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

Background: Our aim was to evaluate the correlation between the radiation doses to parotid gland (PG) stem cells and xerostomia.

Methods: Patients diagnosed with head and neck cancer (HNC) were retrospectively evaluated, and xerostomia inventory (XI) was applied to these patients. PG stem cells were delineated on the treatment planning CT, and the mean doses to the PG stem cells calculated.

Results: The total test score and mean doses to bilateral PGs were significantly correlated (r = .34, P = .001), and the mean doses to bilateral PG stem cell niches were significantly correlated with the total test score (r = .32, P = .002).

Conclusions: In this study, we found that the mean dose to PG stem cells can predict dry mouth as much as the mean dose to the PG.
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http://dx.doi.org/10.1002/hed.26556DOI Listing
April 2021

Gemcitabine based trimodality treatment in patients with muscle invasive bladder cancer: May neutrophil lymphocyte and platelet lymphocyte ratios predict outcomes?

Urol Oncol 2020 Nov 11. Epub 2020 Nov 11.

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

Purpose: Cisplatin based chemoradiation has been commonly used as a definitive treatment for muscle-invasive bladder cancer (MIBC). The aim of the current study is to evaluate oncologic results and toxicity profile of bladder-sparing treatment with external beam radiotherapy (EBRT) and gemcitabine chemotherapy (ChT) in patients with MIBC.

Materials And Methods: Between April 2005 and November 2018 44 patients with nonmetastatic and N0 MIBC were treated with transurethral resection of bladder (TURB), EBRT and concurrent gemcitabine. All patients were staged using thorax-abdomen-pelvic CT and pelvic MRI. EBRT was delivered using 3D conformal technique or intensity modulated radiotherapy. Patients received 50 Gy in 25 to 28 fractions to full bladder followed by a boost dose of 10 Gy in 5 fractions to empty bladder with weekly concurrent gemcitabine of 50 mg/m. All patients were evaluated for age, gender, smoking status, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) at diagnosis, presence of hydroureteronephrosis (HUN), preoperative tumor size, tumor multifocality, presence of CIS, clinical tumor stage. Acute/late genitourinary (GUS) and gastrointestinal (GIS) toxicity, recurrence status, cancer specific survival (CSS) and overall survival (OS) were evaluated. Statistical analysis was performed using SPSS v21.0. Kaplan-Meier survival estimates were calculated to describe CSS and OS. The effect of different parameters on survival was investigated using the log rank test.

Results: Median age of the patients was 72 years (interquartile [IQR]; 66-80). The median tumor size was 30 mm (IQR, 15-59 mm). Thirty-two (77%) patients had T2, 6 (14%) patients had T3, and 4 (9%) patients had T4a disease. Median NLR was 2.6 (IQR, 1.7-3.8) and median PLR was 126.47 (IQR, 77.4-184.8). Median follow-up time was 21 months (range, 6-153 months). At the first TURB performed 6 weeks after CRT, complete response, partial response, stable disease, and progression was detected in 37 (84%), 3 (7%), 1 (2%), and 3 (7%) patients, respectively. One- and 2-year OS, CSS, LRFS, and DMFS rates were 86% and 64%; 88% and 66%; 65% and 44%; 68% and 48%, respectively. In univariate analysis; prognostic factors were age and presence of HUN for OS and DMFS; age, HUN, presence of CIS, NLR, and PLR for DSS; HUN, NLR, and PLR for LRFS, respectively. In multivariate analysis, the independent predictor was the presence of HUN for OS, LRFS, and DMFS; NLR for DSS; PLR for LRFS and age for DMSF. For a subgroup of 17 patients with complete TURB and no CIS and HUN symptoms, 2-year OS, DSS, LRFS, and DMFS rates were 88%, 88%, 72%, and 79%, respectively. The treatment was well-tolerated and all patients completed the planned EBRT and ChT. No acute or late ≥ grade 3 toxicity was observed. Grade II acute GIS toxicity was detected in 3 (7%) patients and grade II acute GUS toxicity was detected in 9 (21%) patients, respectively. Grade II late GUS toxicity was observed in 2 (5%) patients.

Conclusion: Gemcitabine based trimodality treatment is well-tolerated with similar oncologic outcomes reported in the literature. Older age, presence of CIS and high NLR and PLR values seem to deteriorate DSS.
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http://dx.doi.org/10.1016/j.urolonc.2020.11.006DOI Listing
November 2020

Characterization of 3D-printed bolus produced at different printing parameters.

Med Dosim 2021 Summer;46(2):157-163. Epub 2020 Nov 8.

Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, 06100, Ankara, Turkey.

We aimed to analyze the effects of printing parameters on characterization of three-dimensional (3D) printed bolus used in external beam radiotherapy. Two sets of measurements were performed to investigate the dosimetric and physical characterization of 3D-printed bolus at different printing parameters. In the first step, boluses were produced at different infill-percentages, infill-patterns and printing directions. Two-dimensional (2D) dose measurements were performed in Elekta Versa HD linear accelerator using 6 MV photon energy. Measured 2D dose maps for both printed and reference bolus materials were compared using the 2D gamma analysis method. Additionally, patient-specific bolus was produced with defined optimum printing parameters for anthropomorphic head and neck phantom. Then, point dose measurements were performed to evaluate the feasibility of printed bolus in clinical use. In the second step, physical measurements were carried out to evaluate the printing accuracy, the mean hounsfield unit (HU) value and the weight of 3D-printed boluses. According to our measurement, infill-percentage, infill-pattern and printing direction significantly changed the dosimetric and physical properties of the 3D-printed bolus independently. Maximum gamma passing rate at 1.5 and 5 cm depths were found as 93.8% and 98.8%, respectively, for 60% infill-percentage, sunglass fill infill-pattern and horizontal printing direction. The printing accuracy of the products was within 0.4 mm. Dosimetric and physical properties of the printed bolus material changed significantly with the selected printing parameters. Therefore, it is important to note that each combination of these printing parameters that will be used in the production of patient-specific bolus should be investigated separately.
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http://dx.doi.org/10.1016/j.meddos.2020.10.005DOI Listing
November 2020

Factors affecting post-treatment radiation-induced lung disease in patients receiving stereotactic body radiotherapy to lung.

Radiat Environ Biophys 2021 03 24;60(1):87-92. Epub 2020 Oct 24.

Department of Radiation Oncology, Hacettepe University Faculty of Medicine, 06100, Ankara, Turkey.

The aim of the study is to investigate factors that may cause radiation-induced lung disease (RILD) in patients undergoing stereotactic body radiotherapy (SBRT) for lung tumors. Medical records of patients treated between May 2018 and June 2019 with SBRT were retrospectively evaluated. All patients should have a diagnosis of either primary non-small cell lung cancer (NSCLC) or less than three metastases to lung from another primary. The median treatment dose was 50 Gy in 4-5 fractions. Tumor response and RILD were evaluated in thoracic computer tomography (CT) using RECIST criteria. 82 patients with 97 lung lesions were treated. The median age was 68 years (IQR = 62-76). With a median follow-up of 7.2 months (3-18 months), three patients had grade 3 radiation pneumonitis (RP). RILD was observed in 52% of cases. Patients who had RILD had a higher risk of symptomatic RP (p = 0.007). In multivariate analyses older age, previous lung radiotherapy history, and median planning treatment volume (PTV) D95 value of ≥ 48 Gy were associated with RILD. Local recurrence (LR) was observed in 5.1% of cases. There was no difference in overall survival and LR with the presence of RILD. Older age, previous lung radiotherapy history, and median PTV D95 value of ≥ 48 Gy seems to be associated with post-SBRT RILD.
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http://dx.doi.org/10.1007/s00411-020-00878-3DOI 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

Stereotactic body radiotherapy in patients with early-stage non-small cell lung cancer: Does beam-on time matter?

Jpn J Clin Oncol 2020 Sep;50(10):1182-1187

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

Purpose: Stereotactic body radiotherapy (SBRT) is an effective treatment option for patients with early-stage non-small cell lung cancer (NSCLC). In this study, we evaluated the treatment results using two different SBRT techniques and the effect of beam-on time (BOT) on treatment outcomes.

Methods: Between July 2007 and January 2018, 142 patients underwent SBRT for primary NSCLC. We have delivered SBRT using either respiratory tracking system (RTS) or internal-target-volume (ITV)-based motion management techniques. The effect of age, tumor size, pretreatment tumor SUVmax value, presence of tissue diagnosis, histopathological subtype, operability status, tumor location, motion management technique, BED10 value, BOT on overall survival (OS), loco-regional control (LRC), event-free survival (EFS) and primary tumor control (PTC) were evaluated.

Results: Median age of the patients was 70 years (range, 39-91 years). Most of the patients were inoperable (90%) at the time of SBRT. Median BED10 value was 112.5 Gy. With a median follow-up of 25 months, PTC was achieved in 91.5% of the patients. Two-year estimated OS, LRC, PTC and EFS rates were 68, 63, 63 and 53%, respectively. For the entire group, OS was associated with BOT (P = 0.027), and EFS was associated with BOT (P = 0.027) and tumor size (P = 0.015). For RTS group, OS was associated with age (P = 0.016), EFS with BOT (P = 0.05) and tumor size (P = 0.024), LRC with BOT (P = 0.008) and PTC with BOT (P = 0.028). The treatment was well tolerated in general.

Conclusion: SBRT is an effective and safe treatment with high OS, LRC, EFS and PTC rates in patients with primary NSCLC. Protracted BOT might deteriorate SBRT outcomes.
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http://dx.doi.org/10.1093/jjco/hyaa093DOI Listing
September 2020

In Regard to Aksnessætheret al.

Int J Radiat Oncol Biol Phys 2020 06 26;107(2):387-388. Epub 2020 Feb 26.

Department of Radiation Oncology, Hacettepe University Medical School, Ankara, Turkey.

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http://dx.doi.org/10.1016/j.ijrobp.2020.02.028DOI Listing
June 2020

Dosimetric comparison of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for left-sided chest wall and lymphatic irradiation.

J Appl Clin Med Phys 2019 Dec 3;20(12):36-44. Epub 2019 Nov 3.

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

Introduction: The aim of this study was to compare five different techniques for chest wall (CW) and lymphatic irradiation in patients with left-sided breast carcinoma.

Methods: Three-dimensional conformal radiotherapy (3DCRT), forward-planned intensity-modulated radiotherapy (FP-IMRT), inverse-planned IMRT (IP-IMRT; 7- or 9-field), and hybrid IP-/FP-IMRT were compared in 10 patients. Clinical target volume (CTV) included CW and internal mammary (IM), supraclavicular (SC), and axillary nodes. Planning target volumes (PTVs), CTVs, and organs at risks (OARs) doses were analyzed with dose-volume histograms (DVHs).

Results: No differences could be observed among the techniques for doses received by 95% of the volume (D95%) of lymphatics. However, the FP-IMRT resulted in a significantly lower D95% dose to the CW-PTV compared to other techniques (P = 0.002). The 9-field IP-IMRT achieved the lowest volumes receiving higher doses (hotspots). Both IP-IMRT techniques provided similar mean doses (Dmean) for the left lung which were smaller than the other techniques. There was no difference between the techniques for maximum dose (Dmax) of right breast. However, FP-IMRT resulted in lower Dmean and volume of right breast receiving at least 5 Gy doses compared to other techniques.

Conclusion: The dose homogeneity in CW-CTV was better using IMRT techniques compared to 3DCRT. Especially 9-field IP-IMRT provided a more homogeneous dose distribution in IM and axillary CTVs. Moreover, the OARs volumes receiving low radiation doses were larger with IP-IMRT technique, while volumes receiving high radiation doses were larger with FP-IMRT technique. Hybrid IMRT plans were found to have the advantages of both FP- and IP-IMRT techniques.
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http://dx.doi.org/10.1002/acm2.12757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909119PMC
December 2019

Prognostic significance of castrate testosterone levels for patients with intermediate and high risk prostate cancer.

World J Clin Oncol 2019 Aug;10(8):283-292

Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey M.D.

Background: Testosterone level of < 50 ng/dL has been used to define castrate level after surgery or after androgen deprivation treatment (ADT) in metastatic prostate cancer (PC).

Aim: To evaluate the effect of two different castrate testosterone levels, < 50 and < 20 ng/dL, on biochemical relapse free survival (BRFS) in patients with non-metastatic intermediate and high risk PC receiving definitive radiotherapy (RT) and ADT.

Methods: Between April 1998 and February 2011; 173 patients with intermediate and high risk disease were treated. Radiotherapy was delivered by either three-dimensional-conformal technique to a total dose of 73.4 Gy at the ICRU reference point or intensity modulated radiotherapy technique to a total dose of 76 Gy. All the patients received 3 mo of neoadjuvant ADT followed by RT and additional 6 mo of ADT. ASTRO Phoenix definition was used to define biochemical relapse.

Results: Median follow up duration was 125 months. Ninety-six patients (56%) had castrate testosterone level < 20 ng/dL and 139 patients (80%) had castrate testosterone level < 50 ng/dL. Both values are valid at predicting BRFS. However, patients with testosterone < 20 ng/dL have significantly better BRFS compared to other groups ( = 0.003). When we compare two values, it was found that using 20 ng/dL is better than 50 ng/dL in predicting the BRFS (AUC = 0.63 0.58, respectively).

Conclusion: Castrate testosterone level of less than 20 ng/dL is associated with better BRFS and is better in predicting the BRFS. Further studies using current standard of care of high dose IMRT and longer ADT duration might support these findings.
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http://dx.doi.org/10.5306/wjco.v10.i8.283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717705PMC
August 2019

Feasibility of novel in vivo EPID dosimetry system for linear accelerator quality control tests.

Australas Phys Eng Sci Med 2019 Dec 12;42(4):995-1009. Epub 2019 Sep 12.

Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, 06100, Ankara, Turkey.

The main aim was to validate the capability of a novel EPID-based in vivo dosimetry system for machine-specific quality control (QC) tests. In current study, two sets of measurements were performed in Elekta Versa HD linear accelerator using novel iViewDose™ in vivo dosimetry software. In the first part, measurements were carried out to evaluate the feasibility of novel in vivo system for daily dosimetric QC tests including output constancy, percentage depth dose (PDD) and beam profile measurements. In addition to daily QC tests, measured output factor as a function of field size, leaf transmission and tongue and groove effect were compared with calculated TPS data. In the second part of the measurements, detection capability of iViewDose software for basic mechanical QC tests were investigated for different setup conditions. In dosimetric QC tests, measured output factor with changing field size, PDD, beam profile and leaf transmission factors were found to be compatible with calculated TPS data. Additionally, the EPID-based system was capable to detect given dose calibration errors of 1% with ± 0.02% deviation. In mechanical QC tests, it was found that iViewDose software was sensitive for catching errors in collimator rotation (≥ 1°), changes in phantom thickness (≥ 1 cm) and major differences in irradiated field size down to 1 mm. In conclusion, iViewDose was proved to be as useful EPID-based software for daily monitoring of linear accelerator beam parameters and it provides extra safety net to prevent machine based radiation incidents.
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http://dx.doi.org/10.1007/s13246-019-00798-7DOI Listing
December 2019

Feasibility study of an electronic portal imaging based in vivo dose verification system for prostate stereotactic body radiotherapy.

Phys Med 2019 Aug 24;64:204-209. Epub 2019 Jul 24.

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

Purpose: We evaluated the feasibility of electronic portal imaging based 3D in-vivo dosimetry for stereotactic body radiation therapy (SBRT) technique in prostate cancer.

Methods And Materials: To investigate error detectability limitations of iViewDose™ v.1.0.1 (Elekta, Stockholm, Sweden) for prostate SBRT cases, ten prostate cancer patients were selected and in-vivo electronic portal imaging devices dosimetry was performed. Also possible error scenarios including dose calibration, setup, collimator, multi leaf collimator and patient anatomy related inaccuracies were created to investigate detectability of EPID. For this purpose, a SBRT treatment was planned on BrainLab pelvis phantom (BrainLab Medical Systems, Westchester, IL) and irradiated after proving setup with cone beam computer tomography. After that incorrect plans were irradiated and obtained results were compared with original in vivo measurements.

Results: Mean gamma analysis (γ% ≤ 1) passing rate of ten patients was found as 96.2%. Additionally, mean dose reference point difference between measurement and calculated in treatment planning system for clinical target volume, rectum, bladder, left and right femur heads were found as 1.4%, 8%, 20.8%, 2.3% and 4.5%, respectively. Phantom measurements showed that positional errors can be escape from detection. However, the incorrect treated plans including linac calibration, MLC positions and patient anatomy based errors could not have passed the in vivo dosimetry analysis.

Conclusions: EPID-based 3D in vivo dosimetry software (iViewDose) provides an efficient safety check on the accuracy of dose delivery during prostate SBRT treatments. However, phantom results showed some limitation of the system.
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http://dx.doi.org/10.1016/j.ejmp.2019.07.008DOI Listing
August 2019

Integration of 68Ga-PSMA-PET/CT in Radiotherapy Planning for Prostate Cancer Patients.

Clin Nucl Med 2019 Sep;44(9):e510-e516

Departments of Radiation Oncology.

To assess the role of Gallium-labeled-prostate-specific membrane antigen PET/CT (Ga-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-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-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-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-PSMA-PET/CT.

Conclusions: We found that Ga-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-PSMA-PET/CT seems to have a great influence on RT decision making in prostate cancer patients.
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http://dx.doi.org/10.1097/RLU.0000000000002691DOI Listing
September 2019

Radiotherapy After Skin-Sparing Mastectomy and Implant-Based Breast Reconstruction.

Clin Breast Cancer 2019 10 11;19(5):e611-e616. Epub 2019 Apr 11.

Department of Radiation Oncology, Hacettepe University Medical School, Ankara, Turkey. Electronic address:

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.
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http://dx.doi.org/10.1016/j.clbc.2019.04.002DOI Listing
October 2019

Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy : TROD 09-001 multi-institutional study.

Strahlenther Onkol 2019 Oct 29;195(10):882-893. Epub 2019 May 29.

Department of Radiation Oncology, Hacettepe University, Faculty of Medicine, 06100, Ankara, Turkey.

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 70 Gy 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 (≥78 Gy) 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 <78 Gy and ADT period <2 years) had the worst treatment outcomes.
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http://dx.doi.org/10.1007/s00066-019-01476-zDOI Listing
October 2019

The hematologic parameters in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

Future Oncol 2019 May 12;15(13):1469-1479. Epub 2019 Apr 12.

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

Currently, there are no predictive markers of response to abiraterone. We calculated neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline and at 4 and 12 weeks after initiation of abiraterone, and we evaluated prostate-specific antigen (PSA) response every 4 weeks in 102 metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone either pre- or postchemotherapy. With a median follow-up was 24.0 months (range: 0.3-54.9), median overall survival (OS) was 20.8 months. High-NLR patients who remained high or who returned to low NLR after 4 and 12 weeks showed significantly worse OS than patients with low baseline NLR. NLR and prostate-specific antigen response to abiraterone was a significant predictor of OS and progression-free survival (PFS) in metastatic castration-resistant prostate cancer patients treated with abiraterone delivered either pre- or postchemotherapy.
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http://dx.doi.org/10.2217/fon-2018-0635DOI Listing
May 2019

In Regard to Bryant et al.

Int J Radiat Oncol Biol Phys 2019 05;104(1):224-225

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

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http://dx.doi.org/10.1016/j.ijrobp.2019.01.083DOI Listing
May 2019

Performance evaluation of the X-sight spine tracking system for abdominal tumors distal to spine: A 2D dosimetric analysis.

Med Dosim 2019 Winter;44(4):370-374. Epub 2019 Feb 22.

Hacettepe University Faculty of Medicine, Department of Radiation Oncology, Ankara 06100, Turkey.

The X-sight spine tracking system was integrated with Cyberknife unit to deliver radiosurgery treatments for spinal tumors without fiducial placement. However the tracking system can also be used for the treatment of abdominal tumors located in a certain distance from the spine. The aim of our study is to evaluate the tracking performance of the X-sight spine system for abdominal tumors distal to spine based on the 3 factors: tumor distance from the reference vertebra, the angle of tumor with the vertebra, and the amplitude of tumor motion due to respiration. An experimental setup was designed mainly with ovine lumbar vertebrae and the BrainLab ExacTrac gating phantom. Planning Target Volume (PTV) structures were delineated at different vertical distances from the reference vertebra. The dosimetric measurements were taken with GafChromic EBT3 film placed between slab phantoms so that they corresponded to centers of the target volumes. Dosimetric comparisons were performed based on dose-volume parameters and the gamma analysis. The measurements were then repeated for the same experimental conditions by using the Synchrony system to compare tracking performances. Using the X-sight system, percentage differences between the dose-volume parameters of the Treatment Planning System (TPS) calculations and the EBT3 film readings went up to 12% for the motion amplitude of 8 mm. The differences decreased with small motions while angles and vertical distances of the lesion locations did not induce major changes in dose discrepancies. Percentages of pixels passing gamma analysis were found to be below the acceptance threshold of 95%. Using the Synchrony system, the measured dose distributions had more similar patterns with those of the TPS system such that the percentage differences in the dose parameters were less than 4% and the gamma passing rates were found to be higher than 95%. Our results showed that the X-sight spine system should not be chosen for tracking abdominal tumors distal to the spine or osseous structures because of the effect of diaphragmatic motion on entire abdominal region. The fiducial-based Synchrony tracking system can be preferred for these tumors.
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http://dx.doi.org/10.1016/j.meddos.2019.01.003DOI Listing
April 2020

Outcome of loco-regional radiotherapy in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

Strahlenther Onkol 2019 Oct 30;195(10):872-881. Epub 2019 Jan 30.

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

Purpose: To evaluate the potential benefit of curative radiotherapy (RT) to the primary tumor in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone.

Materials And Methods: The clinical parameters of 106 mCRPC patients treated with abiraterone were retrospectively evaluated. Patients were either oligometastatic (≤5 metastases) at diagnosis or became oligometastatic after the systemic treatment was analyzed. Local RT to the primary tumor and pelvic lymphatics was delivered in 44 patients (41%), and 62 patients (59%) did not have RT to the primary tumor. After propensity match analysis, a total of 92 patients were analyzed.

Resultsn: Median follow-up time was 14.2 months (range: 2.3-54.9 months). Median overall survival (OS) was higher in patients treated with local RT to the primary tumor than in those treated without local RT with borderline significance (24.1 vs. 21.4 months; p = 0.08). Local RT to the prostate and pelvic lymphatics significantly diminished the local recurrence rate (16 patients, 31% vs. 2 patients, 5%; p = 0.003). In multivariate analysis, the prostate specific antigen (PSA) response ≥50% of the baseline obtained 3 weeks after abiraterone therapy was the only significant prognostic factor for better OS and progression-free survival (PFS). Patients treated with primary RT to the prostate had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT.

Conclusions: Local prostate RT significantly improved OS and local control in mCRPC patients treated with abiraterone. The patients treated with primary RT had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT.
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http://dx.doi.org/10.1007/s00066-019-01429-6DOI Listing
October 2019

The Synergistic Effect of Immune Checkpoint Blockade and Radiotherapy in Recurrent/Metastatic Sinonasal Cancer.

Cureus 2018 Oct 29;10(10):e3519. Epub 2018 Oct 29.

Radiation Oncology, Hacettepe University Medical School, Ankara, TUR.

Treatment options for recurrent/metastatic sinonasal cancer (RMSNC) patients are limited. We present two cases with RMSNC treated with a combination of immune checkpoint blockade and hypo-fractionated stereotactic radiotherapy (HSRT).  Case 1 presented with RMSNC three months after the primary treatment. The patient progressed under first-line chemotherapy and pembrolizumab was offered. The disease progressed after the sixth cycle. We performed reirradiation with HSRT to the primary site. Case 2 presented with local recurrence eight years after the primary treatment for maxillary sinus cancer. He refused surgery and chemotherapy and was offered nivolumab treatment. After two doses, we performed reirradiation with HSRT. Case 1 showed regression at both the local and the metastatic sites after radiotherapy. The second patient's symptoms resolved completely three months after radiotherapy. The HSRT and immune checkpoint blockade combination is a promising treatment option for patients with RMSNC.
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http://dx.doi.org/10.7759/cureus.3519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318133PMC
October 2018

Fitting NTCP models to SBRT dose and carotid blowout syndrome data.

Med Phys 2018 Oct 31;45(10):4754-4762. Epub 2018 Aug 31.

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

Purpose: To estimate the radiobiological parameters of three popular NTCP models, which describe the dose-response relations of carotid blowout syndrome (CBOS) after stereotactic body radiotherapy (SBRT). To evaluate the goodness-of-fit and the correlation of those models with CBOS.

Methods: The study included 61 patients with inoperable locally recurrent head and neck cancer treated with SBRT using CyberKnife (Accuray, Sunnyvale, CA) at the Department of Radiation Oncology, Hacettepe University, Ankara, Turkey between June 2007 and March 2011. The dose-volume histograms of the internal carotid were exported from the plans of all the patients. The follow-up results regarding the end point of carotid blowout syndrome were collected retrospectively. Initially, univariable analyses (Wilcoxon rank-sum or Chi-square tests) and a multivariate logistic regression analysis were performed between the outcome data and a list of clinical and treatment factors to identify significant correlations. Additionally, the Lyman-Kutcher-Burman (LKB), Relative Seriality (RS), and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC), and Odds Ratio methods.

Results: The clinical/treatment factors that were found to have a significant or close to significant correlations with acute CBOS were Age at the time of CK (P-value = 0.03), Maximum carotid dose (P-value = 0.06), and CK prescription dose (P-value = 0.08). Using D , physical DVH, and EQD -DVH as the dosimetric metrics in the NTCP models, the derived LKB model parameters were: (a) D  = 45.8 Gy, m = 0.24, n = n/a; (b) D  = 44.8 Gy, m = 0.28, n = 0.01; and (c) D  = 115.8 Gy, m = 0.45, n = 0.01, respectively. The AUC values for the dosimetric metrics were 0.70, 0.68, and 0.61, respectively. The differences in AIC between the different models were less than 2 and ranged within ±0.9.

Conclusion: The maximum dose to the internal carotid less than 34 Gy appears to significantly reduce the risk for CBOS. Age at the time of CK, Maximum carotid dose, and CK prescription dose were also found to correlate with CBOS. The values of the parameters of three NTCP models were determined for this endpoint. A threshold of gEUD <34.5 Gy appears to be significantly associated with lower risks of CBOS.
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http://dx.doi.org/10.1002/mp.13121DOI Listing
October 2018

In Regard to Nantavithya et al.

Int J Radiat Oncol Biol Phys 2018 07;101(3):744-745

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

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http://dx.doi.org/10.1016/j.ijrobp.2018.03.044DOI Listing
July 2018