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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.


Safavi-Naeini M.,University of Wollongong | Safavi-Naeini M.,University of Technology, Sydney | Safavi-Naeini M.,Czech Technical University | Safavi-Naeini M.,St George Hospital Cancer Care Center | And 45 more authors.
Medical Physics | Year: 2013

Purpose: High dose rate (HDR) brachytherapy is a form of radiation therapy for treating prostate cancer whereby a high activity radiation source is moved between predefined positions inside applicators inserted within the treatment volume. Accurate positioning of the source is essential in delivering the desired dose to the target area while avoiding radiation injury to the surrounding tissue. In this paper, HDR BrachyView, a novel inbody dosimetric imaging system for real time monitoring and verification of the radioactive seed position in HDR prostate brachytherapy treatment is introduced. The current prototype consists of a 15 × 60 mm2 silicon pixel detector with a multipinhole tungsten collimator placed 6.5 mm above the detector. Seven identical pinholes allow full imaging coverage of the entire treatment volume. The combined pinhole and pixel sensor arrangement is geometrically designed to be able to resolve the three-dimensional location of the source. The probe may be rotated to keep the whole prostate within the transverse plane. The purpose of this paper is to demonstrate the efficacy of the design through computer simulation, and to estimate the accuracy in resolving the source position (in detector plane and in 3D space) as part of the feasibility study for the BrachyView project. Methods: Monte Carlo simulations were performed using the GEANT4 radiation transport model, with a 192Ir source placed in different locations within a prostate phantom. A geometrically accurate model of the detector and collimator were constructed. Simulations were conducted with a single pinhole to evaluate the pinhole design and the signal to background ratio obtained. Second, a pair of adjacent pinholes were simulated to evaluate the error in calculated source location. Results: Simulation results show that accurate determination of the true source position is easily obtainable within the typical one second source dwell time. The maximum error in the estimated projection position was found to be 0.95 mm in the imaging (detector) plane, resulting in a maximum source positioning estimation error of 1.48 mm. Conclusions: HDR BrachyView is a feasible design for real-time source tracking in HDR prostate brachytherapy. It is capable of resolving the source position within a subsecond dwell time. In combination with anatomical information obtained from transrectal ultrasound imaging, HDR BrachyView adds a significant quality assurance capability to HDR brachytherapy treatment systems. © 2013 American Association of Physicists in Medicine.


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.


PubMed | Fondazione IRCCS Instituto Nazionale dei Tumori, St George Hospital Cancer Care Center, University of Wollongong, University of Technology, Sydney and Sloan Kettering Cancer Center
Type: Evaluation Studies | Journal: Medical physics | Year: 2015

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.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.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.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 BrachyViews image processing algorithms.


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.


Metharom E.,Cancer Pharmacology Therapeutics Group | Metharom E.,University of New South Wales | Galettis P.,Cancer Pharmacology Therapeutics Group | Galettis P.,University of New South Wales | And 11 more authors.
Asia-Pacific Journal of Clinical Oncology | Year: 2011

Aim: Controversy exists over the optimal dosing for the nucleoside analogue gemcitabine. A pharmacological advantage is achieved by prolonging infusion times but evidence for a clinical benefit has been conflicting. We hypothesized that polymorphisms in genes involved in gemcitabine accumulation, particularly the cytidine deaminase CDA c.79A>C, may influence the optimal dosing regimen in individual patients. Methods: DNA was collected from 32 patients participating in a randomized crossover study comparing 30-min with 100-min infusions of gemcitabine. The relationships between seven polymorphisms among three genes (CDA, RRM1 and DCK) and (i) gemcitabine triphosphate accumulation; (ii) gemcitabine-induced toxicity; and (iii) dose delivery were examined for each infusion time and week of administration. Results: There were trends for increased accumulation of gemcitabine-triphosphate (GEM-TP) with the variant alleles of CDA c.79A>C, and RRM1-37C>A and -524T>C but none of these reached statistical significance in a univariate analysis. In a multivariable model there were significant effects of infusion duration and week of administration on GEM-TP accumulation. There were significant interactions between CDA c.79A>C (P=0.01) and RRM1-37C>A (P=0.019) genotypes, infusion time, and arm. More patients with one or two CDA c.79 variant alleles had doses delays (57 vs 13 %, P=0.03) and a pharmacological advantage for prolonged infusion after week 1. Conclusion: It is important to consider both pharmacokinetics and pharmacogenetics in optimizing gemcitabine accumulation. This represents a classical interaction between genes and environment and provides support for the consideration of both CDA genotype and infusion duration in development of an individualized dosing strategy. © 2010 Blackwell Publishing Asia Pty Ltd.


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.


Metharom E.,St George And Sutherland Hospitals | Metharom E.,University of New South Wales | Galettis P.,St George And Sutherland Hospitals | Galettis P.,University of New South Wales | And 4 more authors.
Anticancer Research | Year: 2010

Self-potentiation of the intracellular accumulation of gemcitabine accumulation occurs with repeated administration. Understanding the mechanism of this phenomena and its occurrence with other drugs is important for rational dosing of gemcitabine and design of gemcitabine combinations. The HCT116 cell line was used as a model of the in vivo findings to examine the effect of repeated gemcitabine exposure. HPLC analysis revealed a 10-fold increase in gemcitabine-triphosphate accumulation upon repeated gemcitabine exposure. The induction of accumulation was not associated with any changes in the dCK mRNA level. Comparable increases in gemcitabine-triphosphate were seen when the cells were pre-incubated with cytarabine and cisplatin. A lesser increase and no increase in GEM-TP were seen with oxaliplatin and 5′-azacytidine, respectively. In this model, induction of gemcitabine accumulation is likely to be mediated by post translational modification of dCK. The reduced effect of oxaliplatin compared to cisplatin is worthy of further study.

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