A humanized orthotopic tumor microenvironment alters the bone metastatic tropism of prostate cancer cells.

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men, and bone is the most frequent site of metastasis. The tumor microenvironment (TME) impacts tumor growth and metastasis, yet the role of the TME in PCa metastasis to bone is not fully understood. We used a tissue-engineered xenograft approach in NOD-scid IL2Rγnull (NSG) mice to incorporate two levels of humanization; the primary tumor and TME, and the secondary metastatic bone organ. Bioluminescent imaging, histology, and immunohistochemistry were used to study metastasis of human PC-3 and LNCaP PCa cells from the prostate to tissue-engineered bone. Here we show pre-seeding scaffolds with human osteoblasts increases the human cellular and extracellular matrix content of bone constructs, compared to unseeded scaffolds. The humanized prostate TME showed a trend to decrease metastasis of PC-3 PCa cells to the tissue-engineered bone, but did not affect the metastatic potential of PCa cells to the endogenous murine bones or organs. On the other hand, the humanized TME enhanced LNCaP tumor growth and metastasis to humanized and murine bone. Together this demonstrates the importance of the TME in PCa bone tropism, although further investigations are needed to delineate specific roles of the TME components in this context.

Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial.

PURPOSE: Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist. METHODS: Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m2 once every 3 weeks for three cycles before RT and 20 mg/m2 once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 v 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors. RESULTS: After a median follow-up of 10.2 years, 89 men died (25.43%); of these, 42 from PC (47.19%). Although OS was not significantly increased in the docetaxel arm (the restricted mean survival time over 10 years was 9.11 v 8.82 years; P = .22), significantly fewer RT-induced cancers were observed (10-year estimates: 0.61% v 4.90%; age-adjusted hazard ratio of 0.13; 95% CI, 0.02 to 0.97; P = .046). The treatment effect of adding docetaxel to ADT + RT on OS significantly differed in men with a PSA < 4 ng/mL versus 4-20 ng/mL (adjusted hazard ratio: 0.27 and 1.51, respectively) because of less PC-specific mortality on the docetaxel arm (0.00% v 28.57%) among men with PSA < 4 ng/mL. CONCLUSION: Adding docetaxel to ADT + RT did not prolong OS in men with unfavorable-risk PC, but decreased RT-induced cancer incidence, and may prolong OS in the subgroup of men with a PSA < 4 ng/mL by reducing PC-specific mortality.

Voxel-based supervised machine learning of peripheral zone prostate cancer using noncontrast multiparametric MRI.

PURPOSE: The aim of this study was to develop and assess the performance of supervised machine learning technique to classify magnetic resonance imaging (MRI) voxels as cancerous or noncancerous using noncontrast multiparametric MRI (mp-MRI), comprised of T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and advanced diffusion tensor imaging (DTI) parameters. MATERIALS AND METHODS: In this work, 191 radiomic features were extracted from mp-MRI from prostate cancer patients. A comprehensive set of support vector machine (SVM) models for T2WI and mp-MRI (T2WI + DWI, T2WI + DTI, and T2WI + DWI + DTI) were developed based on novel Bayesian parameters optimization method and validated using leave-one-patient-out approach to eliminate any possible overfitting. The diagnostic performance of each model was evaluated using the area under the receiver operating characteristic curve (AUROC). The average sensitivity, specificity, and accuracy of the models were evaluated using the test data set and the corresponding binary maps generated. Finally, the SVM plus sigmoid function of the models with the highest performance were used to produce cancer probability maps. RESULTS: The T2WI + DWI + DTI models using the optimal feature subset achieved the best performance in prostate cancer detection, with the average AUROC , sensitivity, specificity, and accuracy of 0.93 ± 0.03, 0.85 ± 0.05, 0.82 ± 0.07, and 0.83 ± 0.04, respectively. The average diagnostic performance of T2WI + DTI models was slightly higher than T2WI + DWI models (+3.52%) using the optimal radiomic features. CONCLUSIONS: Combination of noncontrast mp-MRI (T2WI, DWI, and DTI) features with the framework of a supervised classification technique and Bayesian optimization method are able to differentiate cancer from noncancer voxels with high accuracy and without administration of contrast agent. The addition of cancer probability maps provides additional functionality for image interpretation, lesion heterogeneity evaluation, and treatment management.

The Membrane Protein Sortilin Can Be Targeted to Inhibit Pancreatic Cancer Cell Invasion.

Pancreatic cancer has a dismal prognosis, and there is no targeted therapy against this malignancy. The neuronal membrane protein sortilin is emerging as a regulator of cancer cell development, but its expression and impact in pancreatic cancer are unknown. This study found that sortilin expression was higher in pancreatic cell lines versus normal pancreatic ductal epithelial cells, as shown by Western blot analysis and mass spectrometry. The increased sortilin level in pancreatic cancer cells was confirmed by immunohistochemistry in a series of 99 human pancreatic adenocarcinomas versus 48 normal pancreatic tissues (P = 0.0014). Sortilin inhibition by siRNA and the pharmacologic inhibitor AF38469 strongly reduced the adhesion and invasion of pancreatic cancer cells without affecting cell survival and viability. Sortilin inhibition also decreased the phosphorylation of the focal adhesion kinase in Tyr925. Together, these data show that sortilin contributes to pancreatic cancer invasion and could eventually be targeted in therapy.

Tumour innervation and neurosignalling in prostate cancer.

Prostate cancer progression has been shown to be dependent on the development of autonomic nerves into the tumour microenvironment. Sympathetic nerves activate adrenergic neurosignalling that is necessary in early stages of tumour progression and for initiating an angiogenic switch, whereas parasympathetic nerves activate cholinergic neurosignalling resulting in tumour dissemination and metastasis. The innervation of prostate cancer seems to be initiated by neurotrophic growth factors, such as the precursor to nerve growth factor secreted by tumour cells, and the contribution of brain-derived neural progenitor cells has also been reported. Current experimental, epidemiological and clinical evidence shows the stimulatory effect of tumour innervation and neurosignalling in prostate cancer. Using nerves and neurosignalling could have value in the management of prostate cancer by predicting aggressive disease, treating localized disease through denervation and relieving cancer-associated pain in bone metastases.

Characterization of prostate cancer using diffusion tensor imaging: A new perspective.

PURPOSE: This study is aimed at evaluating the potential role of quantitative magnetic resonance diffusion tensor imaging (DTI) and tractography parameters in the detection and characterization of peripheral zone prostate cancer with a particular attention for fiber tract density. MATERIALS AND METHODS: DTI was acquired from eleven high risk, transrectal ultrasound (TRUS)-guided biopsy proven prostate cancers with perineural invasion (histological Gleason score ≥ 7) on a 3 T magnet. Twenty parameters derived from DTI were quantified in cancer and healthy regions of the prostate. In addition, fiber tract density in normal versus cancer tissues was also calculated using DTI tractography. Support vector machine with a radial basis function kernel and area under receiver operator characteristic (ROC) were used to describe and compare the diagnostic performance of combined fractional anisotropy (FA) and mean diffusivity (MD) and other statistically significant DTI parameters. Spearman correlation analysis between DTI parameters and Gleason scores was conducted. RESULTS: Eighteen DTI parameters yielded statistically significant differences between cancer and healthy regions (p-value < 0.05). The ROC curve of all statistically significant DTI parameters between cancer and healthy regions was higher than the area under ROC curve using FA + MD alone (95% confidence interval = 0.988, range = 0.975-1.00) vs (95% confidence interval = 0.935, range = 0.898-0.999), respectively (p-value < 0.05). Fiber tract density was also found to be higher in cancer than in healthy tissues (+38.22%, p-value = 0.010) and may be related to the increase in nerve and vascular density reported in prostate cancer. The linear and relative anisotropy were highly correlated with Gleason score (Spearman correlation factor r = 0.655, p-value = 0.001 and r = 0.667, p-value < 0.001, respectively). CONCLUSIONS: DTI has the potential to provide imaging biomarkers in the detection and characterization of prostate cancer. Novel quantitative parameters derived from DTI and DTI tractography, including fiber tract density, support the use of DTI in the assessment of high grade prostate cancer.

Multi-observer contouring of male pelvic anatomy: Highly variable agreement across conventional and emerging structures of interest.

INTRODUCTION: This study quantified inter-observer contouring variations for multiple male pelvic structures, many of which are of emerging relevance for prostate cancer radiotherapy progression and toxicity response studies. METHODS: Five prostate cancer patient datasets (CT and T2-weighted MR) were distributed to 13 observers for contouring. CT structures contoured included the clinical target volume (CTV), seminal vesicles, rectum, colon, bowel bag, bladder and peri-rectal space (PRS). MR contours included CTV, trigone, membranous urethra, penile bulb, neurovascular bundle and multiple pelvic floor muscles. Contouring variations were assessed using the intraclass correlation coefficient (ICC), Dice similarity coefficient (DSC), and multiple additional metrics. RESULTS: Clinical target volume (CT and MR), bladder, rectum and PRS contours showed excellent inter-observer agreement (median ICC = 0.97; 0.99; 1.00; 0.95; 0.90, DSC = 0.83 ± 0.05; 0.88 ± 0.05; 0.93 ± 0.03; 0.81 ± 0.07; 0.80 ± 0.06, respectively). Seminal vesicle contours were more variable (ICC = 0.75, DSC = 0.73 ± 0.14), while colon and bowel bag contoured volumes were consistent (ICC = 0.97; 0.97), but displayed poor overlap (DSC = 0.58 ± 0.22; 0.67 ± 0.21). Smaller MR structures showed significant inter-observer variations, with poor overlap for trigone, membranous urethra, penile bulb, and left and right neurovascular bundles (DSC = 0.44 ± 0.22; 0.41 ± 0.21; 0.66 ± 0.21; 0.16 ± 0.17; 0.15 ± 0.15). Pelvic floor muscles recorded moderate to strong inter-observer agreement (ICC = 0.50-0.97), although large outlier variations were observed. CONCLUSIONS: Inter-observer contouring variation was significant for multiple pelvic structures contoured on MR.

Spinal Cord Injuries and Nerve Dependence in Prostate Cancer.

Nerves are emerging as drivers of tumorigenesis, as demonstrated in the mouse where denervation suppresses prostate cancer; however, clinical evidence is needed. Patients with spinal cord injuries (SCIs) resulting in functional denervation of the prostate have a lower incidence of prostate cancer. This may constitute a clinical evidence for nerve dependence in human prostate tumorigenesis.

Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography for Prostate Cancer: Distribution of Disease and Implications for Radiation Therapy Planning.

PURPOSE: To explore the prostate-specific membrane antigen (PSMA)-avid distribution of prostate cancer (PC) on positron emission tomography (PET), both at the time of initial diagnosis and at the time of relapse after definitive local treatment. METHODS AND MATERIALS: A total of 179 PSMA PET scans in patients with nil or ≤3 lesions on conventional imaging were retrospectively categorized into 3 subgroups: group A, high-risk PC with no prior definitive therapy (n=34); group B, prior prostatectomy (n=75); and group C, prior radiation therapy (n=70). The numbers and locations of the PSMA-avid lesions were mapped. The PSMA-positive lesions were identified subjectively by a nuclear medicine physician on the basis of clinical experience and taking into account the recent literature and artefacts. RESULTS: A total of 893 PSMA-avid lesions were identified; at least 1 lesion was detected in 80% of all scans. A high detection rate was present even at very low serum PSA levels (eg, at PSA ≤0.20 ng/mL in group B, the detection rate was 46%). Thirty-eight percent of studies revealed extrapelvic disease (41%, 31%, and 46% in groups A, B, and C, respectively). Almost one-third of all studies showed only oligometastases (24%, 36%, and 31% in groups A, B, and C, respectively). A large proportion of these (40%) were a solitary lesion. CONCLUSIONS: Prostate-specific membrane antigen PET demonstrated a large number of otherwise unknown metastatic lesions. Therefore we recommend PSMA PET for more accurate assessment of disease burden in initial staging of high-risk PC, as well as for restaging in patients with prostate-specific antigen relapse after primary therapies. Furthermore, a high proportion of oligometastases on PSMA PET provides a prime opportunity to investigate the role of targeted local therapies for oligometastatic PCs.

Tissue engineering and regenerative medicine in musculoskeletal oncology.

Currently used surgical techniques to reconstruct tissue defects after resection of musculoskeletal tumours are associated with high complication rates. This drives a strong demand for innovative therapeutic concepts that are able to improve the clinical outcomes of patients suffering from bone and soft tissue tumours. Tissue engineering and regenerative medicine (TE&RM) provides a technology platform based on biochemical, molecular, cellular and biomaterials modules to selectively direct tissue healing processes for improved defect regeneration. At the same time, precautionary measures have to be taken when these instruments are used in cancer patients to prevent any promotion of tumour growth or metastatic spread. On the other hand, several innovative TE&RM tools are being developed such as multi-functionalized biomaterials, drug-delivering nanomaterials or genetically engineered stem cells that per se have the potential to mediate anti-cancer effects, act synergistically with currently used chemotherapeutics and/or radiotherapy regimens and reduce their side effects. Recently, scientists became conscious that TE&RM strategies may not only be utilized to advance contemporary tissue reconstruction techniques but also to develop personalized diagnostic tools and clinically relevant disease models for cancer patients. Eventually, prospective randomized clinical trials combined with comparative outcome analyses are a conditio sine qua non to shape the benefits of personalized regenerative therapies for the standardized management of patients with musculoskeletal tumours.

Dosimetry, clinical factors and medication intake influencing urinary symptoms after prostate radiotherapy: An analysis of data from the RADAR prostate radiotherapy trial.

PURPOSE/OBJECTIVE: To identify dosimetry, clinical factors and medication intake impacting urinary symptoms after prostate radiotherapy. MATERIAL AND METHODS: Data describing clinical factors and bladder dosimetry (reduced with principal component (PC) analysis) for 754 patients treated with external beam radiotherapy accrued by TROG 03.04 RADAR prostate radiotherapy trial were available for analysis. Urinary symptoms (frequency, incontinence, dysuria and haematuria) were prospectively assessed using LENT-SOMA to a median of 72months. The endpoints assessed were prevalence (grade ⩾1) at the end of radiotherapy (representing acute symptoms), at 18-, 36- and 54-month follow-ups (representing late symptoms) and peak late incidence including only grade ⩾2. Impact of factors was assessed using multivariate logistic regression models with correction for over-optimism. RESULTS: Baseline symptoms, non-insulin dependent diabetes mellitus, age and PC1 (correlated to the mean dose) impact symptoms at >1 timepoints. Associations at a single timepoint were found for cerebrovascular condition, ECOG status and non-steroidal anti-inflammatory drug intake. Peak incidence analysis shows the impact of baseline, bowel and cerebrovascular condition and smoking status. CONCLUSIONS: The prevalence and incidence analysis provide a complementary view for urinary symptom prediction. Sustained impacts across time points were found for several factors while some associations were not repeated at different time points suggesting poorer or transient impact.

Wellbeing during Active Surveillance for localised prostate cancer: a systematic review of psychological morbidity and quality of life.

BACKGROUND: Active Surveillance (AS) is recommended for the treatment of localised prostate cancer; however this option may be under-used, at least in part because of expectations of psychological adverse events in those offered or accepting AS. OBJECTIVE: (1) Determine the impact on psychological wellbeing when treated with AS (non-comparative studies). (2) Compare AS with active treatments for the impact on psychological wellbeing (comparative studies). METHOD: We used the PRISMA guidelines and searched Medline, PsychInfo, EMBASE, CINHAL, Web of Science, Cochrane Library and Scopus for articles published January 2000-2014. Eligible studies reported original quantitative data on any measures of psychological wellbeing. RESULTS: We identified 34 eligible articles (n=12,497 individuals); 24 observational, eight RCTs, and two other interventional studies. Studies came from North America (16), Europe (14) Australia (3) and North America/Europe (1). A minority (5/34) were rated as high quality. Most (26/34) used validated instruments, whilst a substantial minority (14/34) used watchful waiting or no active treatment rather than Active Surveillance. There was modest evidence of no adverse impact on psychological wellbeing associated with Active Surveillance; and no differences in psychological wellbeing compared to active treatments. CONCLUSION: Patients can be informed that Active Surveillance involves no greater threat to their psychological wellbeing as part of the informed consent process, and clinicians need not limit access to Active Surveillance based on an expectation of adverse impacts on psychological wellbeing.

Impact of treatment planning and delivery factors on gastrointestinal toxicity: an analysis of data from the RADAR prostate radiotherapy trial.

BACKGROUND: To assess the impact of incremental modifications of treatment planning and delivery technique, as well as patient anatomical factors, on late gastrointestinal toxicity using data from the TROG 03.04 RADAR prostate radiotherapy trial. METHODS: The RADAR trial accrued 813 external beam radiotherapy participants during 2003-2008 from 23 centres. Following review and archive to a query-able database, digital treatment plans and data describing treatment technique for 754 patients were available for analysis. Treatment demographics, together with anatomical features, were assessed using uni- and multivariate regression models against late gastrointestinal toxicity at 18-, 36- and 54-month follow-up. Regression analyses were reviewed in the context of dose-volume data for the rectum and anal canal. RESULTS: A multivariate analysis at 36-month follow-up shows that patients planned using a more rigorous dose calculation algorithm (DCA) was associated with a lower risk of stool frequency (OR: 0.435, CI: 0.242-0.783, corrected p = 0.04). Patients using laxative as a method of bowel preparation had higher risk of having increased stool frequency compared to patients with no dietary intervention (OR: 3.639, CI: 1.502-8.818, corrected p = 0.04). Despite higher risks of toxicities, the anorectum, anal canal and rectum dose-volume histograms (DVH) indicate patients using laxative had unremarkably different planned dose distributions. Patients planned with a more rigorous DCA had lower median DVH values between EQD23 = 15 Gy and EQD23 = 35 Gy. Planning target volume (PTV), conformity index, rectal width and prescription dose were not significant when adjusted for false discovery rate. Number of beams, beam energy, treatment beam definition, positioning orientation, rectum-PTV separation, rectal length and mean cross sectional area did not affect the risk of toxicities. CONCLUSIONS: The RADAR study dataset has allowed an assessment of technical modifications on gastrointestinal toxicity. A number of interesting associations were subsequently found and some factors, previously hypothesised to influence toxicity, did not demonstrate any significant impact. We recommend trial registries be encouraged to record technical modifications introduced during the trial in order for more powerful evidence to be gathered regarding the impact of the interventions.

Do women have a role in early detection of prostate cancer? - Lessons from a qualitative study.

BACKGROUND: Prostate cancer is the most common internal cancer in Australian men; more than 3000 men die annually from it. Public awareness of prostate cancer is an important factor in early detection and treatment. Women are known to act as 'health managers' for their families and may have a role to play in early detection. OBJECTIVE: To describe community perceptions of prostate cancer and identify information needs within the Australian context. METHOD: A qualitative study using focus group and individual interviews with 44 community volunteers, 18 men with recent diagnosis of prostate cancer and nine of their wives/partners (n=71). DISCUSSION: Men in the community are poorly informed about prostate cancer, prefer to ignore (male) health issues, and expect their general practitioners to provide authoritative advice on testing for prostate cancer. While women are also poorly informed, they are keen to change the prevailing situation of silence and lack of information in the community, and need to be included in public education campaigns.

Telling their stories, telling our stories: physicians' experiences with patients who decide to forgo or stop treatment for cancer.

There is currently very little research on how physicians respond to patients with cancer who decide to forgo or stop medically recommended "curative" therapy. The purpose of this article is to report on a qualitative study with 12 oncology specialists in Israel and Australia that addresses this question. The findings indicate that physicians tend to construct patients and their decisions in terms of mutually exclusive categories that focus on curability of the disease, rationality of the patient's decision, and patients' personal attributes. Physicians' constructions of their experience focus on uncertainty and concern. Although contextual factors play a role in how physicians act in this situation, Israeli and Australian oncologists are remarkably similar in how they describe their own and their patients' experiences.

Tirapazamine, Cisplatin, and Radiation versus Fluorouracil, Cisplatin, and Radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02).

PURPOSE: To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost). RESULTS: Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms. CONCLUSION: Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.

Dosimetric intercomparison for two Australasian clinical trials using an anthropomorphic phantom.

INTRODUCTION: Many different factors can affect the accurate delivery of dose to the clinical target volume in radiotherapy. This is particularly important in the context of multicenter clinical trials where different equipment and techniques may be used for supposedly identical treatments. A dosimetric intercomparison employing an anthropomorphic phantom (level III dosimetric intercomparison) can be used to check many of the factors that could affect treatment by mimicking the radiotherapy pathway of a patient as closely as possible. METHODS AND MATERIALS: An anthropomorphic phantom (ART) was taken to 18 radiotherapy centers in Australia and New Zealand and treated for two different treatment scenarios based on current clinical trials of the Trans-Tasman Radiation Oncology Group (TROG): a two-field treatment of a carcinoma of the tonsil (TROG 91.01), and a four-field prostate treatment (TROG 96.01). The dose distribution was assessed in two consecutive treatments using thermoluminescence dosimeters (TLDs) placed throughout the target volume and in "critical" structures such as the lens of the eye or the rectum. The study also included a check of absolute dose calibration in a slab phantom (level I dosimetric intercomparison). The influence of a variety of treatment parameters on the dose homogeneity in the target and the measured dose in the target and the critical organs was evaluated. RESULTS: The dose measurements confirmed that in all participating centers the correct dose was delivered to the ICRU reference point (tonsil: 99.8 +/- 2.3%; prostate: 100.9 +/- 1.9% [1 SD]). Also the absolute dose calibration and the mean dose in the target volume were within the specified action levels of plus minus 5% for all participating centers. No influence of shielding, beam modifiers, beam weighting, treatment planning approach (CT, 2D, 3D), and type of equipment used on the dose in the target and its homogeneity could be demonstrated. However, treatment technique and energy used influenced the dose to the critical organs. It was shown that the interpretation of results could be improved by including two complementary treatment scenarios and a level I intercomparison with the level III dosimetric intercomparison. CONCLUSION: The study demonstrated the feasibility of a level III dosimetric intercomparison service at a cost of approximately $1000(US) per center in Australasia. It confirmed that the dose delivered by all participating centers was as intended in the two treatment scenarios chosen. While this provides reassurance to the oncology community and the general public, the service must be extended to all centers and other potentially more complex treatment scenarios. The present study has built the foundation for this by establishing a baseline and action levels and suggesting improvements in phantom design which will be included in future TROG quality assurance exercises.