[This corrects the article DOI: 10.1016/j.phro.2025.100850.].

Introduction Within the UK there are 33 deaths every day from prostate cancer, second only to lung cancer as the most common cause of cancer death in males in the UK. Of the 55 000 new cases each year, up to 50% of these patients will receive radiotherapy either alone or after prostatectomy. Although there have been significant improvements in the accuracy of radiotherapy delivery leading to better tumour targeting and a reduction in dose to normal tissues, significant permanent genito-urinary or gastrointestinal-related side effects are all too common. With nearly 80% of patients with prostate cancer surviving for 10 years or more, minimising life-limiting radiation damage to normal tissues is vitally important. However, at present, it is not possible to identify which patients will suffer a poorer outcome after radiotherapy. The aim of this study, improving radiotherapy in PROState cancer using EleCtronic population-based healthCAre data (PROSECCA), is to do this by using the existing information in a patient’s digital healthcare record. By linking primary, secondary and tertiary clinical data, including digital image information, with radiotherapy treatment plans and outcome data, the PROSECCA study will identify de novo predictive biomarkers of radiation response and provide clinicians with a tool to individualise a radiotherapy dose and plan to maximise cure and minimise toxicity.Methods and analysis The PROSECCA study is a large multidisciplinary project, the purpose of which is to analyse healthcare records from up to 15 000 patients with prostate cancer who underwent radiotherapy in the treatment of their cancer in Scotland between 2010 and 2022. Through the linkage of data obtained specifically for radiotherapy and data held within each patient’s unique electronic health record (EHR), the factors that indicate why some patients have a poor response to treatment, or an increased risk of side effects from radiation, will be identified. This will be made possible by the use of artificial intelligence and machine learning (AL/ML), which will help to identify at-risk patients earlier and allow adaptation of their treatment accordingly.Ethics and dissemination The study is being conducted in accordance with the ethical principles set out in the Declaration of Helsinki and Good Clinical Practice that respects and protects the rights, and maintains confidentiality, of all trial participants. The study protocol (V.1.0) was reviewed by the South Central Oxford A Research Ethics Committee (REC) on 13 December 2021 and received a favourable opinion subject to each National Health Service (NHS) organisation confirming permission for patients treated within their area. Approval for the use of unconsented healthcare record data for patients included in the study and treated at one of the five Scottish Cancer Centres required an application to the NHS Scotland Public Benefit and Privacy Panel for Health and Social Care (HSC-PBPP). Full approval from the HSC-PBPP panel was received on 1 July 2024, which covered the use of pseudoanonymised EHR data for all patients participating in the study. The study is publicly listed on the NHS Health Research Authority site, with IRAS ID 306245 and REC reference 21/SC/0402. Dissemination of the study findings will take place through field-leading cancer, radiation oncology and medical physics journals. All manuscripts will be approved by the main study team and authorship determined by mutual agreement.Trial registration number NCT06714630.

Background and purpose:Adaptive radiotherapy (ART) in prostate cancer (PCa), although not yet standard practice, is typically triggered by inter-fractional anatomical changes that emerge progressively during treatment. This study investigates whether radiomics extracted before and during treatment can identify the optimal time point for re-planning, with the goal of reducing late rectal bleeding. Materials and methods:This study included 187 PCa patients from the single-centre, prospectively collected VoxTox dataset (UK-CRN-ID-13716), treated with image-guided radiotherapy using TomoTherapy and daily MVCT. Patients received either 74 Gy in 37 fractions (N = 110) or 60 Gy in 20 fractions (N = 77). Radiomic features were extracted from pre-treatment planning CTs and daily MVCTs. Grade ≥ 1 rectal bleeding was assessed at 2 years post-treatment using CTCAE v4.03. Two analysis strategies were employed: a separate analysis, where weekly features were evaluated independently; and a cumulative analysis, which progressively incorporated features from previous weeks. Logistic regression models with elastic net penalty were trained and evaluated using AUC. Results:In both groups, week 1 provided the highest standalone predictive performance (test AUC = 0.766 for 74 Gy; 0.734 for 60 Gy). In the cumulative analysis, week 3 was optimal for the 74 Gy group (test AUC = 0.767), balancing performance and timing. For the 60 Gy group, week 1 remained optimal but suffered from reduced generalisability (test AUC = 0.643). Conclusions:Radiomic analysis of daily imaging can support early, proactive ART in PCa, offering a personalised strategy to reduce late rectal bleeding beyond conventional anatomy-based approaches.

OBJECTIVES:To evaluate the treatment patterns and outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 dichloride in the UK. METHODS:Patients initiating treatment with radium-223 from 1 September 2017 to 1 September 2019 in 15 UK oncology centres were included. Demographics, treatment, clinical, biochemical, and outcome data were collected prospectively. Quality of life data were obtained using analgesic scores and components of the Functional Assessment Cancer Therapy - Prostate (FACT-P) questionnaire. RESULTS:A total of 550 consecutive, evaluable patients were included. The most common prior therapy for mCRPC was enzalutamide. At final analysis, after a median follow-up of 13.3 months, 55% of patients had completed six cycles of treatment. Median overall survival was 13.7 months (95% confidence interval, 12.6-14.8 months). Poor performance status, prior use of docetaxel in the metastatic hormone sensitive prostate cancer (mHSPC) setting, number of lines of prior treatment, and abnormal platelet count were independent variables associated with poor prognosis. Adverse events led to treatment discontinuation in 5.5% of patients. WHO analgesic scores and FACT-P questionnaire scores did not significantly change after treatment administration. CONCLUSION:The National Radium-223 Dichloride Audit was the first and largest multicentre prospective analysis of treatment patterns, outcomes, and quality of life data in patients treated with radium-223 in the UK. Radium-223 can be administered safely to patients previously treated with other life-prolonging therapies. Efficacy and safety data compare favourably with clinical trial and other real-world data. Our results suggest that its use earlier in the treatment pathway is associated with longer survival.

BackgroundPTEN loss and aberrations in PI3K/AKT signaling kinases associate with poorer response to abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC). In this study, we assessed antitumor activity of the AKT inhibitor capivasertib combined with enzalutamide in mCRPC with prior progression on AA and docetaxel.MethodsThis double-blind, placebo-controlled, randomized phase 2 trial, recruited men ≥18 years with progressing mCRPC and performance status 0-2 from 15 UK centers. Randomized participants (1:1) received enzalutamide (160mg orally, once daily) with capivasertib (400mg)/ placebo orally, twice daily on an intermittent (4 days on, 3 days off) schedule. Primary endpoint was composite response rate (RR): RECIST 1.1 objective response, ≥50% PSA decrease from baseline, or circulating tumor cell count conversion (from ≥5 at baseline to <5 cells/7·5 mL). Subgroup analyses by PTENIHC status were pre-planned.ResultsOverall, 100 participants were randomized (50:50); 95 were evaluable for primary endpoint (47:48); median follow-up was 43 months. RR were 9/47 (19.1%) enzalutamide/capivasertib and 9/48 (18.8%) enzalutamide/placebo (absolute difference 0.4% 90%CI -12.8 to 13.6, p=0.58), with similar results in the PTENIHC loss subgroup. Irrespective of treatment, OS was significantly worse for PTENIHC loss (10.1 months [95%CI: 4.6-13.9] vs 14.8 months [95%CI: 10.8-18]; p =0.02). Most common treatment-emergent grade≥3 adverse events for the combination were diarrhea (13% vs 2%) and fatigue (10% vs 6%).ConclusionsCombined capivasertib/enzalutamide was well tolerated but didn’t significantly improve outcomes from abiraterone pre-treated mCRPC.

Background and purpose The adoption of hypo-fractionated stereotactic body radiotherapy (SBRT) for treating prostate cancer has led to an increase in specialised techniques for monitoring prostate motion. The aim of this study was to comprehensively review a radiation therapist (RTT) led treatment process in which two such systems were utilised, and present initial findings on their use within a SBRT prostate clinical trial. Materials and Methods 18 patients were investigated, nine were fitted with the Micropos RayPilotTM (RP) system (Micropos Medical, Gothenburg, SE) and nine were fitted with the Micropos Raypilot Hypocath TM (HC) system. 36.25 Gray (Gy) was delivered in 5 fractions over 7 days with daily pre- and post-treatment cone beam computed tomography (CBCT) images acquired. Acute toxicity was reported on completion of treatment at six- and 12-weeks post-treatment, using the Radiation Therapy Oncology Group (RTOG) grading system and vertical (Vrt), longitudinal (Lng) and lateral (Lat) transmitter displacements recorded. Results A significant difference was found in the Lat displacement between devices (P=0.003). A more consistent bladder volume was reported in the HC group (68.03 cc to 483.7 cc RP, 196.11 cc to 313.85 cc HC). No significant difference was observed in mean dose to the bladder, rectum and bladder dose maximum between the groups. Comparison of the rectal dose maximum between the groups reported a significant result (P=0.09). Comparing displacements with toxicity endpoints identified two significant correlations: Grade 2 Genitourinary (GU) at 6 weeks, P=0.029; and no toxicity, Gastrointestinal (GI) at 12 weeks P=0.013. Conclusion Both the directly implanted RP device and the urinary catheter-based HC device are capable of real time motion monitoring. Here, the HC system was advantageous in the SBRT prostate workflow.

Background and objective Delivering radiotherapy to the bladder is challenging as it is a mobile, deformable structure. Dose-escalated adaptive image-guided radiotherapy could improve outcomes. RAIDER aimed to demonstrate the safety of such a schedule. Methods RAIDER is an international phase 2 noncomparative randomised controlled trial (ISRCTN26779187). Patients with unifocal T2-T4a urothelial bladder cancer were randomised (1:1:2) to standard whole bladder radiotherapy (WBRT), standard-dose adaptive radiotherapy (SART), or dose-escalated adaptive radiotherapy (DART). Two fractionation (f) schedules recruited independently. WBRT and SART dose was 55 Gy/20f or 64 Gy/32f, and DART dose was 60 Gy/20f or 70 Gy/32f. For SART and DART, a radiotherapy plan (small, medium, or large) was chosen daily. The primary endpoint was the proportion of patients with radiotherapy-related late Common Terminology Criteria for Adverse Events grade ≥3 toxicity; the trial was designed to rule out >20% toxicity with DART. Key findings and limitations A total of 345 patients were randomised between October 2015 and April 2020: 41/46 WBRT, 41/46 SART, and 81/90 DART patients in the 20f/32f cohorts, respectively. The median age was 72/73 yr; 78%/85% had T2 tumours, 46%/52% had neoadjuvant chemotherapy, and 70%/71% had radiosensitising therapy. The median follow-up was 42.1/38.2 mo. Sixty-six of 77 (86%) 20f and 74 of 82 (90%) 32f participants planned for DART met the mandatory medium plan dose constraints. Radiotherapy-related grade ≥3 toxicity was reported in one of 58 patients (90% confidence interval [CI] 0.1, 7.9) with 20f DART and zero of 56 patients with 32f DART. Two-year overall survival was 77% (95% CI 69, 82) for WBRT + SART and 80% (95% CI 73, 85) for DART (hazard ratio = 0.84, 95% CI 0.59, 1.21, p = 0.4). Thirteen of 345 (3.8%) participants had salvage cystectomy. Conclusions and clinical implications Grade ≥3 late toxicity was low. DART was safe and feasible to deliver, meeting preset toxicity thresholds. Disease-related outcomes are promising for dose-escalated treatments, with a low salvage cystectomy rate and overall survival similar to that seen in cystectomy cohorts.

Background: The irradiation of sub-regions of the parotid has been linked to xerostomia development in patients with head and neck cancer (HNC). In this study, we compared the xerostomia classification performance of radiomics features calculated on clinically relevant and de novo sub-regions of the parotid glands of HNC patients.Material and Methods: All patients (N = 117) were treated with TomoTherapy in 30-35 fractions of 2-2.167 Gy per fraction with daily mega-voltage-CT (MVCT) acquisition for image-guidance purposes. Radiomics features (N = 123) were extracted from daily MVCTs for the whole parotid gland and nine sub-regions. The changes in feature values after each complete week of treatment were considered as predictors of xerostomia (CTCAEv4.03, grade >= 2) at 6 and 12 months. Combinations of predictors were generated following the removal of statistically redundant information and stepwise selection. The classification performance of the logistic regression models was evaluated on train and test sets of patients using the Area Under the Curve (AUC) associated with the different sub-regions at each week of treatment and benchmarked with the performance of models solely using dose and toxicity at baseline.Results: In this study, radiomics-based models predicted xerostomia better than standard clinical predictors. Models combining dose to the parotid and xerostomia scores at baseline yielded an AUC(test) of 0.63 and 0.61 for xerostomia prediction at 6 and 12 months after radiotherapy while models based on radiomics features extracted from the whole parotid yielded a maximum AUC(test) of 0.67 and 0.75, respectively. Overall, across sub-regions, maximum AUC(test) was 0.76 and 0.80 for xerostomia prediction at 6 and 12 months. Within the first two weeks of treatment, the cranial part of the parotid systematically yielded the highest AUC(test).Conclusion: Our results indicate that variations of radiomics features calculated on sub-regions of the parotid glands can lead to earlier and improved prediction of xerostomia in HNC patients.

Background and purpose: This study aims to build machine learning models to predict radiation-induced rectal toxicities for three clinical endpoints and explore whether the inclusion of radiomic features calculated on radiotherapy planning computerised tomography (CT) scans combined with dosimetric features can enhance the prediction performance. Materials and methods: 183 patients recruited to the VoxTox study (UK-CRN-ID-13716) were included. Toxicity scores were prospectively collected after 2 years with grade >= 1 proctitis, haemorrhage (CTCAEv4.03); and gastrointestinal (GI) toxicity (RTOG) recorded as the endpoints of interest. The rectal wall on each slice was divided into 4 regions according to the centroid, and all slices were divided into 4 sections to calculate region-level radiomic and dosimetric features. The patients were split into a training set (75%, N = 137) and a test set (25%, N = 46). Highly correlated features were removed using four feature selection methods. Individual radiomic or dosimetric or combined (radiomic + dosimetric) features were subsequently classified using three machine learning classifiers to explore their association with these radiation-induced rectal toxicities. Results: The test set area under the curve (AUC) values were 0.549, 0.741 and 0.669 for proctitis, haemorrhage and GI toxicity prediction using radiomic combined with dosimetric features. The AUC value reached 0.747 for the ensembled radiomic-dosimetric model for haemorrhage. Conclusions: Our preliminary results show that region-level pre-treatment planning CT radiomic features have the potential to predict radiation-induced rectal toxicities for prostate cancer. Moreover, when combined with region-level dosimetric features and using ensemble learning, the model prediction performance slightly improved. (c) 2023 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 183 (2023) 109593 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

AimsAdding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination.Materials and methodsParticipants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests.ResultsBetween September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts.ConclusionGrade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.

Identification and quantification of pulmonary fibrosis and other anomalies are challenging problems in Radiotherapy. This paper introduces a block matching technique that characterises the voxel displacements as a geometrical relationship between lung CT scans. The proposed block matching technique uses two-pass distance and orientation-based regularisation to restrict unnatural and unrealistic tissue deformations. Also, this technique uses both texture maps and voxel intensities as block matching criteria. This yields a displacement vector field whose predicted motion vectors are closer to the actual displacements evaluated at every slice location using image quality-based performance metrics-namely structural similarity index (0.9959), mean squared error (0.0029), and peak signal-to-noise ratio (46.6). Thus providing a quantitative approach to the clinicians aiding in identifying and quantifying the clinically significant geometrical changes, eventually characterising the tumour degradation or pulmonary fibrosis in terms of volumetric and shape changes.

Purpose: Muscle-invasive bladder cancer (MIBC) constitutes about 30% of newly diagnosed bladder cancers. Only approximately 45% of patients survive for 5 years regardless of the type of treatment they receive [1]. Radical cystectomy has previously been considered standard therapy for MIBC. More recently, concurrent chemoradiotherapy (CRT) has emerged as an alternative treatment option [2]. A retrospective audit was carried out to review recurrence and survival rates amongst patients with MIBC treated with CRT at the Edinburgh Cancer Centre.

446 Background: The bladder is a mobile, deformable structure which makes radiotherapy (RT) delivery challenging. Plan of the day (POD) adaptive image guided RT and tumour boost dose escalation can optimise treatment. We aimed to define a feasible, safe schedule for muscle invasive bladder cancer (BC) using these techniques. Methods: RAIDER (ISRCTN 26779187) is a 3-arm, international phase II trial. Participants (pts) had unifocal T2-T4a urothelial BC and were randomized (1:1:2) to: standard whole bladder RT (WBRT), standard dose adaptive tumour focused RT (SART) or dose escalated adaptive tumour boost RT (DART). Two fractionation (f) schedules recruited independently. WBRT and SART dose was 64Gy/32f or 55Gy/20f and DART was 70Gy/32f or 60Gy/20f. For SART and DART, POD (small, medium, large) was chosen daily. Neoadjuvant chemotherapy (NAC) and concomitant radiosensitising therapy (CTh) were permitted. Primary endpoint is proportion of pts with RT related CTCAE grade≥3 (G≥3) toxicity 6-18 months (m) after RT. A non-comparative design to rule out >20% G≥3 toxicity in DART pts required 57 evaluable DART pts in each fractionation cohort (90% power, 5% 1-sided alpha). Adverse events (AE) are treatment emergent with RT relatedness assessed blind to treatment allocation. In each fractionation cohort, toxicity analysis is by treatment received in the evaluable population (pts with at ≥1 toxicity assessment between 6-18m). 3m local control was assessed by cystoscopic biopsy. Cancer outcomes are analysed by intention-to-treat with fractionation cohorts combined. Results: 345 pts were randomised (Oct 2015 - Apr 2020): 46/41 WBRT, 46/41 SART and 90/81 DART pts in 32f/20f cohorts respectively. Baseline characteristics for 32f/20f were median age 73 years (IQR 67, 79)/ 72 (67, 79); 83%/ 78% T2; 46%/ 52% had NAC and 71%/ 70% CTh. Median follow-up was 32f: 38.2m (IQR 26.2, 50.2), 20f: 42.1m (35.6, 50.1). 3588/6222 (58%) fractions delivered to SART and DART pts used small or large POD. Late toxicity outcomes are shown in table. RT related G≥3 in 20f DART was 1/58 (90% CI 0.1, 7.9) and in 32f DART was 0/57. 3m local control was achieved in 44/51 (86%) WBRT, 45/53 (85%) SART and 82/92(89%) DART. 2 year survival was 79% (95% CI: 69, 86) WBRT, 74% (63, 82) SART and 80% (73, 85) DART. Conclusions: Late G≥3 toxicity was low in all treatment groups. 20f and 32f DART was safe and feasible to deliver with toxicity rates below predefined thresholds. Local control for image guided (chemo)RT was good. CTCAE G≥3 and G≥2 treatment emergent toxicity 6-18m after RT. Clinical trial information: 26779187 . [Table: see text]

Precision radiotherapy refers to the ability to deliver radiation doses with sub-millimetre accuracy. It does not however consider individual variation in tumour or normal tissue response, failing to maximise tumour control and minimise toxicity. Combining precise delivery with personalised dosing, through analysis of cell-free DNA, would redefine precision in radiotherapy.