We collaborated with patients and healthcare professionals through focus groups and an online questionnaire, to learn about their experience and needs in the detection, diagnosis and surveillance of prostate cancer. We identified a need for clear and understandable written information to be given to people at the start of their journey. Whilst patients are generally satisfied with the different tests, prostate biopsies had the highest dissatisfaction rates and were particularly disliked by patients on active surveillance, who experience multiple surveillance biopsies. Background: Our understanding of patient experiences with prostate cancer testing for diagnosis and surveillance is limited. The aim of this study was to collaborate with patients and clinicians to understand their lived experience and unmet needs around the early detection, diagnosis and monitoring (active surveillance) of prostate cancer. Methods: Two focus groups were held with patients (n = 20) and healthcare professionals (n = 16), to identify the main challenges in prostate cancer detection, diagnosis, and monitoring. This information formed the basis of an online questionnaire for broader dissemination. Results: A total of 1138 analyzable responses were obtained from people tested for prostate cancer (69% tested positive) in Europe and the US. Only 29 healthcare professionals completed the survey. Almost one-third of people reported knowing very little/nothing about prostate cancer prior to testing. Prior disease awareness was significantly higher in those who tested negative (P < .0001). Most respondents (n = 857; 75%) felt informed about the steps involved in testing. Receiving written information was a key factor; 91% of those who felt uninformed were not given any written information. Overall, most people felt "satisfied" with the typical prostate cancer tests: PSA, DRE, mpMRI, and biopsy. However, dissatisfaction for prostate biopsy (12%) was almost double that of other tests (P < .0001). Most patients understood why each test was done, and felt that their results and next steps were clearly explained to them; though PSA scored lowest in all of these fields. Apart from PSA, test satisfaction was lower when used repeatedly for surveillance, compared to once -off detection/diagnosis. Conclusions: Greater public awareness and education around prostate cancer, as well as clear and accessible written information for patients at the beginning of their cancer journey is needed. Further research is needed into alternative, less invasive tests, particularly when used repeatedly in the surveillance population.

Background and purposes: To assess osteoradionecrosis (ORN) incidence in a population of Irish Head and Neck cancer (HNC) patients, and assess precipitating factors that may contribute to ORN development to aid prevention. Materials and methods: Review of 1050 HNC patients attending the Dental Oncology Clinic, CUDSH between 2010 and 2021 identified 47 cases of ORN. Medical, dental and radiotherapy records of these forty-seven patients were retrospectively reviewed. Patient-, tumour-, and treatment-related variables were investigated in association with osteoradionecrosis development. Analysis conducted using SPSS, Pearson's Chi-square test (p < 0.05), and ordinal regression model. Results: ORN incidence was 4.4 %. Median time from radiotherapy (RT) to ORN development was 9.5 months (range 1-98.5 months). ORN development within the mandibular surgical site was significant (p <.001), presenting at a higher Notani grade (p =.002), in mid-mandibular body region (p =.028), at radiation doses >= 60 Gy (p =.035), due to induced causes (p =.029), and without resolution (p =.019). Conclusion: This is the first retrospective study of ORN in HNC patients in Ireland over 10-year period. ORN incidence was extremely low (4.4%). As patients reported high smoking/alcohol use and poor dental attendance pre-diagnosis, this suggests intensive dental intervention pre/post-diagnosis contributed to low ORN rates. Mandibular surgery pre-RT increased risk of developing ORN at the surgical site. Therefore, we recommend future treatment planning should contour the surgical site, designating it an organ at risk (OAR), assigning a dose constraint, where oncologically possible, with emphasis on reducing the hot-spot to this region; findings reinforce importance of life-long expert dental care to reduce ORN incidence.

Purpose: The aim of this study was to establish the feasibility of a randomized clinical trial comparing SABR with prostateonly (P-SABR) or with prostate plus pelvic lymph nodes (PPN-SABR) in patients with unfavorable intermediate- or high-risk localized prostate cancer and to explore potential toxicity biomarkers.Methods and Materials: Thirty adult men with at least 1 of the following features were randomized 1:1 to P-SABR or PPNSABR: clinical magnetic resonance imaging stage T3a N0 M0, Gleason score >= 7 (4+3), and prostate-specific antigen >20 ng/mL. P-SABR patients received 36.25 Gy/5 fractions/29 days, and PPN-SABR patients received 25 Gy/5 fractions to pelvic nodes, with the final cohort receiving a boost to the dominant intraprostatic lesion of 45 to 50 Gy. Phosphorylated gammaH2AX (gH2AX) foci numbers, citrulline levels, and circulating lymphocyte counts were quantified. Acute toxicity information (Common Terminology Criteria for Adverse Events, version 4.03) was collected weekly at each treatment and at 6 weeks and 3 months. Physician-reported late Radiation Therapy Oncology Group (RTOG) toxicity was recorded from 90 days to 36months postcompletion of SABR. Patient-reported quality of life (Expanded Prostate Cancer Index Composite and Interna-tional Prostate Symptom Score) scores were recorded with each toxicity time point.Results: The target recruitment was achieved, and treatment was successfully delivered in all patients. A total of 0% and 6.7% (P-SABR) and 6.7% and 20.0% (PPN-SABR) experienced acute grade >= 2 gastrointestinal (GI) and genitourinary (GU) toxicity, respectively. At 3 years, 6.7% and 6.7% (P-SABR) and 13.3% and 33.3% (PPN-SABR) had experienced late grade >= 2 GI and GU toxicity, respectively. One patient (PPN-SABR) had late grade 3 GU toxicity (cystitis and hematuria). No other grade >= 3 toxicity was observed. In addition, 33.3% and 60% (P-SABR) and 64.3% and 92.9% (PPN-SABR) experienced a minimally clin-ically important change in late Expanded Prostate Cancer Index Composite bowel and urinary summary scores, respectively. yH2AX foci numbers at 1 hour after the first fraction were significantly higher in the PPN-SABR arm compared with the P-SABR arm (P = .04). Patients with late grade >= 1 GI toxicity had significantly greater falls in circulating lymphocytes (12 weeks post-radiation therapy, P = .01) and a trend toward higher yH2AX foci numbers (P = .09) than patients with no late toxicity. Patients with late grade >= 1 bowel toxicity and late diarrhea experienced greater falls in citrulline levels (P = .05).Conclusions: A randomized trial comparing P-SABR with PPN-SABR is feasible with acceptable toxicity. Correlations of yH2AX foci, lymphocyte counts, and citrulline levels with irradiated volume and toxicity suggest potential as predictive bio-markers. This study has informed a multicenter, randomized, phase 3 clinical trial in the United Kingdom. (c) 2023 Elsevier Inc. All rights reserved.

Background Our radiotherapy department is situated onsite at a university-affiliated hospital where medical students undertake clinical rotations. However, no formal programme for attachments to the radiation oncology service was previously in place. Student experience was limited to occasional classroom-based lectures and sporadic contact with cancer patients while rotating through other clinical services. Under-exposure to radiation oncology (RO) (and oncology generally) during medical school is common. A 2016 survey of medical students at two US universities found that only 4% of third year and 7% of fourth year students completed an RO rotation (Osvarak et al 2016). And 47% of Australian and New Zealand medical students recently reported that RO was not incorporated into their curriculum at all (Bravery et al 2020). We identified improving medical student involvement as a priority for our department. Methods We collaborated with tutors at the University to arrange for medical students to have allocated RO rotations during their clinical attachments at the hospital. Agreed learning objectives fitted into three categories: -fundamental clinical skills in history taking and physical examination -care of cancer patients -an introduction to RO and its role in the care of cancer patients. A multidisciplinary effort with involvement of consultant and trainee radiation oncologists, radiation therapists, nurses, and university representatives allowed us to develop a programme to deliver these learning objectives. Results The programme began in January 2022. One radiation oncologist takes overall responsibility for day-to-day operations and acts as the primary point of contact for the students and other staff members in case of any issues. Students receive tutorials on oncological emergencies and are involved in academic sessions in the department. They are supervised as they spend time contouring organs at risk and clinical targets and also have dedicated sessions with radiation therapists where they observe the delivery of external beam radiotherapy. Clinical experience is gained via attendance at outpatient clinics and on the inpatient oncology ward. Feedback on history taking and clinical examination is provided via tutorials with radiation oncologists and trainees. Students provided feedback which indicated that they had enjoyed their experience of the specialty and found the rotation beneficial. Discussion The rotation has been well-received by students and the university tutors. The primary goal of incorporating RO rotations into the medical school curriculum was successful and these attachments will continue in future. Involvement of relevant stakeholders within the department and the university contributed to the successful implantation. Our radiotherapy department is situated onsite at a university-affiliated hospital where medical students undertake clinical rotations. However, no formal programme for attachments to the radiation oncology service was previously in place. Student experience was limited to occasional classroom-based lectures and sporadic contact with cancer patients while rotating through other clinical services. Under-exposure to radiation oncology (RO) (and oncology generally) during medical school is common. A 2016 survey of medical students at two US universities found that only 4% of third year and 7% of fourth year students completed an RO rotation (Osvarak et al 2016). And 47% of Australian and New Zealand medical students recently reported that RO was not incorporated into their curriculum at all (Bravery et al 2020). We identified improving medical student involvement as a priority for our department. We collaborated with tutors at the University to arrange for medical students to have allocated RO rotations during their clinical attachments at the hospital. Agreed learning objectives fitted into three categories: -fundamental clinical skills in history taking and physical examination -care of cancer patients -an introduction to RO and its role in the care of cancer patients. A multidisciplinary effort with involvement of consultant and trainee radiation oncologists, radiation therapists, nurses, and university representatives allowed us to develop a programme to deliver these learning objectives. The programme began in January 2022. One radiation oncologist takes overall responsibility for day-to-day operations and acts as the primary point of contact for the students and other staff members in case of any issues. Students receive tutorials on oncological emergencies and are involved in academic sessions in the department. They are supervised as they spend time contouring organs at risk and clinical targets and also have dedicated sessions with radiation therapists where they observe the delivery of external beam radiotherapy. Clinical experience is gained via attendance at outpatient clinics and on the inpatient oncology ward. Feedback on history taking and clinical examination is provided via tutorials with radiation oncologists and trainees. Students provided feedback which indicated that they had enjoyed their experience of the specialty and found the rotation beneficial. The rotation has been well-received by students and the university tutors. The primary goal of incorporating RO rotations into the medical school curriculum was successful and these attachments will continue in future. Involvement of relevant stakeholders within the department and the university contributed to the successful implantation.

234 Background: A full bladder for prostate radiotherapy treatment limits overall dose to the bladder and displaces bowel from high dose regions. There is currently no clear consensus on optimum bladder volume for prostate radiotherapy. Inconsistent bladder volumes can cause dosimetric uncertainty, distress, treatment delay and negative toxicity outcomes for patients. To identify potential ways to improve bladder filling consistency we retrospectively analysed bladder volume variation over the course of patients’ treatment and its relationship to various patient and treatment factors. Methods: We included all patients treated with 60gy in 20 fractions to the prostate only over a 1-year period. Standard fractionation, palliative, post-operative, and whole pelvis treatment regimens were excluded from our study. Patient, tumour, and treatment characteristics were collected retrospectively. We recorded patient reported IPSS scores that were completed pre and post treatment. Daily bladder volumes were recorded from cone beam CT (CBCT) retrospectively for a subset of 34 patients and included in correlative analyses with various treatment and patient factors. Results: 69 men were included in this study with a mean planning CT bladder volume of 272ml (79-574). Patients were divided into large ( > 180ml) and small subgroups (N = 46 vs 23). Smaller bladders resulted in a greater post treatment IPSS score (10.2 vs 7.7 (p = 0.2)) and greater change in IPSS (+3.3 vs +1.4 (p = 0.23). The variation of daily bladder volumes as measured by the standard deviation was positively associated with planning CT volume (p < 0.05), variation in daily treatment time (p < 0.05) and urinary symptoms (p = 0.29). Greater discordances between planning CT time and mean radiotherapy time resulted in a greater average difference between CBCT bladder volume and planning CT volume (p = 0.16). There were no appreciable seasonal or diurnal associations for all recorded bladder volumes. Conclusions: Smaller bladder volumes at planning CT are associated with increased urinary symptoms whereas larger volumes undergo more daily variation. This data suggests an optimal planning bladder volume of 200-400ml to minimise on treatment variation. This is the first study to demonstrate a relationship between variation in daily treatment times and daily bladder variation. Synchronisation of planning CT time with patient treatment time preference will enable patients to better replicate planning CT bladder volumes. This, along with several other areas for improvement highlighted by this study have formed the basis for a prospective single centre pilot study.

Objectives: Radiotherapy is a key cancer treatment modality but is poorly understood by doctors. We sought to evaluate radiation oncology (RO) teaching in medical schools within the United Kingdom (UK) and Republic of Ireland (RoI), as well as any impacts on RO teaching delivery from the coronavirus disease 2019 (COVID-19) pandemic. Methods: A bespoke online survey instrument was developed, piloted and distributed to oncology teaching leads at all UK and RoI medical schools. Questions were designed to capture information on the structure, format, content and faculty for RO teaching, as well as both the actual and the predicted short- and long-term impacts of COVID-19. Results: Responses were received from 29/41 (71%) UK and 5/6 (83%) RoI medical schools. Pre-clinical and clinical oncology teaching was delivered over a median of 2 weeks (IQR 1–6), although only 9 (27%) of 34 responding medical schools had a standalone RO module. RO teaching was most commonly delivered in clinics or wards (n = 26 and 25 respectively). Few medical schools provided teaching on the biological basis for radiotherapy (n = 11) or the RO career pathway (n = 8), and few provide teaching delivered by non-medical RO multidisciplinary team members. There was evidence of short- and long-term disruption to RO teaching from COVID-19. Conclusions: RO teaching in the UK and RoI is limited with minimal coverage of relevant theoretical principles and little exposure to radiotherapy departments and their non-medical team members. The COVID-19 pandemic risks exacerbating trainee doctors’ already constrained exposure to radiotherapy. Advances in knowledge: This study provides the first analysis of radiotherapy-related teaching in the UK and RoI, and the first to explore the impact of the COVID-19 pandemic on radiationoncology teaching.

248 Background: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat low/intermediate risk localised prostate cancer (PCa). However, data on SABR +/- pelvic nodal irradiation (PNI) in high-risk disease is limited to single institution, single-arm studies. The Stereotactic Prostate Radiotherapy (SPORT) trial examined the feasibility of delivering a randomised trial of SABR ± PNI. The composite primary endpoint to determine feasibility comprised: recruitment rate, technical feasibility, acute toxicity (CTCAE v4.0) and quality of life (QoL)(EPIC). Secondary and exploratory endpoints including late toxicity (RTOG) and QoL and potential biomarkers of toxicity (plasma citrulline and DNA damage in circulating lymphocytes) are also presented. Methods: Men with localised PCa demonstrating one of T3a, Gleason score ≥4+3 or PSA>20 were eligible. T3b and T4 disease were excluded. 30 participants were randomised 1:1 to prostate SABR (P-SABR) or prostate and pelvis SABR (PPN-SABR). The prostate and proximal 1-2cm seminal vesicles received 36.25 Gy in 5 fractions over 29 days (prostate CTV 40Gy). The PPN-SABR arm also received 25 Gy in 5 fractions to the pelvic nodes. All patients had fiducial markers and a rectal spacer gel in-situ. As initial toxicity rates were low, the final 10 men received an additional integrated boost to the dominant intraprostatic lesion of up to 50 Gy, irrespective of randomisation. Results: Feasibility was demonstrated. The target recruitment of 30 men was met (83% high risk). Treatment, including an integrated boost plus PNI, was achievable using strict normal tissue constraints. Acute toxicity and QoL were acceptable (Table: Grade≥2 GU 7%, 27% and GI 0%, 7%; minimal clinically important change (MCIC) in EPIC urinary 40%, 60% and bowel score 33%, 47% in P and PPN arms respectively). At median follow up of 30 months (range 18-42 months), late toxicity and QoL were acceptable (Grade≥2 GU 7%, 20% and GI 0%, 13%; MCIC in EPIC urinary 33%, 67% and bowel score 33%, 67% in P and PPN arms respectively). All toxicity was ≤ grade 2 with the exception of one late grade 3 GU toxicity occurring in the PPN arm. Serum citrulline, a marker of small bowel function, trended towards lower levels in the PPN arm, in keeping with a significantly higher dose delivered to the small bowel in this arm. DNA damage foci in circulating lymphocytes increased at 1 hour after radiation. Foci count and repair correlated to toxicity measures will be presented. Conclusions: A randomised clinical trial comparing P-SABR to PPN-SABR is feasible. There was a suggestion of increased toxicity with PPN-SABR, but this remained acceptable. This data will inform a UK multi-centre phase 2 study. Clinical trial information: NCT03253978 . [Table: see text]

73 Background: Plasma levels of citrulline, an amino acid, are derived mainly from small bowel enterocytes. Decreased levels occur in a range of bowel conditions and citrulline has been proposed as a biomarker of bowel toxicity in pelvic radiotherapy. In a prospective study, we identify no correlation between plasma citrulline and toxicity in men receiving prostate stereotactic radiotherapy randomized to receive either pelvic nodal irradiation or not. Furthermore, citrulline levels were not significantly different between these two groups. Methods: As part of an approved clinical trial, men with intermediate to high risk prostate cancer were randomised 1:1 to prostate only or prostate + pelvic nodal radiotherapy, delivered with a rectal spacer gel in situ. The prostate and proximal seminal vesicles received 40 Gy in 5 fractions. Those randomised to the pelvic nodal arm also received 25 Gy in 5 fractions to pelvic nodes. Citrulline was measured at 10 points during treatment – consent, before fraction 1, 1 and 24 hours following fraction 1, prior to each fraction 2 – 5 and at 6 weeks’ and 3 months’ follow up. Bowel toxicity was measured by EPIC patient reported scores. Results: 16 men with follow up of at least 3 months (median 9, maximum 18 months) were analysed. Reported toxicity was significantly higher in the prostate and pelvis arm: 5 of 9 men showed a decrease in EPIC bowel domain summary score of 10 points or more compared to 0 of 7 in the prostate-only arm (p = 0.0337, two tailed Fisher’s exact test). No significant correlation between toxicity and citrulline levels was seen, nor did citrulline vary significantly between arms or fall as treatment progressed. Data analysis for a further 8 men already recruited to the study is ongoing. Conclusions: Toxicity was more commonly reported by men randomised to receive pelvic radiotherapy, suggesting that the small bowel irradiated in pelvic fields plays a role in bowel toxicity experienced during stereotactic radiotherapy. Citrulline levels showed no significant correlation with toxicity or radiation dose to small bowel. We propose that citrulline is not a useful biomarker of small bowel toxicity in this setting. Clinical trial information: NCT03253978.

Purpose: To explore the role of Computed tomography (CT)-based radiomics features in prostate cancer risk stratification. Methods and Materials: The study population consisted of 506 patients with prostate cancer collected from a clinically annotated database. After applying exclusion criteria, 342 patients were included in the final analysis. CT-based radiomics features were extracted from planning CT scans for prostate gland-only structure, and machine learning was used to train models for Gleason score (GS) and risk group (RG) classifications. Repeated cross-validation was used. The discriminatory performance of the developed models was assessed using receiver operating characteristic area under the curve (AUC) analysis. Results: Classifiers using CT-based radiomics features distinguished between GS <= 6 versus GS >= 7 with AUC = 0.90 and GS 7(3 + 4) versus GS 7(4 + 3) with AUC = 0.98. Developed classifiers also showed excellent performance in distinguishing low versus high RG (AUC = 0.96) and low versus intermediate RG (AUC = 1.00), but poorer performance was observed for GS 7 versus GS > 7 (AUC = 0.69). An overall modest performance was observed for validation on holdout data sets with the highest AUC of 0.75 for classifiers of low versus high RG and an AUC of 0.70 for GS 7 versus GS > 7. Conclusions: Our results show that radiomics features from routinely acquired planning CT scans could provide insights into prostate cancer aggressiveness in a noninvasive manner. Assessing models on training data sets, the classifiers were especially accurate in discerning high-risk from low-risk patients and in classifying GS 7 versus GS > 7 and GS 7(3 + 4) versus G 7(4 + 3); however, classifiers were less adept at distinguishing high RG versus intermediate RG. External validation and prospective studies are warranted to verify the presented findings. These findings could potentially guide targeted radiation therapy strategies in radical intent radiation therapy for prostate cancer. (C) 2019 Elsevier Inc. All rights reserved.

Purpose Advances in radiotherapy planning and delivery have made target definition increasingly important. While CT images are required for plan calculation, MR fusion is increasingly used to more accurately define tumour and normal tissue. There is often significant variation seen between diagnostic and therapeutic imaging; hence, MR carried out in the treatment position is desirable. Materials and methods A multidisciplinary team of diagnostic and therapeutic radiographers, treatment planners, medical physicists and clinicians was convened. Planning MR was integrated into the radiotherapy pathway and carried out in the days immediately following CT simulation. All men underwent identical preparation (administration of a micro-enema and drinking 300 mL of water thirty minutes prior to imaging/treatment). Patients were set up in the treatment position using MR-compatible radiotherapy immobilisation. T2SE axial and sagittal images were acquired (Siemens Aera 1.5T E11, incorporating RT software platforms/LAP Laser Bridge/Civco RT Indexing Flat couch top/coil bridges), imported into the Eclipse planning system (V13.6, Varian), and fused to the planning CT for volume delineation. Results The service opened in mid-September 2017. 26 patients were scanned to the end of November 2017. All patients tolerated preparation and imaging without difficulty. Conclusion This service has been successfully introduced and will shortly expand to include other sites (rectum, lung, head and neck, complex palliative). A study is planned to assess the impact of the addition of MR on target delineation. Additional considerations include the need for dedicated radiology input and the potential role of collaboration with industry with a view to stand-alone MR simulation. Advances in radiotherapy planning and delivery have made target definition increasingly important. While CT images are required for plan calculation, MR fusion is increasingly used to more accurately define tumour and normal tissue. There is often significant variation seen between diagnostic and therapeutic imaging; hence, MR carried out in the treatment position is desirable. A multidisciplinary team of diagnostic and therapeutic radiographers, treatment planners, medical physicists and clinicians was convened. Planning MR was integrated into the radiotherapy pathway and carried out in the days immediately following CT simulation. All men underwent identical preparation (administration of a micro-enema and drinking 300 mL of water thirty minutes prior to imaging/treatment). Patients were set up in the treatment position using MR-compatible radiotherapy immobilisation. T2SE axial and sagittal images were acquired (Siemens Aera 1.5T E11, incorporating RT software platforms/LAP Laser Bridge/Civco RT Indexing Flat couch top/coil bridges), imported into the Eclipse planning system (V13.6, Varian), and fused to the planning CT for volume delineation. The service opened in mid-September 2017. 26 patients were scanned to the end of November 2017. All patients tolerated preparation and imaging without difficulty. This service has been successfully introduced and will shortly expand to include other sites (rectum, lung, head and neck, complex palliative). A study is planned to assess the impact of the addition of MR on target delineation. Additional considerations include the need for dedicated radiology input and the potential role of collaboration with industry with a view to stand-alone MR simulation.

OBJECTIVE:This study assessed the use of implanted hydrogel rectal spacers for stereotactic ablative radiotherapy-volumetric modulated arc therapy (SABR-VMAT) patients, investigating practicality, dosimetric impact, normal tissue complication probability (NTCP) and early toxicity.METHODS:Data from the first 6 patients treated within a prostate SABR and rectal spacer trial were examined to determine spacer insertion tolerability, resultant changes in treatment planning and dosimetry and early toxicity effects. CT scans acquired prior to spacer insertion were used to generate SABR plans which were compared to post-insertion plans. Plans were evaluated for target coverage, conformity, and organs at risk doses with NTCPs also determined from resultant dose fluences. Early toxicity data were also collected.RESULTS:All patients had successful spacer insertion under local anaesthetic with maximal Grade 1 toxicity. All plans were highly conformal, with no significant differences in clinical target volume dose coverage between pre- and post-spacer plans. Substantial improvements in rectal dose metrics were observed in post-spacer plans, e.g. rectal volume receiving 36 Gy reduced by ≥42% for all patients. Median NTCP for Grade 2 + rectal bleeding significantly decreased from 4.9 to 0.8% with the use of a rectal spacer (p = 0.031). To date, two episodes of acute Grade 1 proctitis have been reported following treatment.CONCLUSION:The spacer resulted in clinically and statistically significant reduction in rectal doses for all patients. Advances in knowledge: This is one of the first studies to investigate the efficacy of a hydrogel spacer in prostate SABR treatments. Observed dose sparing of the rectum is predicted to result in meaningful clinical benefit.

Traditional CTV-PTV margin recipes are not generally applicable in the situation of stereotactic ablative radiotherapy (SABR) treatments of multiple target volumes with a single isocentre. In this work, we present a novel geometric method of margin derivation based on CBCT-derived anatomical data.

Background: Radiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however,> 30% of patients relapse within 5 years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Patients and methods: A bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold before further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasisfree survival (MFS). Results: Gene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients [HR = 3.21 (1.35-7.67); P = 0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR = 2.71 (1.11-6.63); P = 0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR = 3.23 (1.22-8.59); P = 0.019] whilst CAPRA itself was not significant [HR = 1.88, (0.52-6.77); P = 0.332]. A high concordance [100% (61.5-100)] for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance. Conclusions: The Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource.

Low-dose-rate permanent prostate brachytherapy (PPB) is an attractive treatment option for patients with localised prostate cancer with excellent outcomes. As standard CT-based post-implant dosimetry often correlates poorly with late treatment-related toxicity, this exploratory (proof of concept) study was conducted to investigate correlations between radiation − induced DNA damage biomarker levels, and acute and late bowel, urinary, and sexual toxicity.

Background: Prostate Cancer (PC) has a low alpha-beta ratio, making it sensitive to hypofractionated radiotherapy. Stereotactic ablative radiotherapy (SABR) provides an opportunity for dose escalation beyond that achievable with conventional radiotherapy. Additionally, there is a lack of novel biomarkers in use in the management of localized PC.