Inter-institutional studies highlighted correlation between consistent radiotherapy quality and improved overall patient survival. In treatment planning automation has the potential to address differences due to user-experience and training, promoting standardisation. The aim of this study was to evaluate implementation and clinical effect of a multicentre collaboratively-developed automated planning model for Intensity-Modulated Radiation Therapy/Volumetric-Modulated Arc Therapy of prostate. The model was built using a variety of public institutions’ clinical plans, incorporating different contouring and dose protocols, aiming at minimising their variation. A model using 110 clinically approved and treated prostate plans provided by different radiotherapy centres was built with RapidPlan (RP), for use on intact and post-prostatectomy prostate cases. The model was validated, distributed and introduced into clinical practice in all institutions. To investigate its impact a total of 126 patients, originally manually inverse planned (OP), were replanned using RP without additional planner manual intervention. Target and organ-at-risk (OAR) metrics were statistically compared between original and automated plans. For all centres combined and individually, RP provided plans comparable or superior to OP for all dose metrics. Statistically significant reductions with RP were found in bladder (V40Gy) and rectal (V50Gy) low doses (within 2.3% and 3.4% for combined and 4% and 10% individually). No clinically significant changes were seen for the PTV, independently of seminal vesicle inclusion. This project showed it is feasible to develop, share and implement RP models created with plans from different institutions treated with a variety of techniques and dose protocols, with the potential of improving treatment planning results and/or efficiency despite the original variability.

Purpose: For prostate cancer treatment, comparable or superior biochemical control was reported when using External-Beam-Radiotherapy (EBRT) with High-Dose-Rate-Brachytherapy (HDRB)-boost, compared to dose-escalation with EBRT alone. The conformal doses produced by HDRB could allow further beneficial prostate dose-escalation, but increase in dose is limited by normal tissue toxicity. Previous works showed correlation between urethral dose and incidence of urinary toxicity, but there is a lack of established guidelines on the dose constraints to this organ. This work aimed at fitting a Normal-Tissue-Complication-Probability model to urethral stricture data collected at one institution and validating it with an external cohort, looking at neo-adjuvant androgen deprivation as dose-modifying factor. Materials and Methods: Clinical and dosimetric data of 258 patients, with a toxicity rate of 12.8%, treated at a single institution with a variety of prescription doses, were collected to fit the Lyman–Kutcher–Burman (LKB) model using the maximum likelihood method. Due to the different fractionations, doses were converted into 2 Gy-equivalent doses (α/β = 5 Gy), and urethral stricture was used as an end-point. For validation, an external cohort of 187 patients treated as part of the TROG (Trans Tasman Radiation Oncology Group) 03.04 RADAR trial with a toxicity rate of 8.7%, was used. The goodness of fit was assessed using calibration plots. The effect of neo-adjuvant androgen deprivation (AD) was analyzed separating patients who had received it prior to treatment from those who did not receive it. Results: The obtained LKB parameters were TD50 = 116.7 Gy and m = 0.23; n was fixed to 0.3, based on numerical optimization of the likelihood. The calibration plot showed a good agreement between the observed toxicity and the probability predicted by the model, confirmed by bootstrapping. For the external validation, the calibration plot showed that the observed toxicity obtained with the RADAR patients was well-represented by the fitted LKB model parameters. When patients were stratified by the use of AD TD50 decreased when AD was not present. Conclusions: Lyman–Kutcher–Burman model parameters were fitted to the risk of urethral stricture and externally validated with an independent cohort, to provide guidance on urethral tolerance doses for patients treated with a HDRB boost. For patients that did not receive AD, model fitting provided a lower TD50 suggesting a protective effect on urethra toxicity.

It has been shown lately that gold nanoparticles (AuNPs) and ionizing radiation (IR) have inhibitory effects on cancer cell migration while having promoting effects on normal cells' motility. Also, IR increases cancer cell adhesion with no significant effects on normal cells. In this study, synchrotron-based microbeam radiation therapy, as a novel pre-clinical radiotherapy protocol, is employed to investigate the effects of AuNPs on cell migration. Experiments were conducted utilizing synchrotron X-rays to investigate cancer and normal cell morphology and migration behaviour when they are exposed to synchrotron broad beams (SBB) and synchrotron microbeams (SMB). This in vitro study was conducted in two phases. In phase I two cancer cell lines – human prostate (DU145) and human lung (A549) – were exposed to various doses of SBB and SMB. Based on the phase I results, in phase II two normal cell lines were studied: human epidermal melanocytes (HEM) and human primary colon epithelial (CCD841), along with their respective cancerous counterparts, human primary melanoma (MM418-C1) and human colorectal adenocarcinoma (SW48). The results show that radiation-induced damage in cells' morphology becomes visible with SBB at doses greater than 50 Gy, and incorporating AuNPs increases this effect. Interestly, under the same conditions, no visible morphological changes were observed in the normal cell lines post-irradiation (HEM and CCD841). This can be attributed to the differences in cell metabolic and reactive oxygen species levels between normal and cancer cells. The outcome of this study highlights future applications of synchrotron-based radiotherapy, where it is possible to deliver extremely high doses to cancer tissues whilst preserving surrounding normal tissues from radiation-induced damage.

To determine the optimal volume of barium for oesophageal localisation on cone-beam CT (CBCT) for locally-advanced non-small cell lung cancers (NSCLC) and quantify the interfraction oesophageal movement relative to tumour. Twenty NSCLC patients with mediastinal and/or hilar disease receiving radical radiotherapy were recruited. The first five patients received 25 ml of barium prior to their planning CT and alternate CBCTs during treatment. Subsequent five patient cohorts, received 15 ml, 10 ml and 5 ml. Six observers contoured the oesophagus on each of the 107 datasets and consensus contours were created. Overall 642 observer contours were generated and interobserver contouring reproducibility was assessed. The kappa statistic, dice coefficient and Hausdorff Distance (HD) were used to compare barium-enhanced CBCTs and non-enhanced CBCTs. Oesophageal displacement was assessed using the HD between consensus contours of barium-enhanced CBCTs and planning CTs. Interobserver contouring reproducibility was significantly improved in barium-enhanced CBCTs compared to non-contrast CBCTs with minimal difference between barium dose levels. Only 10 mL produced a significantly higher kappa (0.814, p = 0.008) and dice (0.895, p = 0.001). The poorer the reproducibility without barium, the greater the improvement barium provided. The median interfraction HD between consensus contours was 4 mm, with 95% of the oesophageal displacement within 15 mm. 10 mL of barium significantly improves oesophageal localisation on CBCT with minimal image artifact. The oesophagus moves substantially and unpredictably over a course of treatment, requiring close daily monitoring in the context of hypofractionation.