Publications by authors named "Beste M Atasoy"

20 Publications

  • Page 1 of 1

Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience.

J Oncol Pharm Pract 2021 Mar 29;27(2):329-339. Epub 2020 Apr 29.

Division of Medical Oncology, Department of Internal Medicine, Marmara University Faculty of Medicine, Istanbul, Turkey.

Purpose: Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals.

Methods: Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival.

Results: At the time of diagnosis, the median age was 48 (17-77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1-68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05).

Conclusion: Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.
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http://dx.doi.org/10.1177/1078155220920684DOI Listing
March 2021

Long-term neuromusculoskeletal side effects and quality of life in nasopharyngeal cancer patients receiving radiochemotherapy.

Eur Arch Otorhinolaryngol 2020 Aug 31;277(8):2325-2333. Epub 2020 Mar 31.

School of Medicine, Department of Radiation Oncology, Marmara University, Istanbul, Turkey.

Aim: In this study, we aimed to evaluate the neuromusculoskeletal late side effects and their impact on the quality of life of patients with nasopharyngeal carcinoma treated with radiochemotherapy.

Patients And Methods: Twenty-seven patients were included. The mean follow-up was 61 months (range, 18-111 months). The median external radiotherapy dose applied to the nasopharynx and primary tumor was 70 Gy (range, 61-73 Gy). The mean dose received by the temporomandibular joint in the dose-volume histograms of these patients was 60.7 Gy. The maximal doses of the muscles responsible for cervical motion in different ranges were greater than 60 Gy, and the mean doses were greater than 40 Gy in the muscle groups, except for the extensor muscles.

Results: Two patients had brachial plexus involvement, while 89% of the patients had restriction in flexion and extension movements. Of the patients, 52% had trismus. There was a significant correlation between extension restriction and general heath score and the physical subscale of the quality-of-life questionnaire (p = 0.01). There was also a correlation between trismus and pain killer usage (p = 0.004).

Conclusion: This is the first study to analyze long-term muscle and nerve toxicity and their correlation between doses in nasopharyngeal cancer patients following radiochemotherapy. Despite the advances in radiotherapy techniques, it is necessary to pay attention to the doses of the nerves and muscles for late effects.
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http://dx.doi.org/10.1007/s00405-020-05932-wDOI Listing
August 2020

Comparison of Three Nutritional Screening Tools to Predict Malnutrition Risk and Detect Distinctions Between Tools in Cancer Patients Receiving Radiochemotherapy.

Nutr Cancer 2018 Aug-Sep;70(6):867-873. Epub 2018 Oct 1.

b Department of Radiation Oncology , Marmara University School of Medicine , Istanbul , Turkey.

The aim of this study was to compare three screening tools for malnutrition in patients with head and neck cancers or central nervous system tumors (CNS) who are undergoing radiochemotherapy. The study evaluated 124 adult cancer patients. The Subjective Global Assessment (SGA), Mini-Nutritional Assessment (MNA), and Nutritional Risk Screening 2002 (NRS-2002) were chosen to assess the risk of malnutrition. The prevalence of patients at nutritional risk was 31% with SGA, 31% with MNA and 23% with NRS-2002 in all patients. The agreement between SGA and MNA was substantial (κ = 0.886, P < 0.001); the agreement between SGA and NRS-2002 was moderate (κ = 0.713, P < 0.001); and the agreement between MNA and NRS-2002 was also moderate (κ = 0.795, P < 0.001). In subgroup analysis, SGA and MNA substantially (κ = 0.973, P < 0.001), SGA and NRS-2002 moderately (κ = 0.722, P < 0.001), and MNA and NRS-2002 moderately (κ = 0.747, P < 0.001) agreed in head and neck cancer patients. In CNS tumor patients, SGA and MNA slightly (κ = 0.390, P = 0.005), SGA and NRS-2002 fairly (κ = 0.457, P =0.001), and MNA and NRS-2002 substantially (κ = 0.878, P < 0.001) agreed. The best agreement in tools was observed between SGA with MNA in all patients. Further studies in different tumor groups will enhance our understanding of current tools for malnutrition detection of radiotherapy patient.
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http://dx.doi.org/10.1080/01635581.2018.1491606DOI Listing
June 2019

Early effects of irradiation on laryngeal mucosa in a gastroesophageal reflux model: an experimental study.

Eur Arch Otorhinolaryngol 2018 Aug 4;275(8):2089-2094. Epub 2018 Jun 4.

Clinic of Radiation Oncology, Ministry of Health-Marmara University Pendik Training and Research Hospital, Istanbul, Turkey.

Objective: The aim of this study was to evaluate the early histopathological changes of gastroesophageal reflux and irradiation on laryngeal mucosa in rats.

Study Design: Animal study.

Setting: Experimental animal laboratory, tertiary referral center.

Subject And Method: Twenty-four adult female Wistar Albino rats were grouped as: control (n = 6), reflux and irradiation (n = 10), and irradiation (n = 8). Rats were operated to create a reflux model 30 days before irradiation. Ionizing radiation was administered in a single fraction of a 20 Gy to the larynx. Laryngeal tissue samples were taken at the 4th day of irradiation and all specimens underwent histopathological examination.

Results: Edema and vascular dilation in lamina propria were higher in the reflux and irradiation, and irradiation groups than control group. Inflammation was higher in the reflux and irradiation group than the control group. Inflammation in squamous epithelium was higher in the reflux and irradiation and irradiation groups compared to the control group. Inflammation in the squamous epithelium of the irradiation group was higher than the reflux and irradiation group. In the respiratory tract epithelium, inflammation was higher in the reflux and irradiation group; additionally, a significant loss of cilia was present in the reflux and irradiation and irradiation groups while pseudostratification was higher in the reflux and irradiation group.

Conclusion: Ionizing radiation-induced inflammation may increase on previously inflammated area due to gastroesophageal reflux. Therefore, it may be helpful to investigate and treat the reflux in laryngeal cancer patients that will receive ionizing radiation.
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http://dx.doi.org/10.1007/s00405-018-5010-8DOI Listing
August 2018

A Diet Containing Beta-Hydroxy-Beta-Methylbutyrate, L-Glutamine and L-Arginine Ameliorates Chemoradiation-Induced Gastrointestinal Injury in Rats.

Radiat Res 2015 Oct 2;184(4):411-21. Epub 2015 Oct 2.

e  Multidisciplinary Laboratories, Dokuz Eylül University School of Medicine, Izmir, Turkey.

The aim of this study was to investigate the effects of a specific diet, containing beta-hydroxy-beta-methylbutyrate, L-glutamine and L-arginine (HMB/Glu/Arg), on chemoradiation-induced injuries of the rat gastrointestinal mucosa. Wistar albino rats were divided into 4 groups: control (n = 5); radiation (n = 14); 5-fluorouracil treatment (5-FU; n = 14); and radiation and 5-FU treatment (n = 14). Rats were fed either a standard diet or a specific diet (SpD) containing HMB/Glu/Arg supplementation for 7 days prior to radiation exposure and/or 5-FU treatment. The irradiated groups were exposed to an 1 Gy dose of 6 MV x rays delivered to the who-abdominal. The animals receiving 5-FU treatment were given a 100 mg/kg dose of the drug. In the radiation and 5-FU treatment group, the 5-FU was administered 30 min prior to irradiation. After irradiation and/or 5-FU treatment, feeding with either the standard rat diet or specific diet continued as before. All animals were sacrificed on day 4 after irradiation and 5-FU treatment. Data collected included microbiological, histological and immunohistochemical end points. We found that bacterial colony counts in the ceca and mesenteric lymph nodes of irradiated rats treated with 5-FU were significantly lower in the specific diet (SpD) group than in the standard diet group (P = 0.002-0.05). Morphometrically, gastric, duodenal and colonic mucosal injuries were less severe in the irradiated animals fed the specific diet, as well as the 5-FU-treated animals fed the specific diet, compared to the similarly treated standard diet groups. Apoptosis, measured by TUNEL, revealed significantly lower numbers of TUNEL positive cells in irradiated animals fed the specific diet, and irradiated animals treated with 5-FU and fed the specific diet compared to irradiated animals fed the standard diet, and irradiated animals treated with 5-FU and fed the standard diet. In the 5-Fu-treated and SpD group, the extent of apoptosis was significantly lower than that of the 5-Fu-treated and standard diet group in both the stomach and duodenum (P = 0.0001), but not in the colon. Apoptosis, measured by caspase 3 staining, was significantly less in all three organs of the SpD groups. In conclusion, these findings suggest that a diet supplemented with HMB/Glu/Arg may ameliorate the effect of radiation-induced gastrointestinal injury, coinciding with reduced bacterial growth.
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http://dx.doi.org/10.1667/RR14088.1DOI Listing
October 2015

Long-term effects of neoadjuvant chemoradiotherapy followed by sphincter-preserving resection on anal sphincter function in relation to quality of life among locally advanced rectal cancer patients: a cross-sectional analysis.

Radiat Oncol 2015 Aug 12;10:168. Epub 2015 Aug 12.

Department of Internal Medicine, Marmara University Faculty of Medicine, Istanbul, Turkey.

Background: There is growing recognition for the consequences of rectal cancer treatment to maintain an adequate functional sphincter in the long-term rather than preserving the anal sphincter itself. This study aims to evaluate long-term effects of neoadjuvant chemoradiotherapy (nCRT) followed by sphincter-preserving resection on anal sphincter function in relation to quality of life (QoL) among locally advanced rectal cancer patients.

Methods: Twenty-nine patients treated with nCRT followed by low anterior resection surgery were included in this study. Data on patient demographics, tumor location and symptoms of urgency and fecal soiling were recorded and evaluated with respect to Wexner Fecal Incontinence Scoring Scale, European Organization for Research and Cancer (EORTC) cancer-specific (EORTC QLQ-C30) and colorectal cancer-specific (EORTC QLQ-CR38) questionnaires and anorectal manometrical findings. Correlation of manometrical findings with Wexner Scale, EORTC QLQ-CR38 scores and EORTC QLQ-C30 scores was also evaluated.

Results: Median follow-up was 45.6 months (ranged 7.5-98 months. Higher scores for incontinence for gas (p = 0.001), liquid (p = 0.048) and solid (p = 0.019) stool, need to wear pad (p = 0.001) and alteration in life style (p = 0.004) in Wexner scale, while lower scores for future perspective (p = 0.010) and higher scores for defecation problems (p = 0.001) in EORTC QLQ-CR38 were noted in patients with than without urgency. Manometrical findings of resting pressure (mmHg) was positively correlated with body image (r = 0.435, p = 0.030) and sexual functioning (r = 0.479, p = 0.011) items of functional scale, while rectal sensory threshold (RST) volume (mL) was positively correlated with defecation problems (r = 0.424, p = 0.031) items of symptom scale in EORTC QLQ-CR38 and negatively correlated with social function domain (r = -0.479, p = 0.024) in EORTC QLQ-C30. RST volume was also positively correlated with Wexner scores including incontinence for liquid stool (r = 0.459, p = 0.024), need to wear pad (r = 0.466, p = 0.022) and alteration in lifestyle (r = 0.425, p = 0.038).

Conclusion: The high risk of developing functional anal impairment as well as the systematic registration of not only oncological but also functional and QoL related outcomes seem important in rectal cancer patients in the long-term disease follow-up.
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http://dx.doi.org/10.1186/s13014-015-0479-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554367PMC
August 2015

V30 as a predictor for radiation-induced hypothyroidism: a dosimetric analysis in patients who received radiotherapy to the neck.

Radiat Oncol 2014 May 2;9:104. Epub 2014 May 2.

Department of Radiation Oncology, Bezmi Alem Vakif University Medical School, Adnan Menderes Bulvari, 34093 Istanbul, Fatih, Turkey.

Introduction: The purpose of this study is to evaluate the possible predictors of thyroid disorders after neck radiotherapy, with a focus on radiation dose-volume factors.

Methods: Thyroid function was measured in 100 patients who had received radiotherapy to the neck, including the thyroid. All radiation-induced thyroid dysfunctions were determined with an endpoint of abnormal thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and thyroxine (fT4) and thyroid peroxidase antibodies and (TPA). The total volume of the thyroid, mean radiation dose to the thyroid (Dmean) and thyroid volume percentage that received radiation doses of 10-50 Gy (V10-V50) were calculated in all patients. The evaluated risk factors for thyroid dysfunction included dose-volume parameters, sex, age, previous surgery, chemotherapy and comorbidity.

Results: There were 52 patients with hypothyroidism and V30 (p = 0.03), thyroid volume (p = 0.01) and Dmean (p = 0.03) appeared to be correlated with hypothyroidism in univariate analysis. However, there was not association found in multivariate analysis for these factors.

Conclusions: Thyroid disorders after radiation therapy to the neck still represent a clinically underestimated problem. V30 may be a useful tool for evaluating the risk of hypothyroidism when determining an individual patient's treatment.
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http://dx.doi.org/10.1186/1748-717X-9-104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029831PMC
May 2014

The benefit of whole brain reirradiation in patients with multiple brain metastases.

Radiat Oncol 2013 Jul 24;8:186. Epub 2013 Jul 24.

Background: To assess the outcomes, symptom palliation and survival rates in patients who received repeat whole brain radiotherapy (WBRT).

Methods: Twenty-eight patients who had progression of brain metastasis received a second course of WBRT. Univariate log-rank testing and multivariate Cox regression analysis were used to determine the factors for death among several variables (cumulative BED [BEDcumulative], primary tumor site, Karnofsky performance scale [KPS], previous SRS, number of metastases and absence of extracranial metastases). Correlations between variables and treatment response were evaluated with the Chi-squared test.

Results: The median KPS was 60 (range 50 to 100) at the initiation of reirradiation. The median time interval between the two courses of WBRT was 9.5 months (range 3-27 months). The median doses of the first course and the second course of WBRT were 30 Gy (range 20 to 30 Gy) and 25 Gy (range 20 to 30 Gy), respectively. The mean BEDcumulative was 129.5 Gy (range 110 to 150 Gy). Severe or unexpected toxicity was not observed. Symptomatic response was detected in 39% of the patients. The median overall survival following reirradiation was 3 months (range 1 to 12 months, 95% CI 1.82-4.118). Survival was significantly better in responders (median 10 months, 95% CI 3.56-16.43) compared with non-responders (median 2 months, 95% CI 1.3-2.64) (p = 0.000). In multivariate analysis, patients that had lung cancer (p = 0.01), initial KPS ≥60 (p = 0.03) or longer intervals to reirradiation (p = 0.01) had significantly better survival rates.

Conclusions: A careful second course of whole brain irradiation might provide a symptomatic and survival benefit in patients with good performance status and longer cranial progression-free intervals.
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http://dx.doi.org/10.1186/1748-717X-8-186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726464PMC
July 2013

Who may benefit from prophylactic cranial irradiation amongst stage III non-small cell lung cancer patients?

J BUON 2013 Apr-Jun;18(2):453-8

Department of Radiation Oncology, Division of Medical Oncology, Marmara University School of Medicine, Istanbul, Turkey.

Purpose: To identify a high risk group of non-small cell lung cancer (NSCLC) patients who may benefit from preventive strategies in order to reduce the rate of brain metastasis.

Methods: Two-hundred stage IIIA (47.5%) and IIIB (52.5%) NSCLC patients were analysed (median age 61 years, range 29-82). Pathological diagnosis consisted of 27% adenocarcinomas, 48.5% squamous cell carcinomas, and 24.5% non-small cell lung carcinomas. Brain metastasis rate was calculated and compared in relation to age, gender, stage, histology, chemotherapy and surgery.

Results: Median follow-up was 15 months (range 2-65), and the 2-year survival rate was 35%. Two-year incidence of brain metastasis was 23%. In univariate analysis, 32.9% of the patients younger than 60 years of age developed brain metastasis, in contrast to 15.3% of those older than 60 years (p=0.003). Brain was the first metastatic site in younger patients (44.4%) which was significantly higher than in the older age group (23%) (p=0.03). Adenocarcinoma had higher risk (39.6%) than squamous cell carcinoma (15.7%) for brain metastasis (p<0.0001). Patients 60 years old or younger with adenocarcinoma (53.3%) had higher risk for brain metastasis than all the others (18%; p<0.0001).

Conclusion: In locally advanced NSCLC patients, age and adenocarcinoma histology represent high risk factors for early development of brain metastasis. Many of the failures are isolated brain lesions and future studies are required to assess the benefit of preventive strategies in selected patients.
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November 2013

Metastasis to paranasal sinuses and orbita of breast cancer with a rare metachronous tumor of the uterine cervix.

J Craniofac Surg 2013 Jan;24(1):e64-5

Department of Radiation Oncology, Division of Medical Oncology, School of Medicine, Marmara University, Istanbul, Turkey.

Breast cancer metastases are rarely seen in paranasal sinuses or orbit with a poor prognosis, and these cases were published as case reports. Moreover, metachronous tumors following breast cancer diagnosis are somewhat common, but uterine cervix is infrequent in them. In the present case, we report a 61-year-old female patient who had a biopsy-proven metastatic breast cancer to paranasal sinuses and orbita. She also had a cervical uterine cancer which is also unusually diagnosed following breast cancer. Palliative radiotherapy to paranasal sinuses (30 Gy) achieved a good response. However, she died due to leptomeningeal progression.
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http://dx.doi.org/10.1097/SCS.0b013e3182700748DOI Listing
January 2013

Impact of adjuvant chemoradiotherapy for rectal cancer on the long-term quality of life and late side effects: a multicentric clinical evaluation by the Turkish Oncology Group.

Asian Pac J Cancer Prev 2012 ;13(11):5741-6

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

Aim: Although preoperative chemoradiatherapy (CRT) has proven its benefits in terms of decreased toxicity, there is still a considerable amount of cases that do not receive postoperative CRT. Oncologists at different geographic locations still need to know the long-term effects of this treatment in order to manage patients successfully. The current paper reports on long-term quality of life (QOL) and late side effects after adjuvant CRT in rectal cancer patients from 5 centers in Anatolia.

Methods: Rectal cancer patients treated with postoperative CRT with minimum 1-year follow-up and were in complete remission, were evaluated according to RTOG and LENT-SOMA scales. They were also asked to complete Turkish version of EORTCQLQ-C30 questionnaire and the CR-38 module. Each center participated with the required clinical data.

Results: Two hundred and thirty patients with median age of 55 years participated and completed the study. Median follow-up time was 5 years. All patients received RT concomitant with chemotherapy. Common parameters that both increased functional health scales and yielded better symptom scores were long term interval after treatment and sphincter-saving surgery. In addition, surgery type and follow-up time were determined to be predictors of QOL scores and late toxicity grade.

Conclusion: Postoperative CRT was found to have a great impact on the long term QOL and side effects in rectal cancer survivors. The factors that adversely affect these are abdominoperineal resection and shorter interval. The findings may encourage life-long follow-up and cooperation with patients, which should be mentioned during the initial counseling.
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http://dx.doi.org/10.7314/apjcp.2012.13.11.5741DOI Listing
July 2013

Health-related quality of life during postoperative chemoradiotherapy with oral uracil-tegafur and leucovorin in rectal cancer patients.

Hepatogastroenterology 2013 May;60(123):533-7

Ministry of Health-Marmara University Pendik Education and Research H ospital Radiotherapy Clinic, Istanbul, Turkey.

Background/aims: The objective of this study was to report on the quality of life of locally advanced rectal cancer patients that were treated with uracil-tegafur (UFT)/leucovorin (LV)-based concurrent chemoradiotherapy.

Methodology: Twenty-five patients were enrolled into this prospective study. Radiotherapy (50.4Gy) was given with concurrent UFT (300mg/m2/day) and LV (30mg/day). Turkish versions of EORTC-QLQC30 and EORTC QLQCR38 were applied at the beginning (HRQoL-1) and at the end (HRQoL-2) of chemoradiotherapy. Paired samples t-test was used to compare the difference of means for each scale between HRQoL1 and HRQoL2 and p values <0.05 were considered statistically significant.

Results: Study compliance was 80.6%. From baseline to the end of chemoradiotherapy, the mean scores of dyspnea (p=0.006) diarrhea (p=0.005) and micturition (p=0.005) increased significantly. Chemotherapy side effects also increased at the end of therapy (p=0.07). Seventy-six percent (76%) of male patients replied to questions related to sexual problems and functions, whereas no female patients replied.

Conclusions: Although, diarrhea and micturition are the major problems, quality of life scores indicate that concurrent oral fluoropyrimidine-based chemoradiotherapy is a feasible treatment.
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http://dx.doi.org/10.5754/hge12792DOI Listing
May 2013

Students meeting with caregivers of cancer patient: results of an experience-based learning project.

J Cancer Educ 2012 Dec;27(4):656-63

Department of Radiation Oncology, Marmara University School of Medicine, Istanbul, Turkey.

The communication between medical students and cancer caregivers, and the problems they have experienced as well as the outcomes for their professional development before starting clinical practice was assessed in the context of a student research project. Data were collected by questionnaires or by 20 to 40-min long interviews with cancer caregivers. Their communications with physicians, hearing the bad news, and health service satisfaction were questioned. Therefore, the caregivers trusted the professional approach of their physician. However, they expected more empathic communication in the process of diagnosis and therapy. Development of empathy and trust-based communication between patients and physicians and enhancement of the quality of devoted time to cancer patients and caregivers may have an effect on the course of disease. Interviewer students mentioned that they developed communication skills about difficult clinical tasks and in delivering bad news face to face to cancer caregivers before starting their clinical education.
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http://dx.doi.org/10.1007/s13187-012-0387-3DOI Listing
December 2012

The effect of magnesium and vitamin E pre-treatments on irradiation-induced oxidative injury of cardiac and pulmonary tissues in rats: a randomized experimental study.

Anadolu Kardiyol Derg 2012 Sep 20;12(6):508-14. Epub 2012 Jun 20.

Department of Radiation Oncology, Vocational School of Health Related Professions, Marmara University, İstanbul-Turkey.

Objective: The aim of this study was to investigate the effect of pre-treatment with the free radical scavenging molecules, magnesium and vitamin E, on lipid peroxidation to limit radiation-induced heart and lung injury.

Methods: Female Sprague-Dawley rats were divided into 4 groups by a simple randomization method as saline-treated control (n=4), saline-treated irradiated (IR; n=6), magnesium sulphate-treated irradiation (IR) (Mg+IR; n=6) and vitamin E-treated IR (vit E+IR; n=6), respectively. The animals were given either saline, Mg (600 mg/kg/day) or vit E (100 mg/kg/day) intraperitoneally for five days prior to irradiation. Twelve hours after the fifth injection, animals in irradiation groups were irradiated to 20 Gy using 6 MV photons in linear accelerator. Twenty-four hours later cardiac and lung tissue samples were obtained for determination of myeloperoxidase activity (MPO), malondialdehyde (MDA) levels, and luminol and lucigenin levels measured by chemiluminescence (CL) methods.

Results: No significant changes were observed between cardiac and pulmonary MDA and CL results of the experimental groups. However, cardiac and pulmonary MPO activities in the saline-treated IR group were increased as compared to control group (p<0.05 for all), while in the Mg-pretreated and vit E pretreated groups neutrophil infiltration was reduced, reaching to statistical significance only in the Mg-pretreated group (p<0.05).

Conclusion: Prophylactic use of magnesium sulfate has limited the infiltration of neutrophils to both the cardiac and pulmonary tissues at the early 24 h of irradiation. However, how limiting neutrophils as the sources of free radicals and inflammatory mediators would alter oxidative stress of heart and lung tissues in the long-term is not clear yet.
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http://dx.doi.org/10.5152/akd.2012.159DOI Listing
September 2012

The impact of early percutaneous endoscopic gastrostomy placement on treatment completeness and nutritional status in locally advanced head and neck cancer patients receiving chemoradiotherapy.

Eur Arch Otorhinolaryngol 2012 Jan 7;269(1):275-82. Epub 2011 Apr 7.

S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Fevzi Cakmak mah. Mimar Sinan cad No 41, Ust Kaynarca Pendik, 34899 Istanbul, Turkey.

To investigate the impact of early insertion of percutaneous endoscopic gastrostomy-tube on nutritional status and completeness of concurrent chemotherapy in locally advanced head and neck cancer patients treated with chemoradiotherapy. Twenty-three patients were enrolled into this prospective study. Gastrostomy-tube was inserted in patients before the initiation of chemoradiotherapy. There was not any significant change in nutritional parameters of patients that used their tube during treatment. Despite the grade 3 mucositis, the planned concurrent chemotherapy could be given in 70% of the patients. However, nine patients had weak compliance and their body weight (P = 0.01) and body mass index (P = 0.01) deteriorated in the first 4 weeks of chemoradiotherapy. The completeness of concurrent chemo-rate was 44% in these patients. Toxicity, requiring aggressive supportive care, may limit the chemotherapy part of curative concomitant chemoradiotherapy. By providing adequate enteral nutrition the insertion of gastrostomy-tube can increase the completeness rate of concurrent chemotherapy.
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http://dx.doi.org/10.1007/s00405-010-1477-7DOI Listing
January 2012

Efficacy of protracted dose-dense temozolomide in patients with recurrent high-grade glioma.

J Neurooncol 2011 Jul 29;103(3):585-93. Epub 2010 Sep 29.

Radiation Oncology Department, Marmara University Hospital, Tophanelioglu Cad. 13/15 Altunizade, 34660 Istanbul, Turkey.

The current standard therapy for newly diagnosed glioblastoma is multimodal, comprising surgical resection plus radiotherapy and concurrent temozolomide, then adjuvant temozolomide for 6 months. This has been shown to provide survival benefits; however, the prognosis for these patients remains poor, and most relapse. The objective of this prospective Phase II study was to evaluate the efficacy and tolerability of protracted, dose-dense temozolomide therapy (100 mg/m(2) for 21 consecutive days of a 28-day cycle) in patients with recurrent glioblastoma or grade 3 gliomas who had previously received standard therapy. Of the 25 patients included (median age 50 years), 20 were evaluable for radiologic response. Two patients had partial responses and 10 had stable disease (60% overall clinical benefit); 8 patients (40%) progressed after the first treatment cycle. Five patients were not assessed for radiologic response due to early clinical progression but were included in the progression-free survival (PFS) and overall survival (OS) analyses. The median follow-up time was 7 months (range, 1-14 months). The median PFS was 3 months (95% confidence interval, CI, 1.8-4.2) and the median OS was 7 months (95% CI 5.1-8.9). The 6-month PFS rate (primary endpoint) was 17.3% (95% CI 1.7-32.2) and the 1-year OS rate was 12% (95% CI -1-25). This regimen was well tolerated. The most frequent adverse event was lymphopenia (grade 3-4 in 20 patients); no opportunistic infections were reported. Treatment was discontinued due to toxicity in 2 patients (grade 4 hepatic toxicity and thrombocytopenia). These data suggest that protracted, dose-dense temozolomide had modest activity with manageable toxicity in patients with recurrent high-grade glioma previously treated with temozolomide.
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http://dx.doi.org/10.1007/s11060-010-0423-2DOI Listing
July 2011

Prophylactic feeding with immune-enhanced diet ameliorates chemoradiation-induced gastrointestinal injury in rats.

Int J Radiat Biol 2010 Oct;86(10):867-79

Departments of Radiation Oncology, Marmara University School of Medicine, Istanbul.

Purpose: To investigate the protective effect of immune-enhanced diet (IED) on chemoradiation-induced injury of the gastrointestinal mucosa.

Materials And Methods: Forty-eight Sprague-Dawley rats were divided into control (C, n=6), irradiation (IR, n=14), fluoropyrimidine (5-FU, n=14)-treated, IR + 5-FU (n=14)-treated groups. Half of each irradiated and/or 5-FU-treated groups were previously fed with IED containing arginine, omega-3-fatty acids and RNA fragments, while the other half were fed a standard rat diet (SD) for eight days before the induction of IR or injection of 5-FU. In IR groups, whole abdominal irradiation (11 Gy) was performed with 6 MV photons. In the 5-FU groups, fluoropyrimidine (100 mg/kg) was administered intraperitoneally 30 min prior to irradiation. All animals were sacrificed on the 4th day of IR or 5-FU injection.

Results: Bacterial colony counts in the ceca and mesenteric lymph nodes of IED-fed rats, which have received either 5-FU and/or irradiation were significantly lower than the corresponding SD-fed groups. Morphometric results revealed that gastric, ileal and colonic injuries were less in IED-treated IR or IR + 5-FU + IED groups, as compared to SD-fed groups. However, IED did not alter DNA fragmentation ratios.

Conclusion: Prophylactic feeding of IED has a protective effect on chemoradiation-induced gastrointestinal injury, which appears to involve the eradication of bacterial overgrowth.
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http://dx.doi.org/10.3109/09553002.2010.487026DOI Listing
October 2010

T4N0M0 nasopharyngeal carcinoma patients: do they have a distinct tumor biology?

Kulak Burun Bogaz Ihtis Derg 2010 Mar-Apr;20(2):89-96

Department of Radiation Oncology, Medicine Faculty of Marmara University, Istanbul, Turkey.

Objectives: To investigate the clinical manifestations and treatment outcomes of non-metastatic T4N0 nasopharyngeal cancer patients, and to compare them with other stage IVA subgroups of patients.

Patients And Methods: A retrospective analysis of 775 non-metastatic nasopharyngeal cancer patients, treated in four radiotherapy centers between 1990 and 2005, was undertaken. Among 197 stage IVA patients, 90 (11.6%) patients were staged as T4N0, 32 (4.1%) as T4N1, and 75 (9.7%) as T4N2. T4N0 patients constituted 40.8% of all T4 cases (median age 53 years; range 15 to 76 years). Cranial nerve involvement was detected in 59 (65.5%) of these cases.

Results: The median follow-up period was 38 months. There were only nine (10%) patients younger than 30 years of age with T4N0 tumors, for patients with diseases other than T4N0, 27.1% of the patients were under 30. Survival rates for five-year loco-regional progression free survival, distant failure free survival, and disease specific survival were 65.9%, 94%, and 71.4%, respectively. Distant failure free survival of T4N0 patients was more probable than for stage T4N1 (p=0.06) and T4N2 (p=0.008) patients.

Conclusion: Non-metastatic T4N0 tumors have some distinct features, including a unimodal age distribution and a better distant failure free survival than the other subgroups of stage IVA. Therefore, it may be better to include T4N0 patients in stage III instead of stage IVA.
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October 2010

Epidermal growth factor receptor expression in pretreatment biopsies from head and neck squamous cell carcinoma as a predictive factor for a benefit from accelerated radiation therapy in a randomized controlled trial.

J Clin Oncol 2005 Aug;23(24):5560-7

Gray Cancer Institute, The Cancer Centre, and Department of Pathology, Mount Vernon Hospital, United Kingdom.

Purpose: Accelerated repopulation is a main reason for locoregional failure after fractionated radiotherapy for head and neck squamous cell carcinoma (HNSCC). Epidermal growth factor receptor (EGFR) is a key controller of cellular proliferation in HNSCC, which stimulated the current study to look for a direct link between EGFR status and a possible clinical advantage of accelerated radiotherapy.

Patients And Methods: Immunohistochemical staining for EGFR was performed in 304 patients with available pretreatment tumor biopsy material among 918 patients randomized to receive continuous hyperfractionated accelerated radiotherapy versus conventionally fractionated radiotherapy. The EGFR index was estimated as the proportion of tumor cells with EGFR membrane staining.

Results: Significant benefit in locoregional tumor control from continuous hyperfractionated accelerated radiotherapy was seen in patients with HNSCC with high EGFR expression (2P = .010) but not in those with low EGFR expression (2P = .85). EGFR status had no significant effect on survival or rate of distant metastases. The EGFR index was significantly associated with histologic grade and microvessel density. There was moderate support for an association between EGFR status and subsite within the head and neck region but no significant association with Ki-67 index, Ki-67 pattern, p53 index, p53 intensity, bcl-2 expression, or cyclin D1 index.

Conclusion: This study indicates a key role for the EGFR receptor in determining the proliferative cellular response to fractionated radiotherapy in HNSCC. It also shows that we can select the dose-fractionation regime that has the greatest chance of benefiting the patient. These results also encourage further development of EGFR targeting combined with fractionated radiotherapy in HNSCC.
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http://dx.doi.org/10.1200/JCO.2005.06.411DOI Listing
August 2005

Melatonin protects against ionizing radiation-induced oxidative damage in corpus cavernosum and urinary bladder in rats.

J Pineal Res 2004 Nov;37(4):241-6

Marmara University, School of Pharmacy, Department of Pharmacology, Tibbiye Cad. 34668 Istanbul, Turkey.

The objective of this study was to examine the potential radioprotective properties of pharmacological doses of melatonin on corpus cavernosum and bladder tissues of whole-body irradiated (IR) rats. A total of 32 male Sprague-Dawley rats were exposed to irradiation performed with a LINAC which produced 6 MV photons at a focus 100 cm distant from the skin. Under ketamine anesthesia, each rat received a single whole-body dose of 800 cGy. Immediately before and after IR, rats were treated with either saline or melatonin (20 and 10 mg/kg, i.p.) and decapitated at 12 hr after exposure to irradiation. Another group of rats was followed for 72 hr after IR, where melatonin injections were repeated once daily. Tissue levels of malondialdehyde (MDA), an index of lipid peroxidation, and glutathione (GSH), a key antioxidant, were estimated in corpus cavernosum and urinary bladder. Tissues were also examined microscopically. The results demonstrate that both 12 and 72 hr following IR, tissue levels of MDA were elevated (P < 0.001), while GSH levels were reduced (P < 0.01) in both tissues. On the other hand, melatonin reversed these changes significantly (P < 0.05-0.01), concomitant with the improvement in histological appearances. Our results show that whole-body irradiation causes oxidative damage in the tissues of the genitourinary system. As melatonin administration reversed oxidative organ injury, as assessed by biochemical and histopathological findings, it is suggested that supplementing cancer patients with adjuvant therapy of melatonin may have some benefit for successful radiotherapy.
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http://dx.doi.org/10.1111/j.1600-079X.2004.00161.xDOI Listing
November 2004