Publications by authors named "Fulya Agaoglu"

36 Publications

Stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of liver metastases in oligometastatic patients: initial clinical experience.

Radiat Oncol J 2021 Mar 26;39(1):33-40. Epub 2021 Mar 26.

Department of Radiation Oncology, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey.

Purpose: We aimed to present our initial clinical experience on the implementation of a stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of liver metastases in oligometastatic disease.

Materials And Methods: Twenty-one patients (24 lesions) with liver metastasis treated with SMART were included in this retrospective study. Step-and-shoot intensity-modulated radiotherapy technique was used with daily plan adaptation. During delivery, real-time imaging was used by acquiring planar magnetic resonance images in sagittal plane for monitoring and gating. Acute and late toxicities were recorded both during treatment and follow-up visits.

Results: The median follow-up time was 11.6 months (range, 2.2 to 24.6 months). The median delivered total dose was 50 Gy (range, 40 to 60 Gy); with a median fraction number of 5 (range, 3 to 8 fractions) and the median fraction dose was 10 Gy (range, 7.5 to 18 Gy). Ninety-three fractions (83.7%) among 111 fractions were re-optimized. No patients were lost to follow-up and all patients were alive except one at the time of analysis. All of the patients had either complete (80.9%) or partial (19.1%) response at irradiated sites. Estimated 1-year overall survival was 93.3%. Intrahepatic and extrahepatic progression-free survival was 89.7% and 73.5% at 1 year, respectively. There was no grade 3 or higher acute or late toxicities experienced during the treatment and follow-up course.

Conclusion: SMART represents a new, noninvasive and effective alternative to current ablative radiotherapy methods for treatment of liver metastases in oligometastatic disease with the advantages of better visualization of soft tissue, real-time tumor tracking and potentially reduced toxicity to organs at risk.
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http://dx.doi.org/10.3857/roj.2020.00976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024184PMC
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

Evaluation of the relationship between serum ghrelin levels and cancer cachexia in patients with locally advanced nonsmall-cell lung cancer treated with chemoradiotherapy.

J Cancer Res Ther 2020 Jul-Sep;16(4):855-859

Department of Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Background: Ghrelin plays a role in mechanisms related to cancer progression - including cell proliferation, invasion and migration, and resistance to apoptosis in the cell lines from several cancers. We investigated the role of ghrelin levels in cancer cachexia-anorexia in patients with locally advanced nonsmall-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT).

Materials And Methods: This study involved 84 NSCLC patients who had received concomitant CRT. Blood ghrelin levels were compared before and 3 months after CRT. Meanwhile, changes in body weight of the patients were also investigated with changes in ghrelin levels before and after CRT.

Results: Ghrelin levels were significantly decreased in line with changes in patients' weights in patients receiving CRT (P < 0.001). Serum albumin levels and inflammatory-nutritional index were significantly decreased after radiotherapy (RT) (3.01 ± 0.40 g/dL, 0.38 ± 0.20) when compared with its baseline levels (3.40 ± 0.55 g/dL,P < 0.001; 0.86 ± 0.71,P < 0.001, respectively). Serum C-reactive protein levels were significantly increased after CRT (7.49 ± 6.53 mg/L) when compared with its baseline levels (9.54 ± 3.80 mg/L,P = 0.038). After RT, ghrelin levels in patients were positively correlated with body mass index (r = 0.830,P < 0.001) and albumin (r = 0.758,P < 0.001).

Conclusion: Ghrelin may play a role in the pathogenesis of weight loss in NSCLC patients. Ghrelin seems to be implicated in cancer-related weight loss. Ghrelin, cancer, and RT all together have a role in tumor-related anorexia-cachexia in patients with NSCLC. Results of this study need further evaluation as regards to its potential role as an adjuvant diagnostic or prognostic marker.
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http://dx.doi.org/110.4103/jcrt.JCRT_10_19DOI Listing
November 2020

Radionuclide Therapy With 177Lu-PSMA in a Case of Metastatic Adenoid Cystic Carcinoma of the Parotid.

Clin Nucl Med 2019 Sep;44(9):764-766

From the Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University.

In vivo prostate-specific membrane antigen (PSMA) overexpression creates an opportunity for PSMA-directed theranostic approach in adenoid cystic carcinoma of the parotid. Herein, we illustrate a patient with metastatic PSMA-directed theranostic approach in adenoid cystic carcinoma of the parotid who had intense PSMA uptake on metastatic lesions, followed by radionuclide therapy with Lu-PSMA.
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http://dx.doi.org/10.1097/RLU.0000000000002645DOI Listing
September 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

RE: Osteosarcoma of the rib: a rare presentation.

Turk Pediatri Ars 2018 Dec 1;53(4):270. Epub 2018 Dec 1.

Istanbul University, Oncology Institute, Department of Radiation Oncology, Istanbul, Turkey.

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http://dx.doi.org/10.5152/TurkPediatriArs.2016.48048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408185PMC
December 2018

Dealing with the gray zones in the management of gastric cancer: The consensus statement of the İstanbul Group.

Turk J Gastroenterol 2019 Jul;30(7):584-598

Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey.

The geographical location and differences in tumor biology significantly change the management of gastric cancer. The prevalence of gastric cancer ranks fifth and sixth among men and women, respectively, in Turkey. The international guidelines from the Eastern and Western countries fail to manage a considerable amount of inconclusive issues in the management of gastric cancer. The uncertainties lead to significant heterogeneities in clinical practice, lack of homogeneous data collection, and subsequently, diverse outcomes. The physicians who are professionally involved in the management of gastric cancer at two institutions in Istanbul, Turkey, organized a consensus meeting to address current problems and plan feasible, logical, measurable, and collective solutions in their clinical practice for this challenging disease. The evidence-based data and current guidelines were reviewed. The gray zones in the management of gastric cancer were determined in the first session of this consensus meeting. The second session was constructed to discuss, vote, and ratify the ultimate decisions. The identification of the T stage, the esophagogastric area, imaging algorithm for proper staging and follow-up, timing and patient selection for neoadjuvant treatment, and management of advanced and metastatic disease have been accepted as the major issues in the management of gastric cancer. The recommendations are presented with the percentage of supporting votes in the results section with related data.
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http://dx.doi.org/10.5152/tjg.2018.18737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629281PMC
July 2019

Nimotuzumab-containing regimen for pediatric diffuse intrinsic pontine gliomas: a retrospective multicenter study and review of the literature.

Childs Nerv Syst 2019 01 11;35(1):83-89. Epub 2018 Nov 11.

Oncology Institute, Istanbul University, Istanbul, Turkey.

Purpose: Nimotuzumab is an IgG1 antibody that targets epidermal growth factor receptor (EGFR). Overexpression of EGFR is detected in some pediatric brain tumors including diffuse intrinsic pontine gliomas (DIPG)s.

Methods: Since May 2010, nimotuzumab, combined with carboplatin or vinorelbine or Temozolomide (TMZ), was administered during progressive disease (PD) after the use of the institutional protocol consisting of radiotherapy (RT) + TMZ and adjuvant TMZ. After May 2012, children with newly diagnosed disease received TMZ during RT, and nimotuzumab and TMZ after RT. Nimotuzumab was given as 150 mg/m/dose once a week for 12 weeks, and then every other week with TMZ until PD. PD patients were switched to nimotuzumab + vinorelbine combination until death.

Results: Nimotuzumab was used in 24 children with DIPG (seven in the PD group, 17 in the newly diagnosed patient group). In the PD group, median survival time was 12 months (7-42 months); 1-year and 2-year overall survival (OS) rates were 42.9 ± 18% and 14.3 ± 13%, respectively. The median survival in this group, after the initiation of nimotuzumab was 6 months (3-8 months). In the newly diagnosed patient group, median survival time was 11 months (3-35 months) and median progression free survival was 4 months (1-21 months). The 1-year OS in this group was 35.3 ± 11% and 2 year OS was 11.8 ± 7%. Nimotuzumab ± chemotherapy was well tolerated with no major adverse effect.

Conclusion: Nimotuzumab-containing regimens are feasible and tolerable; it might be that some patients either with newly diagnosed DIPG or with progressive disease may benefit modestly from nimotuzumab-containing combinations.
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http://dx.doi.org/10.1007/s00381-018-4001-9DOI Listing
January 2019

Monitoring of platelet function parameters and microRNA expression levels in patients with prostate cancer treated with volumetric modulated arc radiotherapy.

Oncol Lett 2018 Oct 18;16(4):4745-4753. Epub 2018 Jul 18.

Department of Biophysics, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul 34098, Turkey.

Radiotherapy (RT) may result in platelet activation and thrombosis development. To the best of our knowledge, the potential effect of volumetric-modulated arc therapy (VMAT), a novel radiotherapy technique, on platelet function and microRNA (miRNA/miR) expression has not been previously investigated. The present study aimed to determine the effect of VMAT on the alterations in platelet function parameters and miRNA expression levels. A total of 25 patients with prostate cancer and 25 healthy subjects were included in the present study. Blood samples were collected from the patient group on the day prior to RT (pre-RT), the day RT was completed (post-RT day 0), and 40 days following the end of therapy (post-RT day 40). Platelet count, mean platelet volume (MPV) value, platelet aggregation, plasma P-selectin, thrombospondin-1, platelet factor 4, plasma miR-223 and miR-126 expression levels were measured. A significant decrease in platelet count in the post-RT day 0 group was measured in comparison with the pre-RT and the post-RT day 40 groups. Pre-RT MPV values were higher than those of the post-RT day 0 and the post-RT day 40 groups. No significant differences were observed in the levels of platelet activation markers or miR-223 and miR-126 expression levels between the RT groups. Although RT may result in a reduction in platelet and MPV counts, the results of the present study indicate that platelet activation markers are not affected by VMAT. Therefore, it is possible that no platelet activation occurs during VMAT, owing to the conformal dose distributions, improved target volume coverage and the sparing of normal tissues from undesired radiation.
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http://dx.doi.org/10.3892/ol.2018.9167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144890PMC
October 2018

Osteosarcoma of the rib: A rare presentation.

Turk Pediatri Ars 2018 Mar 1;53(1):57-60. Epub 2018 Mar 1.

Istanbul University, Oncology Institute, Department of Radiation Oncology, Istanbul, Turkey.

In children and adolescents with chest pain and dyspnea, pneumonia, pleural effusion, and empyema are the frequent causes in the differential diagnosis. Malignant tumors of the chest wall are rare and most originate from the ribs. In children, the most frequent malignant tumor of the rib is Ewing's sarcoma. Osteosarcomas of the rib are very rare. Osteosarcoma has a predilection for rapidly growing long bones including the femur, tibia and humerus in adolescents. In this paper, we present an adolescent girl who presented with chest pain and dyspnea with osteosarcoma that originated from the rib and extended to the right hemithorax.
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http://dx.doi.org/10.5152/TurkPediatriArs.2018.4689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070218PMC
March 2018

Management of primary malignant bone and soft tissue tumors of foot and ankle: Is it worth salvaging?

J Surg Oncol 2018 Feb 6;117(2):307-320. Epub 2017 Sep 6.

Department of Radiation Oncology, Istanbul University Oncology Institute, Fatih/Capa, Istanbul, Turkey.

Background And Objective: Performing limb salvage with safe margins and preserving meaningful function is very difficult in the setting of primary malignant bone and soft tissue tumors due to the complex and constrained anatomy of the foot and ankle. The study aims to evaluate the efficacy of limb salvage procedures in terms of functional and oncological outcomes.

Methods: Clinical data of 48 patients, who underwent surgical treatment between 1992 and 2015 in our institution, were retrospectively analyzed. Twenty-one (43.7%) patients had unplanned resections elsewhere previously. Limb salvage surgery (LSS) was the index surgery in 43 (89.6%) patients. In the LSS group, 28 (65.1%) received preoperative radiotherapy and 13 (30.2%) underwent complex reconstruction. The functional outcomes were assessed with Musculoskeletal Tumor Society (MSTS) scores. Limb survival and oncological outcomes were evaluated according to Kaplan-Meier curves.

Results: The mean follow-up time was 32.7 (3-115) months. Mild deformities and wound healing problems were the most common problems. While the functional scores were significantly higher in the LSS group, no significant difference was detected between amputation and LSS patients in terms of survival rates.

Conclusion: LSS performed in specialized centers is an effective treatment method for malignant tumors of the foot and ankle.
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http://dx.doi.org/10.1002/jso.24817DOI Listing
February 2018

Neoadjuvant radiotherapy for myxoid liposarcomas: Oncologic outcomes and histopathologic correlations.

Acta Orthop Traumatol Turc 2017 Oct 30;51(5):355-361. Epub 2017 Aug 30.

Istanbul University, Istanbul Medical Faculty, Department of Orthopedics and Traumatology, Turkey.

Objective: The aim of this study was to evaluate the histopathological features of primary extremity myxoid liposarcoma before and after neoadjuvant radiation therapy, and to evaluate the oncological outcomes of the patients.

Methods: The study included 23 patients (16 men and 7 women with a mean age of 43 (24-69) years) with primary myxoid liposarcoma of the extremities, who were treated between January 1998 and December 2015. Inclusion criteria were histopathological confirmation of the diagnosis with both the initial biopsy and the resection specimen, and having undergone neoadjuvant radiotherapy. Demographic, clinical and histopathological data were evaluated.

Results: Over a mean follow-up time of 55.2 (8-139) months, 5 patients (21.7%) died secondary to disease progression, leaving 18 patients (78.3%) still alive at the time of last follow-up. Only one patient (4%) experienced local recurrence and six (26%) patients developed distant metastases. Disease-free survival at 5 and 10 years were 66%; whereas, overall patient survival at 5 and 10 years were 78.1% and 71.0%, respectively. Tumor size (>15 cm) and presence of metastasis were significantly associated with increased overall mortality. On histopathology, necrosis was present in 12/23 resection specimens. Hyalinization/fibrosis and residual viable tumor was present in all specimens. Adipocytic maturation/cytodifferentiation was seen in 8/23 patients.

Conclusion: Neoadjuvant radiotherapy was effective for myxoid liposarcomas histopathologically, although these histopathological features did not affect the patients' oncological outcomes. Favorable oncological outcomes were obtained with neoadjuvant radiotherapy, surgical resection and chemotherapy.

Level Of Evidence: Level IV, therapeutic study.
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http://dx.doi.org/10.1016/j.aott.2017.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197565PMC
October 2017

Neoadjuvant sequential chemoradiotherapy versus radiotherapy alone for treatment of high-risk extremity soft tissue sarcoma: a single-institution experience.

Contemp Oncol (Pozn) 2017 22;21(1):60-65. Epub 2017 Mar 22.

Department of Radiation Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.

Aim Of The Study: Patients with large and high-grade extremity soft-tissue sarcoma are at significant risk for distant metastasis and sarcoma-related death. There is no randomized trial comparing chemoradiotherapy to radiotherapy in the neoadjuvant setting for high risk extremity soft-tissue sarcoma. The aim of this study is to evaluate the outcomes of patients treated with two different modalities (neoadjuvant sequential chemoradiotherapy vs. radiotherapy alone) in a single center.

Material And Methods: Data of 67 patients were analyzed retrospectively. Thirty-four patients received neoadjuvant sequential chemoradiotherapy (2-3 cycles of doxorubicin (75 mg/m) and ifosfamide (6 g/m) followed by radiotherapy of 28 Grays (Gy) administered as 8 fractions of 35 Gy) and 33 patients received radiotherapy alone. R0 resection rates and 3-year survival estimates were evaluated.

Results: Median follow-up time was 37 months. The estimated 3-year overall and disease-free survival rates for the whole patient group were 79% (95% CI: 67.0-86.4) and 57.9% (95% CI: 46.3-69.0), respectively. The most common side effects were nausea and leucopenia. Three-year overall, disease-free, local recurrence-free and distant recurrence-free survival rates did not differ significantly. All patients except one underwent wide excision or compartmental resection. R0 resection rate for the whole patient group was 92.5% ( = 62). Sites of progression were similar across both treatment arms.

Conclusions: Preoperative hypofractionated radiotherapy alone or sequentially with chemotherapy result in high rates of limb salvage and acceptable toxicity. Our study results did not show a statistically significant treatment effect regarding survival and patterns of failure.
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http://dx.doi.org/10.5114/wo.2017.66658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385480PMC
March 2017

Conventionally Fractionationed Volumetric Arc Therapy versus Hypofractionated Stereotactic Body Radiotherapy: Quality of Life, Side Effects, and Prostate-Specific Antigen Kinetics in Localized Prostate Cancer.

Value Health Reg Issues 2016 09 6;10:91-99. Epub 2016 Oct 6.

Department of Radiation Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.

Objectives: To compare conventionally fractionationed volumetric arc therapy (VMAT) and hypofractionated stereotactic body radiotherapy (SBRT) modalities in terms of prostate-specific antigen (PSA) kinetics, toxicity, and quality of life (QOL) in patients with localized prostate cancer.

Methods: Patients received radical radiotherapy as either 33.5 Gy/5 fr for SBRT or 75.6 Gy/35 fr for VMAT. International Prostate Symptom Score (IPSS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module (QLQ-PR25) forms were used to assess QOL.

Results: Of the 48 patients (28 in SBRT and 20 in VMAT) included in the study, 40 (20 in SBRT and 20 in VMAT) were evaluated for QOL status. PSA control rate was 100% and PSA nadir value was 0.5 ng/dl in both arms during the median follow-up period of 23 months. The magnitude of PSA bounce was higher in the SBRT arm than in the VMAT arm (P = 0.01). The PSA decline rate in the VMAT arm was higher than in the SBRT arm (P = 0.028). Three (10.7%) patients treated with SBRT who had a history of transurethral resection of the prostate (TURP) experienced grade 3 urinary toxicity. No significant difference was observed concerning sexual activity and sexual functioning scores, whereas scores at 10.5 and 13.5 months were decreased in both arms. The SBRT and VMAT arms had similar urinary incontinence, bowel symptoms, and IPSS obstruction scores. The magnitude of increase in IPSS scores at treatment completion was higher in the VMAT arm than in the SBRT arm (P = 0.046). The decrease in hormonal symptom scores at 4.5, 10.5, and 13.5 months was higher in the VMAT arm than in the SBRT arm (P = 0.007, 0.027, and 0.021, respectively).

Conclusions: Both treatment modalities had similar effectiveness and provided acceptable outcomes in terms of toxicity and QOL. Grade 3 urinary toxicities might be eliminated with careful patient selection for SBRT.
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http://dx.doi.org/10.1016/j.vhri.2016.08.001DOI Listing
September 2016

Impact of Superoxide Dismutase-Gliadin on Radiation-induced Fibrosis: An Experimental Study.

In Vivo 2016 Jul-Aug;30(4):451-6

Department of Radiation Oncology, Medical Faculty, Istanbul University, Istanbul, Turkey.

Aim: Radiation-induced fibrosis (RIF) has since long been considered as irreversible. Further understanding of its mechanisms has led to trials investigating RIF treatment and prevention. The effect of superoxide dismutase (SOD)-gliadin, an oral form of SOD that resists gastrointestinal inactivation, on RIF treatment was evaluated in this experimental study.

Materials And Methods: A total of 36 Wistar albino mice were randomly distributed into four groups. According to group, 25 Gy radiation or sham-radiation were performed on day 0. Acute and late reactions were recorded. After 6 months, mice were treated with SOD-gliadin, 10,000 units per kg per day, or placebo. SOD-gliadin and placebo treatments were administered daily for 8 days by oral gavage. Later the mice were sacrificed, dissected and histopathologically analyzed. Accumulated hyaline and collagen at the dermis is an indicator of fibrosis. Therefore measurements of the dermal thickness were used to quantify the degree of RIF. Additionally, the morphological changes were analyzed, and the differences reported.

Results: The mean and standard deviation for dermal thickness were 0.45±0.09 mm in the sham-irradiated placebo-treated group, 0.51 mm±0.16 mm in the sham-irradiated SOD-gliadin-treated group, 0.92 mm±0.23 mm in the irradiated placebo-treated group and 0.71 mm±0.17 mm in the irradiated SOD-gliadin-treated group. The difference in mean dermal thickness between irradiated placebo-treated and irradiated SOD-gliadin-treated mice was statistically significant (p=0.002).

Conclusion: Quality of life while prolonging survival has an increasing importance in patients with cancer. RIF can be a crucial problem after all radiotherapy modalities. SOD-gliadin has advantageous effects on conditions that call for an increased expression of antioxidant enzymes. The results of our study suggest that oral SOD-gliadin may prevent or ameliorate RIF and patients can benefit from the positive effects of SOD.
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July 2017

Comparison of three dimensional conformal radiation therapy, intensity modulated radiation therapy and volumetric modulated arc therapy for low radiation exposure of normal tissue in patients with prostate cancer.

Asian Pac J Cancer Prev 2015 ;16(8):3365-70

Department of Radiation Oncology, Oncology Institute, Istanbul University, Istanbul, Turkey E-mail :

Radiotherapy has an important role in the treatment of prostate cancer. Three-dimensional conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques are all applied for this purpose. However, the risk of secondary radiation-induced bladder cancer is significantly elevated in irradiated patients compared surgery-only or watchful waiting groups. There are also reports of risk of secondary cancer with low doses to normal tissues. This study was designed to compare received volumes of low doses among 3D-CRT, IMRT and VMAT techniques for prostate patients. Ten prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated using 3D-CRT, IMRT and VMAT techniques. Conformity index (CI), homogenity index (HI), receiving 5 Gy of the volume (V5%), receiving 2 Gy of the volume (V2%), receiving 1 Gy of the volume (V1%) and monitor units (MUs) were compared. This study confirms that VMAT has slightly better CI while thev olume of low doses was higher. VMAT had lower MUs than IMRT. 3D-CRT had the lowest MU, CI and HI. If target coverage and normal tissue sparing are comparable between different treatment techniques, the risk of second malignancy should be a important factor in the selection of treatment.
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http://dx.doi.org/10.7314/apjcp.2015.16.8.3365DOI Listing
February 2016

Survival and prognostic factors in adult patients with recurrent or refractory ewing sarcoma family tumours: a 13-years retrospective study in Turkey.

In Vivo 2014 May-Jun;28(3):403-9

Division of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.

Aim: The aim of the present study was to evaluate the results of treatment and prognostic factors in adult patients with recurrent or refractory Ewing's sarcoma family tumors (ESFT).

Patients And Methods: We retrospectively evaluated treatment outcomes of 54 consecutive patients with ESFT (aged 15 years or more) with complete medical records, who were treated with multimodal therapies after recurrence at the Istanbul University, Institute of Oncology.

Results: The commonly used chemotherapy regimens at relapse were ifosfamide and etoposide (IE), ifosfamide and etoposide plus carboplatin (ICE), and oral etoposide. The median progression-free survival and overall survival for the entire group were 6.3 (95% confidence interval, 3.08-9.60) and 8.6 (95% confidence interval CI, 4.7-12.4) months, respectively. Multivariate analysis using a Cox proportional hazards model showed that non-IE/ICE chemotherapy regimens (p=0.003, hazard ratio=2.38) and the presence extrapulmonary metastases (p=0.045, hazard ratio=2.15) were associated with worse overall survival.

Conclusion: In primary refractory or relapsed ESFT, the presence of extrapulmonary metastases and treatment with salvage regimens other than ifosfamide and etoposide and/or carboplatin correlate with a poor prognosis.
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January 2015

The clinical effect of a positive surgical margin and adjuvant postoperative radiotherapy in the treatment of resectable desmoid tumors.

Mol Clin Oncol 2013 Nov 17;1(6):1061-1064. Epub 2013 Sep 17.

Departments of Medical Oncology, Istanbul University, 34390 Istanbul, Turkey.

Desmoid tumors (DTs) are benign tumors that exhibit fibroblastic proliferation, which arises from fascial or musculoaponeurotic structures. The aim of this study was to investigate the characteristics and outcomes of patients with resectable DTs. A total of 21 patients were included and their clinicopathological characteristics were retrospectively analyzed. The 21 patients (16 females and 5 males) were identified through reviewing the patient charts at our institute. The tumor was located in the lower extremities in 7 cases, in the upper extremities in 4 cases, in the abdominal region in 9 cases and in the neck region in 1 case. Patients who had been initially treated by surgical excision were included in the study. Of these 21 patients, a positive surgical margin (SM) was reported in 11 patients, 7 of whom received postoperative radiotherapy (RT). Ten patients had a negative SM and 6 received RT. A total of 5 patients (46%) in the positive SM group and 4 (40%) in the negative SM group had documented disease relapse (P>0.05). The median relapse-free survival (RFS) was 20.5 months for the patients treated by surgery alone and 50 months for those treated with surgery followed by adjuvant RT (P>0.05). Age, gender, SM and adjuvant RT were not identified as predictors of recurrence. No predictive factors appeared to indicate local DT recurrence following surgery.
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http://dx.doi.org/10.3892/mco.2013.185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915283PMC
November 2013

A modified protocol with vincristine, topotecan, and cyclophosphamide for recurrent/progressive ewing sarcoma family tumors.

Pediatr Hematol Oncol 2013 Apr;30(3):170-7

Department of Pediatric Hematology-Oncology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.

Purpose: Topotecan has recently been used in the treatment of pediatric cancer. We evaluated our experience with the modified combination of vincristine, topotecan, and cyclophosphamide (VTC) given in 3 days, in children with recurrent Ewing sarcoma.

Method: Children received vincristine (1.5 mg/m(2)/1st day), cyclophosphamide (600 mg/m(2)/day × 2 days) + mesna, and topotecan (1 mg/m(2)/day × 3 days) every 21 days.

Result: A total of 118 courses of VTC were given to 13 patients. One patient received VTC both at first and at second relapse. Thus, 14 relapse episodes in 13 patients were evaluated. After three courses of VTC chemotherapy (CT), two achieved complete response (CR), five achieved partial response, thus an objective response was attained in 7/14 (50%) episodes. Two patients had stable disease and two patients progressed. In three episodes, CR was achieved by surgery before CT. One of them had a second relapse and attained CR with VTC. Median time from diagnosis to relapse was 23 months (5-45 months). Site of relapse was local in four patients, and metastatic in 10 episodes of nine patients. Seven patients are alive, three with no evidence of disease and four alive with disease; six have died of disease. Local treatment was used in 11 episodes. The toxicity of the VTC combination was limited mainly to the hematopoietic system.

Conclusion: In conclusion, the modified VTC protocol in 3 days every 3 weeks seems to be effective and tolerable in children and adolescents with recurrent/progressive Ewing sarcoma.
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http://dx.doi.org/10.3109/08880018.2013.767868DOI Listing
April 2013

Pediatric diffuse intrinsic pontine glioma patients from a single center.

Childs Nerv Syst 2013 Apr 8;29(4):583-8. Epub 2012 Dec 8.

Pediatric Hematology-Oncology, Cerrahpasa Medical Faculty and Oncology Institute, Istanbul University, Istanbul, Turkey.

Background: The prognosis of children with diffuse intrinsic pontine gliomas (DIPG) is dismal. This study aims to evaluate the characteristics and treatment outcome of children with DIPG in a single center.

Methods: We reviewed the outcome of children with DIPG treated at the Oncology Institute of Istanbul University from February 1999 to May 2012.

Results: Fifty children (26 female, 24 male) with the median age of 7 years were analyzed. The median duration of symptoms was 30 days. All patients received radiotherapy (RT). Before the year 2000, 12 patients received only RT. Thirty-eight had concomitant and/or adjuvant chemotherapy with RT. Between 2000 and 2004, 17 patients received cis-platinum or vincristine as sensitizers during RT and CCNU + vincristine combination after RT. Since 2004, 21 patients received temozolomide (TMZ) concomitantly during RT and as adjuvant chemotherapy after RT. The median survival time of all patients was 13 months (1-160 months). Patients receiving RT + TMZ had a significantly higher overall survival than patients with only RT (p = 0.018). Patients receiving RT + chemotherapy other than TMZ also had a significantly higher overall survival than patients receiving only RT (p = 0.013). Patients receiving RT + TMZ + and chemotherapy other than TMZ had a significantly higher survival than patients receiving only RT (p = 0.005).

Conclusion: In our series, patients receiving RT + TMZ and also patients receiving RT + chemotherapy other than TMZ had a significantly higher overall survival than patients treated with only RT. Hence, administering chemotherapy during and after RT seems to prolong survival in some DIPG patients.
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http://dx.doi.org/10.1007/s00381-012-1986-3DOI Listing
April 2013

[Sinonasal extranodal natural killer/T-cell lymphoma: a case report and review of recent developments in the management].

Kulak Burun Bogaz Ihtis Derg 2012 May-Jun;22(3):164-71

Department of Radiation Oncology, Medical Faculty of İstanbul University, İstanbul, Turkey.

Nasal extranodal natural killer/T-cell lymphoma, which is a highly aggressive disease, is more frequently seen in Asia than in Western countries. No consensus has been reached on the management of the disease and the survival depends on the stage of the disease. Localized NK/T-cell lymphoma often responds to radiotherapy well. However, patients with advanced disease or recurrence after chemoradiotherapy, similar to our patient, have a very poor prognosis. In this article, we present a 52-year-old male patient with early recurrence and who was refractory to chemotherapy. The management of the disease was reviewed in the light of the recent literature data.
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http://dx.doi.org/10.5606/kbbihtisas.2012.031DOI Listing
February 2014

A review for solitary plasmacytoma of bone and extramedullary plasmacytoma.

ScientificWorldJournal 2012 2;2012:895765. Epub 2012 May 2.

Radiation Oncology Clinic, Okmeydani Training and Research Hospital, Ministry of Health, Istanbul, Turkey.

Solitary plasmacytoma (SP) is characterized by a mass of neoplastic monoclonal plasma cells in either bone (SBP) or soft tissue without evidence of systemic disease attributing to myeloma. Biopsy confirmation of a monoclonal plasma cell infiltration from a single site is required for diagnosis. The common presentation of SBP is in the axial skeleton, whereas the extramedullary plasmacytoma (EMP) is usually seen in the head and neck. The ratio of SP seen at males to females is 2 : 1 and the median age of patients is 55 years. The incidence rate of SP in black race is approximately 30% higher than the white race. Incidence rate increases exponentially by advancing age. SBP has a significant higher risk for progression to myeloma, and the choice of treatment is radiotherapy (RT) that is applied with curative intent at min. 4000 cGy. By only RT application, long-term disease-free survival (DFS) is possible for approximately 30% of patients with SBP and 65% of patients with EMP.
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http://dx.doi.org/10.1100/2012/895765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3354668PMC
September 2012

Mucoepidermoid carcinoma of the parotid gland in childhood survivor of acute lymphoblastic leukemia with need of radiotherapy for treatment and review of the literature.

Pediatr Hematol Oncol 2012 May;29(4):380-5

Diagnosis of secondary malignancies began with the increasing survival in childhood cancer. Children treated for acute lymphoblastic leukemia (ALL) have an increased risk for developing mucoepidermoid carcinoma (MEC) of the parotid gland. The latent period ranges from 5 to 16 years. A 2 6/12-year-old girl was treated for pro-B ALL. Treatment included multidrug chemotherapy, prophylactic intrathecal methotrexate, and cranial radiotherapy. MEC of the left parotid gland was diagnosed at the age of 8 years, 3 years after completing treatment. She was treated with multiple surgery and radiotherapy. The authors aimed to emphasize the need for concern about second cancers of the parotid gland in children treated for ALL.
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http://dx.doi.org/10.3109/08880018.2012.673696DOI Listing
May 2012

Response rates and adverse effects of continuous once-daily sunitinib in patients with advanced renal cell carcinoma: a single-center study in Turkey.

Jpn J Clin Oncol 2011 Dec 19;41(12):1380-7. Epub 2011 Oct 19.

Division of Medical Oncology, Specialist in Internal Medicine, Institute of Oncology, Istanbul University, Istanbul, Turkey.

Objective: Therapy targeted against the vascular endothelial growth factor pathway is a standard of care for patients with metastatic renal cell carcinoma. This study assessed the response rates and toxicity profiles of sunitinib on a continuous once-daily dosing regimen in Turkish patients with metastatic renal cell carcinoma.

Methods: Between April 2006 and August 2010, 74 patients with metastatic renal cell carcinoma who received sunitinib on a continuous, once-daily dosing regimen were included. Sunitinib was administered daily at a dose of either 37.5 mg (94% of the patients) or 25 mg (6% of the patients), without interruption, either as a second-line treatment after interferon-α or as a first-line treatment. Response, toxicity, progression-free survival and overall survival were evaluated.

Results: Of the 74 patients, 65 (88%) were diagnosed with clear cell renal cell carcinoma. The median treatment duration was 10 months (range, 2-42 months). The most common treatment-related adverse events were fatigue (75%), stomatitis (51%) and hypertension (50%). The most common Grade 3 or 4 adverse events were anemia (10%) and hand-foot syndrome (7%). Dose reductions were required in 50% of the patients, and early treatment discontinuation was necessary in 16% of the patients. Cardiovascular events were the most common adverse events that resulted in drug discontinuation. The objective response rate and the disease control rate were 30 and 78%, respectively. The median progression-free survival and overall survival were 13 and 25 months, respectively.

Conclusions: Continuous, once-daily administration of sunitinib was generally well tolerated in Turkish patients with advanced renal cell carcinoma in a daily practice setting. This study's response rates were comparable to those in previous randomized trials.
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http://dx.doi.org/10.1093/jjco/hyr151DOI Listing
December 2011

Clinical and prognostic features of plasmacytomas: a multicenter study of Turkish Oncology Group-Sarcoma Working Party.

Am J Hematol 2008 Sep;83(9):702-7

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

To identify the outcomes of prognostic factors of solitary plasmacytoma mainly treated with local radiotherapy (RT). The data were collected from 80 patients with solitary plasmacytoma (SP). Forty patients (50.0%) received radiotherapy (RT) alone while 38 of them (47.5%) were treated with surgery (S) and RT. The median radiation dose was 46 Gy (range 30-64). The median follow up was 2.41 years (range 0.33-12.33). Ten-year overall survival (OS) and local relapse-free survival (LRFS) were 73% and 94%, respectively. The median progression-free survival (PFS) and multiple myeloma-free survival (MMFS) were 3.5 years and 4.8 years, respectively. On multivariate analyses, the favorable factors were radiotherapy dose of > or =50 Gy and RT + S for PFS and younger age for MMFS. For the patients with medullary plasmacytoma, the favorable factor was younger age for MMFS. RT at > or =50 Gy and RT + S may be favorable prognostic factors on PFS. Younger patients, especially with head-neck lesion and without pre-RT macroscopic tumor, seem to have the best outcome when treated with RT +/- S. Progression to MM remains as the main problem especially for older patients.
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http://dx.doi.org/10.1002/ajh.21211DOI Listing
September 2008

[Evaluation of prognostic factors affecting recurrences and disease-free survival in extra-abdominal desmoid tumors].

Acta Orthop Traumatol Turc 2007 Aug-Oct;41(4):291-4

Istanbul University Istanbul Medical School, Department of Orthopaedics and Traumatology, Istanbul.

Objectives: We investigated treatment results and the role of potential prognostic factors in patients treated by surgery with or without adjuvant radiotherapy for primary or recurrent extra-abdominal desmoid tumors.

Methods: The study included 38 patients (23 females, 15 males; mean age 24 years; range 5 to 61 years) who underwent surgical treatment for extra-abdominal desmoid tumors. Of these, eight patients (21.1%) already had recurrences before treatment. Involvement was in the upper extremity in 12 cases (31.6%), in the lower extremity in 22 cases (57.9%), and in the axial region in four cases (10.5%). Twenty-two patients received adjuvant radiotherapy following surgical resection. Survival was analyzed by the Kaplan-Meier method. The mean follow-up period was 7.3 years (2.5 to 228 months).

Results: Twenty patients (52.6%) developed recurrences after treatment. Of these, recurrences were already present in six patients, and adjuvant radiotherapy was administered to 11 patients (55%). Recurrences developed at the irradiated site in eight patients, and in other regions in three patients. The mean disease-free survival was 38+/-8 months, and eight-year disease-free survival was 35.7+/-8.5%. Disease-free survival did not differ significantly between patients receiving adjuvant radiotherapy (47.9+/-7.9 months) and those treated with surgery alone (37.9+/-12.4 months), and between patients who developed a recurrence at the resection site (12.1+/-4.7 months) or at a different site (24.3+/-1.0 months) (p>0.05). None of the potential prognostic factors including gender, age, localization, surgical margin, or adjuvant irradiation were found to affect disease-free survival.

Conclusion: In our series, no prognostic factor could be identified as having an association with the high recurrence rate.
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April 2008

Clinical outcome of rhabdomyosarcoma in adolescent and adult patients: single center experience from Turkey.

Tohoku J Exp Med 2007 Nov;213(3):221-9

Department of Medical Oncology, Istanbul University Institute of Oncology, Istanbul, Turkey.

Rhabdomyosarcoma (RMS) is rare disease in adults (age >or= 16 years). The data from randomized prospective trials are scarce; the clinical outcome of these patients seems poor with the currently available treatment strategies. In this study, we report a single institution's experience in the treatment of adult RMS. We reviewed the medical records of patients with RMS who were >or= 16 years and have been treated in our institution between 1988 and 2003 retrospectively. We analyzed the survival outcome of these patients and the prognostic impact of clinical/pathological factors on their survival. In total, 23 patients with RMS were identified. Median age was 26 years (range, 16-72 years). Majority of patients were male (n: 17, 73.9%), and had large tumors (>or= 5 cm, n: 13, 56.5%), localized disease (N0, M0, n: 12, 52.2%), and embryonal histology (n: 10, 43.5%). Median overall survival was 31.3 months, and the 3-year progression-free survival and overall survival rates were 19.9% and 34.94%, respectively. Patients with smaller tumors (< 5 cm) (p < 0.04), local disease (p < 0.01), and normal lactic dehydrogenase (LDH) level (p < 0.01) at the time of diagnosis were found to have better survival outcome. The tumor size, serum LDH level, and metastatic disease at the time of diagnosis are potential predictors of outcome in patients with adult RMS. Adult RMS is an aggressive disease with poor survival despite treatment. The data from prospective, randomized multicenter trials are necessary in order to improve the clinical outcome of adult RMS patients.
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http://dx.doi.org/10.1620/tjem.213.221DOI Listing
November 2007

[Survival analysis and the effects of prognostic factors in patients treated for osteosarcoma].

Acta Orthop Traumatol Turc 2007 ;41(3):211-9

Istanbul Universitesi Istanbul Tip Fakültesi, Ortopedi ve Travmatoloji Anabilim Dali.

Objectives: We evaluated long-term treatment results of patients with primary osteosarcoma and the effect of prognostic factors on overall survival and disease-free survival.

Methods: Between 1995 and 2005, 180 patients (111 males, 69 females; mean age 21+/-10 years; range 7 to 64 years) were treated for primary osteosarcoma. Overall and disease-free survival rates were analyzed for 165 patients with high-grade osteosarcoma with the Kaplan-Meier method. The effects of potential prognostic factors were assessed, including age, gender, localization, tumor size, primary metastasis on presentation, the presence of pathologic fractures, necrosis rate, and infection. All the patients received chemotherapy before and after surgery. The mean follow-up period was 49.7 months (range 6 to 185) months.

Results: Sixty-nine patients were below 16 years of age. The most frequent involvement was in the distal femur (47.2%), followed by the proximal tibia (25%). Sixteen patients presented with a pathologic fracture, and 12 patients with metastasis. The median tumor size was 10 cm. The overall five- and 10-year survival rates were 68% and 60%, and disease-free survival rates were 50% and 44%, respectively. Only the presence of a pathologic fracture and primary metastasis on presentation were found to affect prognosis.

Conclusion: The two conditions, primary metastasis and a pathologic fracture, found as the most important prognostic factors in our study are mainly associated with late presentation. As in every malignant disease, early admission would provide better survival rates.
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March 2008
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