Velindre NHS Trust

<h3>Introduction</h3> High-quality palliative and end-of-life care (PEOLC) research is essential to meet the needs of changing populations with increasingly complex care requirements. Despite this, the UK palliative care research workforce faces persistent barriers. Understanding these and identifying strategies to build capacity is essential to ensure the future growth of the field. <h3>Aims</h3> To examine the characteristics of the UK PEOLC research workforce and explore factors influencing its capacity and sustainability. <h3>Methods</h3> A mixed-Methods online survey of UK-based self-identified PEOLC researchers (PhD level and above). Responses were analysed using descriptive statistics and framework analysis. <h3>Results</h3> Overall, 256 researchers responded (80% female, 85% white, 83% aged over 35). Overall, 79% worked at a university, 67% were full-time, 47% had a permanent contract and 9% were clinical academics. While 90% wished to continue PEOLC research for the next five years, only 69% believed this was likely. Perceived barriers included lack of funding (56%), heavy workload (42%), job insecurity (39%), and limited career opportunities (33%). To sustain and grow research activity, participants identified the need for: (i) Greater recognition and visibility of PEOLC as a critical research field; (ii) A range of funding opportunities to support researchers across career stages and disciplines, alongside investment in larger PEOLC research networks; (iii) Dedicated research time for clinical-academics and lecturers, alongside pathways to permanent contracts for those on fixed-term contracts; (iv) Increased opportunities for mentorship, networking, and collaboration; (v) Structural support to build a more diverse research community. <h3>Conclusion</h3> Despite their commitment, researchers working on PEOLC research face barriers to remaining research active. Greater investment in career development and research workforce infrastructure, alongside promotion of PEOLC as a critically important interdisciplinary research field, is necessary to sustain and grow the research workforce. <h3>Impact</h3> These findings inform strategies to strengthen the capacity and sustainability of UK PEOLC research.

Abstract Background: Detection of circulating tumour DNA (ctDNA) in plasma predicts future recurrence in early breast cancer (EBC). Previous studies have relied on tumour-informed approaches with personalised assays. In this study, we performed orthogonal testing on plasma samples collected prospectively in the c-TRAK-TN study to compare a tissue-free assay with digital droplet PCR (ddPCR) for ctDNA analysis. Methods: c-TRAK-TN recruited 161 patients with early triple negative breast cancer (TNBC) deemed clinically high risk of relapse. Patients underwent ctDNA analysis by ddPCR starting within 4 weeks of completion of treatment and continuing every 3 months for up to 2 years. ddPCR tracked 1 or 2 patient specific variants as previously described. We further analysed 1062 timepoints from a total of 159 patients (median 7 per patient, range 1-11) using Guardant Reveal assay, a tissue-free approach that exploits differential methylation patterns in breast cancer compared with normal tissue. Results: Samples were successfully analysed from 95.3% (1012/1062) timepoints from 159 patients with the tissue-free Reveal assay. CtDNA was detected in 34.0% (54/159) of patients in at least 1 timepoint, with a median methylation tumour fraction of 0.266% (range 0.002 to 51.0%). Detection of ctDNA with the tumour agnostic assay strongly associated with future risk of relapse (HR 20.62, p&amp;lt;0.0001; logrank). Of patients who relapsed by 24 months follow up, 89.5% (34/38) of relapses were detected by prior ctDNA analysis. There were 159 patients available for comparison between ddPCR and the tissue-free assay (Reveal), in 1005 timepoints (median 7 per patient, range 1-11). Concordant test results were observed in 950/1005 timepoints with an overall agreement rate of 94.5%. In this cohort, 63.5% (101/159) of patients did not have ctDNA detected by either assay; 26.4% (42/159) had ctDNA detected by both assays and 10.1% (16/159) had discordant results. Of those detected, 44.8% (26/58) were detected by the tissue-free assay first and 6.9% (4/58) by ddPCR (p&amp;lt;0.0001, Fisher exact test). The median time from first detection of ctDNA to relapse for the tissue-free assay was 7.9 months (95% confidence interval (CI): 5.7-10.5 months) compared to ddPCR assay with 5.7 months (95% CI: 2.9-9.7 months) (HR = 0.6, p=0.0574; mixed effects cox model). Conclusion: Detection of ctDNA with a tissue-free assay anticipated relapse with high accuracy, in patients with early TNBC. The tissue-free assay frequently detected ctDNA at an earlier timepoint than ddPCR, trending towards a longer lead time from detection of ctDNA to relapse. Tissue-free approaches might offer simpler workflows for ctDNA analysis than tumour-informed approaches, and further assessment in clinical trials is warranted. Citation Format: N. Cunningham, R. J. Cutts, C. Swift, K. Dunne, M. Dewan, L. Kilburn, K. Goddard, P. Hall, C. Harper-Wynne, T. Hickish, I. Macpherson, A. Okines, A. Wardley, S. Waters, C. Palmieri, M. Winter, J. Bliss, D. Dustin, M. Ellis, I. Garcia- Murillas, N. C. Turner. Tissue-free circulating tumour DNA detection in patients with early triple negative breast cancer from the c-TRAK-TN trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF3-05.

Abstract Aim Current recommendations for the clinical staging of patients undergoing resection for early oesophago-gastric (OG) cancer are variable and the value of staging investigations is unclear. The aim of this study was to assess current practice for staging early OG cancers across the UK, and the accuracy of staging with reference to nodal disease at surgery. Method Data for surgical patients was extracted from the CONGRESS database, a large UK-based multi-centre dataset for patients with T1N0 OG cancer between 2015 and 2022. Logistic regression analysis was performed to assess the association of different staging investigations on subsequent nodal upstaging. Cox regression analysis was used to analyse for impact on overall survival (OS). Results 497 patients from 28 centres were included, 13.1% of which underwent N upstaging from clinical to pathological staging. The rate of unexpected LNM was 12.7% in patients who underwent a CT pre-treatment, compared to 18.2% in patients with no staging investigations. Patients that underwent no staging investigations were also more likely to have unexpected nodal metastases at surgery (OR 6.66 (95%CI 1.34-33.24), p=0.021). The addition of PET-CT, EUS and staging laparoscopy had no significant impact on N upstaging (p=0.062, 0.053, and 0.690 respectively). No combination of staging modality had a significant impact on OS. Conclusions Current guidelines are variable in their recommendation of pre-operative staging investigations for early OG cancer. This study suggests CT plays an important role in the staging of this population. Other staging modalities could be considered selectively, rather than routinely, to preserve resources and accelerate treatment pathways.

Cardio-oncology remains a speciality dominated by cardiologists despite the importance of doctors from other specialties, such as oncology and haematology, for managing the cardiovascular health of patients living with cancer. A major reason for this is a distinct lack of cardio-oncology training opportunities for the noncardiology trainee. This is because of several factors, including a lack of awareness of cardio-oncology as a specialty. We propose a cardio-oncology training programme that involves early exposure to cardio-oncology as a specialty and provides the noncardiologist with a good understanding of cardiological investigations and treatment in the context of cancer treatment. Future work should elucidate additional barriers to cardio-oncology training as well as identifying programmes that have integrated cross-disciplinary cardio-oncology content to inform future curriculum development. Future work should also focus on establishing pilot cardio-oncology training programmes for the noncardiologist.

BackgroundSeizures are a common consequence of acute hemorrhagic stroke, which has a high morbidity and fatality rate. It is yet unknown how they relate to age, the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and discharge status.MethodsWe conducted a cross-sectional study of 75 patients (aged 16-92 years) with acute hemorrhagic stroke admitted to the Neuropsychiatry Department of Qena University Hospitals, a tertiary care center serving a large catchment area in Upper Egypt. Data were collected over six months, from September 2024 to February 2025. Neurological impairment was assessed using the NIHSS, and functional outcome was measured using the mRS at admission and discharge. Statistical comparisons included paired t-tests and Wilcoxon signed-rank tests. Associations between seizures, age, stroke severity, and outcomes were also analyzed.ResultsSeizures were not correlated with age. During hospitalization, a noteworthy mean improvement in NIHSS (+0.97; t = 10.70 and p < 0.0001; W = 21.50 and p < 0.0001) was noted, suggesting neurological recovery. On the other hand, mRS remained at a median 3 (t = -0.51 and p = 0.6113; W = 275 and p = 0.9173), indicating no discernible change. There was no discernible change in NIHSS or mRS among patients who were released on demand (n = 10). Ten out of the 12 in-hospital fatalities had seizures, and the majority had moderate-to-severe strokes (NIHSS ≥9; mRS ≥3). Patients with very severe strokes (NIHSS 16-17; mRS = 5) and no recovery experienced two non-seizure fatalities. Admission NIHSS (1-17) and mRS (1-5) showed a broad variety of stroke presentations and recovery trajectories.ConclusionThe baseline of stroke severity was the best indicator of a bad prognosis in acute hemorrhagic stroke, and seizure incidence was not age-dependent. Significant neurological recovery was recorded by NIHSS, but short-term functional improvement was not reflected by mRS. These results indicate that seizures are more common in fatal cases but secondary to the total load of strokes, underscoring the prognostic significance of baseline severity.

BackgroundCancers of the oesophagus and stomach are a major cause of morbidity and mortality. Research is crucial to improving outcomes. However, to maximise value and impact, areas of focus should be prioritised in partnership with patients.ObjectiveWe undertook a comprehensive analysis of UK and Ireland patient and healthcare professional (HCP) priorities for research into oesophagogastric cancers across the domains of prevention, diagnosis and staging, treatment, palliative care and survivorship.DesignA scoping exercise sourced research questions from patients and HCPs. These were consolidated and then confirmed by systematic review to represent a true research uncertainty. Research questions were scored on potential impact by an interdisciplinary group of HCPs and prioritised using a weighting derived from a patient survey.ResultsThere were 835 (395 HCP, 440 patient) respondents to the scoping (n=455) and prioritisation (n=380) surveys. Across these, 4295 suggested research uncertainties were consolidated to 92 uncertainties that were prioritised. HCP respondents represented 25 professional groups from community and hospital settings. Patient weighting changed 22.2–46.3% of priority rankings established by HCPs. All domains were represented by the 20 highest priority questions, 5 of which focused on personalising and optimally combining treatment modalities. Two other key themes related to optimising nutrition and improving quality of life during and after treatment, including in patients not cured of their cancer.ConclusionThis work highlights the impact of patient input on HCP-ranked research priorities and provides a robust list of priorities to guide funders, policymakers and researchers to support and undertake impactful research.

PurposeInPACT addresses the optimal management of locally advanced penile cancer, aiming to prospectively evaluate the relative benefits and sequencing of surgery, chemotherapy, and chemoradiotherapy. At trial inception, radiation therapy protocols for this rare cancer lacked consistency and standardization, necessitating multicenter, international collaboration to develop comprehensive radiation therapy planning, delivery, and quality assurance guidelines.Methods and MaterialsInPACT has 2 main aims; to establish the efficacy of neoadjuvant chemotherapy or chemoradiotherapy in patients with macroscopically-involved inguinal nodes. Second, to compare prophylactic pelvic lymph node dissection plus chemoradiation to the inguinal and pelvic fields versus chemoradiation alone in patients whose inguinal node histology predicts a high risk of occult pelvic node involvement. The primary outcome measure for the trial is survival time.An international group was convened to achieve consensus on radiation therapy contouring, planning, dose, fractionation, and delivery for this rare cancer. These guidelines have been used throughout the conduct of the trial to date and form part of the radiation therapy quality assurance for each participating center.ResultsInternational consensus radiation therapy guidelines were established, encompassing risk status assessment and indications for each treatment region based on radiological and pathologic risk status of nodal basins. Guidance provides a nodal contouring atlas, addresses prepubic fat coverage, and specifies dose fractionation for both neoadjuvant and adjuvant settings, including recommendations for macroscopic disease. Trial recruitment is ongoing. Oncological and toxicity outcomes will be reported in due course.ConclusionsThe InPACT radiation therapy guidelines offer a step toward international consensus on contouring for inguino-pelvic radiation therapy in penile cancer.

BackgroundRisk stratification is fundamental in guiding treatment decisions for mRCC patients. The Meet-URO score is a novel prognostic model (IMDC score + NLR + Bone metastases, PMID 36493602) developed in the immunotherapy era. This innovative score enhanced the prognostic discrimination compared with the IMDC score in patients receiving different therapeutic strategies in different settings.MethodsA previous external validation on a retrospective real-world cohort of 1174 mRCC patients receiving first-line immune-combinations from 27 centers showed the higher prognostic accuracy of the Meet-URO score compared with the IMDC score ( n. IUC20761-50). Here, we report the updated OS assessment with an exploratory analysis for PFS and ORR.Results: A total of1,418 patients from 31 cancer centers were assessed: 54% of patients received IO-IO (Nivolumab + Ipilimumab), 46% IO-TKI, mainly Avelumab + Axitinib (24%); 52.5% of patients had NLR ≥ 3.2, and 32% had bone metastases. After an mFU of 16.5 months, the overall mOS was 34.7 months and resulted in more distinction within the Meet-URO score groups (Table 1), confirming its better prognostic accuracy compared with the IMDC score (c-index: 0.68 vs 0.64), especially for intermediate- and poor-risk patients, while for favorable patients, more FU is needed. Although the Meet-URO score was developed as an OS model, it showed better performance also in terms of PFS (c-index: 0.60 vs 0.58) and ORR (c-index: 0.57 vs 0.54).ConclusionsThe Meet-URO score demonstrated robust and better performance compared with the IMDC score in a large-scale UK mRCC cohort receiving first-line immune-combinations, not only in terms of OS but also in terms of PFS and ORR. The adoption of the Meet-URO score in clinical practice and as a stratification factor of clinical trials could support more individualized patient management.ScoreGroup distributionHR (95% CI)P valuemOS(mo)3y-OSMeet-URO 113%1.00 (ref)45.866% 227%1.23 (0.88-1.72).2351.462% 322%1.74 (1.24-2.44).00137.653% 430%3.31 (2.42-4.51)<.00119.732% 58%4.82 (3.35-6.94)<.00111.526%IMDC Favorable19%1.00 (ref)45.861% Intermediate53%1.40 (1.09-1.79).00737.654% Poor28%3.23 (2.51-4.16)<.00114.930%