Publications by authors named "Ufuk Abacioglu"

43 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

Magnetic resonance image-guided adaptive stereotactic body radiotherapy for prostate cancer: preliminary results of outcome and toxicity.

Br J Radiol 2021 Jan 29;94(1117):20200696. Epub 2020 Oct 29.

Department of Radiation Oncology, Acıbadem MAA University School of Medicine, Istanbul, Turkey.

Objective: Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. We present our preliminary results on the clinical utilization of MRI-guided adaptive radiotherapy (MRgRT) for prostate cancer patients with the workflow, dosimetric parameters, toxicities and prostate-specific antigen (PSA) response.

Methods: 50 prostate cancer patients treated with ultra-hypofractionation were included in the study. Treatment was performed with intensity-modulated radiation therapy (step and shoot) technique and daily plan adaptation using MRgRT. The SBRT consisted of 36.25 Gy in 5 fractions with a 7.25 Gy fraction size. The time for workflow steps was documented. Patients were followed for the acute and late toxicities and PSA response.

Results: The median follow-up for our cohort was 10 months (range between 3 and 29 months). The median age was 73.5 years (range between 50 and 84 years). MRgRT was well tolerated by all patients. Acute genitourinary (GU) toxicity rate of Grade 1 and Grade 2 was 28 and 36%, respectively. Only 6% of patients had acute Grade 1 gastrointestinal (GI) toxicity and there was no Grade ≥ 2 GI toxicity. To date, late Grade 1 GU toxicity was experienced by 24% of patients, 2% of patients experienced Grade 2 GU toxicity and 6% of patients reported Grade 2 GI toxicity. Due to the short follow-up, PSA nadir has not been reached yet in our cohort.

Conclusion: In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation has an acceptable acute and very low late toxicity profile.

Advances In Knowledge: MRgRT represents a new markerless method for delivering SBRT for localized prostate cancer providing online adaptive planning and real-time tracking and acute and late toxicity profile is acceptable.
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http://dx.doi.org/10.1259/bjr.20200696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774684PMC
January 2021

Prognostic factors in medically inoperable early stage lung cancer patients treated with stereotactic ablative radiation therapy (SABR): Turkish Radiation Oncology Society Multicentric Study.

Clin Respir J 2020 Nov 17;14(11):1050-1059. Epub 2020 Aug 17.

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

Objective: We identified factors influencing outcomes in patients with medically inoperable early stage lung cancer (MIESLC) treated with stereotactic ablative radiation therapy (SABR) at 14 centers in Turkey.

Materials And Methods: We retrospectively analyzed 431 patients with stage I-II MIESLC treated with SABR from 2009 through 2017. Age; sex; performance score; imaging technique; tumor histology and size; disease stage radiation dose, fraction and biologically effective dose with an α/β ratio of 10 (BED ); tumor location and treatment center were evaluated for associations with overall survival (OS), local control (LC) and toxicity.

Results: Median follow-up time was 27 months (range 1-115); median SABR dose was 54 Gy (range 30-70) given in a median three fractions (range 1-10); median BED was 151 Gy (range 48-180). Tumors were peripheral in 285 patients (66.1%), central in 69 (16%) and <1 cm from mediastinal structures in 77 (17.9%). Response was evaluated with PET/CT in most cases at a median 3 months after SABR. Response rates were: 48% complete, 36.7% partial, 7.9% stable and 7.4% progression. LC rates were 97.1% at 1 year, 92.6% at 2 years and 91.2% at 3 years; corresponding OS rates were 92.6%, 80.6% and 72.7%. On multivariate analysis, BED > 100 Gy (P = .011), adenocarcinoma (P = .025) and complete response on first evaluation (P = .007) predicted favorable LC. BED > 120 Gy (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.1-3.2, P = .019) and tumor size (<2 cm HR 1.9, 95% CI 1.3-3, P = .003) predicted favorable OS. No grade 4-5 acute side effects were observed; late effects were grade ≤3 pneumonitis (18 [4.2%]), chest wall pain (11 [2.5%]) and rib fracture (1 [0.2%]).

Conclusion: SABR produced encouraging results, with satisfactory LC and OS and minimal toxicity. BED > 120 Gy was needed for better LC and OS for large, non-adenocarcinoma tumors.
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http://dx.doi.org/10.1111/crj.13240DOI Listing
November 2020

Urethra-Sparing Stereotactic Body Radiation Therapy for Prostate Cancer: Quality Assurance of a Randomized Phase 2 Trial.

Int J Radiat Oncol Biol Phys 2020 11 12;108(4):1047-1054. Epub 2020 Jun 12.

Radiation Oncology, University Hospital of Geneva, Geneva, Switzerland; Faculty of Medicine, Geneva University, Geneva, Switzerland; Radiation Oncology, Teknon Oncologic Institute, Barcelona, Spain.

Purpose: To present the radiation therapy quality assurance results from a prospective multicenter phase 2 randomized trial of short versus protracted urethra-sparing stereotactic body radiation therapy (SBRT) for localized prostate cancer.

Methods And Materials: Between 2012 and 2015, 165 patients with prostate cancer from 9 centers were randomized and treated with SBRT delivered either every other day (arm A, n = 82) or once a week (arm B, n = 83); 36.25 Gy in 5 fractions were prescribed to the prostate with (n = 92) or without (n = 73) inclusion of the seminal vesicles (SV), and the urethra planning-risk volume received 32.5 Gy. Patients were treated either with volumetric modulated arc therapy (VMAT; n = 112) or with intensity modulated radiation therapy (IMRT; n = 53). Deviations from protocol dose constraints, planning target volume (PTV) homogeneity index, PTV Dice similarity coefficient, and number of monitor units for each treatment plan were retrospectively analyzed. Dosimetric results of VMAT versus IMRT and treatment plans with versus without inclusion of SV were compared.

Results: At least 1 major protocol deviation occurred in 51 patients (31%), whereas none was observed in 41. Protocol violations were more frequent in the IMRT group (P < .001). Furthermore, the use of VMAT yielded better dosimetric results than IMRT for urethra planning-risk volume D (31.1 vs 30.8 Gy, P < .0001), PTV D (37.9 vs 38.7 Gy, P < .0001), homogeneity index (0.09 vs 0.10, P < .0001), Dice similarity coefficient (0.83 vs 0.80, P < .0001), and bladder wall V (24.5% vs 33.5%, P = .0001). To achieve its goals volumetric modulated arc therapy required fewer monitor units than IMRT (2275 vs 3378, P <.0001). The inclusion of SV in the PTV negatively affected the rectal wall V (9.1% vs 10.4%, P = .0003) and V (13.2% vs 15.7%, P = .0003).

Conclusions: Protocol deviations with potential impact on tumor control or toxicity occurred in 31% of patients in this prospective clinical trial. Protocol deviations were more frequent with IMRT. Prospective radiation therapy quality assurance protocols should be strongly recommended for SBRT trials to minimize potential protocol deviations.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.002DOI Listing
November 2020

Once-a-week or every-other-day urethra-sparing prostate cancer stereotactic body radiotherapy, a randomized phase II trial: 18 months follow-up results.

Cancer Med 2020 05 11;9(9):3097-3106. Epub 2020 Mar 11.

Geneva University Hospital, Geneva, Switzerland.

Background: To present the 18 months results from a prospective multicenter phase II randomized trial of short vs protracted urethra-sparing stereotactic body radiotherapy (SBRT) for localized prostate cancer (PCa).

Methods: Between 2012 and 2015, a total of 170 PCa patients were randomized to 36.25 Gy in 5 fractions (6.5 Gy × 5 to the urethra) delivered either every other day (EOD, arm A, n = 84) or once a week (QW, arm B, n = 86). Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.0 scale), IPSS, and QoL scores were assessed at baseline, at the 5th fraction (5fx), 12th weeks (12W), and every 6 months after SBRT. The primary endpoint was biochemical control at 18 months and grade ≥ 3 toxicity (including grade ≥ 2 for urinary obstruction/retention) during the first 3 months.

Results: Among the 165 patients analyzed, the toxicity stopping rule was never activated during the acute phase. Maximum acute grade 2 GU toxicity rates at 5fx were 17% and 19% for arms A and B, respectively, with only 2 cases of grade 2 GI toxicity at 5fx in arm A. At month 18, grade ≥ 2 GU and GI toxicity decreased below 5% and 2% for both arms. No changes in EORTC QLQ-PR25 scores for GU, GI, and sexual domains were observed in both arms between baseline and month 18. Four biochemical failures were observed, 2 in each arm, rejecting the null hypothesis of an unfavorable response rate ≤ 85% in favor of an acceptable ≥ 95% rate.

Conclusions: At 18 months, urethra-sparing SBRT showed a low toxicity profile, with minimal impact on QoL and favorable biochemical control rates, regardless of overall treatment time (EOD vs QW).
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http://dx.doi.org/10.1002/cam4.2966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196054PMC
May 2020

Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO).

Neuro Oncol 2017 02;19(2):162-174

Department of Neurology, University Hospital Zurich, Zurich, Switzerland.

The management of patients with brain metastases has become a major issue due to the increasing frequency and complexity of the diagnostic and therapeutic approaches. In 2014, the European Association of Neuro-Oncology (EANO) created a multidisciplinary Task Force to draw evidence-based guidelines for patients with brain metastases from solid tumors. Here, we present these guidelines, which provide a consensus review of evidence and recommendations for diagnosis by neuroimaging and neuropathology, staging, prognostic factors, and different treatment options. Specifically, we addressed options such as surgery, stereotactic radiosurgery/stereotactic fractionated radiotherapy, whole-brain radiotherapy, chemotherapy and targeted therapy (with particular attention to brain metastases from non-small cell lung cancer, melanoma and breast and renal cancer), and supportive care.
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http://dx.doi.org/10.1093/neuonc/now241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620494PMC
February 2017

Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology.

Lancet Oncol 2015 Jul;16(7):e322-32

Department of Neurology, University Hospital Zürich, Zürich, Switzerland.

The management of primary CNS lymphoma is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the very few controlled studies available. In 2013, the European Association of Neuro-Oncology created a multidisciplinary task force to establish evidence-based guidelines for immunocompetent adults with primary CNS lymphoma. In this Review, we present these guidelines, which provide consensus considerations and recommendations for diagnosis, assessment, staging, and treatment of primary CNS lymphoma. Specifically, we address aspects of care related to surgery, systemic and intrathecal chemotherapy, intensive chemotherapy with autologous stem-cell transplantation, radiotherapy, intraocular manifestations, and management of elderly patients. The guidelines should aid clinicians in their daily practice and decision making, and serve as a basis for future investigations in neuro-oncology.
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http://dx.doi.org/10.1016/S1470-2045(15)00076-5DOI Listing
July 2015

Treatment of early stage non-small cell lung cancer: surgery or stereotactic ablative radiotherapy?

Balkan Med J 2015 Jan 1;32(1):8-16. Epub 2015 Jan 1.

Department of Radiation Oncology, Neolife Medical Center, İstanbul, Turkey.

The management of early-stage Non-small Cell Lung Cancer (NSCLC) has improved recently due to advances in surgical and radiation modalities. Minimally-invasive procedures like Video-assisted thoracoscopic surgery (VATS) lobectomy decreases the morbidity of surgery, while the numerous methods of staging the mediastinum such as endobronchial and endoscopic ultrasound-guided biopsies are helping to achieve the objectives much more effectively. Stereotactic Ablative Radiotherapy (SABR) has become the frontrunner as the standard of care in medically inoperable early stage NSCLC patients, and has also been branded as tolerable and highly effective. Ongoing researches using SABR are continuously validating the optimal dosing and fractionation schemes, while at the same time instituting its role for both inoperable and operable patients.
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http://dx.doi.org/10.5152/balkanmedj.2015.15553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342143PMC
January 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

Critical appraisal of RapidArc radiosurgery with flattening filter free photon beams for benign brain lesions in comparison to GammaKnife: a treatment planning study.

Radiat Oncol 2014 May 21;9:119. Epub 2014 May 21.

Medical Physics Unit, Oncology Institute of Southern Switzerland, 6504 Bellinzona, Switzerland.

Background: To evaluate the role of RapidArc (RA) for stereotactic radiosurgery (SRS) of benign brain lesions in comparison to GammaKnife (GK) based technique.

Methods: Twelve patients with vestibular schwannoma (VS, n = 6) or cavernous sinus meningioma (CSM, n = 6) were planned for both SRS using volumetric modulated arc therapy (VMAT) by RA. 104 MV flattening filter free photon beams with a maximum dose rate of 2400 MU/min were selected. Data were compared against plans optimised for GK. A single dose of 12.5 Gy was prescribed. The primary objective was to assess treatment plan quality. Secondary aim was to appraise treatment efficiency.

Results: For VS, comparing best GK vs. RA plans, homogeneity was 51.7 ± 3.5 vs. 6.4 ± 1.5%; Paddick conformity Index (PCI) resulted 0.81 ± 0.03 vs. 0.84 ± 0.04. Gradient index (PGI) was 2.7 ± 0.2 vs. 3.8 ± 0.6. Mean target dose was 17.1 ± 0.9 vs. 12.9 ± 0.1 Gy. For the brain stem, D(1cm3) was 5.1 ± 2.0 Gy vs 4.8 ± 1.6 Gy. For the ipsilateral cochlea, D(0.1cm3) was 1.7 ± 1.0 Gy vs. 1.8 ± 0.5 Gy. For CSM, homogeneity was 52.3 ± 2.4 vs. 12.4 ± 0.6; PCI: 0.86 ± 0.05 vs. 0.88 ± 0.05; PGI: 2.6 ± 0.1 vs. 3.8 ± 0.5; D(1cm3) to brain stem was 5.4 ± 2.8 Gy vs. 5.2 ± 2.8 Gy; D(0.1cm3) to ipsi-lateral optic nerve was 4.2 ± 2.1 vs. 2.1 ± 1.5 Gy; D(0.1cm3) to optic chiasm was 5.9 ± 3.1 vs. 4.5 ± 2.1 Gy. Treatment time was 53.7 ± 5.8 (64.9 ± 24.3) minutes for GK and 4.8 ± 1.3 (5.0 ± 0.7) minutes for RA for schwannomas (meningiomas).

Conclusions: SRS with RA and FFF beams revealed to be adequate and comparable to GK in terms of target coverage, homogeneity, organs at risk sparing with some gain in terms of treatment efficiency.
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http://dx.doi.org/10.1186/1748-717X-9-119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038714PMC
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

A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results.

J Clin Oncol 2013 Jan 3;31(1):65-72. Epub 2012 Dec 3.

University of Torino and San Giovanni Battista Hospital, Turin, Italy.

Purpose: This phase III trial compared adjuvant whole-brain radiotherapy (WBRT) with observation after either surgery or radiosurgery of a limited number of brain metastases in patients with stable solid tumors. Here, we report the health-related quality-of-life (HRQOL) results.

Patients And Methods: HRQOL was a secondary end point in the trial. HRQOL was assessed at baseline, at 8 weeks, and then every 3 months for 3 years with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and Brain Cancer Module. The following six primary HRQOL scales were considered: global health status; physical, cognitive, role, and emotional functioning; and fatigue. Statistical significance required P ≤ .05, and clinical relevance required a ≥ 10-point difference.

Results: Compliance was 88.3% at baseline and dropped to 45.0% at 1 year; thus, only the first year was analyzed. Overall, patients in the observation only arm reported better HRQOL scores than did patients who received WBRT. The differences were statistically significant and clinically relevant mostly during the early follow-up period (for global health status at 9 months, physical functioning at 8 weeks, cognitive functioning at 12 months, and fatigue at 8 weeks). Exploratory analysis of all other HRQOL scales suggested worse scores for the WBRT group, but none was clinically relevant.

Conclusion: This study shows that adjuvant WBRT after surgery or radiosurgery of a limited number of brain metastases from solid tumors may negatively impact some aspects of HRQOL, even if these effects are transitory. Consequently, observation with close monitoring with magnetic resonance imaging (as done in the EORTC trial) is not detrimental for HRQOL.
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http://dx.doi.org/10.1200/JCO.2011.41.0639DOI Listing
January 2013

Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial.

Lancet Oncol 2012 Sep 8;13(9):916-26. Epub 2012 Aug 8.

Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Unit of Advanced Palliative Home Care, County Council of Östergötland, Linköping, Sweden.

Background: Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma.

Methods: Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34·0 Gy administered in 3·4 Gy fractions over 2 weeks), or standard radiotherapy (60·0 Gy administered in 2·0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623.

Findings: 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8·3 months [95% CI 7·1-9·5; n=93] vs 6·0 months [95% CI 5·1-6·8; n=100], hazard ratio [HR] 0·70; 95% CI 0·52-0·93, p=0·01), but not with hypofractionated radiotherapy (7·5 months [6·5-8·6; n=98], HR 0·85 [0·64-1·12], p=0·24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8·4 months [7·3-9·4; n=119] vs 7·4 months [6·4-8·4; n=123]; HR 0·82, 95% CI 0·63-1·06; p=0·12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0·35 [0·21-0·56], p<0·0001; HR for hypofractionated vs standard radiotherapy 0·59 [95% CI 0·37-0·93], p=0·02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9·7 months [95% CI 8·0-11·4] vs 6·8 months [5·9-7·7]; HR 0·56 [95% CI 0·34-0·93], p=0·02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0·97 [95% CI 0·69-1·38]; p=0·81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed.

Interpretation: Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.

Funding: Merck, Lion's Cancer Research Foundation, University of Umeå, and the Swedish Cancer Society.
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http://dx.doi.org/10.1016/S1470-2045(12)70265-6DOI Listing
September 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

Concomitant chemoradiotherapy with low-dose weekly gemcitabine for nonmetastatic unresectable pancreatic cancer.

Turk J Gastroenterol 2011 Feb;22(1):60-4

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

Background/aims: This study aimed to demonstrate the efficacy and tolerability of low-dose weekly gemcitabine as a radiosensitizer in unresectable pancreatic cancer patients treated with chemoradiotherapy.

Methods: Twenty-four histologically confirmed pancreatic carcinoma patients (female/male: 10/14, median age: 60) were evaluated. Seven (29%) patients received gemcitabine either as a single agent or in combination prior to chemoradiotherapy. Concurrent 75 mg/m2 gemcitabine was infused weekly. Radiotherapy was delivered to the primary tumor and positive lymphatics with 3D-conformal radiotherapy to a total dose of 4500 cGy. Local progression-free survival, distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier method.

Results: Median follow-up was 36 weeks. Median local progression-free survival, distant metastasis-free survival and overall survival were 22 weeks (95% confidence interval [CI]: 5-59 weeks), 19 weeks (95%CI: 6.9-31 weeks) and 36 weeks (95%CI: 28-43 weeks), respectively. All patients completed radiotherapy as scheduled. Concurrent gemcitabine was given fully in 58.3% of patients. Gemcitabine was terminated in four (16.6%) patients due to grade 3 neutropenia (n=1), grade 3 nausea/vomiting (n=2) or patient's reluctance (n=1). Patients with local response and stable disease to chemoradiotherapy revealed a median survival of 39 weeks (95%CI: 30-47.9 weeks) compared to 36 weeks (95%CI: 9.7-62.2 weeks) in patients with locally progressive disease (p=0.52). Pain was improved in 50% of patients.

Conclusions: Weekly low-dose radiosensitizing gemcitabine is effective and safe in unresectable pancreatic cancer patients.
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http://dx.doi.org/10.4318/tjg.2011.0158DOI Listing
February 2011

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

Information for decision making by patients with early-stage prostate cancer: a comparison across 9 countries.

Med Decis Making 2011 Sep-Oct;31(5):754-66. Epub 2011 Jan 27.

Klinik fu¨ r Strahlentherapie, Magdeburg, Germany (HW)

Purpose: To describe decisional roles of patients with early-stage prostate cancer in 9 countries and to compare the information they rated important for decision making (DM).

Method: A survey of recently treated patients was conducted in Canada, Italy, England, Germany, Poland, Portugal, Netherlands, Spain, and Turkey. Participants indicated their decisional role in their actual decision and the role they would prefer now. Each participant also rated (essential/desired/no opinion/avoid) the importance of obtaining answers, between diagnosis and treatment decision, to each of 92 questions. For each essential/desired question, participants specified all purposes for that information (to help them: understand/decide/plan/not sure/other).

Results: A total of 659 patients participated with country-specific response rates between 58%-77%. Between 83%-96% of each country's participants recalled actually taking an active decisional role and, in most countries, that increased slightly if they were to make the decision today; there were no significant differences among countries. There was a small reliable difference in the mean number of questions rated essential for DM across countries. More striking, however, was the wide variability within each country: no question was rated essential for DM by even 50% of its participants but almost every question was rated essential by some.

Conclusions: Almost all participants from each country want to participate in their treatment decisions. Although there are country-specific differences in the amount of information required, wide variation within each country suggests that information that patients feel is essential or desired for DM should be addressed on an individual basis in all countries.
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http://dx.doi.org/10.1177/0272989X10395029DOI Listing
January 2012

Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study.

J Clin Oncol 2011 Jan 1;29(2):134-41. Epub 2010 Nov 1.

University of Cologne, Cologne, Germany.

Purpose: This European Organisation for Research and Treatment of Cancer phase III trial assesses whether adjuvant whole-brain radiotherapy (WBRT) increases the duration of functional independence after surgery or radiosurgery of brain metastases.

Patients And Methods: Patients with one to three brain metastases of solid tumors (small-cell lung cancer excluded) with stable systemic disease or asymptomatic primary tumors and WHO performance status (PS) of 0 to 2 were treated with complete surgery or radiosurgery and randomly assigned to adjuvant WBRT (30 Gy in 10 fractions) or observation (OBS). The primary end point was time to WHO PS deterioration to more than 2.

Results: Of 359 patients, 199 underwent radiosurgery, and 160 underwent surgery. In the radiosurgery group, 100 patients were allocated to OBS, and 99 were allocated to WBRT. After surgery, 79 patients were allocated to OBS, and 81 were allocated to adjuvant WBRT. The median time to WHO PS more than 2 was 10.0 months (95% CI, 8.1 to 11.7 months) after OBS and 9.5 months (95% CI, 7.8 to 11.9 months) after WBRT (P = .71). Overall survival was similar in the WBRT and OBS arms (median, 10.9 v 10.7 months, respectively; P = .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%, P < .001; radiosurgery: 31% to 19%, P = .040) and at new sites (surgery: 42% to 23%, P = .008; radiosurgery: 48% to 33%, P = .023). Salvage therapies were used more frequently after OBS than after WBRT. Intracranial progression caused death in 78 (44%) of 179 patients in the OBS arm and in 50 (28%) of 180 patients in the WBRT arm.

Conclusion: After radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.
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http://dx.doi.org/10.1200/JCO.2010.30.1655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058272PMC
January 2011

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

Outcomes of gamma knife treatment for solid intracranial hemangioblastomas.

J Clin Neurosci 2010 Jun 19;17(6):706-10. Epub 2010 Mar 19.

Department of Neurosurgery, Selcuklu Medical Faculty, Selcuk University, Konya, Turkey.

The aim of this study was to examine the results of gamma knife radiosurgery for 13 patients with residual/recurrent or newly diagnosed solid hemangioblastomas. The 13 patients had 34 solid hemangioblastomas, and all patients underwent gamma knife radiosurgery. Seven patients had von Hippel-Lindau disease and six had sporadic disease. When individual lesions were considered, the overall mean dose at the tumor periphery was 15.8 Gy (range: 12-25 Gy) and the average maximum tumor dose was 31.6 Gy (range: 24-50 Gy). The mean duration of follow-up with MRI was 50.2 months. At the last follow-up evaluation, growth control was achieved for all tumors (partial remission in three tumors [8.8%] and no change in 31 tumors [91.2%]). No radiation-related complications were encountered. Our findings reinforce the view that gamma knife radiosurgery is effective and safe for the management of solid hemangioblastomas with a diameter less than 3 cm, whether they are sporadic or associated with von Hippel-Lindau disease. The high response rate and lack of any radiation-induced side-effects confirms the suitability of the doses used in the present study.
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http://dx.doi.org/10.1016/j.jocn.2009.09.028DOI Listing
June 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

Gamma knife stereotactic radiosurgery yields good long-term outcomes for low-volume uveal melanomas without intraocular complications.

J Clin Neurosci 2010 Apr 2;17(4):441-5. Epub 2010 Feb 2.

Laboratory of Molecular Neurosurgery, Institute of Neurological Sciences, Marmara University, PK 53 Maltepe 34853, Istanbul, Turkey.

We present the outcomes of 35 uveal melanoma patients treated with gamma knife stereotactic radiosurgery. All cases were previously untreated. During follow-up, regular MRI examinations were used to detect any changes in tumor size and estimate the local long-term tumor control rate. Treatment-related complications were also recorded. During follow-up, systemic dissemination was observed in two patients, one of whom died of metastases. The most frequent complication was retinal detachment (17.1%). Three patients required enucleation. Cumulative 1-year and 3-year local tumor growth control rates were 97% and 83%, respectively. The mean and median times to local tumor progression were 48.0 and 51.7 months, respectively. Gamma knife surgery may be a suitable alternative for the treatment of low-volume uveal tumors without intraocular complications, as the control rate and long-term outcomes compare favorably with those of surgical excision and brachytherapy.
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http://dx.doi.org/10.1016/j.jocn.2009.08.004DOI Listing
April 2010

Information needs of early-stage prostate cancer patients: a comparison of nine countries.

Radiother Oncol 2010 Mar 28;94(3):328-33. Epub 2010 Jan 28.

Division of Cancer Care and Epidemiology, Queen's University, Kingston, Canada.

Background And Purpose: Providing information to patients can improve their medical and psychological outcomes. We sought to identify core information needs common to most early-stage prostate cancer patients in participating countries.

Material And Methods: Convenience samples of patients treated 3-24 months earlier were surveyed in Canada, England, Italy, Germany, Poland, Portugal, Netherlands, Spain, and Turkey. Each participant rated the importance of addressing each of 92 questions in the diagnosis-to-treatment decision interval (essential/desired/no opinion/avoid). Multivariate modelling determined the extent of variance accounted by covariates, and produced an unbiased prediction of the proportion of essential responses for each question.

Results: Six hundred and fifty-nine patients responded (response rates 45-77%). On average, 35-53 questions were essential within each country; similar questions were essential to most patients in most countries. Beyond cross-country similarities, each country showed wide variability in the number and which questions were essential. Multivariate modelling showed an adjusted R-squared with predictors country, age, education, and treatment group of only 6% of the variance. A core of 20 questions were predicted to be essential to >2/3 of patients.

Conclusions: Core information can be identified across countries. However, providing the core should only be a first step; each country should then provide information tailored to the needs of the individual patient.
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http://dx.doi.org/10.1016/j.radonc.2009.12.038DOI Listing
March 2010

Pulmonary toxicity in patients receiving docetaxel chemotherapy.

Med Oncol 2010 Dec 25;27(4):1381-8. Epub 2009 Dec 25.

Department of Medical Oncology, Marmara University School of Medicine, and Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey.

Pulmonary toxicity can rarely be seen with cytotoxic agents. We aimed at investigating the pulmonary toxicity of docetaxel in patients other than lung carcinoma. Forty patients were investigated prospectively. Spirometry, DLCO and high-resolution computed tomography (HRCT) scans were applied to all patients before and 14-21 days after completion of docetaxel. We used a HRCT scoring system that was based on the previous studies. We have seen no pulmonary symptoms that may reflect pulmonary toxicity. There were statistically significant differences between pre- and post-treatment values of FEV1 (L/s), FEV1/FVC (%), DLCO/VA (DLCO/L), DLCO/VA (%) (P<0.05), FEF25-75 (L/s), FEF25-75 (%) (P<0.01), DLCO (mL/mmHg/min), DLCO (%) (P<0.001), Also, there was a statistically significant difference between the pre- and post-treatment HRCT scores. There was a statistical relationship between post-treatment HRCT scores, number of docetaxel cycles (r=0.49, P<0.0001) and docetaxel cumulative dose (r=0.61, P<0.0001). Docetaxel caused a significant decline in pulmonary function tests (PFTs) and progression in HRCT scores but the symptoms of patients were not consistent with these differences. The negative effects of docetaxel on PFTs and HRCT scores should be investigated more reliably by increasing the number of patients with further studies.
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http://dx.doi.org/10.1007/s12032-009-9391-9DOI Listing
December 2010

Gamma knife radiosurgery for the treatment of glomus jugulare tumors.

J Neurooncol 2010 Mar 26;97(1):101-8. Epub 2009 Aug 26.

Department of Neurosurgery, Marmara University Medical Faculty, Istanbul, Turkey.

The treatment of glomus jugulare tumors represents a challenge for the neurosurgeon, since they invade major vessels and compress critical cranial nerves, resulting in significant morbidity from tumor resection. Among alternative and complementary treatment options, gamma knife radiosurgery is a less invasive procedure and may provide better protection of vital structures. This study aimed to evaluate the efficacy and long-term outcomes of gamma knife surgery in the treatment of these tumors in a large series with the longest follow-up period compared with previous reports. A total of 18 patients with glomus jugulare tumors that underwent gamma knife radiosurgery (GKS) were included. Eleven patients had a history of previous microsurgical treatment. The mean marginal radiation dose was 15.6 Gy (median 15 Gy, range 13-20 Gy). Patients were followed for a mean period of 52.7 months (median 41.5 months); the effect of gamma knife radiosurgery was evaluated using magnetic resonance (MR) images. Based on the last MR images, tumor control could be achieved in 17 out of 18 patients (94.4%). No complications such as radiation-induced peritumoral edema or radiation necrosis occurred. Neurological follow-up examinations revealed improved clinical status in ten patients (55.6%), stable neurological status in seven (38.9%), and deterioration in one patient (5.5%). At the last visit, 17 out of 18 patients were alive. Our results indicate that stereotactic radiosurgery is an effective and safe treatment modality in the management of glomus jugulare tumors, particularly for residual or previously untreated small tumors.
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http://dx.doi.org/10.1007/s11060-009-0002-6DOI Listing
March 2010

Curative external beam radiotherapy in patients over 80 years of age with localized prostate cancer: a retrospective rare cancer network study.

Crit Rev Oncol Hematol 2010 Apr 5;74(1):66-71. Epub 2009 May 5.

Department of Radiation Oncology, Institute Jean-Godinot, Reims, France.

Purpose: To analyse tolerance and outcome of patients over 80 years of age who choose external beam radiation therapy to the prostate as a curative treatment.

Methods And Material: We evaluated acute and late side effects, biological DFS (bDFS) and actuarial survival as well as causes of death in relation to the clinical status including co-morbidity, PSA value, Gleason score and modalities of external radiotherapy in patients with localised prostate cancer >80 years of age.

Results: From January 1990 to December 2000, 65 eligible cases (median age: 81) were treated by 12 different participating institutions in the Rare Cancer Network. Tumour stage was T1N0M0, T2N0M0 and T3N0M0 for 10, 40, and 15 patients, respectively. Median follow-up was 65 months (range 22-177). Five-year overall survival rate was 77% with a 5-year bDFS rate of 73%. The incidence of grade 3 early toxicity was 12% and 9% for urinary and digestive tract, respectively.

Conclusions: Radiation therapy given with curative intent is well tolerated in this selected group of patients aged over 80 years with localised prostate cancer. Results in terms of survival do not suggest a deleterious impact of this treatment. Therefore the authors recommend that radiation therapy with curative intent should not be withheld in selected elderly patients with localised prostate cancer.
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http://dx.doi.org/10.1016/j.critrevonc.2009.04.004DOI Listing
April 2010

Analysis of p53 gene polymorphisms and protein over-expression in patients with breast cancer.

Pathol Oncol Res 2009 Sep;15(3):359-68

Marmara University School of Medicine, Department of Medical Biology, Tibbiye Cad, No: 49, Haydarpasa, Istanbul 34668, Turkey.

p53 polymorphic variants play an important role in the determination of tumor phenotype and characteristics in breast cancer. In this study, we examined three common polymorphisms in p53 gene and their haplotype combinations to assess their potential association with inherited predisposition to breast cancer development, in relations with the protein over-expression and patients' demographic data. A total of 99 patients with breast cancer and 107 age-matched healthy controls were included in the study. Genotypes were determined using PCR-RFLP and DNA sequencing techniques. Evaluation of p53 protein over-expression was also examined by immunohistochemistry. Among three polymorphisms, increased codon 72 Pro allele frequency (p = 0.0067) and the presence of Pro allele were found to be significantly associated with breast cancer (p = 0.013). A significant risk was also found in subjects with combinations of specific haplotypes and genotypes. Most of breast cancer women especially younger than 50 years carry at least one p53 polymorphism (p = 0.001). There was no any association between these three p53 polymorphisms and the protein over-expression, separately or in interaction, with breast cancer. In conclusion, presence of proline allele at codon 72 alone, and its special combinations with other two polymorphisms appear to be a significant risk factor for breast cancer. Determination of well-known p53 polymorphisms might be a good predictor for breast cancer development especially in women younger than 50 years.
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http://dx.doi.org/10.1007/s12253-008-9129-6DOI Listing
September 2009

Outcome after combined modality treatment for uterine papillary serous carcinoma: a study by the Rare Cancer Network (RCN).

Gynecol Oncol 2008 Feb 21;108(2):298-305. Epub 2007 Dec 21.

Division of Oncology, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion, Haifa, Israel.

Objectives: Uterine papillary serous carcinoma (UPSC) is a rare subtype of endometrial carcinoma, characterized by a poor outcome. We sought to better analyze the effect of surgery and adjuvant therapies on this disease.

Methods: A retrospective analysis was performed on the records of 138 women diagnosed with UPSC between 1986 and 2003 in the framework of the Rare Cancer Network.

Results: Median age at diagnosis was 67 years. Pure UPSC was found in 107 patients and mixed histology in 30. Fifty-four patients had stage I, 20 stage II, 41 stage III and 23 stage IV disease. Median follow-up for the surviving patients was 44 months. Surgery was performed in 129 patients, after which 122 were rendered free of gross disease and comprised the adjuvant group. Of these, 23 received platinum-based chemotherapy. Radiotherapy was applied in 52 patients and 28 underwent combined chemo-radiotherapy. At last follow-up, 57 patients were alive free of disease, 10 were alive with disease, 62 died of disease, 8 died of other causes and 1 died due to toxicity. Five-year disease-free survival (DFS), disease-specific survival (DSS) and overall survival for the 122 patients treated with curative intent were 42%, 56% and 54%, respectively. In multivariate analysis, age, stage, histology and adjuvant chemotherapy were significant for DFS; age, stage and histology were significant for DSS. Radiotherapy reduced the pelvic recurrence rate from 29% to 14% (p=0.047).

Conclusions: UPSC harbours a moderate prognosis, with age, stage and histology as significant prognosticators. Conservative surgery followed by adjuvant chemotherapy and pelvic radiotherapy can be suggested as an appropriate treatment approach for patients treated with curative intent.
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http://dx.doi.org/10.1016/j.ygyno.2007.10.037DOI Listing
February 2008

Pituitary adenomas treated with gamma knife radiosurgery: volumetric analysis of 100 cases with minimum 3 year follow-up.

Neurosurgery 2007 Aug;61(2):270-80; discussion 280

Department of Neurosurgery, Gamma Knife Center, Marmara University, Istanbul, Turkey.

Objective: To analyze pituitary adenoma volume changes after gamma knife radiosurgery (GKRS) in patients with 3 years of follow-up and to investigate factors that might affect these changes.

Methods: Between January 1997 and March 2004, a total of 1930 patients were treated in the Gamma Knife Unit of the Marmara University Department of Neurosurgery in Istanbul, Turkey. Three hundred sixty of these patients had pituitary adenomas (PAs). This prospectively designed clinical study documents the radiological-volumetric analysis for the first 100 of these patients with PAs who had a minimum of 3 years of follow-up and met the study requirements. Each tumor was assessed with serial magnetic resonance imaging scans after radiosurgery; at each time point, adenoma volume was expressed as a percentage of the tumor's initial volume. Volume changes were investigated relative to margin dose, the cavernous sinus infiltration, and endocrinological type of adenoma.

Results: At the end of the first year after GKRS, the PA volumes had decreased to approximately 90% of the initial volume on average. The corresponding approximate averages for the ends of Years 2 and 3 were 80 and 70% of the initial volume, respectively. At 3 years after GKRS, the PAs in the group with a peripheral dose of less than 17 Gy were reduced to approximately 80% of the initial volume on average. In contrast, the tumors in the patients with marginal doses of 21 to 23 Gy were reduced to approximately 60% of the initial volume at this stage. The adenomas treated with the highest marginal doses (>27 Gy) showed the earliest volume decreases after GKRS (6-9 mo after the procedure). Cavernous sinus noninfiltrating adenomas showed greater volume decreases after GKRS; on average, these masses were reduced to approximately 50% of their initial volume at 3 years. In contrast, the PAs that had infiltrated the cavernous sinus had only dropped to approximately 80% of their initial volume at this stage. The growth hormone-secreting PAs showed the maximum volume decrease with GKRS. On average, these lesions were approximately 60% of their initial volume at the 3-year stage. The nonfunctioning tumors and the prolactin-secreting adenomas showed similar volume changes over time. On average, these tumors had dropped to approximately 75 and 70% of the initial volume, respectively, by 3 years after GKRS.

Conclusion: Gamma knife radiosurgery halts the growth of pituitary adenomas. Cavernous sinus extension and margin dose are the most important determinants of adenoma volume after this type of therapy.
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http://dx.doi.org/10.1227/01.NEU.0000255519.96837.C7DOI Listing
August 2007