Publications by authors named "Melek Yavuz"

29 Publications

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Dosimetric comparison of different treatment planning techniques with International Commission on Radiation Units and Measurements Report-83 recommendations in adjuvant pelvic radiotherapy of gynecological malignancies.

J Cancer Res Ther 2016 Apr-Jun;12(2):975-80

Department of Radiation Oncology, Akdeniz University School of Medicine, Antalya, Turkey.

Aim: The study evaluates the different treatment planning techniques according to three recommendation levels of the International Commission on Radiation Units and Measurements Report-83 in gynecologic cancer patients treated with adjuvant pelvic radiotherapy (APR).

Materials And Methods: Computerized tomography images of ten endometrial and cervical cancer patients who were treated with APR were assessed. For each patient, five different treatment plans were created. One homogeneity index and four different conformity indexes (CIs) were calculated for three-dimensional conformal radiotherapy (3D-CRT), field-in-field (FIF), seven-field intensity modulated radiotherapy (7-IMRT) with two different degrees beginning (7A-IMRT, 7B-IMRT) and 9-IMRT treatment plans. Dose volume histogram parameters and normal tissue complication probability (NTCP) were compared for organs at risk (OAR).

Results: The CI values of the IMRT were closer to 1 with respect to other plans (P < 0.05). The rectum and the bladder volumes which received more than 40 Gy were decreased with IMRT compared to 3D-CRT (P < 0.05). Doses received by the 195 cc volume of the small intestine and NTCP values were significantly decreased with IMRT (P < 0.05).

Conclusion: IMRT provided more protection than FIF plans at high dose volumes of the OAR; however, it did not show any superiority at low-dose volumes. The NTCP results supported IMRT for only small intestine protection. Because IMRT is increasingly used clinically, the comparison of NTCP will become more common in the near future. Therefore, new prospective studies with sufficient number of patients and appropriate NTCP models are needed for this treatment modality.
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http://dx.doi.org/10.4103/0973-1482.179189DOI Listing
March 2017

Long-term results of a concomitant boost radiotherapy technique for elderly patients with muscle-ınvasive bladder cancer.

J Geriatr Oncol 2015 07 8;6(4):316-23. Epub 2015 May 8.

Department of Radiation Oncology, Faculty of Medicine, Akdeniz University, Antalya,Turkey. Electronic address:

Objectives: To evaluate the long-term clinical efficacy and toxicity of concomitant boost radiotherapy (CBRT) in elderly patients with invasive bladder cancer.

Methods And Materials: Elderly patients (n=188; mean 75-year-old, range 70-91 years; 88.3% male/11.7% female) with T1-T4a bladder carcinoma were irradiated with CBRT. A total of 24 (12.8%) patients were diagnosed at stage T1, 117 (62.2%) were at stage T2, 28 (14.9%) at were stage T3a, 14 (7.4%) were stage T3b, and 5 (2.7%) were stage T4a. A dose of 45Gy in 1.8Gy fractions was administered to the whole pelvis 5 days/week over 5 weeks. A concomitant boost limited to the bladder tumor area plus margin or whole bladder of 22.5Gy in 1.5Gy fractions was administered from weeks 3×5. Thus, irradiation totalled 67.5Gy over 5 weeks. The interfraction interval was ≥6h/treatment day. We assessed prognostic factors for overall survival (OS), cause-specific survival (CSS) and relapse-free survival (RFS).

Results: Median follow-up was 46.2 months (range 4.7-155.7 months). Median overall survival was 27 months (95% CI:21-33 months). In this study, 146 (77.7%) patients had complete response, 39 (20.7%) had residual disease and 4 (1.6%) had progressive disease. The mean 3-, 5- and 10-year OS rates were respectively 41.2% (S.E.±0.036), 29% (S.E.±0.034), and 13.8% (S.E.±0.031). Significant prognostic factors for OS and CSS, by multivariate analysis, were tumor T-stage and urothelial obstruction.

Conclusion: This CBRT protocol provided excellent results with a high complete response rate and good tolerance. This approach may therefore be particularly appropriate for elderly patients with invasive bladder cancer.
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http://dx.doi.org/10.1016/j.jgo.2015.04.004DOI Listing
July 2015

Long-term outcomes in treatment of invasive bladder cancer with concomitant boost and accelerated hyperfractionated radiation therapy.

Int J Radiat Oncol Biol Phys 2014 Nov 23;90(3):562-9. Epub 2014 Aug 23.

Department of Radiation Oncology, Karadeniz Technical University, Trabzon, Turkey.

Purpose: The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer.

Methods And Materials: Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a.

Results: The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively.

Conclusions: The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy.
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http://dx.doi.org/10.1016/j.ijrobp.2014.06.055DOI Listing
November 2014

In regard to Kennedy et al.

Int J Radiat Oncol Biol Phys 2014 Jul;89(4):928

Medical Faculty, Akdeniz University, Antalya, Turkey.

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http://dx.doi.org/10.1016/j.ijrobp.2014.04.016DOI Listing
July 2014

Commentary on "late bone and soft tissue sequelae of childhood radiotherapy".

Strahlenther Onkol 2014 Oct 3;190(10):962. Epub 2014 Jun 3.

Medical Faculty, Akdeniz University, Antalya, Turkey,

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http://dx.doi.org/10.1007/s00066-014-0691-4DOI Listing
October 2014

Comparison of computed tomography- and positron emission tomography-based radiotherapy planning in cholangiocarcinoma.

Onkologie 2013 19;36(9):484-90. Epub 2013 Aug 19.

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

Introduction: The aim of this study was to compare computed tomography (CT)- and positron emission tomography (PET)/CT-based gross tumor volume (GTV) delineation and its subsequent expansion to the planning target volume (PTV), and to analyze the resultant doses of 3-dimensional conformal radiotherapy (3D-CRT) to critical organs.

Methods: 15 patients with unresectable extrahepatic cholangiocarcinoma (EHCC) were enrolled into this study. PTVCT-based plans were initially made, and then PTVPET-CT-based plans were created using the same beam angles and isocenter. The dosimetric parameters analyzed included GTVCT, PTVCT, GTVPET-CT and PTVPET-CT. Prescribed and delivered radiation doses to target volumes and delineated organs at risk were also compared.

Results: Mean GTV and PTV were significantly reduced in the PET/CT-based plan compared to the CT-based plan; the mean reductions of GTV and PTV were 28.7% and 15.2%, respectively. The mean value for GTVPET/GTVCT mismatch was 49.5 ± 28.9%, and that for GTVCT/GTVPET was 95.9 ± 19.5%. The mean value for PTVPET-CT/PTVCT mismatch was 21.9 ± 7.0% and that for PTVCT/PTVPET-CT was 39.1 ± 9.2%. Liver doses were significantly reduced (17.1%) in the PET/CT-based plan compared to the CT-based plan; the doses received by at least 30% and 50% of the liver were 30.0%, and 27.3%, respectively.

Conclusion: The potential benefit of PET/CT is the reduction in geographic misses and regional treatment failures associated with CT-based planning.
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http://dx.doi.org/10.1159/000354630DOI Listing
May 2014

Plasma citrulline levels predict intestinal toxicity in patients treated with pelvic radiotherapy.

Acta Oncol 2011 Nov 24;50(8):1167-74. Epub 2011 Aug 24.

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

Background: Radiotherapy (RT) for abdominal and pelvic malignancies often causes severe small bowel toxicity. Citrulline concentrations are known to decrease with intestinal failure. We thus evaluated the feasibility of plasma citrulline levels in predicting radiation-induced intestinal toxicity.

Material And Methods: Fifty-three patients (36 prostate cancer, 17 endometrial cancer) who received 45 Gy pelvic RT using conventional fractionation were prospectively evaluated. Patients with prostate cancer received an additional 25-30.6 Gy conformal boost. Plasma citrulline levels were assessed on day 0, mid- (week 3) and post-RT (week 8), and four months post-RT. Dose-volume histogram, citrulline concentration changes, and weekly intestinal toxicity scores were analyzed.

Results: Mean age was 63 years (range: 43-81 years) and mean baseline citrulline concentration was 38.0 ± 10.1 μmol/l. Citrulline concentrations were significantly reduced at week 3 (27.4 ± 5.9 μmol/l; p < 0.0001), treatment end (29.9 ± 8.8 μmol/l; p < 0.0001), and four months post-treatment (34.3 ± 12.1; p = 0.01). The following factor pairs were significantly positively correlated: Citrulline concentration/mean bowel dose during, end of treatment, and four months post-RT; dose-volume parameters/citrulline change groups; cumulative mean radiation dose/intestinal toxicity at end and four months post-RT; citrulline changes/intestinal toxicity during and end of RT. Citrulline concentration changes significantly differed during treatment according to RTOG intestinal toxicity grades (p < 0.0001). Although the citrulline changes differed significantly within RTOG intestinal toxicity grades (p = 0.003), the difference between Grade 0 and Grade 1 did not differ significantly at the end of the treatment. At four months after RT, no significant differences were apparent.

Conclusion: Citrulline-based assessment scores are objective and should be considered in measuring radiation-induced intestinal toxicity.
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http://dx.doi.org/10.3109/0284186X.2011.584557DOI Listing
November 2011

Protective effects of melatonin and octreotide against radiation-induced intestinal injury.

Dig Dis Sci 2011 Feb 23;56(2):359-67. Epub 2010 Jul 23.

Department of Radiation Oncology, Adana Research and Treatment Centre, Baskent University Medical Faculty, Adana, Turkey.

Purpose: To compare the protective effects of the potent antioxidants, melatonin and octreotide, against radiation-induced intestinal injury.

Methods: A total of 42 male 3-month-old Swiss albino mice (40 ± 10 g) were matched according to body weight and randomly assigned to one of six groups: control; radiation treatment (RT) only; melatonin only (15 mg/kg, i.p.); melatonin + RT; octreotide only (50 μg/kg i.p.); and octreotide + RT. Intestinal damage was induced by exposure to a single whole-body radiation dose of 8 Gy. All mice tolerated the experimental interventions, and no deaths were observed.

Results: Irradiation induced architectural disorganization, including inflammatory mononuclear cell infiltration, villitis, and desquamation with eosinophilic necrosis, and diminished mucosal thickness, crypt height, and villous height. In the melatonin + RT and octreotide + RT groups, the villous pattern was well preserved; desquamation at villous tips and edema was prominent, but necrosis was absent. The radiation-induced decrease in mucosal thickness was significantly reduced by pretreatment with melatonin (p < 0.001) or octreotide (p = 0.01), although the protective effect was significantly greater for melatonin (p = 0.04). Pretreatment with melatonin also preserved villous height (p = 0.009) and crypt height (p = 0.03); although a similar trend was observed for pre-irradiation octreotide, the differences were not significant.

Conclusions: Melatonin and octreotide potently protected against radiation-induced intestinal injury in mice, but melatonin was significantly more effective in preserving the histological structure of the intestines, a finding that warrants confirmation in clinical studies.
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http://dx.doi.org/10.1007/s10620-010-1322-2DOI Listing
February 2011

Comparison of CT and integrated PET-CT based radiation therapy planning in patients with malignant pleural mesothelioma.

Radiat Oncol 2009 Sep 16;4:35. Epub 2009 Sep 16.

Department of Radiation Oncology, Baskent University Medical Faculty, Adana Medical and Research Center, Kisla Campus, Adana, Turkey.

Background: When combined with adequate tumoricidal doses, accurate target volume delineation remains to be the one of the most important predictive factors for radiotherapy (RT) success in locally advanced or medically inoperable malignant pleural mesothelioma (MPM) patients. Recently, 18-fluorodeoxyglucose positron emission tomography (PET) has demonstrated significant improvements in diagnosis and accurate staging of MPM. However, role of additional PET data has not been studied in RT planning (RTP) of patients with inoperable MPM or in those who refuse surgery. Therefore, we planned to compare CT with co-registered PET-CT as the basis for delineating target volumes in these patients group.

Methods: Retrospectively, the CT and co-registered PET-CT data of 13 patients with histologically proven MPM were utilized to delineate target volumes separately. For each patient, target volumes (gross tumor volume [GTV], clinical target volume [CTV], and planning target volume [PTV]) were defined using the CT and PET-CT fusion data sets. The PTV was measured in two ways: PTV1 was CTV plus a 1-cm margin, and PTV2 was GTV plus a 1-cm margin. We analyzed differences in target volumes.

Results: In 12 of 13 patients, compared to CT-based delineation, PET-CT-based delineation resulted in a statistically significant decrease in the mean GTV, CTV, PTV1, and PTV2. In these 12 patients, mean GTV decreased by 47.1% +/- 28.4%, mean CTV decreased by 38.7% +/- 24.7%, mean PTV1 decreased by 31.1% +/- 23.1%, and mean PTV2 decreased by 40.0% +/- 24.0%. In 4 of 13 patients, hilar lymph nodes were identified by PET-CT that was not identified by CT alone, changing the nodal status of tumor staging in those patients.

Conclusion: This study demonstrated the usefulness of PET-CT-based target volume delineation in patients with MPM. Co-registration of PET and CT information reduces the likelihood of geographic misses, and additionally, significant reductions observed in target volumes may potentially allow escalation of RT dose beyond conventional limits potential clinical benefits in tumor control rates, which needs to be tested in future studies.
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http://dx.doi.org/10.1186/1748-717X-4-35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754492PMC
September 2009

Comparison of conventional and CT-based planning for intracavitary brachytherapy for cervical cancer: target volume coverage and organs at risk doses.

J Exp Clin Cancer Res 2009 Jul 1;28:95. Epub 2009 Jul 1.

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

Background: To compare intracavitary brachytherapy (ICBT) planning methods for cervical cancer, based on either orthogonal radiographs (conventional plan) or CT sections (CT plan); the comparison focused on target volume coverage and dose volume analysis of organs at risk (OARs), by representing point doses defined by the International Commission on Radiation Units and Measurement (ICRU) and dose volume histograms (DVHs) from 3D planning.

Methods: We analyzed the dosimetric data for 62 conventional and CT-based ICBT plans. The gross tumor volume (GTV), clinical target volume (CTV) and organs at risk (OAR)s were contoured on the CT-plan. Point A and ICRU 38 rectal and bladder points were defined on reconstructed CT images.

Results: Patients were categorized on the basis of whether the >95% isodose line of the point-A prescription dose encompassed the CTV (group 1, n = 24) or not (group 2, n = 38). The mean GTV and CTV (8.1 cc and 20.6 cc) were smaller in group 1 than in group 2 (24.7 cc and 48.4 cc) (P <0.001). The mean percentage of GTV and CTV coverage with the 7 Gy isodose was 93.1% and 88.2% for all patients, and decreased with increasing tumor size and stage. The mean D2 and D5 rectum doses were 1.66 and 1.42 times higher than the corresponding ICRU point doses and the mean D2 and D5 bladder doses were 1.51 and 1.28 times higher. The differences between the ICRU dose and the D2 and D5 doses were significantly higher in group 2 than in group 1 for the bladder, but not for the rectum.

Conclusion: The CT-plan is superior to the conventional plan in target volume coverage and appropriate evaluation of OARs, as the conventional plan overestimates tumor doses and underestimates OAR doses.
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http://dx.doi.org/10.1186/1756-9966-28-95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711061PMC
July 2009

Comparison of rectal volume definition techniques and their influence on rectal toxicity in patients with prostate cancer treated with 3D conformal radiotherapy: a dose-volume analysis.

Radiat Oncol 2009 May 11;4:14. Epub 2009 May 11.

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

Background: To evaluate the impact of four different rectum contouring techniques and rectal toxicities in patients with treated with 3D conformal radiotherapy (3DCRT).

Methods: Clinical and dosimetric data were evaluated for 94 patients who received a total dose 3DCRT of 70 Gy, and rectal doses were compared in four different rectal contouring techniques: the prostate-containing CT sections (method 1); 1 cm above and below the planning target volume (PTV) (method 2); 110 mm starting from the anal verge (method 3); and from the anal verge to the sigmoid flexure (method 4). The percentage of rectal volume receiving RT doses (30-70 Gy) and minimum, mean rectal doses were assessed.

Results: Median age was 69 years. Percentage of rectal volume receiving high doses (>or= 70 Gy) were higher with the techniques that contoured smaller rectal volumes. In methods 2 and 3, the percentage of rectal volume receiving >or= 70 Gy was significantly higher in patients with than without rectal bleeding (method 2: 30.8% vs. 22.5%, respectively (p = 0.03); method 3: 26.9% vs. 18.1%, respectively (p = 0.006)). Mean rectal dose was significant predictor of rectal bleeding only in method 3 (48.8 Gy in patients with bleeding vs. 44.4 Gy in patients without bleeding; p = 0.02).

Conclusion: Different techniques of rectal contouring significantly influence the calculation of radiation doses to the rectum and the prediction of rectal toxicity. Rectal volume receiving higher doses (>or= 70 Gy) and mean rectal doses may significantly predict rectal bleeding for techniques contouring larger rectal volumes, as was in method 3.
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http://dx.doi.org/10.1186/1748-717X-4-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684071PMC
May 2009

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

Prophylactic cranial irradiation in locally advanced non-small cell lung cancer: outcome of recursive partitioning analysis group 1 patients.

J Exp Clin Cancer Res 2008 Dec 4;27:80. Epub 2008 Dec 4.

Department of Radiation Oncology, Baskent University Medical Faculty, Adana Medical and Research Center, Kisla Saglik Yerleskesi, Adana, Turkey.

Background: Prophylactic cranial irradiation (PCI) has been demonstrated to reduce or delay the incidence of brain metastases (BM) in locally advanced non-small cell lung carcinoma (LA-NSCLC) patients with various prognostic groups. With this current cohort we planned to evaluate the potential usefulness of prophylactic cranial irradiation (PCI) specifically in recursive partitioning analysis (RPA) Group 1, which is the most favorable group of LA-NSCLC patients.

Methods: Between March 2007 and February 2008, 62 patients in RPA group 1 were treated with sequential chemoradiotherapy and PCI for stage IIIB NSCLC. The induction chemotherapy consisted of 3 courses of cisplatin (80 mg/m2) and docetaxel (80 mg/m2); each course was given every 21 days. Thoracic radiotherapy (TRT) was given at a dose of 60 Gy using 3-D conformal planning. All patients received a total dose of 30 Gy PCI (2 Gy/fr, 5 days a week), beginning on the first day of the TRT. Then, all patients received 3 further courses of the same chemotherapy protocol.

Results: Six (9.7%) patients developed brain metastases during their clinical course. Only one (2%) patient developed brain metastasis as the site of first treatment failure. Median brain metastasis-free survival, overall survival, and progression free survival were 16.6, 16.7, and 13.0 months, respectively. By univariate analysis, rates of BM were significantly higher in patients younger than 60 years of age (p = 0.03). Multivariate analysis showed no significant difference in BM-free survival according to gender, age, histology, and initial T- and N-stage.

Conclusion: The current finding of almost equal bone metastasis free survival and overall survival in patients with LA-NSCLC in RPA group 1 suggests a longer survival for patients who receive PCI, and thereby have a reduced risk of BM.
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http://dx.doi.org/10.1186/1756-9966-27-80DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612647PMC
December 2008

Comparison of the protective effects of melatonin and amifostine on radiation-induced epiphyseal injury.

Int J Radiat Biol 2008 Oct;84(10):796-802

Baskent University Medical Faculty, Adana Medical and Research Center, Department of Radiation Oncology, Kisla Saglik Yerleskesi, Adana, Turkey.

Purpose: We compared the effects of amifostine and melatonin in preventing radiation-induced epiphyseal growth plate injury in rats.

Materials And Methods: Four-week-old (65-85 g), growing male Sprague-Dawley rats were randomly assigned to receive radiation alone, at 25 Gy in three fractions (group R), or this dose of fractionated radiation proceeded by prophylactic amifostine 200 mg/kg i.p. (group A), melatonin 15 mg/kg i.p. (group M), or amifostine + melatonin (group AM). The right rear extremity of each animal was irradiated while the contralateral leg was shielded from radiation, as a control. Bone growth based on the length of the tibia, femur, and overall limb was calculated 6 weeks after the treatment.

Results: In groups R, A, M, and AM, the mean growth loss (GL) for the overall limb was 56.9 +/- 8.1%, 46.8 +/- 7.7%, 36.6 +/- 4.3%, and 38.5 +/- 5.1%, respectively. The limb length discrepancies (LLD) in groups R, A, M, and AM were 13.8 +/- 1.4%, 10.5 +/- 0.3%, 7.4 +/- 0.7%, and 8.8 +/- 1.1%, respectively. Differences in LLD were significant between each treatment group and group R (range: p = 0.0001-0.001). Differences in either of mean GL and LLD were not significant between groups M and AM; however both of these groups had significantly less GL and LLD than group A.

Conclusions: We observed a superior radioprotective function of melatonin over amifostine in preventing radiation-induced epiphyseal growth plate injury, without any increase in radioprotective effect by adding amifostine to melatonin.
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http://dx.doi.org/10.1080/09553000802389678DOI Listing
October 2008

Comparison of CT and PET-CT based planning of radiation therapy in locally advanced pancreatic carcinoma.

J Exp Clin Cancer Res 2008 Sep 23;27:41. Epub 2008 Sep 23.

Department of Radiation Oncology, Baskent University Medical Faculty, Adana Medical and Research Center, Kisla Saglik Yerleskesi, Adana, Turkey.

Background: To compare computed tomography (CT) with co-registered positron emission tomography-computed tomography (PET-CT) as the basis for delineating gross tumor volume (GTV) in unresectable, locally advanced pancreatic carcinoma (LAPC).

Methods: Fourteen patients with unresectable LAPC had both CT and PET images acquired. For each patient, two three-dimensional conformal plans were made using the CT and PET-CT fusion data sets. We analyzed differences in treatment plans and doses of radiation to primary tumors and critical organs.

Results: Changes in GTV delineation were necessary in 5 patients based on PET-CT information. In these patients, the average increase in GTV was 29.7%, due to the incorporation of additional lymph node metastases and extension of the primary tumor beyond that defined by CT. For all patients, the GTVCT versus GTVPET-CT was 92.5 +/- 32.3 cm3 versus 104.5 +/- 32.6 cm3 (p = 0.009). Toxicity analysis revealed no clinically significant differences between two plans with regard to doses to critical organs.

Conclusion: Co-registration of PET and CT information in unresectable LAPC may improve the delineation of GTV and theoretically reduce the likelihood of geographic misses.
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http://dx.doi.org/10.1186/1756-9966-27-41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562364PMC
September 2008

Prevention of acute radiation-induced esophagitis with glutamine in non-small cell lung cancer patients treated with radiotherapy: evaluation of clinical and dosimetric parameters.

Lung Cancer 2009 Mar 8;63(3):393-9. Epub 2008 Aug 8.

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

Background: The purpose of this study was to evaluate the efficacy of oral glutamine in the prevention of acute radiation-induced esophagitis (ARIE) and weight loss in lung carcinoma patients, and to determine the clinical/dosimetric predictors of ARIE.

Patients And Methods: Data from 41 patients with stage III lung carcinoma treated with thoracic irradiation were retrospectively analyzed. Twenty-two patients (53.6%) received prophylactic powdered glutamine in doses of 10g/8h. Prescribed radiation dose to planning target volume was 60Gy, in 30 fractions, 5 days/week. The primary endpoint included the ARIE incidence and its correlation with clinical/dosimetric factors relative to treatment with glutamine.

Results: Glutamine was well tolerated. Grade 2 or 3 ARIE occurred in 20 (48.8%) of 41 patients: seven in the glutamine-supplemented group, and 13 in the glutamine-free group (p=0.002). All seven patients with grade 3 esophagitis were in the glutamine-free group (36.8% vs. 0%). Glutamine supplementation appeared to significantly delay ARIE onset for six days (22 days vs. 16 days; p=0.002). Glutamine-supplemented patients demonstrated a lower incidence of grade 2 or 3 ARIE (27.2%), and gained weight during radiotherapy (p=0.04). V55 was the only dosimetric parameter that correlated with the severity of ARIE in glutamine-free patients: a V55 of <35% had a 31% risk of ARIE grade 2 or 3, and the risk increased to 76% with a V55 of >or=35% (p=0.01).

Conclusion: This schedule and dosage of glutamine may be beneficial in the prevention of ARIE and weight loss in lung cancer patients undergoing thoracic irradiation.
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http://dx.doi.org/10.1016/j.lungcan.2008.06.015DOI Listing
March 2009

Managing liver metastases with conformal radiation therapy.

J Support Oncol 2008 Jan;6(1):9-13, 15

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

A subgroup of liver metastases, especially those emanating from colorectal carcinoma, may be cured. Surgical excision is accepted as the mainstay of treatment for these malignancies; unfortunately, however, the majority of patients presents with advanced unresectable hepatic involvement and have no standard treatment option available. Radiation therapy (RT) has not played a significant role in managing liver metastases, because the liver has little tolerance to radiation. In patients with good hepatic function, however, very-high-dose RT may be used safely and effectively if a small volume of the liver (< 25%) is irradiated. In particular, RT, and especially three-dimensional conformal RT (3D-CRT), may be used to manage medically unfit patients or those with an unresectable metastatic liver lesion. This review discusses existing literature on use of various types of RT, including whole-liver irradiation, partial hepatic irradiation with 3D-CRT, and hypofractionated high-dose irradiation with stereotactic body RT, and future directions for this treatment modality.
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January 2008

Radiation port wart: a distinct cutaneous lesion after radiotherapy.

J Natl Med Assoc 2006 Jul;98(7):1193-6

Department of Radiation Oncology, Selcuk University, Meram Medical Faculty, Akyokus, Konya, Turkey.

Unlabelled: LABELED BACKGROUND: Radiotherapy may cause common cutaneous side effects such as acute and chronic radiodermatitis and also rare skin conditions.

Case Report: A 42-year-old woman who received radiotherapy for invasive breast carcinoma developed multiple, scaly, rough papules and nodules restricted to treatment fields six months after completion of the treatment. A relapse of the breast cancer and/or seborrheic keratosis was ruled out by histological confirmation of verruca vulgaris.

Conclusion: We report the first case of verruca vulgaris associated with radiation treatment. Radiotherapists and dermatologists should be aware of this possibility and be able to differentiate it from other skin lesions associated with irradiation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569464PMC
July 2006

Effect of the farnesyl transferase inhibitor L-744,832 on the colon cancer cell line DLD-1 and its combined use with radiation and 5-FU.

Chemotherapy 2005 Oct 13;51(6):319-23. Epub 2005 Oct 13.

Department of Medical Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.

Background: Ras oncogenes are found in 25% of human tumors and they significantly affect prognosis. One of the major fields studied to improve anticancer drugs is blockade of the oncogenic ras protein function. One of the mechanisms to block the function of these proteins is to block farnesylation using a farnesyl transferase inhibitor (FTI) and thus to prevent the ras from anchoring to the cell membrane.

Methods: In this study, we investigated the effects of FTI L-744,832 either alone or in combination with 5-fluorouracil (5-FU; 1 microM/l) and radiotherapy (2, 6, and 10 Gy) on the colon cancer cell line DLD-1 with mutations in K-, N- and H-ras, c-myb, c-myc, p53, fos, sis and DNA repair genes. Drugs were added 3 h after cultivation. Radiotherapy was performed on the 3rd day of the study. On the 3rd day, medium and drugs were changed. Evaluations were performed on the 6th day.

Results: Administration of L-744,832, neither alone nor its combination with 5-FU and radiation, affected the number of DLD-1 cells and apoptosis rates. Regarding its effects on the cell cycle, L-744,832 was shown to lead to G(0)/G(1) and G(2)/M accumulation in a dose-dependent manner when administered alone. However, in combination with 5-FU, only a G(0)/G(1) accumulation was observed.

Conclusion: Our study showed that FTI L-744,832 does not effect the cell number and apoptosis rate of DLD-1 cells and it cannot overcome 5-FU and radiation resistance, although it is able to modify some phases of the cell cycle.
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http://dx.doi.org/10.1159/000088954DOI Listing
October 2005

Malignant fibrous histiocytoma of the thyroid gland: recurrence treated by radiotherapy.

J Otolaryngol 2005 Jun;34(3):216-20

Department of Radiation Oncology, Karadeniz Technical University School of Medicine, Trabzon, Turkey.

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http://dx.doi.org/10.2310/7070.2005.04002DOI Listing
June 2005

Thymic carcinoma in children.

Pediatr Blood Cancer 2006 Aug;47(2):224-7

Department of Pediatric Oncology, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey.

Thymic epithelial neoplasms consist of thymomas, thymic carcinoids, and thymic carcinomas. Carcinomas are malignant tumors of the thymus characterized by obvious cytological anaplasia. They constitute only 4%-14% of thymic epithelial neoplams. Thymic carcinoma rarely occurs in children. Research in the English literature carried out for the present study revealed only 14 cases younger than 18 years-of-age. Here we have reported a 16-year old girl who presented with respiratory distress due to huge anterior mediastinal mass. Histological and immunohistochemical studies confirmed lymphoepithelioma-like thymic carcinoma. She received systemic chemotherapy and radiotherapy. However, she died within 15 months due to progressive disease.
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http://dx.doi.org/10.1002/pbc.20468DOI Listing
August 2006

Primary cerebral neuroblastoma: a case treated with adjuvant chemotherapy and radiotherapy.

Turk J Pediatr 2004 Apr-Jun;46(2):182-5

Department of Pediatric Oncology, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey.

Neuroblastoma is the most common extracranial solid tumor of childhood. A wide variety of tumor locations and clinical presentations have been described. However, neuroblastoma is rarely located in the central nervous system, except in the case of esthesioneuroblastoma. We report a child with primary central nervous system (CNS) neuroblastoma who admitted to the hospital in coma. The tumor could be partially removed in our patient. After surgery, we treated the patient successfully with combined radiotherapy and eight courses of cisplatin-based chemotherapy. Our patient was followed-up for 34 months without any evidence of relapse.
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August 2004

Protective effect of melatonin against fractionated irradiation-induced epiphyseal injury in a weanling rat model.

J Pineal Res 2003 Nov;35(4):288-94

Department of Radiation Oncology, Karadeniz Technical University School of Medicine, Trabzon, Turkey.

The effects of melatonin, a free-radical scavenger and a general antioxidant, on radiation-induced growth plate injury have not been studied previously. The purpose of this study was to determine the potential benefits of sparing longitudinal bone growth by fractionated radiotherapy alone compared with pretreatment with melatonin that provides differential radioprotection of normal cells. Weanling 4-wk-old (75-100 g) male Sprague-Dawley rats were randomly assigned to one of three groups: Group R received fractionated radiation alone (n = 8); groups M5 (n = 8) and M15 (n = 7) received 5 or 15 mg/kg melatonin prior to fractionated radiation, respectively. The distal femur and proximal tibia in the right leg of each animal were exposed to a therapeutic X-irradiation dose (25 Gy total in three fractions) with the contralateral left leg as the non-irradiated control. Melatonin was administered intraperitoneally to the animals 30 min before radiation exposure. Six weeks after treatment, the rats were killed and the lower limbs disarticulated, skeletonized, radiographed, and bone growth was calculated based on measurement of the bone lengths. Fractionated radiation resulted in a mean percent overall limb growth loss of 41.2 +/- 9.5 and a mean percent overall limb discrepancy of 11.2 +/- 2.2. The administration of 5 or 15 mg/kg melatonin before each of the three fractions of radiotherapy reduced the mean percent overall limb growth loss to 33.9 +/- 5.8 and 32.2 +/- 4.5, respectively, and the mean percent overall limb discrepancy to 9.4 +/- 1.6 and 8.9 +/- 1.1, respectively; these values were significantly different compared with irradiation alone (range: P = 0.01-0.04). When compared with Group R, the growth arrest recovered by 5 or 15 mg/kg melatonin was 19.7 and 24.1% for the tibia, 7 and 18.6% for the femur, and 17.7 and 21.8% for the total limb, respectively. These results support further investigation of melatonin in combination with fractionation for potential use in growing children requiring radiotherapy to the extremity for malignant tumors.
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http://dx.doi.org/10.1034/j.1600-079x.2003.00089.xDOI Listing
November 2003

Accelerated superfractionated radiotherapy with concomitant boost for invasive bladder cancer.

Int J Radiat Oncol Biol Phys 2003 Jul;56(3):734-45

Department of Radiation Oncology, Karadeniz Technical University School of Medicine, Trabzon, Turkey.

Purpose: To determine the toxicity and clinical effectiveness of accelerated superfractionated radiotherapy with delayed concomitant boost (ASCBRT) in locally invasive carcinoma of the bladder.

Methods And Materials: Between July 1997 and December 2001, 87 patients (unsuitable or refusing cystectomy) with invasive bladder cancer underwent ASCBRT. The mean patient age was 66 years (range 40-90). The stage distribution was as follows: 2 T1, 51 T2, 13 T3, and 21 T4. Initially, the whole pelvis was treated by 1.8-Gy conventional daily fractions up to a total dose of 45 Gy. A small field boost covering gross disease was added as a second daily fraction (1.5 Gy) during the last 3 weeks of the 5-week schedule up to a total dose of 67.5 Gy. The interfraction interval was a minimum of 6 h. The patients were evaluated in follow-up for toxicity, local control, and survival.

Results: All but 2 patients completed the study protocol. Grade 3 acute urinary toxicity was observed in 2 patients. Grade 2 and 3 late bladder toxicity was observed in 12 patients and 1 patient, respectively. Grade 2 and 3 late bowel toxicity was observed in 5 and 3 patients, respectively. The 3-year actuarial local control, distant disease control, cause-specific survival, and overall survival rate was 64%, 78%, 58%, and 46%, respectively. Multivariate analysis revealed T stage as independent predictor of complete response. For Stage T2 and T3, the 3-year local control rate was 77% and 48%, respectively. At the last follow-up, 53 patients (61%) were still alive with a survival time between 6 and 62 months.

Conclusion: ASCBRT is feasible with acceptable tolerance even in relatively old patients with Stage T3 or greater tumor. The encouraging locoregional control and survival results of this institutional experience, favorable compared with conventional radical and other accelerated fractionated (with or without a concomitant boost) RT series, make ASCBRT worthy of further study in a Phase III trial.
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http://dx.doi.org/10.1016/s0360-3016(03)00111-1DOI Listing
July 2003

Correlation of serum IL-2, IL-6 and IL-10 levels with International Prognostic Index in patients with aggressive non-Hodgkin's lymphoma.

Am J Clin Oncol 2002 Dec;25(6):570-2

Department of Medical Oncology, Karadeniz Technical University School of Medicine, Trabzon, Turkey.

Cytokines play important roles in the pathogenesis of lymphomas. The aim of this study was to determine the relations between serum levels of interleukin-2 (IL-2), IL-6, and IL-10 and parameters of International Prognostic Index (IPI). Serum levels of IL-2, IL-6, and IL-10 were measured using a sensitive enzyme-linked immunosorbent assay in the pretreatment frozen sera from 43 patients with non-Hodgkin's lymphoma. The patients we included in the study were divided into two groups, one with high risk and the other with low risk according to the IPI in regard to their ages, stages, performance status, extranodal involvements, and serum levels of lactate dehydrogenase. In the high-risk group, serum levels of IL-2 (0.852 +/- 0.268 ng/ml), IL-6 (0.461 +/- 0.206 ng/ml), and IL-10 (0.816 +/- 0.240 ng/ml) were found to be higher than serum levels of IL-2 (0.667 +/- 0.170 ng/ml), IL-6 (0.355 +/- 0.075 ng/ml), and IL-10 (0.643+0.177 ng/ml) in the low-risk group ( < 0.05). There was a correlation between the patients with high risk according to the IPI criteria and high levels of serum cytokines (IL-2, IL-6, IL-10). Knowledge of the serum levels of these cytokines in patients with newly diagnosed aggressive non-Hodgkin's lymphoma may help us to have some information about the possible prognosis, the activation of disease, and to decide on appropriate therapeutic approaches for individual patients.
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http://dx.doi.org/10.1097/00000421-200212000-00007DOI Listing
December 2002

The efficacy of octreotide in the therapy of acute radiation-induced diarrhea: a randomized controlled study.

Int J Radiat Oncol Biol Phys 2002 Sep;54(1):195-202

Department of Radiation Oncology, School of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey.

Purpose: Although the somatostatin analog octreotide is currently used in the treatment of chemotherapy-induced diarrhea and secretory diarrhea associated with various disorders, its role in the management of radiation enteritis is not well defined. We performed a randomized study that compared octreotide acetate with diphenoxylate hydrochloride plus atropine sulfate, the drug commonly used as therapy for acute radiation-induced diarrhea (ARID).

Methods And Materials: Sixty-one patients with Grade 2 (four to six stools per day) or Grade 3 (> or = seven stools per day, National Cancer Institute Common Toxicity Criteria) diarrhea associated with pelvic radiotherapy were assigned randomly to receive octreotide s.c., 100 microg three times daily (n = 33) or diphenoxylate and atropine orally, 2.5 mg four times daily (n = 28). Radiotherapy was delivered to all patients in a conventional manner, with high-energy photons in a total dose > or =45 Gy, which exceeds the tolerance of intestine. Overall, there was no significant difference in patient characteristics or radiotherapy applied between the two arms. Patients were evaluated daily for the primary study end point, resolution of diarrhea, as well as for interruption of pelvic radiotherapy.

Results: Within 3 days, ARID completely resolved in 20 patients in the octreotide arm (2 within the first day, 11 within the second day, and 7 within the third day) vs. only 4 (all within the second day of therapy) in the diphenoxylate arm (p = 0.002). On the diphenoxylate arm, 15/28 patients were required to discontinue pelvic radiotherapy; on the octreotide arm, 6/33 patients were required to discontinue pelvic radiotherapy for an average of 1.89 +/- 0.5 and 0.45 +/- 0.2 days, respectively (p = 0.003). No side effects were observed in either arm. Three patients on the diphenoxylate arm and only 1 on the octreotide arm required further treatment for parenteral replenishment of fluids and electrolytes or other antidiarrheal treatments.

Conclusion: Octreotide seems to be more effective than conventional therapy with diphenoxylate and atropine in controlling ARID and eliminating the need for radiotherapy interruptions.
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http://dx.doi.org/10.1016/s0360-3016(02)02870-5DOI Listing
September 2002

Primary intraspinal primitive neuroectodermal tumor: case report of a tumor arising from the sacral spinal nerve root and review of the literature.

Am J Clin Oncol 2002 Apr;25(2):135-9

Department of Radiation Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.

Primary spinal primitive neuroectodermal tumor (PNET) is a rare condition, 18 cases of which have been reported in the literature. In general, this tumor is treated with surgery followed by radiotherapy and chemotherapy, but prognosis is still poor. An 18-year-old female patient with an intradural, extramedullary mass at L3-L5 levels is presented in this report. This is the first female patient with primary spinal PNET at lumbar region, second patient with spinal nerve root origin, and third one with intradural, extramedullary localization ever reported in the literature. After surgery, she was treated with craniospinal radiotherapy and four cycles of combination chemotherapy regimen consisting of vincristine, cyclophosphamide, doxorubicin alternated with ifosfamide, and VP-16. Currently, she is asymptomatic and alive at 25 months. The histopathologic, radiologic, and clinical findings of the patient are presented and relevant literature is reviewed.
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http://dx.doi.org/10.1097/00000421-200204000-00007DOI Listing
April 2002
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