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DemIroz C.,Uludag University | Ozkan L.,Uludag University | CebellI G.,Clinic of Radiation Oncology | Karadag O.,Uludag University | OzsahIn E.M.,University of Lausanne
Turkiye Klinikleri Journal of Medical Sciences

Objective: We aimed to investigate the effect of amifostine on acute and late side effects, and its tolerability in head and neck cancer patients treated with radiotherapy (RT). Material and Methods: The study included 87 patients with primary head and neck cancers and cervical lymph node metastases from unknown primary cancers treated with RT alone or combined with chemotherapy (CT). Forty-one patients (47%) received amifostine combined with RT (ART group) and 46 patients (52%) received RT without amifostine (RT group). The patients were evaluated every week during the treatment and at month 1 and 2 after the completion of RT for acute side effects and month 3, 6, 9, 12, and 24 after the treatment for late side effects according to SOMA/LENT scale. Amifostine was administered prior to RT, along with anti-emetic prophylaxis. The two groups were compared with the Student's t and Mann- Whitney U and Chi-square tests. Results: The ART group had significantly less toxicity (grade 1 mucositis, grade 2 fibrosis) than patients in the RT group (p=0.001, p=0.03, respectively). At week 3 of RT grade 2 mucositis developed in two patients (5%) in the ART group and 10 patients (22%) in the RT group (p=0.02). The protective effect of amifostine on skin reactions developed at week 4 of RT (p=0.05). Grade 3 xerostomia at 9, 12, and 15 months of follow-up (p=0.02, p=0.02, and p=0.02, respectively), grade 2 xerostomia at 18 and 24 months (p=0.02 and p=0.01, respectively) and fibrosis at 15, 18 and 24 months (p=0.05, p=0.02 and p=0.02, respectively) decreased markedly in the ART group compared with the RT group. Emesis was the most common adverse effect of amifostine. Conclusion: Daily administration of amifostine during RT was effective in avoiding late grade 2-3 xerostomia, as well as grade 2 fibrosis. © 2012 by Türkiye Klinikleri. Source

Benderli Cihan Y.,Clinic of Radiation Oncology | Arsav V.,Kayseri Education and Research Hospital
Anadolu Kardiyoloji Dergisi

Objective: This experimental study aims to investigate whether radiotherapy (RT) plus trastuzumab (T) followed by subsequent hormonotherapy increase the cumulative toxic effect on cardiac functions in rats. Methods: A total of 70 Wistar Albino female rats with a mean weight 213±27 g were randomly divided into equal seven groups. The first group (C) underwent no procedure. The second group (RT) underwent the whole thoracic radiation including heart. The third group (T) was administered T through tail vein alone. The fourth group (RT+T+Tx) was administered T initially and the whole thoracic radiation at two hours, followed by tamoxifen at one week. The fifth group (RT+T+Le) was administered T and then underwent thoracic radiation, followed by letrozole. The sixth group (T+RT+An) was administered T and then underwent thoracic radiation, followed by anastrazole. The seventh group (T+RT+Ex) was administered T and then underwent thoracic radiation, followed by exemestane at one week. Hormonotherapy was administered to the rats in the Group 5, 6 and 7, as indicated in the Group 4. Radiation therapy was administered following T treatment at two hours as a single 12 Gy fraction. After the rats were sedated under anesthesia and sacrificed at 24 weeks, cardiac tissues were removed. Serial sections obtained following paraffin blockage were stained and the ratio of myocardial fibrosis was assessed. According to statistical analyses by the one-way ANOVA test and Tukey HSD test, a significant difference between test components. Results: At the end of the study, no loss and adverse effects were seen in any group. There was a statistically significant difference among atrium, ventricle and aorta (p<0.001). The mean value of fibrosis scores increased in the rats which underwent R T. In the assessment of atrium, a significant difference was found between RT group and RT+T+An group and also T group and RT+T+Fe group (p<0.001). In the assessment of ventricule, a statistically significant difference was observed among RT, RT+T+An and RT+T+Ex. In the assessment of aorta, the scores of RT group was significantly higher than RT+T+An and RT+T+Ex. A statistically significant difference was observed among these groups (p<0.001). Conclusion: Our study results suggested that there was no significant additional cardiotoxicity of adjuvant hormonotherapy following concomitant RT and T treatment, compared to RT in terms of cardiac fibrosis. © 2014 by Turkish Society of Cardiology. Source

Davis M.P.,Cleveland Clinic | Feyer P.C.,Clinic of Radiation Oncology | Ortner P.,German Supportive Care in Cancer Group ASORS | Zimmermann C.,University of Toronto | Zimmermann C.,Ontario Cancer Institute
Supportive Oncology

The first reference of its kind, Supportive Oncology, by Drs. Davis, Feyer, Ortner, and Zimmermann, is your practical guide to improving your patients' quality of life and overall outcomes by integrating palliative care principles into the scope of clinical oncologic practice at all points along their illness trajectories. A multidisciplinary editorial team, representing the dual perspectives of palliative medicine and supportive oncology, offers expert guidance on how to effectively communicate diagnoses and prognoses with cancer patients and their families, set treatment goals, and manage symptoms through pharmacological therapies, as well as non-pharmacological therapies and counselling when appropriate. The complete contents are available Integrate complementary palliative principles as early as possible after diagnosis with guidance from a multidisciplinary editorial team whose different perspectives and collaboration provide a well-balanced approach. Effectively communicate diagnoses and prognoses with cancer patients and their families, set treatment goals, and manage symptoms through pharmacological therapies, as well as non-pharmacological therapies and counseling when appropriate. Improve patients' quality of life with the latest information on pain and symptom management including managing side effects of chemotherapy and radiotherapy, rehabilitating and counselling long-term survivors, and managing tumor-related symptoms and other complications in the palliative care setting. Prescribe the most effective medications, manage toxicities, and deal with high symptom burdens with online access to the Gold Standard drug database. Access the complete contents online plus the Gold Standard database, clinical assessment tools and more-at Improve quality of life at all points in a patient's illness. © 2011 Elsevier Inc. All rights reserved. Source

Ozden S.A.,Dr Lutfi Kirdar Kartal Education And Research Hospital | Ozyurt H.,Dr Lutfi Kirdar Kartal Education And Research Hospital | Ozgen Z.,Clinic of Radiation Oncology | Kilinc O.,Marmara University | And 8 more authors.
World Journal of Gastroenterology

AIM: To investigate the association between prognosis of rectal cancer treated with chemoradiotherapy (CRT) and expression of sensitive-to-apoptosis (SAG), B-cell lymphoma-extra large (Bcl-XL) and Bcl-2 homologous antagonist/killer (Bak). METHODS: Real-time quantitative polymerase chain reaction was used to determine the expression of proteins of interest, namely SAG, Bcl-XL, Bak and β-actin, in rectal carcinoma patients who had a follow-up period of 3 years after CRT. Biopsy specimens were excised from the rectal tumor preceding CRT. RESULTS: SAG, Bcl-XL and Bak proteins showed significant correlations with each other. In multivariate analysis, patients with high vs low SAG expression showed a statistically significant difference in 2-year survival rates: 56% vs 73%, respectively (P = 0.056). On the other hand, there were no significant correlations between the expression levels of all three genes and metastatic rates or tumor responses to CRT. Mean overall survival in the patients with elevated SAG expression was 27.1 mo ± 3.9 mo [95% confidence interval (CI): 19.3-34.9], and in patients with reduced expression, it was 32.1 mo ± 2.5 mo (95% CI: 27.3-36.9). The corresponding values for Bcl-XL were 28.0 mo ± 4.1 mo (95% CI: 19.9-36.1) and 31.7 mo ± 2.9 mo (95% CI: 26.0-37.5), and those for Bak were 29.8 mo ± 3.7 mo (95% CI: 22.5-37.2) and 30.6 mo ± 2.4 mo (95% CI: 25.5-35.0), respectively. CONCLUSION: Two-year survival rates significantly correlated with low SAG expression, and SAG may be a candidate gene for good prognosis, independent of therapeutic response of different individuals. © 2011 Baishideng. All rights reserved. Source

Rudner J.,University of Tubingen | Ruiner C.-E.,University of Tubingen | Handrick R.,University of Duisburg - Essen | Handrick R.,Biberach University of Applied Sciences | And 4 more authors.
Radiation Oncology

Background and Purpose: The phosphatidylinositol-3-kinase (PI3K)/Akt pathway is frequently deregulated in prostate cancer and associated with neoplastic transformation, malignant progression, and enhanced resistance to classical chemotherapy and radiotherapy. Thus, it is a promising target for therapeutic intervention. In the present study, the cytotoxic action of the Akt inhibitor Erufosine (ErPC3) was analyzed in prostate cancer cells and compared to the cytotoxicity of the PI3K inhibitor LY294002. Moreover, the efficacy of combined treatment with Akt inhibitors and ionizing radiation in prostate cancer cells was examined.Materials and methods: Prostate cancer cell lines PC3, DU145, and LNCaP were treated with ErPC3 (1-100 μM), LY294002 (25-100 μM), irradiated (0-10 Gy), or subjected to combined treatments. Cell viability was determined by the WST-1 assay. Apoptosis induction was analyzed by flow cytometry after staining with propidium iodide in a hypotonic citrate buffer, and by Western blotting using antibodies against caspase-3 and its substrate PARP. Akt activity and regulation of the expression of Bcl-2 family members and key downstream effectors involved in apoptosis regulation were examined by Western blot analysis.Results: The Akt inhibitor ErPC3 exerted anti-neoplastic effects in prostate cancer cells, however with different potency. The anti-neoplastic action of ErPC3 was associated with reduced phosphoserine 473-Akt levels and induction of apoptosis. PC3 and LNCaP prostate cancer cells were also sensitive to treatment with the PI3K inhibitor LY294002. However, the ErPC3-sensitive PC3-cells were less susceptible to LY294002 than the ErPC3-refractory LNCaP cells. Although both cell lines were largely resistant to radiation-induced apoptosis, both cell lines showed higher levels of apoptotic cell death when ErPC3 was combined with radiotherapy.Conclusions: Our data suggest that constitutive Akt activation and survival are controlled by different different molecular mechanisms in the two prostate cancer cell lines - one which is sensitive to the Akt-inhibitor ErPC3 and one which is more sensitive to the PI3K-inhibitor LY294002. Our findings underline the importance for the definition of predictive biomarkers that allow the selection patients that may benefit from the treatment with a specific signal transduction modifier. © 2010 Rudner et al; licensee BioMed Central Ltd. Source

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