Search

Bairen Pang,1,2 Ying Zhu,1– 3 Jie Ni,1,2 Juanfang Ruan,4,5 James Thompson,1,6,7 David Malouf,2,6 Joseph Bucci,1,2 Peter Graham,1,2 Yong Li1,2,8 1St George and Sutherland Clinical School, UNSW Sydney, NSW 2052, Australia; 2Cancer Care Centre, St. George Hospital, Sydney, NSW 2217, Australia; 3School of Biomedical Engineering, University of Technology Sydney, NSW 2007, Australia; 4Electron Microscope Unit, UNSW Sydney, NSW 2052, Australia; 5School of Biotechnology and Biomolecular Sciences, UNSW Sydney, NSW 2052, Australia; 6Department of Urology, St George Hospital, Sydney, NSW 2217, Australia; 7Garvan Institute of Medical Research/APCRC, Sydney, UNSW 2010, Australia; 8School of Basic Medical Sciences, Zhengzhou University, Henan 450001, People’s Republic of ChinaCorrespondence: Ying Zhu; Yong LiResearch and Education Centre, St George Hospital, 4– 10 South St, Kogarah, NSW 2217, AustraliaEmail ying.zhu@unsw.edu.au; y.li@unsw.edu.auIntroduction: Current standard biomarkers in clinic are not specific enough for prostate cancer (PCa) diagnosis. Extracellular vesicles (EVs) are nano-scale vesicles released by most mammalian cells. EVs are promising biomarker source for PCa liquid biopsy due to its minimal invasive approach, rich information and improved accuracy compared to the clinical standard prostate-specific antigen (PSA). However, current EV separation methods cannot separate pure EVs and the quality characteristics from these methods remain largely unknown. In this study, we evaluated the quality characteristics of human plasma-derived EVs by comparing three clinical suitable separation kits.Methods: We combined EV separation by commercial kits with magnetic beads capture and flow cytometry analysis, and compared three kits including ExoQuick Ultra based on precipitation and qEV35 and qEV70 based on size exclusion chromatography (SEC).Results: Our results indicated that two SEC kits provided higher EV purity and lower protein contami

Objectives: To report feasibility, early toxicity, and PSA kinetics following gantry-based, stereotactic radiotherapy (SBRT) boost within a prospective, phase 2, multicenter study (PROMETHEUS: ACTRN12615000223538). Methods: Patients were treated with gantry-based SBRT, 19-20 Gy in two fractions delivered 1 week apart, followed by conventionally fractionated IMRT (46 Gy in 23 fractions). The study mandated MRI fusion for RT planning, rectal displacement, and intrafraction image guidance. Toxicity was prospectively graded using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4). Results: Between March 2014 and July 2018, 135 patients (76% intermediate, 24% high-risk) with a median age of 70 years (range 53-81) were treated across five centers. Short course (≤6 months) androgen deprivation therapy (ADT) was used in 36% and long course in 18%. Rectal displacement method was SpaceOAR in 59% and Rectafix in 41%. Forty-two and ninety-three patients were treated at the 19 Gy and 20 Gy dose levels, respectively. Median follow-up was 24 months. Acute grade 2 gastrointestinal (GI) and urinary toxicity occurred in 4.4 and 26.6% with no acute grade 3 toxicity. At 6, 12, 18, 24, and 36 months post-treatment the prevalence of late grade ≥2 gastrointestinal toxicity was 1.6, 3.7, 2.2, 0, and 0%, respectively, and the prevalence of late grade ≥2 urinary toxicity was 0.8, 11, 12, 7.1, and 6.3%, respectively. Three patients experienced grade 3 late toxicity at 12 to 18 months which subsequently resolved to grade 2 or less. For patients not receiving ADT the median PSA value pre-treatment was 7.6 ug/L (1.1-20) and at 12, 24, and 36 months post-treatment was 0.86, 0.36, and 0.20 ug/L. Conclusions: Delivery of a gantry-based SBRT boost is feasible in a multicenter setting, is well-tolerated with low rates of early toxicity and is associated with promising PSA responses. A second transient peak in urinary toxicity was observed at 18 months which subsequently reso

In vivo dosimetry (IVD) is an excellent mode of treatment verification and detection of possible overexposures. A feasibility study was conducted to evaluate a proposed IVD procedure for gynecological HDR brachytherapy procedure quality assurance. MO. Skin dosimeters were selected due to their small size and capability of measuring steep dose gradients, such as those relevant in HDR brachytherapy procedures. Two in-phantom experiments measuring dose with MO. Skins at the position simulating the rectal wall were conducted employing a cylindrical single channel applicator and a multichannel applicator. Three MO. Skins were incorporated onto a rectal catheter, which was then attached to the applicator, separated by a small wooden plaque, simulating the vaginal to rectal wall distance and fixing catheter position. This setup was inserted into a water phantom and three treatment plans prescribing 300 cGy to 3 different targets were assigned with various dose distributions. Each treatment was administered three times, and doses measured by the MO. Skins were recorded. Doses measured by the MO. Skins were within 5% of the dose determined by the treatment planning system (TPS), ranging between 208 and 332 cGy, depending on dosimeter position on the rectal catheter. The overall average dose difference between measured and TPS values was 2.09% ± 1.15% (ranging between 0.83 and 4.27%, with measured values always higher than TPS dose), subdivided in 1.40 ± 0.37% and 2.79 ± 1.27% for single and multichannel applicator experiments, respectively. An overall dose agreement between the TPS and measured values, detector reproducibility, and practicality of the rectal catheter demonstrated the suitability of the proposed method for in vivo real time QA purposes in gynecological HDR brachytherapy.

Purpose BrachyView is a novel in-body imaging system which aims to provide LDR brachytherapy seeds position reconstruction within the prostate in real-time. The first prototype is presented in this study: the probe consists of a gamma camera featuring three single cone pinhole collimators embedded in a tungsten tube, above three, high resolution pixelated detectors (Timepix). Methods The prostate was imaged with a TRUS system using a sagittal crystal with a 2.5 mm slice thickness. Eleven needles containing a total of thirty 0.508 U125I seeds were implanted under ultrasound guidance. A CT scan was used to localise the seed positions, as well as provide a reference when performing the image co-registration between the BrachyView coordinate system and the TRUS coordinate system. An in-house visualisation software interface was developed to provide a quantitative 3D reconstructed prostate based on the TRUS images and co-registered with the LDR seeds in situ. A rigid body image registration was performed between the BrachyView and TRUS systems, with the BrachyView and CT-derived source locations compared. Results The reconstructed seed positions determined by the BrachyView probe showed a maximum discrepancy of 1.78 mm, with 75% of the seeds reconstructed within 1 mm of their nominal location. An accurate co-registration between the BrachyView and TRUS coordinate system was established. Conclusions The BrachyView system has shown its ability to reconstruct all implanted LDR seeds within a tissue equivalent prostate gel phantom, providing both anatomical and seed position information in a single interface.