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De Souza P.L.,University of New South Wales | Russell P.J.,Kelvin Institute | Kearsley J.H.,St George Hospital Cancer Care Center | Howes L.G.,Griffith University
Nutrition Reviews | Year: 2010

Isoflavones are phytoestrogens that have pleiotropic effects in a wide variety of cancer cell lines. Many of these biological effects involve key components of signal transduction pathways within cancer cells, including prostate cancer cells. Epidemiological studies have raised the hypothesis that isoflavones may play an important role in the prevention and modulation of prostate cancer growth. Since randomized phase III trials of isoflavones in prostate cancer prevention are currently lacking, the best evidence for this concept is presently provided by case control studies. However, in vitro data aremuch more convincing in regard to the activity of a number of isoflavones, and have led to the development of genistein and phenoxodiol in the clinic as potential treatments for cancer. In addition, the potential activity of isoflavones in combination with cytotoxics or radiotherapy warrants further investigation. This review focuses on the clinical pharmacology of isoflavones and its relevance to their development for use in the prevention of prostate cancer, and it evaluates some of the conflicting data in the literature. © 2010 International Life Sciences Institute.

De Souza P.L.,St George Hospital Cancer Care Center | North S.,Cross Cancer Institute | Bolger G.B.,University of Alabama at Birmingham | Spiridonidis H.,Hematology Oncology Consultants Inc | And 4 more authors.
Asia-Pacific Journal of Clinical Oncology | Year: 2010

Aim: KW-2170 is a novel pyrazoloacridone derivative that intercalates nucleic acids. It has promising in vitro properties against prostate and other cancers and is active in vivo against doxorubicin-resistant cell lines. We wished to investigate its activity and toxicity profile in this Phase II trial in androgen independent prostate cancer.Methods: Overall 44 men were recruited to this multicenter, open label, non-randomized study, with 35 evaluable for prostatic specific antigen (PSA) response.Results: Five patients had a PSA fall greater than 50% (overall RR 14.3%, 95% CI 4.8-30.3%). Overall median survival was 16months. In the evaluable group (n=35), median survival was 18.9months. The drug was very well tolerated, with the most common toxicities being hematological (anemia, leucopenia, thrombocytopenia), alopecia, fatigue, and nausea. However, most of these were National Cancer Institute Grade 1 or 2; Grade 3 neutropenia occurred in only 11% of patients, and there was no Grade 4 neutropenia. Quality of life as measured by the FACT-P scale was not compromised.Conclusion: KW-2170 is a very well tolerated chemotherapy agent. It has a relatively low PSA response rate, and did not meet the pre-specifed criteria for further studies. © 2010 Blackwell Publishing Asia Pty Ltd.

Safavi-Naeini M.,University of Wollongong | Han Z.,University of Wollongong | Alnaghy S.,University of Wollongong | Cutajar D.,University of Wollongong | And 7 more authors.
Medical Physics | Year: 2015

Purpose: This paper presents initial experimental results from a prototype of high dose rate (HDR) BrachyView, a novel in-body source tracking system for HDR brachytherapy based on a multipinhole tungsten collimator and a high resolution pixellated silicon detector array. The probe and its associated position estimation algorithms are validated and a comprehensive evaluation of the accuracy of its position estimation capabilities is presented. Methods: The HDR brachytherapy source is moved through a sequence of positions in a prostate phantom, for various displacements in x, y, and z. For each position, multiple image acquisitions are performed, and source positions are reconstructed. Error estimates in each dimension are calculated at each source position and combined to calculate overall positioning errors. Gafchromic film is used to validate the accuracy of source placement within the phantom. Results: More than 90% of evaluated source positions were estimated with an error of less than one millimeter, with the worst-case error being 1.3 mm. Experimental results were in close agreement with previously published Monte Carlo simulation results. Conclusions: The prototype of HDR BrachyView demonstrates a satisfactory level of accuracy in its source position estimation, and additional improvements are achievable with further refinement of HDR BrachyView's image processing algorithms. © 2015 American Association of Physicists in Medicine.

Han Z.,University of Wollongong | Safavi-Naeini M.,University of Wollongong | Alnaghy S.,University of Wollongong | Cutajar D.L.,University of Wollongong | And 8 more authors.
Physics in Medicine and Biology | Year: 2014

HDR BrachyView is a novel in-body dosimetric imaging system for real-time monitoring and verification of the source position in high dose rate (HDR) prostate brachytherapy treatment. It is based on a high-resolution pixelated detector array with a semi-cylindrical multi-pinhole tungsten collimator and is designed to fit inside a compact rectal probe, and is able to resolve the 3D position of the source with a maximum error of 1.5 mm. This paper presents an evaluation of the additional dose that will be delivered to the patient as a result of backscatter radiation from the collimator. Monte Carlo simulations of planar and cylindrical collimators embedded in a tissue-equivalent phantom were performed using Geant4, with an 192Ir source placed at two different source-collimator distances. The planar configuration was replicated experimentally to validate the simulations, with a MOSkin dosimetry probe used to measure dose at three distances from the collimator. For the cylindrical collimator simulation, backscatter dose enhancement was calculated as a function of axial and azimuthal displacement, and dose distribution maps were generated at three distances from the collimator surface. Although significant backscatter dose enhancement was observed for both geometries immediately adjacent to the collimator, simulations and experiments indicate that backscatter dose is negligible at distances beyond 1 mm from the collimator. Since HDR BrachyView is enclosed within a 1 mm thick tissue-equivalent plastic shell, all backscatter radiation resulting from its use will therefore be absorbed before reaching the rectal wall or other tissues. dosimetry, brachytherapy, HDR © 2014 Institute of Physics and Engineering in Medicine.

Beydoun N.,St George Hospital Cancer Care Center | Bucci J.,St George Hospital Cancer Care Center | Malouf D.,St George Hospital
Journal of Contemporary Brachytherapy | Year: 2014

Purpose: Prostate cancer is among the most common non-cutaneous neoplasms affecting renal transplant recipients (RTRs). Available treatments including radical prostatectomy and external beam radiotherapy carry a risk of damage to the transplanted kidney, ureters, or bladder. We assessed the safety and efficacy of Iodine-125 (125I) prostate seed brachytherapy as an alternative to surgery and radiotherapy in these individuals. Material and methods: We retrospectively reviewed our brachytherapy database to identify patients with a prior history of renal transplantation, who had undergone seed implantation for localized prostate cancer. Long term PSA control and treatment related toxicity, including graft dysfunction, urinary, rectal, and sexual complications, were assessed and compared with published outcomes for surgery and external beam radiotherapy. Results: Of 1054 patients treated with permanent seed implantation from 2002-2012, we identified four who had a prior history of renal transplantation. Mean time from renal transplantation to prostate cancer diagnosis was 13 years. Mean follow-up after seed implantation was 44 months (range 12-60 months). All four patients remain free of PSA progression. No peri-operative complications were experienced following seed implantation, and all four patients continued to have normal graft function. Long term urinary and rectal function scores were comparable to reported outcomes for seed brachytherapy in the non-transplant population. Conclusions: 125I prostate seed brachytherapy is associated with high rates of biochemical control and minimal toxicity to the renal graft in RTRs. This treatment should be considered as an alternative to surgery in managing RTRs with localized prostate cancer.

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