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Background: The treatment options for high-risk prostate cancer are either radical prostatectomy or radiotherapy/ brachytherapy depending on the patients' prognosis. In older men with multiple comorbidities, radiotherapy with androgen deprivation therapy is an attractive option. Common side effects of androgen deprivation therapy include hot flushes, tiredness, increased risk of fractures, increased risk of metabolic disorders, coronary heart disease, and psychological effects. This case highlights the potential side effect of lipodystrophy secondary to leuprolide acetate injections. To the best of our knowledge, this is the first reported case of such an instance. Case presentation: In this case report, we describe a 70-year-old white man with prostate-specific antigen of 1.8 ng/mL, clinical stage T2bN0M0, Gleason 4+5=9 prostate cancer who developed an unusual side effect from leuprolide acetate as part of his androgen deprivation therapy. Approximately 2 months after the initial 3-monthly injection of leuprolide acetate (Eligard 22.5 mg) our patient developed abnormal lipid deposition particularly in his deltoid and abdominal region. His upper limb mobility gradually became compromised due to the size of these abnormal fat depositions. He had liposuction to correct this lipodystrophy and had a good functional outcome and cosmesis from the procedure. Conclusions: To the best of our knowledge, this is the first reported case of lipodystrophy secondary to leuprolide acetate injections. Leuprolide acetate in commonly used as one of the gonadotrophin-releasing hormone agonists and thus we should be mindful of the potential effect of producing lipodystrophy, especially in patients with cirrhosis, and to watch for any signs and symptoms as appropriate. The implication of this potential side effect poses difficult management strategies for such patients, and second-line alternatives such as chemotherapy may need to be considered. [ABSTRACT FROM AUTHOR]

Introduction Androgen deprivation therapy ( ADT) is an important component of modern prostate cancer treatment. Survival benefits from neo-adjuvant and adjuvant hormones may take years to manifest, and balancing this with potential morbidity of therapy can be challenging. This study aimed to assess whether education and short-term combined aerobic and resistance exercises could help to ameliorate the adverse side effects of ADT. Methods Eight hundred fifty-nine patients with relapsed or metastatic prostate cancer on leuprorelin acetate were allocated to three interventional streams based on patient preference and medical fitness: supervised group (Face-to-Face) exercise sessions, home-based (At Home) exercise or a support programme for those incapable of exercising (Support). Patients enrolled onto Face to Face underwent measurement of body composition and cardiorespiratory fitness variables at baseline and programme completion. Patients in the exercise streams were surveyed to determine the programme's impact on physical fitness and well-being. Results Statistically significant improvements ( p < 0.001) were seen in all measured cardiorespiratory fitness and strength variables. Programme attrition rates were low (75/859; 8.7%), the primary reason for withdrawal being discontinuation of hormones (70%). Programme satisfaction was high, with 98% of surveyed patients reporting a positive impact on fitness and 97% planning to continue exercising after programme completion. At 6 months, improved physical and emotional well-being was reported by 93 and 79% of patients, respectively. Conclusions A short-term structured exercise intervention results in high compliance and significant improvements in muscle strength and cardiorespiratory fitness in prostate cancer patients on ADT. [ABSTRACT FROM AUTHOR]

Introduction Prostate swelling following seed implantation is a well-recognised phenomenon. The purpose of this intervention was to assess whether using thinner seeds reduces post-implant swelling with permanent prostate brachytherapy. Methods Eighteen consecutive patients eligible for prostate seed brachytherapy underwent seed implantation using iodine-125 ( I-125) thin seeds. Operative time, dosimetry, prostate swelling and toxicity were assessed and compared with standard I-125 stranded seed controls, sourced from the department's brachytherapy database. Results A learning curve was noted with the thin seeds in terms of greater bending and deviation of needles from their intended path. This translated into significantly longer total operative time (88 vs 103 minutes; P = 0.009, 95% confidence interval ( CI) 4.1-24.3) and time per needle insertion (2.6 vs 3.7 minutes; P < 0.001, 95% CI 0.5-1.3) for the thin seeds. Day 30 prostate volumes were significantly smaller in the thin seed group compared with standard seeds (40.9 cc vs 46.8 cc; P = 0.001, 95% CI 1.5-5.6). The ratio of preoperative transrectal ultrasound to day 30 post-implant CT volume was also smaller in the thin seed group (1.2 ± 0.1 for standard seeds vs 1.1 ± 0.1 for thin seeds). Post-implant dosimetric parameters were comparable for both groups. No significant differences were seen in acute urinary morbidity or quality of life between the two groups. Conclusions I-125 thin seeds are associated with an initial learning curve, with longer operative time, even for experienced brachytherapists. The significant reduction in day 30 prostate volumes with the thin seeds has useful implications in terms of optimising dose coverage to the prostate in the early period post-implantation, as well as improving the accuracy of post-implant dosimetric assessments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the feasibility of transperineal polyethylene glycol (PEG) hydrogel insertion into anterior perirectal fat for reducing rectal radiation dose in patients with suboptimal rectal dosimetry after permanent iodine-125 prostate brachytherapy. Methods and Materials: Five patients with suboptimal rectal dosimetry after iodine-125 seed brachytherapy implant underwent a single transperineal injection of PEG hydrogel into the anterior perirectal fat under general anesthetic using transrectal ultrasound guidance. Prostate–rectum separation and rectal radiation dose before and after PEG hydrogel spacer insertion were measured. Toxicity because of spacer insertion was assessed at Days 0–1 and 4–6 weeks using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Results: All patients experienced a clinically significant reduction in the volume of rectum receiving greater than or equal to the prescription dose (RV 100) on the postspacer postimplant dosimetry, compared with the prespacer postimplant dosimetry. Mean prostate–rectum separation that was achieved with the insertion of the spacer was 15.1 mm (±3.4). The mean difference in separation from before to after spacer insertion was 12.5 mm (±4.5). This was associated with a reduction in mean RV 100 from 3.04 (±1.2) to 0.06 (±0.1) cc. Toxicities were limited to Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0) perineal pain and rectal discomfort (3/5 patients). There were no Grade 2 or greater toxicities reported after insertion of the spacer. Conclusions: PEG hydrogel is safe and effective at reducing rectal radiation dose in select patients with suboptimal rectal dosimetry after prostate seed brachytherapy. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify ice hockey coaches’ perceptions of the factors influencing athlete leadership. Semi-structured open-ended interviews were conducted with six high performance ice hockey coaches of elite 16- to 20-year-old athletes. The results indicated how coaches selected and developed their athlete leaders, how they fostered the coach-athlete leader relationship and the responsibilities of their athlete leaders. These results provide coaches with new information on how to identify and develop their athlete leaders, as well as how to cultivate positive relationships with them. [ABSTRACT FROM PUBLISHER]

An editorial is presented on prostrate brachytherapy for prostate cancer which has been available as a treatment option for the Australian men for over 15 years, and has been reimbursed through the Medicare. Topics include reports on 10-year biochemical control reflecting pattern of outcomes; use of the seed brachytherapy for treatment of prostate cancer; and need of close collaboration between radiation oncology, urology and medical physics for its effectiveness.

Purpose: To assess and compare two models for a surrogate urethra to be used for postimplant dosimetry in prostate brachytherapy.Methods and Materials: Twenty men with a urinary catheter present at the time of postimplant computed tomographic imaging were studied. Urethral and periurethral volumes were defined as 5-mm and 10-mm diameter volumes, respectively. Three contours of each were used: one contour of the true urethra (and periurethra), and two surrogate models. The true volumes were centered on the catheter center. One surrogate model used volumes centered on the geometrical center of each prostate contour (centered surrogate). The other surrogate model was based on the average deviation of the true urethra from a reference line through the geometrical center of the axial midplane of the prostate (deviated surrogate). Maximum point doses and the D10, D25, D50, D90, V100, V120, and V150 of the true and surrogate volumes were measured and compared (Dn is the minimum dose [Gy] received by n% of the structure, and Vm is the volume [%] of the structure that received m% of the prescribed dose) as well as the distances between the surrogate urethras and the true urethra.Results: Doses determined from both surrogate urethral and periurethral volumes were in good agreement with the true urethral and periurethral doses except in the superior third of the gland. The deviated surrogate provided a physically superior likeness to the true urethra. Certain dose-volume histogram (DVH)-based parameters could also be predicted reasonably well on the basis of the surrogates. Correlation coefficients ≥0.85 were seen for D25, D50, V100, V120, and V150 for both models. All the other parameters had correlation coefficients in the range of 0.73 – 0.85.Conclusions: Both surrogate models predicted true urethral dosimetry reasonably well. It is recommended that the simpler deviated surrogate would be a more suitable surrogate for routine clinical practice. [Copyright &y& Elsevier]

Purpose: To evaluate the incidence and duration of urinary retention requiring catheterization and the factors predictive for these end points.Methods and Materials: Two hundred eighty-two patients treated with prostate brachytherapy alone were evaluated. Clinical and treatment-related factors examined included: age, baseline International Prostate Symptom Score (IPSS), presence of comorbidity, planning ultrasound target volume (PUTV), postimplant prostate CT scan volume, the CT:PUTV ratio, number of seeds inserted, number of needles used, use of neoadjuvant hormones, procedural physician, clinical stage, Gleason score, and pretreatment PSA. Dosimetric quality indicators were also examined.Results: Urinary obstruction after prostate brachytherapy developed in 43 (15%) patients. The median duration of catheter insertion was 21 days (mean 49, range 1–365). Univariate analysis demonstrated that presence of diabetes, preimplant volume, postimplant volume, CT:PUTV ratio, number of needles, and dosimetric parameters were predictive for catheterization. However, in multivariate analysis, only the baseline IPSS, CT:PUTV ratio, and presence of diabetes were significant independent predictive factors for catheterization.Conclusion: Baseline IPSS was the most important predictive factor for postimplantation catheterization. The extent of postimplant edema, as reflected by the CT:PUTV ratio, predicted for need and duration of catheterization. The presence of diabetes was predictive for catheterization, but may relate to the absence of prophylactic steroids, and therefore requires further evaluation. [Copyright &y& Elsevier]

Introduction Methods Results Conclusion Paediatric cancers are rare, and most children requiring radiation therapy receive external beam radiation (EBRT). Although EBRT may offer organ preservation compared to surgery, it can be associated with significant late effects. Image‐guided brachytherapy is a highly specialised technique offering both organ preservation and dose conformity to minimise late toxicity.This is a retrospective mono‐institutional review of paediatric brachytherapy in one of the largest paediatric centres in Australia. Outcomes and toxicities are presented as well as brachytherapy versus proton plan comparison in four patients.A total of 14 patients were treated with adjuvant brachytherapy between 2012 and 2022. The predominant histology was rhabdomyosarcoma, and all patients had pelvic tumours. High‐dose rate (HDR) brachytherapy was given for 13 patients with one patient receiving low‐dose rate (LDR) brachytherapy. Only one grade three late toxicity was reported and two patients developed metastatic disease within one year of completion of treatment. The brachytherapy plan was superior to protons in two of four patients and equivocal in one patient.This is the first Australian publication of a paediatric brachytherapy series from a single institution. This retrospective series demonstrates the feasibility and safety of brachytherapy in paediatric pelvic tumours. The initial work presented here demonstrates the value of a comprehensive radiation plan review in selecting the optimal modality for an individual paediatric patient. [ABSTRACT FROM AUTHOR]

Background: There currently exists no widespread high dose‐rate (HDR) brachytherapy afterloader quality assurance (QA) tool for simultaneously assessing the afterloader's positional, temporal, transit velocity and air kerma strength accuracy. Purpose: The purpose of this study was to develop a precise and rigorous technique for performing daily QA of HDR brachytherapy afterloaders, incorporating QA of: dwell position accuracy, dwell time accuracy, transit velocity consistency and relative air kerma strength (AKS) of an Ir‐192 source. Method: A Sharp ProGuide 240 mm catheter (Elekta Brachytherapy, Veenendaal, The Netherlands) was fixed 5 mm above a 256 channel epitaxial diode array 'dose magnifying glass' (DMG256) (Centre for Medical and Radiation Physics, University of Wollongong). Three dwell positions, each of 5.0 s dwell times, were spaced 13.0 mm apart along the array with the Flexitron HDR afterloader (Elekta Brachytherapy, Veenendaal, The Netherlands). The DMG256 was connected to a data acquisition system (DAQ) and a computer via USB2.0 link for live readout and post‐processing. The outputted data files were analyzed using a Python script to provide positional and temporal localization of the Ir‐192 source by tracking the centroid of the detected response. Measurements were repeated on a weekly basis, for a period of 5 weeks to determine the consistency of the measured parameters over an extended period. Results: Using the DMG256 for relative AKS measurements resulted in measured values within 0.6%–3.0% of the expected activity over a 7‐week period. The sub‐millisecond temporal accuracy of the device allowed for measurements of the transit velocity with an average of (10.88 ± 1.01) cm/s for 13 mm steps. The dwell position localization for 1, 2, 3, 5, and 10 mm steps had an accuracy between 0.1 and 0.3 mm (3σ), with a fixed temporal accuracy of 10 ms. Conclusion: The DMG256 silicon strip detector allows for clinics to perform rigorous daily QA of HDR afterloader dwell position and dwell time accuracy with greater precision than the current standard methodology using closed circuit television and a stopwatch. Additionally, DMG256 unlocks the ability to perform measurements of transit velocity/time and relative AKS, which are not possible using current standard techniques. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a global health concern, ranking as the most common cancer among men in Western countries. Traditional diagnostic methods are invasive with adverse effects on patients. Due to the heterogeneous nature of PCa and their multifocality, tissue biopsies often yield false-negative results. To address these challenges, researchers are exploring innovative approaches, particularly in the realms of proteomics and metabolomics, to identify more reliable biomarkers and improve PCa diagnosis. Liquid biopsy (LB) has emerged as a promising non-invasive strategy for PCa early detection, biopsy selection, active surveillance for low-risk cases, and post-treatment and progression monitoring. Extracellular vesicles (EVs) are lipid-bilayer nanovesicles released by all cell types and play an important role in intercellular communication. EVs have garnered attention as a valuable biomarker resource in LB for PCa-specific biomarkers, enhancing diagnosis, prognostication, and treatment guidance. Metabolomics provides insight into the body's metabolic response to both internal and external stimuli, offering quantitative measurements of biochemical alterations. It excels at detecting non-genetic influences, aiding in the discovery of more accurate cancer biomarkers for early detection and disease progression monitoring. This review delves into the potential of EVs as a resource for LB in PCa across various clinical applications. It also explores cancer-related metabolic biomarkers, both within and outside EVs in PCa, and summarises previous metabolomic findings in PCa diagnosis and risk assessment. Finally, the article addresses the challenges and future directions in the evolving field of EV-based metabolomic analysis, offering a comprehensive overview of its potential in advancing PCa management. [Display omitted] • Current clinical prostate cancer (PCa) diagnosis is challenging due to heterogeneous nature of PCa and their multifocality. • Liquid biopsy (LB) is a promising non-invasive strategy for PCa early detection, biopsy selection and active surveillance. • Extracellular vesicles (EVs) are a valuable biomarker resource in LB for enhancing PCa diagnosis and prognostication. • Metabolomics can aid in the discovery of cancer biomarkers for PCa early detection and progression monitoring. • Exploring the EV metabolic cargo holds promise to develop innovative approaches and personalised medicine in PCa. [ABSTRACT FROM AUTHOR]

Diagnosis and stratification of prostate cancer (PCa) patients using the prostate‐specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label‐free LC‐MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring‐based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high‐risk PCa patients compared to low‐risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification. [ABSTRACT FROM AUTHOR]

Background: In‐vivo source tracking has been an active topic of research in the field of high‐dose rate brachytherapy in recent years to verify accuracy in treatment delivery. Although detection systems for source tracking are being developed, the allowable threshold of treatment error is still unknown and is likely patient‐specific due to anatomy and planning variation. Purpose: The purpose of this study was to determine patient and catheter‐specific shift error thresholds for in‐vivo source tracking during high‐dose‐rate prostate brachytherapy (HDRPBT). Methods: A module was developed in the previously described graphical processor unit multi‐criteria optimization (gMCO) algorithm. The module generates systematic catheter shift errors retrospectively into HDRPBT treatment plans, performed on 50 patients. The catheter shift model iterates through the number of catheters shifted in the plan (from 1 to all catheters), the direction of shift (superior, inferior, medial, lateral, cranial, and caudal), and the magnitude of catheter shift (1–6 mm). For each combination of these parameters, 200 error plans were generated, randomly selecting the catheters in the plan to shift. After shifts were applied, dose volume histogram (DVH) parameters were re‐calculated. Catheter shift thresholds were then derived based on plans where DVH parameters were clinically unacceptable (prostate V100 < 95%, urethra D0.1cc > 118%, and rectum Dmax > 80%). Catheter thresholds were also Pearson correlated to catheter robustness values. Results: Patient‐specific thresholds varied between 1 to 6 mm for all organs, in all shift directions. Overall, patient‐specific thresholds typically decrease with an increasing number of catheters shifted. Anterior and inferior directions were less sensitive than other directions. Pearson's correlation test showed a strong correlation between catheter robustness and catheter thresholds for the rectum and urethra, with correlation values of –0.81 and –0.74, respectively (p < 0.01), but no correlation was found for the prostate. Conclusions: It was possible to determine thresholds for each patient, with thresholds showing dependence on shift direction, and number of catheters shifted. Not every catheter combination is explorable, however, this study shows the feasibility to determine patient‐specific thresholds for clinical application. The correlation of patient‐specific thresholds with the equivalent robustness value indicated the need for robustness consideration during plan optimization and treatment planning. [ABSTRACT FROM AUTHOR]

We assessed the accuracy of a prototype radiation detector with a built in CMOS amplifier for use in dosimetry for high dose rate brachytherapy. The detectors were fabricated on two substrates of epitaxial high resistivity silicon. The radiation detection performance of prototypes has been tested by ion beam induced charge (IBIC) microscopy using a 5.5 MeV alpha particle microbeam. We also carried out the HDR Ir-192 radiation source tracking at different depths and angular dose dependence in a water equivalent phantom. The detectors show sensitivities spanning from (5.8 ± 0.021) × 10−8 to (3.6 ± 0.14) × 10−8 nC Gy−1 mCi−1 mm−2. The depth variation of the dose is within 5% with that calculated by TG-43. Higher discrepancies are recorded for 2 mm and 7 mm depths due to the scattering of secondary particles and the perturbation of the radiation field induced in the ceramic/golden package. Dwell positions and dwell time are reconstructed within ±1 mm and 20 ms, respectively. The prototype detectors provide an unprecedented sensitivity thanks to its monolithic amplification stage. Future investigation of this technology will include the optimisation of the packaging technique. [ABSTRACT FROM AUTHOR]

This study aimed to determine the viability of focal dose escalation to prostate cancer intraprostatic lesions (IPLs) from multiparametric magnetic resonance (mpMRI) and prostate-specific membrane antigen positron emission tomography (PSMA-PET) images using high-dose-rate (HDR) prostate brachytherapy (pBT). Retrospective data from 20 patients treated with HDR pBT was utilized. The interobserver contouring variability of 5 observers was quantified using the dice similarity coefficient (DSC) and mean distance to agreement (MDA). Uncertainty in propagating IPL contours to trans-rectal ultrasound (TRUS) was quantified using a tissue equivalent prostate phantom. Feasibility of incorporating IPLs into HDR pBT planning was tested on retrospective patient data. The average observer DSC was 0.65 (PSMA-PET) and 0.52 (mpMRI). The uncertainty in propagating IPL contours was 0.6 mm (PSMA-PET), and 0.4 mm (mpMRI). Uncertainties could be accounted for by expanding IPL contours by 2 mm to create IPL PTVs. The mean D98% achieved using HDR pBT was 166% and 135% for the IPL and IPL PTV contours, respectively. Focal dose escalation to IPLs identified on either PSMA-PET or mpMRI is viable using TRUS-based HDR pBT. Utilizing HDR pBT allows dose escalation of up to 166% of the prescribed dose to the prostate. [ABSTRACT FROM AUTHOR]

Abstract Objectives Management of end-stage lung cancers focuses on symptom control, requiring multimodality management. Endobronchial brachytherapy (EBB) is an evidence-based approach allowing safe delivery of clinically meaningful radiation doses. We provide a summary of treatment characteristics and clinical outcomes of EBB in a single center. Methods and Materials Our retrospective study examined all EBB procedures performed at St George Hospital, NSW, Australia, between 1997 and 2016. Patients received single-fraction brachytherapy treatment under procedural sedation, using either the pulsed-dose-rate or high dose-rate modality. Symptomatic response was noted at the 4- to 6-week followup consultation. Results Ninety-two EBB procedures were identified in 83 patients, with 75 patients treated with pulsed-dose-rate and 17 with high-dose-rate. Clinical and/or radiological airway obstruction in a prior high-dose irradiated volume was the most common indication for treatment (85%). Sixty (72%) patients had a partial or complete response of symptoms. Patients with hemoptysis were more likely to respond than those with airway obstruction (92% vs. 70%; p = 0.036). There was no difference in clinical response between pulsed-dose-rate and high-dose-rate patients (p = 0.24). Median overall survival was 8 months, with a statistically significant difference in those with clinical response (4 vs. 9 months; p = 0.0101). No Grade >2 toxicities were recorded. Conclusions We present the largest Australian series of EBB to date. We continue to demonstrate that despite a variety of symptomatic presentations and histologies, EBB is an effective approach to the palliation of malignant lung lesions. Given its low risk of toxicity, EBB is recommended as an option in the palliative treatment of endobronchial malignancies. [ABSTRACT FROM AUTHOR]

Although radiation dose escalation improves prostate cancer disease control, it can cause increased toxicity. Genitourinary (GU) symptoms after prostate radiation therapy affect patient health-related quality of life (QoL). We compared patient-reported GU QoL outcomes following 2 alternative urethral sparing stereotactic body radiation therapy regimens. Expanded Prostate Cancer Index Composite (EPIC)–26 GU scores were compared between 2 urethral sparing stereotactic body radiation therapy trials. The SPARK trial prescribed a "Monotherapy" dose of 36.25 Gy in 5 fractions to the prostate. The PROMETHEUS trial prescribed 2 phases: a 19- to 21-Gy in 2 fractions "Boost" to the prostate, followed by 46 Gy in 23 fractions or 36 Gy in 12 fractions. The biological effective dose (BED) for urethral toxicity was 123.9 Gy for Monotherapy and 155.8 to 171.2 Gy for Boost. Mixed effects logistic regression models were utilized to estimate the difference in the odds of a minimal clinically important change from baseline EPIC-26 GU score between regimens at each follow-up. 46 Monotherapy and 149 Boost patients completed baseline EPIC-26 scoring. Mean EPIC-26 GU scores revealed statistically superior urinary incontinence outcomes for Monotherapy at 12 months (mean difference, 6.9; 95% confidence interval [CI], 1.6-12.1; P =.01) and 36 months (mean difference, 9.6; 95% CI, 4.1-15.1; P <.01). Monotherapy also revealed superior mean urinary irritative/obstructive outcomes at 12 months (mean difference, 6.9; 95% CI, 2.0-12.9; P <.01) and 36 months (mean difference, 6.3; 95% CI, 1.9-10.8; P <.01). For both domains and at all time points, the absolute differences were <10%. There were no significant differences in the odds of reporting a minimal clinically important change between regimens at any time point. Even in the presence of urethral sparing, the higher BED delivered in the Boost schedule may have a small adverse effect on GU QoL compared with Monotherapy. However, this did not translate to statistically significant differences in minimal clinically important changes. Whether the higher BED of the boost arm offers an efficacy advantage is being investigated in the Trans Tasman Radiation Oncology Group 18.01 NINJA randomized trial. [ABSTRACT FROM AUTHOR]

Introduction: Radiation therapy is a common cancer treatment, requiring timely information to help patients prepare for treatment. We pilot tested a low literacy, psycho‐educational talking book (written booklet, with accompanying audio recording) to examine (i) the effect of the tool on knowledge, anxiety and communication; (ii) acceptability, and (iii) how it was used in appointments. Methods: A pre‐post design was employed. Patients scheduled to receive radiation therapy for any cancer were recruited from two hospitals in Sydney, Australia. Participants were sent the talking book before treatment planning and completed baseline and follow‐up surveys, before and after the intervention. Results: Forty participants were recruited, and 39 completed all study assessments. Overall, knowledge increased after receiving the talking book by 3.8 points from 13.9 to 17.7/20 (95% confidence interval (CI) 2.7, 4.8, P < 0.001). Anxiety and concerns were significantly lower after receiving the talking book (P = 0.015 and P = 0.004, respectively). Nearly half of participants (s = 17, 48%) reported using the book during appointments. Most reported finding it easier to communicate (n = 31, 89%) and to ask more questions (n = 21, 62%). Conclusion: The talking book shows promise in improving knowledge, reducing anxiety and enhancing communication. Strategies to support the implementation of the talking book are required. Further studies to translate the book into different languages are also planned. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the feasibility of online adaptive transrectal ultrasound (TRUS)-based high-dose-rate prostate brachytherapy (HDRPBT) through retrospective simulation of source positioning and catheter swap errors on patient treatment plans. Source positioning errors (catheter shifts in 1 mm increments in the cranial/caudal, anterior/posterior, and medial/lateral directions up to ±6 mm) and catheter swap errors (between the most and least heavily weighted) were introduced retrospectively into DICOM treatment plans of 20 patients that previously received TRUS HDRPBT. Dose volume histogram (DVH) indices were monitored as errors were introduced sequentially into individual catheters, simulating potential errors throughout treatment. Whenever DVH indices were outside institution thresholds: prostate V100% <95%, urethra D0.1cc >118% and rectum Dmax >80%, the plan was adapted using remaining catheters (i.e., simulating previous catheters as previously delivered). The final DVH indices were recorded. Prostate coverage (V100% >95%) could be maintained for source position errors up to 6 mm through online plan adaptation. The source position error at which the urethra D0.1cc and rectum Dmax was able to return to clinically acceptable levels using online adaptation varied between 6 mm to 1 mm, depending on the direction of the source position error and patient anatomy. After introduction of catheter swap errors to patient plans, prostate V100% was recoverable using online adaptation to near original plan characteristics. Urethra D0.1cc and rectum Dmax showed less recoverability. Online adaptive HDRPBT maintains the prostate V100% to clinically acceptable values for majority of directional shifts. However, the current online adaptive method may not correct for source position errors near organs at risk. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to examine the effect of departmental planning techniques on appropriate in‐vivo source tracking error thresholds for high dose rate (HDR) prostate brachytherapy (BT) treatments, and to determine if a single in‐vivo source tracking error threshold would be appropriate for the same patient anatomy. Methods: The prostate, rectum, and urethra were contoured on a single patient transrectal ultrasound (TRUS) dataset. Anonymized DICOM files were disseminated to 16 departments who created an HDR prostate BT treatment plan on the dataset with a prescription dose of 15 Gy in a single fraction. Departments were asked to follow their own local treatment planning guidelines. Source positioning errors were then simulated in the 16 treatment plans and the effect on dose–volume histogram (DVH) indices calculated. Change in DVH indices were used to determine appropriate in‐vivo source tracking error thresholds. Plans were considered to require intervention if the following DVH conditions occurred: prostate V100% < 90%, urethra D0.1cc > 118%, and rectumtt Dmax > 80%. Results: There was wide variation in appropriate in‐vivo source tracking error thresholds among the 16 participating departments, ranging from 1 to 6 mm. Appropriate in‐vivo source tracking error thresholds were also found to depend on the direction of the source positioning error and the endpoint. A robustness parameter was derived, and found to correlate with the sensitivity of plans to source positioning errors. Conclusions: A single HDR prostate BT in‐vivo source tracking error threshold cannot be applied across multiple departments, even for the same patient anatomy. The burden on in‐vivo source tracking devices may be eased through improving HDR prostate BT plan robustness during the plan optimisation phase. [ABSTRACT FROM AUTHOR]

Alpha particle therapy, such as diffusing alpha-emitters radiation therapy (DaRT) and targeted alpha-particle therapy (TAT), exploits the short range and high linear energy transfer (LET) of alpha particles to destroy cancer cells locally with minimal damage to surrounding healthy cells. Dosimetry for DaRT and TAT is challenging, as their radiation sources produce mixed radiation fields of $\alpha $ particles, $\beta $ particles, and $\gamma $ rays. There is currently no dosimeter for real-time in vivo dosimetry of DaRT or TAT. Metal-oxide-semiconductor field-effect transistors (MOSFETs) have features that are ideal for this scenario. They can be read out in real-time nondestructively, store information permanently, and their sensitivity to radiation can be varied by changing the bias on the gate during irradiation. Moreover, owing to their compactness, MOSFETs can fit into fine-gauge needle applicators, such as those used to carry radioactive seeds into the tumor. This study characterized the response of MOSFETs designed at the Centre for Medical and Radiation Physics, University of Wollongong. Irradiations were performed with a mono-energetic helium ion beam (He2+) of 5.5 MeV and an Americium-241 (241Am) source, for MOSFETs with three different gate oxide thicknesses (0.55, 0.68, and 1.0 $\mu \text{m}$). The results showed that the response was linear with alpha dose up to 25 Gy. Also, it was found that a gate bias of between 15 and 60 V would optimize the sensitivity to alpha particles with energy of 5.5 MeV. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: High-dose-rate (HDR) brachytherapy is an invasive and anxiety-provoking procedure. We sought to determine the subjective experience of patients undergoing inpatient treatment. Methods and materials: Men undergoing HDR prostate brachytherapy at Royal Prince Alfred and St George Hospitals were invited to complete a questionnaire (the Prostate Brachytherapy Questionnaire) for 3 days to assess their perceptions and attitudes during the brachytherapy treatment. Results: Fifty-eight eligible men participated. The aspects rated that the most troublesome were “being stuck in bed” and “discomfort,” with mean scores (0–10) over 3 days of 4.2 and 3.8, respectively; 44% and 34% of men rated these aspects of the procedure as severe (score 7 or more) at any time. The whole experience was rated as mildly troublesome (mean score over 3 days=3.2). The overall experience was rated better than expected by most men (60%), and only 9% found it worse than expected. Conclusions: By using the Prostate Brachytherapy Questionnaire, the patients provided our centers with subjective feedback of the procedure from a consumer’s perspective, enabling us to customize and enhance current educational interventions before treatment, to provide patients with a better understanding of the treatment experience, and to ensure continued support for the patients. These results have prompted us to modify the HDR boost to two fractions, and, at one of the centers, to perform them on an outpatient basis. [Copyright &y& Elsevier]

Abstract: Purpose: We report a case of prostate brachytherapy seed migration to the vertebral venous plexus and subsequently to the renal artery with corresponding dosimetry analysis describing nerve doses. Methods and Materials: A 52-year-old male with low-risk prostate carcinoma (clinical stage T1c; Gleason score=6; prostate-specific antigen level of 5.5) underwent transperineal permanent prostate seed implant. Postimplantation routine imaging had failed to locate the missing seed, but he subsequently presented with back pain and parathesia with radiation down the leg. Results: CT with bony windows and MRI had located the seed in the left L5 vertebral venous plexus. Neurosurgical intervention failed to locate and remove the migrated seed. Postsurgery, the left lower limb parathesia persisted but had normal nerve conduction studies. Dose to the spinal nerve roots and nearby structures were estimated using a GEANT4 Monte Carlo simulation. Serial X-ray imaging and CT had found that the seed had further migrated to left renal hilum. Conclusions: Seed migration to vertebral venous plexus is uncommon and to our knowledge this is the third reported case. Its subsequent migration to the renal hilum is most unusual. CT with bony windows or MRI are required if this is suspected. There is risk of spinal or nerve root damage and dose to these structures has to be estimated using GEANT4, although the tissue tolerance in the setting of low-dose rates are unknown and long-term followup of this patient is required. [Copyright &y& Elsevier]

The use of high dose rate brachytherapy (HDR BT) either as monotherapy, or in combination with external beam radiotherapy (EBRT) is a proven technique in the treatment of prostate cancer. The high dose gradients inherent within HDR BT make it an ideal technique for dose escalation, however the same dose gradients also make HDR BT susceptible to dosimetric errors. Treatment verification is therefore imperative, to ensure correct dose delivery in HDR BT of the prostate. One method of performing treatment verification is in-vivo source tracking (IVST), in which the position of the BT source is tracked in real time as it delivers the treatment. Unfortunately, limited data exists on what would be an appropriate error threshold to interrupt prostate HDRT BT treatments when performing IVST. The purpose of this study was two-fold: 1) To determine an appropriate IVST error thresholds for interrupting prostate HDR BT treatments. 2) To examine the feasibility of performing online adaption of prostate HDR BT plans (as an alternative to interrupting), through retrospective simulation of source positioning errors. Source positioning errors (catheter shifts in 1mm increments in the cranial/caudal, left/right, anterior/posterior directions up to ±6 mm) were simulated in 20 retrospective prostate HDR BT treatment plans. Dose volume histogram (DVH) indices were monitored as errors were introduced into catheters, simulating potential errors during treatment. To derive appropriate IVST error thresholds, the change in DVH indices for simulated errors were used to determine appropriate in-vivo source tracking error thresholds for a total treatment plan. Secondly, to simulate the feasibility of online adaption, whenever DVH indices were outside clinically acceptable criteria (prostate V100% < 95%, urethra D0.1cc > 118%, rectum Dmax > 80%), the plan was adapted via optimisations of the remaining catheters to be delivered (i.e. locking the previously simulated catheters from further optimisation). The final DVH indices were then recorded once all catheters had been deliverd. IVST error thresholds to prevent potentially significant changes in prostate (target) DVH metrics ranged from 2 to 5 mm, dependent on the direction of the source positioning error, as well as the relative weight of the dwell position within the plan, and its position relative to the patient anatomy. Source positioning error thresholds to prevent potentially clinically significant changes in urethra and rectum DVH metrics varied significantly, were found to be complex and patient dependent. Through online adaptation, prostate coverage (V100% > 95%) could be maintained for source position errors up to 6 mm. The source position error at which the urethra D0.1cc and rectum Dmax was able to return to clinically acceptable levels using online adaptation varied between 1 mm to 6 mm, depending on the direction of the source position error and patient anatomy. IVST error thresholds are highly dependent on the treatment plan and patient anatomy, particularly when using organ at risk dose as the primary endpoint. Online adaptation of prostate HDR BT has potential to prevent underdosage of the target, but improvements in the robustness of treatment plans must be made before it is able to resolve source positioning errors near organs at risk. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this investigation was to examine differences in estimates of accumulated rectal dose when using deformable image registration (DIR) compared with rigid image registration (RIR) methods, and parameter addition methods for combined transrectal ultrasound (TRUS)-based high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) treatments of prostate cancer. Material and methods: In this retrospective study, data from 10 patients who had previously received HDR-BT in one 15 Gy fraction, followed by 46 Gy EBRT in twenty-three fractions were used. To estimate total combined dose to the rectum, dose accumulation using both DIR and RIR methods were compared with parameter addition methods, which assume the same region of rectal anatomy receives the maximum dose from both treatment modalities. For both rigid and deformable image registration techniques, the quality of image registration was evaluated through metrics, including mean distance to agreement and dice similarity coefficient of prostate contours. Total D1cc and D2cc for the rectum was calculated and compared using each method. Results: The parameter addition methods predicted the highest accumulated dose to the rectum. On average, the predicted D2cc dose was higher than that calculated by the DIR method by 6.59 Gy EQD2 (range, -3.03 to 13.68 Gy EQD2) for partial parameter addition (PPA), and 4.88 Gy EQD2 (range, --3.41 to 11.97 Gy EQD2) for the full parameter addition (FPA) methods. Similarly, RIR predicted higher average doses compared with DIR, with a difference of 3.46 Gy EQD2 (range, -5.50 to 7.90 Gy EQD2). The results showed a significant difference between DIR and parameter addition methods for dose estimation. Conclusions: This retrospective study demonstrates significant differences in accumulated rectal dose prediction using different image registration methods. Each method has limitations in its application, and when used with realtime HDR-BT dose planning, awareness of these limitations is essential. [ABSTRACT FROM AUTHOR]

• In-vivo rectal dosimetry for 20 HDR prostate brachytherapy fractions with MOSkins. • The average per fraction MOSkin doses agree with TPS to within −1.6% ± 11.1% (k = 1). • The average per catheter MOSkin doses agree with TPS to within +2.5% ± 16.9% (k = 1). • Uncertainty dominated by localisation of the MOSkins within reference frame of TPS. • 64% of per catheter MOSkin doses agreed with TPS within uncertainty of 11.5%. To compare the dose measured by MOSkin dosimeters coupled to a trans-rectal ultrasound (TRUS) probe to the dose predicted by the brachytherapy treatment planning system (BTPS) during high dose rate (HDR) prostate brachytherapy (pBT), and to examine the feasibility of performing real-time catheter-by-catheter analysis of in-vivo rectal dosimetry during TRUS based HDR pBT. Four MOSkin dosimeters were coupled to a TRUS probe during 20 TRUS-based HDR pBT treatment fractions. The measured MOSkin doses were retrospectively compared to those predicted by the BTPS for the total treatment fraction, as well as on a per catheter basis. The average relative percentage difference between MOSkin measured and BTPS predicted doses for a total treatment fraction was 0.3% ± 11.6% (k = 1), with a maximum of 23.2% and a minimum of −29.0%. The average relative percentage difference per catheter was +2.5% ± 16.9% (k = 1). The majority (64%) of per catheter MOSkin measured doses agreed with the treatment planning system within the calculated uncertainty budget of 12.3%. The results of the study agreed well with previously published data, despite differences in clinical workflows. To improve the redundancy to potential dosimeter errors, a minimum of 4 MOSkin dosimeters should be used when performing real-time in-vivo rectal dosimetry for HDR pBT, and error thresholds should be based off the total combined uncertainty estimate of measurement. 'Real time' error thresholds can be more confidently applied in the future through enhanced integration between IVD systems with both the imaging device and the BTPS/afterloader. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) in prostate cancer (CaP) are regarded as major contributors to radioresistance due to complex mechanisms including enhanced DNA repair, increased intracellular reactive oxygen species scavenging, activation of anti-apoptotic pathways, microenvironment hypoxia, epithelial-to-mesenchymal transition (EMT) and autophagy. They are also believed to cause tumour recurrence and metastasis due to their unique capability to survive and replicate the heterogeneity of the original tumour. Finding markers of prostate CSCs (PCSC) for identification, prognostication and targeting is key in enhancing therapeutic and clinical outcomes. Markers such as aldehyde dehydrogenase, CD44, integrins and EMT markers have been proved to show great potential in being sensitive and specific to the presence of PCSCs. Novel therapies such as Hedgehog and Wnt pathway inhibitors, angiogenesis inhibitors and metformin show potential in eliminating PCSCs to improve therapeutic outcomes. Here, we review the current state of the literature regarding mechanisms of PCSC radioresistance, promising PCSC markers and novel PCSC-specific therapeutic approaches and their implications in CaP treatment and prognosis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to simulate treatment planning source positioning errors in transrectal ultrasound–based real-time high-dose-rate prostate brachytherapy treatments and determine appropriate in vivo source tracking error thresholds. Treatment planning source positioning errors were simulated for 20 patient plans in the brachytherapy treatment planning system by manually adjusting the dwell position coordinates within selected catheters without plan reoptimization. The change in dose-volume histogram (DVH) indices was calculated as a function of the source positioning error. The magnitude of the change in the DVH indices was then used to derive appropriate in vivo source tracking error thresholds. Source positioning error thresholds to prevent potentially significant changes in prostate (target) DVH metrics ranged from 2 to 5 mm, dependent on the direction of the source positioning error, as well as the relative weight of the dwell position within the plan, and its position relative to the patient anatomy. Source positioning error thresholds to prevent potentially clinically significant changes in organ at risk DVH metrics were found to be complex and patient-dependent. In vivo source tracking error thresholds for transrectal ultrasound–based real-time high-dose-rate prostate brachytherapy were investigated via the simulation of treatment planning source positioning errors. These error thresholds were found to be dependent not only on the direction of the error, but also on the endpoint. There is still the potential for larger changes in DVH indices to occur for catheter shifts smaller than the proposed threshold levels in this study. [ABSTRACT FROM AUTHOR]

Purpose: To develop a low literacy talking book (written book with accompanying audio-recording) about radiation therapy and explore its acceptability with patients and caregivers.Method: The talking book was developed iteratively using low literacy design principles and a multidisciplinary committee comprising consumers and experts in radiation oncology, nursing, behavioural sciences, and linguistics. It contained illustrations, photos, and information on: treatment planning, daily treatment, side effects, psychosocial health, and a glossary of medical terms. Semi-structured interviews were conducted with patients who self-reported low functional health literacy and caregivers to explore their views on the resource. Thematic analysis using a framework approach informed the analysis.Results: Participants were very satisfied with the content, illustrations, and language in the resource. Most were unfamiliar with the term 'talking book', but liked the option of different media (text and audio). The resource was seen as facilitating communication with the cancer care team by prompting question-asking and equipping patients and their families with knowledge to communicate confidently.Conclusions: The low literacy talking book was well accepted by patients and their caregivers. The next step is to examine the effect of the resource on patients' knowledge, anxiety, concerns, and communication with the cancer care team. [ABSTRACT FROM AUTHOR]

Background: Development of chemo-/radioresistance is a major challenge for the current prostate cancer (CaP) therapy. We have previously demonstrated that epithelial cell adhesion molecule (EpCAM) is associated with CaP growth and therapeutic resistance in vitro, however, the role of EpCAM in CaP in vivo is not fully elucidated. Here, we aimed to investigate how expression of EpCAM is involved in CaP growth and chemo-/radiotherapy response in NOD/SCID mouse models in vivo and to validate its role as a therapeutic target for CaP therapy.Methods: EpCAM was knocked down in PC-3 CaP cell line using short hairpin RNA (shRNA). The effect of EpCAM-knockdown (KD) on tumour growth, chemo-/radiotherapy response and animal survival was evaluated on subcutaneous (s.c) and orthotopic mouse models.Results: We found that KD of EpCAM significantly inhibited tumour growth, increased xenograft sensitivity to chemotherapy/radiotherapy, and prolonged the survival of tumour-bearing mice. In addition, we demonstrated that KD of EpCAM is associated with downregulation of the PI3K/Akt/mTOR pathway.Conclusions: In conclusion, our data confirms that CaP growth and chemo-/radioresistance in vivo is associated with over-expression of EpCAM, which serves both a functional biomarker and promising therapeutic target. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to apply a risk-based approach to the development of a quality management (QM) program for ultrasound-based high-dose-rate (HDR) prostate brachytherapy (pBT) treatment planning and delivery. Methods and Materials A QM program was developed by a multidisciplinary team, using both an in-house risk-and-benefit balance impact template (RABBIT) tool and a failure modes and effect analysis (FMEA). FMEA scores were determined by three physicists, one radiation therapist and two radiation oncologists who were familiar with the protocol. The QM program produced by both risk-based techniques was then compared and consolidated. Results The RABBIT tool identified 26 potential risks during the treatment planning and delivery process. During the FMEA, a total of 35 potential failure modes were identified from the seven major processes in ultrasound-based HDR pBT. For the 35 potential failure modes, risk priority number scores ranged from 14 to 267. The highest ranked failure mode was identified to be mislabeling/connection of the transfer tubes/catheters. From the risks analyses, a comprehensive QM program was developed. Conclusion Both the RABBIT tool and process mapping and FMEA were shown to be valuable tools in developing a QM program for ultrasound-based HDR pBT treatments. A considerable number of the potential failure modes identified in both tools were related to human or procedural errors, highlighting the importance of checklists and protocols in delivering a safe and effective ultrasound-based HDR pBT treatment. [ABSTRACT FROM AUTHOR]

Background: High Dose Rate Brachytherapy (HDRB) boost is a well-established treatment for prostate cancer (PC). We describe the PROstate Multicentre External beam radioTHErapy Using Stereotactic boost (PROMETHEUS) study. Non-surgical stereotactic techniques are used to deliver similar doses to HDRB boost regimens with a dose escalation sub-study.Methods: Eligible patients have intermediate or high risk PC. PROMETHEUS explores the safety, efficacy and feasibility of multiple Australian centres cooperating in the delivery of Prostate Stereotactic Body Radiotherapy (SBRT) technology. A SBRT boost component Target Dose (TD) of 19Gy in two fractions is to be delivered, followed by a subsequent EBRT component of 46Gy in 23 fractions. Once accrual triggers have been met, SBRT doses can be escalated in 1 Gy increments to a maximum of 22Gy in two fractions. Patient safety will also be measured with the rate of both acute and late moderate to severe Gastro-Intestinal (GI) and Genito-Urinary (GU) Common Terminology Criteria for Adverse Events (CTCAE) toxicities as well as patient reported quality of life. Efficacy will be assessed via biochemical control after 3 years.Discussion: PROMETHEUS aims to generate evidence for a non-surgical possible future alternative to HDRB boost regimens, and introduce advanced radiotherapy techniques across multiple Australian cancer centres.Trial Registration: The study was retrospectively registered on the ANZCTR (Australian New Zealand Clinical Trials Registry) with trial ID: ACTRN12615000223538 . [ABSTRACT FROM AUTHOR]

With the increase in complexity of brachytherapy treatments, there has been a demand for the development of sophisticated devices for delivery verification. The Centre for Medical Radiation Physics (CMRP), University of Wollongong, has demonstrated the applicability of semiconductor devices to provide cost-effective real-time quality assurance for a wide range of brachytherapy treatment modalities. Semiconductor devices have shown great promise to the future of pretreatment and in vivo quality assurance in a wide range of brachytherapy treatments, from high-dose-rate (HDR) prostate procedures to eye plaque treatments. The aim of this article is to give an insight into several semiconductor-based dosimetry instruments developed by the CMRP. Applications of these instruments are provided for breast and rectal wall in vivo dosimetry in HDR brachytherapy, urethral in vivo dosimetry in prostate low-dose-rate (LDR) brachytherapy, quality assurance of HDR brachytherapy afterloaders, HDR pretreatment plan verification, and real-time verification of LDR and HDR source dwell positions. [ABSTRACT FROM AUTHOR]

Purpose To report the incidence of second primary cancer (SPC) after 125 I brachytherapy (BT) for early prostate cancer in an Australian institution. Methods and Materials All the patients in our cohort had a cystoscopy before the implant. Data were prospectively collected on all subsequent SPC diagnoses. Standardized incidence ratios (SIRs) were calculated to compare data with the Australian population. Kaplan–Meier analysis was used to determine the actuarial second malignancy and pelvic malignancy rates and the death from SPC and from any cause. Results A total of 889 patients were followed up for a median of 4.16 (0–13) years with 370 (42%) patients having ≥5 years of followup. Sixty patients subsequently developed an SPC of which 11 were pelvic malignancies. The 5- and 10-year cumulative incidences were 1.3% (95% confidence interval [CI]: 0.6–3) and 3.3% (95% CI: 1–7) for any pelvic malignancy and 1% (95% CI: 0.4–2) and 2.6% (1–6) for bladder cancer, respectively. The SIR was significantly higher than expected for all bladder cancers at 2.9 (95% CI: 1–6) and close to significance (SIR, 3.0; 95% CI: 0.97–7) for bladder cancers within the first 5 years of followup in the subgroup analysis. On multivariate analysis, older age was associated with increased SPC risk and older age and positive smoking status were associated with increased overall mortality, mortality due to SPC, and mortality from second malignancy ( p < 0.05). Conclusions There may be a small increased risk of bladder SPC after prostate BT. A tendency toward a higher risk of bladder SPC after BT was found within the first 5 years of followup probably reflecting screening bias. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is one of the most important strategies in cancer treatment. Radioresistance is a major challenge to RT and results in locoregional recurrence and metastasis. Thus, there is a great interest in investigating biomarkers to distinguish radiosensitive from radioresistant (RR) cancer patients. The development of proteomic techniques has sparked new searches for novel proteins for cancer biomarker discovery. Modern proteomic techniques allow for a high-throughput analysis of samples with the visualization and quantification of thousands of potential protein and peptide markers. The discovery of RR biomarkers can provide a clue for predicting RT response and discover therapeutic targets for developing personalised medicine of individual patients. In the past decade, emerging advanced proteomic technologies have been performed to identify radiation-related biomarkers in human cancers. This review discusses the mass spectrometry (MS)-based proteomic techniques in RR cancer biomarker discovery, summarises RR biomarkers identified in cancers from proteomics-based findings and explores potential values of RR biomarkers for future clinical trials. [ABSTRACT FROM AUTHOR]

The phosphatidylinositol-3-kinase/Akt and the mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is one of the most frequently activated signaling pathways in prostate cancer (CaP) and other cancers, and responsible for the survival, metastasis and therapeutic resistance. Recent advances in radiation therapy indicate that activation of this pathway is closely associated with cancer radioresistance, which is a major challenge for the current CaP radiation treatment. Therefore, targeting this pathway by inhibitors to enhance radiosensitivity has great potential for clinical benefits of CaP patients. In this review, we summarize the recent findings in the PI3K/Akt/mTOR pathway in CaP radiotherapy research and discuss the potential use of the PI3K/Akt/mTOR pathway inhibitors as radiosensitizers in the treatment of CaP radioresistance in preclinical studies to explore novel approaches for future clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: We performed the first comprehensive, population-based brachytherapy (BT) Patterns of Care Study in the Australian setting. Herein we report on prostate BT and assess the technical quality of BT practice, focusing on whether a caseload effect could be identified in New South Wales (NSW). Material and methods: Site visits were made to all radiation oncology departments in NSW that delivered prostate BT, collecting relevant data on NSW residents treated with prostate BT in 2003. Overall quality of NSW prostate BT treatment was assessed using benchmarks including treatment of appropriate prostate cancer disease risk category, absence of (relative) physical contraindications, optimal planned and treated dosimetry, and pre-/post-implant planning/CT. Quality was compared between higher and lower caseload departments. Results: One hundred and fifty-seven (67%) patients underwent temporary BT and 79 (33%) permanent seed BT. Prostate BT was concentrated in five departments, with three of four departments with active programmes treating greater than the recommended 25 cases. Rates of concordance with quality benchmarks were high (85-99%) with no consistent caseload effect identified. Conclusions: Prostate BT in NSW in 2003 was generally of high quality and a caseload effect on quality could not be identified. This may be because the number of departments was insufficient to determine a caseload effect, or because the prostate BT was largely concentrated in a small number of high caseload departments. [ABSTRACT FROM AUTHOR]

Abstract: Prostate cancer (CaP) is the second leading malignancy in men. The role of epithelial cell adhesion molecule (EpCAM), also known as CD326, in CaP progression and therapeutic resistance is still uncertain. Here, we aimed to investigate the roles of EpCAM in CaP metastasis and chemo/radioresistance. Expression of EpCAM in CaP cell lines and human CaP tissues was assessed using immunofluorescence and immunohistochemistry, respectively. EpCAM was knocked down (KD) in PC-3, DU145 and LNCaP-C4-2B cells using small interfering RNA (siRNA), and KD results were confirmed by confocal microscope, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Cell growth was evaluated by proliferation and colony formation assays. The invasive potential was assessed using a matrigel chamber assay. Tumorigenesis potential was measured by a sphere formation assay. Chemo-/radiosensitivity were measured using a colony formation assay. Over-expression of EpCAM was found in primary CaP tissues and lymph node metastases including cancer cells and surrounding stromal cells. KD of EpCAM suppressed CaP proliferation and invasive ability, reduced sphere formation, enhanced chemo-/radiosensitivity, and down-regulated E-cadherin, p-Akt, p-mTOR, p-4EBP1 and p-S6K expression in CaP cells. Our findings suggest that EpCAM plays an important role in CaP proliferation, invasion, metastasis and chemo-/radioresistance associated with the activation of the PI3K/Akt/mTOR signaling pathway and is a novel therapeutic target to sensitize CaP cells to chemo-/radiotherapy. [Copyright &y& Elsevier]

Abstract: Purpose: Low-dose-rate brachytherapy using iodine-125 seeds is a highly efficacious treatment for low-risk prostate cancer. We propose a bioeffect model may be used to target an ablative dose to the tumor with a lower, therapeutic dose to low-risk regions to maintain high rates of tumor control with reduced toxicity. We report on the validation of the model and derivation of the optimal cutpoint value of tumor control probability (TCP) that predicts for freedom from biochemical failure. Methods and Materials: The TCP was calculated from postimplant dosimetry data for 423 prostate cancer patients from three Australian institutions. To apply the model, the prostate was mathematically divided into 12 subsections with tumor characteristics, including a nonuniform distribution of tumor cell density, derived from the literature. Results: When TCP values were above and below 0.62, the 5-year freedom from biochemical failure were 93.7% (95% confidence interval [CI], 90.4, 96.4%) and 88.8% (95% confidence interval, 81.3, 94.5%), respectively (p = 0.004). Conclusions: Using postimplant dosimetry data, the TCP model was able to predict for freedom from biochemical failure. The cutpoint value that would be used clinically depends on the selection of the model parameters, but the potential for the model to be used in the optimization of treatment planning is demonstrated. [Copyright &y& Elsevier]

Introduction We present the results of a pilot study to test the feasibility of a brachytherapy dosimetry audit. Methods The feasibility study was conducted at seven sites from four Australian states in both public and private centres. A purpose-built cylindrical water phantom was imaged using the local imaging protocol and a treatment plan was generated to deliver 1 Gy to the central (1 of 3) thermoluminescent dosimeter ( TLD) from six dwell positions. Results All centres completed the audit, consisting of three consecutive irradiations, within a 2-h time period, with the exception of one centre that uses a pulsed dose rate brachytherapy unit. All TLD results were within 4.5% of the predicted value, with the exception of one subset where the dwell position step size was incorrectly applied. Conclusions While the limited data collected in the study demonstrated considerable heterogeneity in clinical practice, the study proved a brachytherapy dosimetry audit to be feasible. Future studies should include verification of source strength using a Standard Dosimetry Laboratory calibrated chamber, a phantom that more closely mimics the clinical situation, a more comprehensive review of safety and quality assurance ( QA) procedures including source dwell time and position accuracy, and a review of patient treatment QA procedures such as applicator position verification. [ABSTRACT FROM AUTHOR]