A High-Throughput In Vitro Radiobiology Platform for Megavoltage Photon Linear Accelerator Studies

We designed and developed a multiwell tissue culture plate irradiation setup, and intensity modulated radiotherapy plans were generated for 96-, 24-, and 6-well tissue culture plates. We demonstrated concordance between planned and measured/imaged radiation dose profiles using radiochromic film, a 2D ion chamber array, and an electronic portal-imaging device. Cell viability, clonogenic potential, and γ-H2AX foci analyses showed no significant differences between intensity-modulated radiotherapy and open-field, homogeneous irradiations. This novel platform may help to expedite radiobiology experiments within a clinical environment and may be used for wide-ranging ex vivo radiobiology applications

Metastatic prostate cancer men’s attitudes towards treatment of the local tumour and metastasis evaluative research (IP5-MATTER) : protocol for a prospective, multicentre discrete choice experiment study

Acknowledgements We would like to thank all the participants, study PIs, trial clinicians, research nurses, Imperial Clinical Trial Unit staff and other site staff who have been responsible for setting up, recruiting participants and collecting the data for the IP5-MATTER trial. We are also grateful for the ongoing support of the Trial Management Group and our IP5-MATTER patient representatives. Finally, we would like to thank our trial funder the Wellcome Trust and University College London Hospitals (UCLH) Charity. Funding MJC’s research is support by University College London Hospitals (UCLH) Charity and the Wellcome Trust. Mesfin Genie and Verity Watson are based at the Health Economics Research Unit (HERU), University of Aberdeen. HERU is funded by the Chief Scientists Office of the Scottish Government Health and Social Care Directorate. KTJ acknowledges research grant from the UK National Institute of Health Research Clinical Research Network Eastern and has received educational grants from Bayer UK, Janssen Oncology, Pfizer, Roche, and Takeda. HUA’s research is supported by core funding from the United Kingdom’s National Institute of Health Research (NIHR) Imperial Biomedical Research Centre.Peer reviewedPublisher PD

Real world prospective evaluation of clinical outcomes in patients with non-metastatic castrate resistant prostate cancer treated with darolutamide

Background: The RECORD Study is a real world data, prospective evaluation of clinical outcomes in patients with nmCRPC treated with Darolutamide. This study will increase the understanding of treatment response and management and in particular inform regarding use of next generation imaging in this setting. Methods: Patient data from 9 UK centres was collected based on the recommendation of NICE for Darolutamide as an option for the treatment of non-metastatic castrate resistant prostate cancer (nmCRPC) from November 2020. Data cut-off was 15 September 2022. The study is ongoing. Results: 87 patients were analysed with a median age of 78 (range 61-92). Median pre-treatment PSA and PSA doubling time (PSAdT) were 13 (range 1.99-110.6) mg/L and 5.05 (range 0.6 - 10) months. 42 patients (49.4%) had pre-treatment PSAdT of <6 months and 43 (50.6%) patients had PSAdT of ≥6 months (2 patients had no pre-treatment PSAdT data). 6 patients (6.90%) had next generation imaging prior to initiation of Darolutamide. Median duration of treatment on Darolutamide was 17 months for patients with pre-treatment PSAdT <6 months but median duration had not been reached for patients with pre-treatment PSAdT ≥6 months after 24 months of treatment, a significant difference p=0.018 (HR=0.385, 95% CI 0.17-0.88). 30 patients have come off treatment so far (34.5%); 21 (70%) for disease progression, 5 (16%) for a medical cause unrelated to the drug (e.g. COVID infection, reduced performance status secondary to pre-existing Parkinson's), 3 (10%) for unacceptable toxicity (rash, Grade3 fatigue, muscle aches, memory issues), and 1 patient died (unrelated). Conclusions: In the RECORD study, predominantly the diagnosis of nmCRPC is based on conventional imaging. The majority of patients respond and tolerate Darolutamide well, comparable with the ARAMIS trial. There is a significant difference between time on Darolutamide for those with pre-treatment PSAdT of <6 months compared with ≥6 months. Further long-term toxicity, MFS and OS data will continue to be collected prospectively within the study

Additional Treatments to the Local tumour for metastatic prostate cancer - Assessment of Novel Treatment Algorithms (IP2-ATLANTA): Protocol for a multicentre, phase II randomised controlled trial

Introduction Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone. Methods A phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024. Ethics and dissemination Approved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals