Publications by authors named "Berna Akkus Yildirim"

32 Publications

Role of vaginal brachytherapy boost following adjuvant external beam radiotherapy in cervical cancer: Turkish Society for Radiation Oncology Gynecologic Group Study (TROD 04-002).

Int J Gynecol Cancer 2021 Feb 30;31(2):185-193. Epub 2020 Sep 30.

Radiation Oncology, Ege University Faculty of Medicine, Izmir, Turkey.

Objective: There are a limited number of studies supporting vaginal brachytherapy boost to external beam radiotherapy in the adjuvant treatment of cervical cancer. The aim of this study was to assess the impact of the addition of vaginal brachytherapy boost to adjuvant external beam radiotherapy on oncological outcomes and toxicity in patients with cervical cancer.

Methods: Patients treated with post-operative external beam radiotherapy ± chemotherapy ± vaginal brachytherapy between January 2001 and January 2019 were retrospectively evaluated. The treatment outcomes and prognostic factors were analyzed in patients treated with external beam radiotherapy with or without vaginal brachytherapy.

Results: A total of 480 patients were included in the analysis. The median age was 51 years (range 42-60). At least two intermediate risk factors were observed in 51% of patients, while 49% had at least one high-risk factor. The patients in the external beam radiotherapy + vaginal brachytherapy group had worse prognostic factors than the external beam radiotherapy alone group. With a median follow-up time of 56 months (range 33-90), the 5-year overall survival rate was 82%. There was no difference in 5-year overall survival (87% vs 79%, p=0.11), recurrence-free survival (74% vs 71%, p=0.49), local recurrence-free survival (78% vs 76%, p=0.16), and distant metastasis-free survival (85% vs 76%, p=0.09) rates between treatment groups. There was no benefit of addition of vaginal brachytherapy to external beam radiotherapy in patients with positive surgical margins. In multivariate analysis, stage (overall survival and local recurrence-free survival), tumor histology (recurrence-free survival, local recurrence-free survival and distant metastasis-free survival), parametrial invasion (recurrence-free survival and distant metastasis-free survival), lymphovascular space invasion (recurrence-free survival), and lymph node metastasis (distant metastasis-free survival) were found as negative prognostic factors.

Conclusion: Adding vaginal brachytherapy boost to external beam radiotherapy did not provide any benefit in local control or survival in patients with cervical cancer.
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http://dx.doi.org/10.1136/ijgc-2020-001733DOI Listing
February 2021

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging.

J Obstet Gynaecol 2020 Apr 29:1-7. Epub 2020 Apr 29.

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

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statement The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous. This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups. Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.
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http://dx.doi.org/10.1080/01443615.2020.1737661DOI Listing
April 2020

Stereotactic radiotherapy in patients with oligometastatic or oligoprogressive gynecological malignancies: a multi-institutional analysis.

Int J Gynecol Cancer 2020 06 8;30(6):865-872. Epub 2020 Apr 8.

Department of Radiation Oncology, Hacettepe Universitesi Tip Fakultesi, Ankara, Turkey.

Introduction: Data supporting stereotactic body radiotherapy for oligometastatic patients are increasing; however, the outcomes for gynecological cancer patients have yet to be fully explored. Our aim is to analyze the clinical outcomes of stereotactic body radiotherapy in the treatment of patients with recurrent or oligometastatic ovarian cancer or cervical cancer.

Methods: The clinical data of 29 patients (35 lesions) with oligometastatic cervical cancer (21 patients, 72%) and ovarian carcinoma (8 patients, 28%) who were treated with stereotactic body radiotherapy for metastatic sites were retrospectively evaluated. All patients had <5 metastases at diagnosis or during progression, and were treated with stereotactic body radiotherapy for oligometastatic disease. Patients with ≥5 metastases or with brain metastases and those who underwent re-irradiation for primary site were excluded. Age, progression time, mean biologically effective dose, and treatment response were compared for overall survival and progression-free survival.

Results: A total of 29 patients were included in the study. De novo oligometastatic disease was observed in 7 patients (24%), and 22 patients (76%) had oligoprogression. The median follow-up was 15.3 months (range 1.9-95.2). The 1 and 2 year overall survival rates were 85% and 62%, respectively, and the 1 and 2 year progression-free survival rates were 27% and 18%, respectively. The 1 and 2 year local control rates for all patients were 84% and 84%, respectively. All disease progressions were observed at a median time of 7.7 months (range 1.0-16.0) after the completion of stereotactic body radiotherapy. Patients with a complete response after stereotactic body radiotherapy for oligometastasis had a significantly higher 2 year overall survival and progression-free survival compared with their counterparts. In multivariate analysis, early progression (≤12 months) and complete response after stereotactic body radiotherapy for oligometastasis were the significant prognostic factors for improved overall survival. However, no significant factor was found for progression-free survival in the multivariable analysis. No patients experienced grade 3 or higher acute or late toxicities.

Conclusions: Patients with early detection of oligometastasis (≤12 months) and with complete response observed at the stereotactic body radiotherapy site had a better survival compared with their counterparts. Stereotactic body radiotherapy at the oligometastatic site resulted in excellent local control rates with minimal toxicity, and can potentially contribute to long-term survival.
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http://dx.doi.org/10.1136/ijgc-2019-001115DOI Listing
June 2020

Is there any benefit of paraaortic field irradiation in pelvic lymph node positive endometrial cancer patients? A propensity match analysis.

J Obstet Gynaecol 2020 Oct 3;40(7):1012-1019. Epub 2019 Dec 3.

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

We evaluated the survival outcomes and recurrence patterns of endometrial cancer (EC) patients with pelvic lymph node metastases who received postoperative radiotherapy (RT) to the pelvis (P-RT) or to the pelvis plus paraaortic lymph nodes (PA-RT) with or without systemic chemotherapy (ChT). The data from 167 patients with stage IIIC1 EC treated with postoperative RT or RT and ChT were collected retrospectively. Those patients with pelvic lymph node metastases were treated with either P-RT (106 patients, 63%) or PA-RT (61 patients, 37%). The median follow-up time for the entire cohort was 49 (range = 5-199) months. The patients receiving adjuvant ChT and RT had significantly higher 5-year OS rates (77% vs. 33%,  < .001) and 5-year PFS rates (71% vs. 30%,  < .001) when compared to those receiving adjuvant RT alone. The patients receiving P-RT and ChT had significantly higher 5-year OS rates and 5-year PFS rates when compared to those treated with adjuvant PA-RT in the entire cohort and matched cohort. Adjuvant ChT together with RT is the strongest predictor of the OS and PFS. Prophylactic PA-RT is unnecessary, even if ChT is used together with P-RT in EC patients with pelvic lymph node metastasis.Impact statement Local and distant recurrence risks are relatively higher in patients with stage IIIC disease, postoperative adjuvant treatment is required to reduce the recurrence risk. Adjuvant RT is a common approach for patients with locally advanced EC. Optimal target volume for RT in patients with stage IIIC EC remains controversial. We demonstrated that extended field RT is unnecessary, even if ChT is used together with pelvic RT in stage IIIC EC patients. We demonstrated that adjuvant ChT together with RT is the strongest predictor of the OS and PFS for EC patients with pelvic lymph node metastases. Extended field RT is unnecessary, even if ChT is used together with pelvic RT in EC patients with pelvic lymph node metastases. Although adjuvant treatment modalities are associated with improvements in survival, distant metastasis still remains the most common site of recurrence in advanced EC patients. Thus, further research is warranted to identify improved combined modality strategies to optimise the outcomes for EC patients with pelvic lymph node metastasis.
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http://dx.doi.org/10.1080/01443615.2019.1679742DOI Listing
October 2020

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

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

Retrospective comparison of standard and escalated doses of radiotherapy in newly diagnosed glioblastoma patients treated with concurrent and adjuvant temozolomide.

Indian J Cancer 2019 Jan-Mar;56(1):59-64

Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana, Turkey.

Background: To compare the efficacies of standard dose-(SDRT) and escalated dose radiotherapy (EDRT) in newly diagnosed glioblastoma (GBM) with concurrent and adjuvant temozolomide (TMZ).

Materials And Methods: Outcomes of 126 newly diagnosed GBM patients who received SDRT (60 Gy, 30 fractions) or EDRT (70 Gy, 30 fractions) with concurrent plus adjuvant TMZ were retrospectively analyzed. Both groups received concurrent TMZ (75 mg/m) during the course of RT and at least one course of adjuvant TMZ (150-200 mg/m), thereafter. Overall survival (OS) and local progression free survival (LPFS) constituted the primary and secondary endpoints, respectively.

Results: At median 14.2 months follow-up, 26 (20.6%) patients were alive. Median LPFS and OS were 9.2 [95% confidence interval (CI); 8.4-10.0] and 15.4 months (95% CI; 12.1-18.8), respectively, for the entire cohort. Although the median OS was numerically superior in the EDRT this difference could not reach statistical significance (22.0 vs. 14.9 months; P = 0.45), Likewise, LPFS was also (9.9 vs. 8.9 months; P = 0.89) not different between the two treatment groups. In multivariate analysis, better recursive partitioning analysis class (3-4 vs. 5; P = 0.044) and extensive surgery (gross total resection vs. subtotal resection/biopsy only; P= 0.021) were identified to associate significantly with superior OS times, irrespective of the RT protocol.

Conclusions: Although the current median OS of 22 months of the EDRT group is promising, no statistically significant survival advantage for EDRT was observed even in the presence of TMZ. Randomized studies with larger population sizes and available genetic markers are warranted to conclude more reliably on the fate of EDRT plus TMZ.
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http://dx.doi.org/10.4103/ijc.IJC_128_18DOI Listing
August 2019

A multi-institutional analysis of sequential versus 'sandwich' adjuvant chemotherapy and radiotherapy for stage IIIC endometrial carcinoma.

J Gynecol Oncol 2019 May;30(3):e28

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

Objective: To analyze the outcomes of sequential or sandwich chemotherapy (ChT) and radiotherapy (RT) in patients with node-positive endometrial cancer (EC).

Methods: Data from 4 centers were collected retrospectively for 179 patients with stage IIIC EC treated with postoperative RT and ChT (paclitaxel and carboplatin). Patients were either treated with 6 cycles of ChT followed by RT (sequential arm; 96 patients) or with 3 cycles of ChT, RT, and an additional 3 cycles of ChT (sandwich arm; 83 patients). Prognostic factors affecting overall survival (OS) and progression-free survival (PFS) were analyzed.

Results: The 5-year OS and PFS rates were 64% and 59%, respectively, with a median follow-up of 41 months (range, 5-167 months). The 5-year OS rates were significantly higher in the sandwich than sequential arms (74% vs. 56%; p=0.03) and the difference for 5-year PFS rates was nearly significant (65% vs. 54%; p=0.05). In univariate analysis, treatment strategy, age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology, rate of myometrial invasion, and grade were prognostic factors for OS and PFS. In multivariate analysis, non-endometrioid histology, advanced FIGO stage, and adjuvant sequential ChT and RT were negative predictors for OS, whereas only non-endometrioid histology was a prognostic factor for PFS.

Conclusion: Postoperative adjuvant ChT and RT for stage IIIC EC patients, either given sequentially or sandwiched, offers excellent clinical efficacy and acceptably low toxicity. Our data support the superiority of the sandwich regimen compared to the sequential strategy in stage IIIC EC patients for OS.
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http://dx.doi.org/10.3802/jgo.2019.30.e28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424855PMC
May 2019

Baseline hemoglobin <11.0 g/dL has stronger prognostic value than anemia status in nasopharynx cancers treated with chemoradiotherapy.

Int J Biol Markers 2019 Jun 13;34(2):139-147. Epub 2019 Mar 13.

5 Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, Turkey.

Background: To retrospectively investigate the influence of pretreatment anemia and hemoglobin levels on the survival of nasopharyngeal carcinoma patients treated with concurrent chemoradiotherapy (C-CRT).

Methods: A total of 149 nasopharyngeal carcinoma patients who received C-CRT were included. All patients had received 70 Gy to the primary tumor plus the involved lymph nodes, and 59.4 Gy and 54 Gy to the intermediate- and low-risk neck regions concurrent with 1-3 cycles of cisplatin. Patients were dichotomized into non-anemic and anemic (hemoglobin <12 g/dL (women) or <13 g/dL (men)) groups according to their pre-treatment hemoglobin measures. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of a pre-treatment hemoglobin cut-off that impacts outcomes. Potential interactions between baseline anemia status and hemoglobin measures and overall survival, locoregional progression-free survival (LRPFS), and progression-free survival were assessed.

Results: Anemia was evident in 36 patients (24.1%), which was related to significantly shorter overall survival (=0.007), LRPFS (<0.021), and progression-free survival (=0.003) times; all three endpoints retained significance in multivariate analyses (<0.05, for each). A baseline hemoglobin value of 11.0 g/dL exhibited significant association with outcomes in ROC curve analysis: hemoglobin <11.0 g/dL (N=26) was linked with shorter median overall survival (<0.001), LRPFS (=0.004), and progression-free survival (<0.001) times, which also retained significance for all three endpoints in multivariate analyses and suggested a stronger prognostic worth for the hemoglobin <11.0 g/dL cut-off value than the anemia status.

Conclusion: Pre-C-CRT hemoglobin <11.0 g/dL has a stronger prognostic worth than the anemia status with regard to LRPFS, progression-free survival, and overall survival for nasopharyngeal carcinoma patients.
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http://dx.doi.org/10.1177/1724600818821688DOI Listing
June 2019

Local control and vertebral compression fractures following stereotactic body radiotherapy for spine metastases.

J Bone Oncol 2019 Apr 24;15:100218. Epub 2019 Jan 24.

Department of Radiation Oncology, Baskent University Medical Faculty, Kisla Saglik Yerleskesi, 01120 Adana, Turkey.

Purpose: We aimed to retrospectively assess the incidence of vertebral compression fractures (VCF), examine clinicopathologic factors potentially associated with VCF, and evaluate treatment response in patients who received stereotactic body radiotherapy (SBRT) for spine metastases (spMets).

Methods And Materials: We identified 78 patients with 125 spMets at baseline and subsequent assessments. Patients received SBRT doses of 16 or 18 Gy. Patients with pre-existing VCF and co-existing local progression were excluded. Spine instability neoplastic score (SINS) was used for spMets categorization. Response to SBRT and VCF were assessed according to the Positron Emission tomography Response Criteria In Solid Tumors (PERCIST) and Genant scores, respectively. Kaplan-Meier analyses were used to assess local control of disease and vertebral compression fracture-free survival (FFS).

Results: We treated 103 cases with single spMets and 11 cases involving double spMets with SBRT. Progressive disease was reported in 3.2% and 8.2% of the cases in the first and last PET/CT reports, respectively. The distribution of treatment response in the remaining patients was: complete response in 30.6% of patients, partial response in 47.1% of patients, and stable disease in 22.3% of patients in the first PET/CT; complete response in 62.3% of patients, partial response in 16.7% of patients, and stable disease in 21% of patients at the last monitoring. Local failures were observed in 15 (12%) of cases. Median SINS was 5 (range: 1-13); majority of patients in our cohort (70.4%) were categorized as stable according to SINS, five (4%) patients had Grade 3 VCF at a median time of 16 months after SBRT (range: 2-22 months), and 60% of VCF occurred after an interval of at least 12 months after SBRT. No bisphosphonate usage was significantly associated with VCF ( = -0.204;  = 0.022). Median FFS was 21 months. Univariate analyses indicated that female gender ( < 0.001), bisphosphonate use ( = 0.005), >6 months of bisphosphonates use ( = 0.002), and the lowest vertebral body collapse score ( = 0.023) were associated with higher FFS. Female gender ( = 0.007), >6 months of bisphosphonates usage ( = 0.018), and the lowest vertebral body collapse score ( = 0.044) retained independent significance.

Conclusions: This study demonstrated that spine SBRT with doses of 16-18 Gy promises good local control of disease with acceptable VCF rates. Lowest vertebral body collapse score, female gender, and >6 months of bisphosphonate use were significantly associated with longer FFS.
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http://dx.doi.org/10.1016/j.jbo.2019.100218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378905PMC
April 2019

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

Treatment outcomes of endometrial cancer patients with paraaortic lymph node metastasis: a multi-institutional analysis.

Int J Gynecol Cancer 2019 01;29(1):94-101

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

Objective: To analyze the prognostic factors and treatment outcomes in endometrial cancer patients with paraaortic lymph node metastasis.

Methods: Data from four centers were collected retrospectively for 92 patients with endometrial cancer treated with combined radiotherapy and chemotherapy or adjuvant radiotherapy alone postoperatively, delivered by either the sandwich or sequential method. Prognostic factors affecting overall survival and progression-free survival were analyzed.

Results: The 5-year overall survival and progression-free survival rates were 35 % and 33 %, respectively, after a median follow-up time of 33 months. The 5-year overall survival and progression-free survival rates were significantly higher in patients receiving radiotherapy and chemotherapy postoperatively compared with patients treated with adjuvant radiotherapy alone (P < 0.001 and P < 0.001, respectively). In a subgroup analysis of patients treated with adjuvant combined chemotherapy and radiotherapy, the 5-year overall survival and progression-free survival rates were significantly higher in patients receiving chemotherapy and radiotherapy via the sandwich method compared with patients treated with sequential chemotherapy and radiotherapy (P = 0.02 and P = 0.03, respectively). In the univariate analysis, in addition to treatment strategy, pathology, depth of myometrial invasion, and tumor grade were significant prognostic factors for both overall survival and progression-free survival. In the multivariate analysis, grade III disease, myometrial invasion greater than or equal to 50%, and adjuvant radiotherapy alone were negative predictors for both overall survival and progression-free survival.

Conclusion: We demonstrated that adjuvant combined treatment including radiotherapyand chemotherapy significantly increases overall survival and progression-free survival rates compared with postoperative pelvic and paraaortic radiotherapy.
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http://dx.doi.org/10.1136/ijgc-2018-000029DOI Listing
January 2019

Dosimetric comparison of vaginal vault brachytherapy vs applicator-guided stereotactic body radiotherapy with volumetric modulated arc therapy and helical tomotherapy for endometrium cancer patients.

Med Dosim 2019 Winter;44(4):332-338. Epub 2018 Dec 11.

Department of Radiation Oncology, Baskent University Faculty of Medicine, 01120 Adana, Turkey. Electronic address:

We performed this dosimetric study to compare a nonstandard volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) techniques with high-dose rate (HDR) brachytherapy (BRT) plan of vaginal vault in patients with postoperative endometrial cancer (EC). Twelve postoperative patients with early stage EC were included in this study. Three plans were performed for each patient; dosimetric and radiobiological comparisons were made using dose-volume histograms and equivalent dose for determining the planning target volume (PTV) coverages in brachytherapy and external beam radiotherapy, and organs-at-risk (OARs) doses between three different delivery techniques. All the plans achieved adequate dose coverage for PTV; however, the VMAT plan yielded better dose conformity, and the HT plan showed better homogeneity for target volume. With respect to the OARs, the bladder D was significantly lower in the BRT plan than in the VMAT and HT plans, with the highest bladder D value being observed in the HT plan. However, no difference was observed in the rectum D of the three plans. Other major advantages of the BRT plan over the VMAT and HT plans were the relatively lower body integral doses and femoral head doses as well as the fact that the integral doses were significantly lower in the BRT plan than in the VMAT and HT plans. This is the first dosimetric comparison of vaginal vault treatment for EC with BRT, VMAT, and HT plans. Our analyses showed the feasibility of stereotactic body radiotherapy technique as an alternative to HDR-BRT for postoperative management of EC patients.
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http://dx.doi.org/10.1016/j.meddos.2018.11.005DOI Listing
April 2020

Epoetin receptor status may alter the outcomes in head and neck cancers treated with radiotherapy and darbepoetin-α.

Radiother Oncol 2019 01 7;130:190. Epub 2018 Nov 7.

Baskent University Adana Medical Faculty, Department of Radiation Oncology, Adana, Turkey. Electronic address:

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http://dx.doi.org/10.1016/j.radonc.2018.07.010DOI Listing
January 2019

Prognostic values of ADC and SUV of the primary tumour in cervical cancer patients treated with definitive chemoradiotherapy.

J Obstet Gynaecol 2019 Feb 24;39(2):224-230. Epub 2018 Oct 24.

b Department of Radiology , Baskent University Faculty of Medicine , Ankara , Turkey.

We analysed the correlation of F-fluorodeoxyglucose uptake into primary tumours using the maximum standardised uptake value (SUV) and the mean apparent diffusion coefficient (ADC) values in magnetic resonance imaging (MRI) with the clinical and pathological factors in patients with cervical cancer who were treated with concurrent chemoradiotherapy. The patients were stratified according to the primary tumour pre-treatment ADC and SUV cut-off values. There were significant correlations between the SUV of the primary tumour and tumour size, and the treatment response. The correlation between the ADC and FIGO stage, tumour size, and the lymph node metastasis was significant. The SUV was significantly and inversely correlated with the ADC for cervical cancer (r = -0.44, p <.001). In the multivariate analysis, the primary tumour ADC, treatment response and the lymph node metastasis emerged as significant independent predictors of both OS and DFS, and of the primary tumour SUV for DFS. Tumour size has a borderline significance for OS. High SUV and low ADC of the primary tumour are important predictive factors for identifying high-risk patients with cervical cancer who are treated with definitive chemoradiotherapy. These results point to a future role for the diffusion-weighted MRI and for F-fluorodeoxyglucose positron emission tomography, not only in the staging of cervical cancer but as an aid in the selection of an adjuvant treatment regimen after chemoradiotherapy for individual patients. Impact statement What is already known on this subject? A negative correlation between primary tumour SUV derived from positron emission tomography (PET/CT) and ADC derived from diffusion weighted magnetic resonance imaging (DW-MRI) in various cancer types and cervical cancer has been demonstrated. However, the prognostic value of primary tumour SUV and ADC in cervical cancer patients treated with definitive chemoradiotherapy is not well studied yet. What the results of this study add? The patients with high-risk features (larger tumours, extensive stage, lymph node metastasis) had higher primary tumour SUV and lower ADC values. Primary tumour ADC and lymph node metastasis emerged as significant independent predictors of both overall and disease-free survival. This study demonstrated that the functional biomarkers delivered from PET-CT and DW-MRI are important in predicting the treatment outcomes in the squamous cell carcinoma of cervix treated with definitive chemoradiotherapy, where clinical and radiological findings are very important, since these patients are not staged surgically. What are the implications of these findings for clinical practice and/or further research? Based on these findings, there may be a future role of DW-MRI and FDG/PET-CT not only in the staging of cervical cancer but as an aid in the selection of an adjuvant treatment regimen after chemoradiotherapy (ChRT) for individual patients.
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http://dx.doi.org/10.1080/01443615.2018.1492528DOI Listing
February 2019

Treatment outcomes of breast cancer liver metastasis treated with stereotactic body radiotherapy.

Breast 2018 Dec 29;42:150-156. Epub 2018 Sep 29.

Department of Radiation Oncology, Baskent University Faculty of Medicine, 01120, Adana, Turkey.

Background: To assess the outcomes of breast cancer liver metastasis (BCLM) treated with stereotactic body radiotherapy (SBRT) and systemic treatment.

Materials And Methods: Patients with oligometastasis at the time of liver metastasis (LM) or who became oligometastatic (≤5 metastases) after systemic treatment were assessed. Twenty-nine liver metastatic lesions were treated with a total of 54 Gy delivered in 3 fractions. The local control (LC), overall survival (OS), and progression-free survival (PFS) rates were calculated using Kaplan-Meier analyses.

Results: A total of 22 patients with 29 liver metastatic lesions treated with liver SBRT between April 2013 and September 2017 were retrospectively analyzed. After a median follow-up time of 16.0 months (range 4.4-59.4 months), 18 patients (82%) had disease recurrence, median of 7.4 months (range 1.0-27.9 months) after completion of liver SBRT. The 1- and 2-year OS rates were 85% and 57%, and the 1- and 2-year PFS rates were 38% and 8%, respectively. The 1- and 2-year LC rates were 100% and 88%, respectively. No significant prognostic factors, including disease extension, size of metastasis, number of liver metastasis and timing of liver metastasis, hormonal status affecting OS, PFS and LC were found. No patients experienced Grade 4 or 5 toxicity; furthermore, only one patient experienced rib fracture 6 months after completion of treatment, and one patient had a duodenal ulcer.

Conclusion: This study is the first to evaluate the feasibility of SBRT to BCLM patients. Liver SBRT is a conservative approach with excellent LC and limited toxicities.
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http://dx.doi.org/10.1016/j.breast.2018.09.006DOI Listing
December 2018

The Utility of Pretreatment and Posttreatment Lymphopenia in Cervical Squamous Cell Carcinoma Patients Treated With Definitive Chemoradiotherapy.

Int J Gynecol Cancer 2018 10;28(8):1553-1559

Medical Oncology, Baskent University Faculty of Medicine, Adana, Turkey.

Objective: The aim of this study was to investigate the prognostic significance of pretreatment and posttreatment lymphopenia in locally advanced squamous cell carcinoma (SCC) cervical cancer patients treated with definitive chemoradiotherapy (ChRT).

Methods: Data from 95 patients with SCC were retrospectively analyzed. Relationships between pretreatment or posttreatment lymphopenia and patient or tumor characteristics, and overall survival (OS) and disease-free survival (DFS) were evaluated.

Results: Median follow-ups for the entire cohort and survivors were 68 months (range, 3-133 months) and 88 months (range, 22-133 months), respectively. Ten patients (11%) exhibited pretreatment lymphopenia, whereas 58 patients (61%) exhibited posttreatment lymphopenia. Median pretreatment total lymphocyte counts decreased from 2029 cells/μL to 506 cells/μL 2 months after ChRT (P < 0.001). The 5-year OS and DFS rates were significantly higher in patients without pretreatment lymphopenia compared with patients with pre-retreatment lymphopenia (61% vs 20% [P < 0.001], 55% vs 20% [P < 0.001]). Patients without posttreatment lymphopenia had significantly higher 5-year OS and DFS rates than their counterparts (70% vs 46% [P = 0.02], 70% vs 39% [P = 0.004]). Complete response (CR) was observed in significantly fewer patients with pretreatment lymphopenia than in those without, after ChRT. Patients with posttreatment lymphopenia had higher rates of lymph node metastasis (P = 0.001) and lower posttreatment CR rates (P = 0.01) versus patients without posttreatment lymphopenia. In univariate analysis, International Federation of Gynecology and Obstetrics stage, tumor size, lymph node metastasis, and treatment response were prognostic for OS and DFS. In multivariate analysis, pretreatment lymphopenia, lymph node metastasis, and treatment response were independent predictors of OS and DFS. Age was predictive of OS. Tumor size was prognostic for DFS.

Conclusions: Pretreatment lymphopenia and posttreatment lymphopenia are associated with worse treatment response in patients given ChRT for cervical SCC. Pretreatment lymphopenia is predictive for OS and DFS. Therapeutic strategies including pretreatment or posttreatment immune preservation or modulation may improve response rates and survival in women with cervical SCC.
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http://dx.doi.org/10.1097/IGC.0000000000001345DOI Listing
October 2018

Local recurrence outcomes after breast conserving surgery and adjuvant radiotherapy in ductal carcinoma in situ of the breast and a comparison with ECOG E5194 study.

Breast 2018 Dec 10;42:10-14. Epub 2018 Aug 10.

Ege University Faculty of Medicine, Radiation Oncology Department, Izmir, Turkey. Electronic address:

Purpose: Turkish Radiation Oncology Study Group investigated local recurrence rates and prognostic factors in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast conservative surgery (BCS) followed by radiotherapy (RT) and Eastern Cooperative Oncology Group (ECOG) Study E5194 were compared with the original study.

Patients And Methods: Totally 252 patients were evaluated retrospectively. Prognostic factors that might influence local control (age, nuclear grade, comedo necrosis, surgical margins, tumor size, hormone receptor status) were compared. The eligibility criteria of ECOG 5194 were stratified into two groups as in the original study and were compared for local control.

Results: The median follow-up time was 59 (21-220) months. Local recurrence was observed in 9 patients (3.6%) who had invasive carcinoma (3 patients) and DCIS (6 patients). Ten years local control rates was 91.8% respectively. We found that the risk of ipsilateral breast recurrence was significantly higher in women younger than 50 years old (p = 0.016). In addition, a statistically significant trend was found in patients with tumor larger than 1 cm and HER2 positive tumors (p = 0.051, p = 0.068 respectively). When 12-year results were compared with the ECOG 5194, adjuvant RT produced an absolute difference of 11% in low-intermediate and 20% in high grade in local control.

Conclusion: In our study, the 10-year local control rate was 92% and younger than 50 years old was the most important unfavorable prognostic factor for local recurrence. There was provided 20% absolute local control with adjuvant radiotherapy which eligibility criteria of ECOG 5194 high grade group.
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http://dx.doi.org/10.1016/j.breast.2018.08.094DOI Listing
December 2018

Responding to Veiga et al. 'Long term radiological features of radiation-induced lung damage'.

Radiother Oncol 2018 12 17;129(3):611-612. Epub 2018 Jul 17.

Başkent University, Faculty of Medicine, Adana Dr Turgut Noyan Research and Treatment Center, Department of Radiation Oncology, Adana, Turkey. Electronic address:

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http://dx.doi.org/10.1016/j.radonc.2018.06.030DOI Listing
December 2018

In Regard to Ward et al.

Int J Radiat Oncol Biol Phys 2018 08;101(5):1273

Department of Radiation Oncology, Baskent University Adana Medical Faculty, Adana, Turkey.

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http://dx.doi.org/10.1016/j.ijrobp.2018.05.008DOI Listing
August 2018

Pretreatment metabolic tumour volume and total lesion glycolysis are not independent prognosticators for locally advanced cervical cancer patients treated with chemoradiotherapy.

Br J Radiol 2018 Apr 10;91(1084):20170552. Epub 2018 Jan 10.

3 Department of Radiation Oncology, Baskent University Faculty of Medicine , Adana , Turkey.

Objective: To evaluate the prognostic significance of metabolic parameters derived from fludeoxyglucose (FDG) positron emission tomography (PET)/CT, in cervical cancer patients treated with concurrent chemoradiotherapy.

Methods: We retrospectively reviewed medical records from 129 biopsy-proven non-metastatic cervical cancer patients treated with external radiotherapy and intracavitary brachytherapy at our department. Correlation between metabolic parameters and tumour characteristics was evaluated. Prognostic factors for survival, local control and distant metastasis were analysed.

Results: The median follow up for all patients and surviving patients was 30.0 months (range, 3.7-94.7 months) and 50.5 months (range, 14.5-94.7 months), respectively. The 2- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 68 42, 54 and 38%, respectively. The maximum standardized uptake value (SUV), SUV, metabolic tumour volume (MTV) and total lesion glycolysis were significantly higher in patients with larger tumours (>4 cm) and partial regression or progressive disease after definitive treatment compared to patients with smaller tumour (≤4 cm) and post-treatment complete response. On univariate analysis, stage, lymph node metastasis, tumour size >4 cm, SUV, MTV, SUV and total lesion glycolysis were prognostic factors for OS and DFS. On multivariate analysis, only larger tumour and presence of lymph node metastasis were significant prognostic factors for both OS and DFS. Additionally, extensive stage was a significant prognosticator for DFS.

Conclusion: Although, metabolic parameters derived from FDG-PET/CT had a prognostic significance in univariate analysis, the significance was lost in multivariate analysis where tumour stage, size and lymph node status were the only independent parameters. Advances in knowledge: The clinical benefit of using FDG-PET/CT metabolic parameters to evaluate the high-risk patients among cervical cancer patients and to eventually change patient management still needs further clarification.
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http://dx.doi.org/10.1259/bjr.20170552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965999PMC
April 2018

Dosimetric comparison of 3-dimensional conformal radiotherapy, volumetric modulated arc therapy, and helical tomotherapy for postoperative gastric cancer patients.

Jpn J Radiol 2018 Jan 3;36(1):30-39. Epub 2017 Nov 3.

Department of Radiation Oncology, Adana Dr Turgut Noyan Research and Treatment Centre, Baskent University Faculty of Medicine, 01120, Adana, Turkey.

Purpose: To compare dosimetric data for the planning target volume (PTV) and organs at risk (OARs) between 3-dimensional conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy [1].

Materials And Methods: The dosimetric data for 15 gastric cancer patients treated with 3DCRT, VMAT, or HT techniques were used. Cumulative dosimetric parameters, homogeneity index (HI), and conformal index (CI) were compared for the PTV and OARs.

Results: The average maximum doses of PTV were significantly higher in VMAT plans than in 3DCRT (p = 0.04) and HT (p = 0.02) plans, whereas minimum dose values were significantly lower in 3DCRT plans compared with VMAT (p < 0.001) and HT (p = 0.02) plans. Liver mean dose (D ) and D values for both kidneys were significantly lower in HT plans than in 3DCRT and VMAT plans. The doses in high dose regions (V30-V45) using 3DCRT plans were significantly higher compared to both VMAT and HT plans. The bowel V5-V30 and V45 was significantly less in HT plans compared to VMAT plans. There were no significant differences in dose sparing of the spinal cord.

Conclusions: The HT plans reduced the maximum dose applied to the target and improved the conformality and homogeneity of radiation, while providing sufficient PTV coverage.
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http://dx.doi.org/10.1007/s11604-017-0696-xDOI Listing
January 2018

Outcomes of aggressive treatment in esophageal cancer patients with synchronous solitary brain metastasis.

Mol Clin Oncol 2017 Jul 16;7(1):107-112. Epub 2017 May 16.

Department of Radiation Oncology, Baskent University Faculty of Medicine, Adana Dr Turgut Noyan Research and Treatment Centre, 01120 Adana, Turkey.

The aim of the present study was to investigate the outcomes of esophageal cancer (EC) patients with isolated synchronous brain oligometastasis (oligo-BM) treated with chemoradiotherapy (CRT) of the primary site and localized treatment of the BM with surgery, radiotherapy (RT) or radiosurgery. Of 125 EC patients investigated, seven patients (6%) had solitary BM. Six patients were diagnosed prior to, and one patient was diagnosed during, treatment. All patients were treated with neoadjuvant chemotherapy and whole-brain RT (WBRT) for BM. All but one patient received definitive CRT with a median RT dose of 50.4 Gy using conventional fractionation RT. The median age at diagnosis was 59 years (range, 48-77 years). Six patients succumbed to mortality, and one continued to receive systemic chemotherapy at the last visit. The median survival time of the patients was 18.9 months (range, 10.0-27.2 months). Median time to progression after completion of the treatments was 8 months (range, 3-9 months). Two patients had progression of the primary tumor, and one patient had progression of the BM. The neurological status of three patients with BM who were identified during the staging work-up did not deteriorate as a consequence of WBRT. In conclusion, the present study has demonstrated that aggressive treatment of the primary tumor and oligo-BM in patients with EC may prolong the survival time.
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http://dx.doi.org/10.3892/mco.2017.1263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492565PMC
July 2017

Whole brain radiotherapy in management of non-small-cell lung carcinoma associated leptomeningeal carcinomatosis: evaluation of prognostic factors.

J Neurooncol 2016 09 15;129(2):329-35. Epub 2016 Jun 15.

Department of Radiation Oncology, Baskent University Adana Medical Faculty, Adana, Turkey.

To assess the efficacy of whole-brain radiotherapy (WBRT) and prognostic factors in leptomeningeal carcinomatosis (LMC) of non-small-cell lung cancer (NSCLC) patients. WBRT records of 51 LMC patients confined to brain were reviewed. Eligible patients had squamous-cell carcinoma (SCC) or adenocarcinoma, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-3. The WBRT was either 20 or 30 Gray. The primary and secondary objectives were to determine overall survival (OS) and prognostic factors for improved treatment response, respectively. Median age was 53 years (range 39-68), 58.8 % had SCC, 74.5 % had ECOG PS 1-2, and 70.6 % had LMC accompanied by parenchymal brain metastases (BM). The median follow-up was 4.1 months (range 0.7-14.4); all patients died due to disease progression. Median OS was 3.9 months (95 % CI 3.3-4.5) with 6 and 12 month estimates of 19.6 and 5.9 %, respectively. Evaluation of prognostic factors revealed that patients with ECOG 1, longer time to LMC (TT-LMC) from NSCLC diagnosis (>11.3 months), and absence of parenchymal BM had significantly superior OS than those patients with ECOG 2 (p = 0.01) or 3 (p < 0.001), TT-LMC < 11.3 months (p = 0.001), and parenchymal BM (p = 0.012). Median OS of 3.9 months after WBRT appeared to confirm the poor prognosis of LMC. WBRT might be most effective for patients with favorable PS, longer TT-LMC, and no accompanying BM. Therefore, we identified ECOG PS 1, TT-LMC > 11.3 months, and no BM as independent prognosticators for better response to WBRT in NSCLC patients with LMC.
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http://dx.doi.org/10.1007/s11060-016-2179-9DOI Listing
September 2016

Impact of presence and degree of pretreatment weight loss in locally-advanced pancreatic cancer patients treated with definitive concurrent chemoradiotherapy.

Pancreatology 2016 Jul-Aug;16(4):599-604. Epub 2016 Mar 17.

Baskent University Adana Medical Faculty, Department of Radiation Oncology, Adana, Turkey.

Background: To assess the impact of the presence and degree of pretreatment weight loss (WL) on the survival of locally-advanced pancreas cancer (LAPC) patients treated with concurrent chemoradiotherapy (C-CRT).

Methods: Seventy-three patients who received 50.4 Gy C-CRT were analyzed. All patients underwent laparoscopy (n = 18) or laparotomy (n = 55), and biopsies were obtained for histologic examination of the primary tumor and enlarged/metabolically active regional lymph nodes. Pretreatment WL and percentage WL (PWL) were calculated by utilizing data obtained 6 months prior to and during hospital admission. The primary objective was to assess the influence WL status on overall survival (OS), and the secondary objective was the identification of a PWL cut-off value, if available.

Results: Forty-five (61.6%) patients had WL. Median OS was 14.4 months for the entire study population which was significantly longer in the non-WL than the WL cohort (21.4 vs. 11.3 months; p < 0.003). On further analysis a cut-off value of 3.1% was identified for WL. Accordingly, patients with WL < 3.1% had significantly longer OS than those with WL ≥ 3.1% (25.8 vs. 10.1 months; p < 0.001). In multivariate analysis, both the WL status (p < 0.001) and PWL (p = 0.002) retained their independent significance.

Conclusion: Both the presence and degree of WL prior to C-CRT had strong adverse effects on the survival of LAPC patients, even if they presented with a BMI > 20 kg/m(2). Additionally, a WL of ≥3.1% in the last 6 months appeared to be a strong cut-off for the stratification of such patients into distinctive survival groups.
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http://dx.doi.org/10.1016/j.pan.2016.03.006DOI Listing
March 2017

Reply: To PMID 25768249.

Retina 2015 Nov;35(11):e71-2

Department of Radiation Oncology, Baskent University Adana Medical Faculty, Adana, Turkey.

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http://dx.doi.org/10.1097/IAE.0000000000000865DOI Listing
November 2015

PREVENTION OF RADIATION-INDUCED RETINOPATHY WITH AMIFOSTINE IN WISTAR ALBINO RATS.

Retina 2015 Jul;35(7):1458-64

*Department of Radiation Oncology, Baskent University Adana Medical Faculty, Adana, Turkey; †Department of Radiation Oncology, Faculty of Medicine, Gazi University, Besevler, Ankara; and Departments of ‡Radiation Oncology, §Anatomy, and ¶Pathology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, Turkey.

Purpose: To evaluate the radioprotective efficacy of amifostine on irradiated mature rat retina.

Methods: A total of 108 Wistar albino rats were categorized into 3 groups, namely, apoptosis (n = 48), acute effects (n = 40), and late changes in retinal cell layers (n = 20). Each group was further subcategorized into 4 arms: control, amifostine (A), radiotherapy + placebo (RT), and RT + A arms, respectively. Intraperitoneal amifostine (260 mg/kg) was administrated to A and RT + A arms 30 minutes before irradiation. Control and A groups were sham-irradiated, whereas a single dose of 20 Gy whole-cranium irradiation was delivered to RT and RT + A arms. Apoptosis was assessed in 8, 12, and 18 hours after irradiation. Electron microscope was used 2 weeks after irradiation for evaluation and scoring of early morphologic changes in retina. Late effects were assessed and scored accordingly by using both the electron and the light microscope on Week 10.

Results: At acute phase, although no notable change was seen in 8 hours, significant increase in apoptosis was detected in 12 hours in RT arm (P = 0.029). Comparative analyses between the groups in 3 different time points displayed a higher apoptotic rate in RT group than the RT + A group (P = 0.008). Similarly, comparisons between groups for late effects on the basis of electron microscopic findings revealed lower scores in the RT + A than the RT arm (P < 0.001).

Conclusion: This study suggested a potential radioprotective role for amifostine on mature rat retina by reducing radiation-induced apoptosis in retinal cells. These results form a basis for such preclinical investigations and call for future clinical studies.
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http://dx.doi.org/10.1097/IAE.0000000000000493DOI Listing
July 2015

Safety and palliative efficacy of single-dose 8-Gy reirradiation for painful local failure in patients with stage IV non-small cell lung cancer previously treated with radical chemoradiation therapy.

Int J Radiat Oncol Biol Phys 2015 Mar;91(4):774-80

Medstar Hospital, Department of Radiation Oncology, Antalya, Turkey.

Purpose: To investigate the safety and efficacy of single-dose 8-Gy palliative chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC) patients with painful thoracic failures (TF) within the previous radiation portal.

Patients And Methods: We retrospectively analyzed the clinical data of 78 M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy between 2007 and 2012. Primary endpoints included significant pain relief (SPR) defined as a ≥2 point decrement in the Visual Analogue Scale for Pain inventory (VAS-P), time to pain relief, and duration of pain control. Secondary objectives were survival and prognostic factors.

Results: Treatment was well tolerated, with only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and post-CRI minimum VAS-P were 7 and 3 (P<.001), respectively. SPR was noted in 67 (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to lowest VAS-P and duration of pain control were 27 days and 6.1 months, respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group score (1-2; P<.001), absence of anemia (P=.001), and fewer metastatic sites (1-2; P<.001) were found to be associated with longer OS.

Conclusions: Single-dose 8-Gy CRI provides safe, effective, and durable pain palliation for TF in radically irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher comfort, the present protocol can be considered an appropriate option for patients with limited life spans.
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http://dx.doi.org/10.1016/j.ijrobp.2014.12.010DOI Listing
March 2015

Cranial prophylactic irradiation in locally advanced non-small cell lung carcinoma: current status and future perspectives.

Oncology 2009 13;76(3):220-8. Epub 2009 Feb 13.

Department of Radiation Oncology, Baskent University School of Medicine, Adana, Turkey.

As a result of improved local and regional control with aggressive multimodality protocols, the brain has become one of the major sites of relapse in patients with locally advanced non-small cell lung carcinoma (LA-NSCLC). The demonstrated efficacy of prophylactic cranial irradiation (PCI) in small-cell lung carcinoma led to studies of its effectiveness in LA-NSCLC, which indicated that PCI also has a high potential to reduce the incidence or delay the occurrence of brain metastases in this patient group. This report provides an extensive review of the current evidence from nonrandomized and randomized trials regarding the use of PCI in LA-NSCLC and discusses related key issues including risk factors, patient selection criteria, timing of PCI, preferred PCI dosing scheme, toxicity profile and potential novel PCI techniques.
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http://dx.doi.org/10.1159/000201933DOI Listing
March 2009