There was no clinical overt cognitive deficit and no significant difference in cognitive function correlating with the used ablation technique. The number of MES correlated with a subtle, diffuse post-procedural impairment of neuropsychological function highlighting the need to reduce microemboli during ablation.

18 Background: ODM-208 is a novel, oral, non-steroidal and selective inhibitor of CYP11A1, the first and rate-limiting enzyme of steroid biosynthesis. ODM-208 suppresses the production of all steroid hormones and their precursors that may activate the androgen receptor (AR) signalling pathway. This is particularly relevant in patients with AR ligand binding domain (LBD) activating somatic point mutations, a mechanism of resistance to hormone-based therapies in metastatic castration-resistant prostate cancer (mCRPC). We report the first results of the first-in-man phase I CYPIDES trial. Methods: ODM-208 was examined in a dose finding phase 1 trial with a 3+3 design in patients with progressive mCRPC who had previously received ≥1 line of AR signalling inhibitor and ≥1 line of taxane-based chemotherapy. ODM-208 was administered up to 150 mg/day with glucocorticoid (GC) and mineralocorticoid replacement therapy and androgen deprivation therapy (ADT). The phase 1 endpoints included dose-limiting toxicities (DLTs), adverse events, pharmacokinetics, pharmacodynamics, PSA and RECIST response, and exploratory genetic profiling. Results: By Jan 22 2021, 41 patients (median age 70 yrs.) had received ODM-208. The dose finding was completed and included doses ranging from 10 to 150 mg/day. 22 (54%) patients had previously received both abiraterone and enzalutamide, and 23 (56%) patients both docetaxel and cabazitaxel. Although tolerated by most patients, the main safety finding was adrenal insufficiency (AI). Overall, 15/41 (37%) patients experienced Grade 3 AI requiring short-term high-dose GC treatment. ODM-208 plasma exposure was dose proportional. Serum testosterone was undetectable after 4 weeks of start of ODM-208 in almost all patients, as were serum DHEA sulphate, androstenedione, 11β-hydroxyandrostenedione, 11-ketotestosterone and pregnenolone. Overall 12/36 (33%) evaluable patients achieved a PSA decline of ≥50%. In evaluable patients with AR LBD mutation 10/15 (67%) achieved a PSA decline of ≥50%. Clinical improvement in symptoms such as pain was also observed in some men. Conclusions: Administration of ODM-208 to mCRPC men pretreated with abiraterone/enzalutamide and taxanes was highly effective in blocking the production of steroid hormones and showed promising antitumor activity, especially in men with AR mutation-positive cancers. The phase 2 dose expansion part of CYPIDES is ongoing. Clinical trial information: NCT03436485.

Background The COVID19 pandemic is one of the greatest modern global healthcare crises. The resultant morbidity and mortality of public and healthcare professionals has led to psychological impacts and economic repercussions. We set out to assess the concerns of doctors in training during this crisis. Methods A questionnaire was developed and delivered via Survey Monkey to doctors in training from 27 March to 6 April 2020, 2 weeks prior to the expected surge in Ireland and UK. The Perceived Stress Scale (PSS) was incorporated to gauge respondent stress as they prepared for the COVID19 impact. Results A total of 285 participants engaged with 197 (69%) completing all questions. Almost 86% of respondents had been trained in donning and doffing personal protective equipment (PPE), and nearly 85% felt confident in the process. Overall, most respondents felt somewhat prepared (60%) or well prepared (20%) to treat COVID19 patients. However, 42% worried that their hospital would struggle, or not cope at all; in particular, 91% highlighted the risk of running out of PPE. Family health (86%), personal health (72%), and social life (47%) topped the list of junior doctor concerns. According to the PSS, the majority of respondents (62%) had moderate stress. Conclusions This survey is the first to measure the concerns of doctors in training in Ireland as regards the COVID19 pandemic. Worries included PPE exhaustion and personal and family health. A significant majority had moderate stress. Additional supports for doctors in training are essential to aid stress and manage concerns better.

228 Background: Radium 223 (Ra-223) has been successfully utilised in the trial setting for the treatment of men with metastatic castrate resistant prostate cancer (mCRPC). To date, no real world outcomes from its use in the Irish population have been described. Methods: From September 2016 to March 2019, data from men referred for Ra-223 treatment at our institution was retrospectively collected. We recorded patient characteristics, treatments received and outcomes. Overall Survival (OS) was analysed using the Kaplan-Meier method. Results: 81 men were referred for Ra 223. Complete data was available for 56 men. Median age was 75. 79%(45/56) had over 6 bone metastases and 21%(12/56) had lymph node involvement. The median number of prior systemic treatments for mCRPC was 2. 84%(47/56) of patients were previously treated with Androgen deprivation therapy (ADT); 48%(27/56) Abiraterone, 36%(20/56) Docetaxel, 45%(25/56) Enzalutamide and 9%(5/56) Cabazitaxel. All patients were receiving bone protection agents; 57%(32/56) Zolendronic acid and 43%(24/56) Denosumab. Median ECOG was 1 at the start of treatment and 2 at completion. The median number of treatments received was 4 with 36%(20/56) completing all 6 treatments. The most common toxicity seen was grade1 fatigue occurring in10% (6/56). 17% (10/56) required a blood transfusion during their treatment course. 53%(30/56) required opioid analgesia prior to Ra 223 treatment. 76% of these men (22/30) described improved pain following Rad-223. At a median follow up of 13 months,41%(23/56) were alive. The median OS for the entire group was 7 months. Factors associated with improved OS included ECOG 0-1,fewer than 6 bone metastases, normal alkaline phosphatase level at start of treatment and no prior chemotherapy use. Median OS for those who had not received prior chemotherapy was significantly better than those who had (9 vs 5 months p=0.04). Conclusions: This real world study demonstrates Ra 223 is a well tolerated palliative treatment amongst Irish men with mCRPC. Good performance status, lower alkaline phosphatase, chemotherapy naivety and a low burden of metastatic disease are factors associated with an improved overall survival.

An article by Patel et al 1 titled "Low-Dose Abiraterone in Metastatic Prostate Cancer: Is it Practice Changing? Facts and Facets" was published in JCO Global Oncology on March 3, 2020. We concur with the findings of Patel et al, 1 as do other commentators, 2,3 that use of a low-dose strategy using 250 mg of abiraterone compared with 1000 mg leads to significant cost savings and will improve access for patients.Unfortunately, a generic formulation of this agent will not be available in Europe until the patent expires in 2022; thus, it is currently available only in a 500-mg formulation, although it was previously available in a 250-mg formulation for landmark clinical trials. This means that physicians cannot prescribe low-dose abiraterone and also places an unnecessary financial burden on patients and health care systems. The 250-mg formulation was available until noninferiority to full-dose abiraterone was demonstrated by Szmulewitz et al. 4 Opportunistic profiteering of this nature that led to the limitation of anticancer agents has been shown to increase their financial toxicity, limit their access worldwide, and lead to poorer survival outcomes for patients. [5][6][7] As the economic impact of the current COVID-19 pandemic increases, the potential cost savings from the availability of cheaper formulations will become increasingly relevant to the global population. 8