PURPOSE:Those living beyond a cancer diagnosis experience unmet supportive care needs due to fragmented post-treatment pathways and limited integration of digital health tools. The Linking You to Support and Advice (LYSA) trial assessed the feasibility of a complex-intervention which incorporated a nurse- and dietitian-led multidisciplinary clinic and a digital platform for capturing and responding to electronic Patient-Reported Outcome (ePRO) data for women with early-stage breast and gynecologic cancer less than 12 months post-primary curative therapy. METHODS:The LYSA trial was an unblinded, randomized, controlled, feasibility trial co-designed with public and patient involvement, conducted across two cancer centers in Ireland. Participants were randomized to the experimental arm, receiving bi-monthly ePRO assessments and trigger-initiated responses to ePROs for 12 months; or the active comparator arm, receiving usual care. Primary feasibility outcomes included participant enrolment, ePRO survey completion, and healthcare professional engagement triggered by ePRO assessments. Secondary outcomes focused on symptom scores, health-related quality of life (HRQOL), and patient satisfaction. A process evaluation explored factors affecting implementation. RESULTS:The trial met its three predefined feasibility outcomes: 200 participants were enrolled (84% breast, 16% gynecologic), >85% of baseline and endpoint surveys were completed, and >70% of participants in the experimental arm engaged in nurse and dietetic consultations following ePRO symptom triggers. The experimental arm demonstrated significant improvements in fatigue (p = 0.018), anxiety (p = 0.012), depression (p < 0.001) and HRQOL (p = 0.031) scores. The process evaluation indicated high levels of satisfaction with the intervention, with positive feedback on the multidisciplinary approach and responsive symptom management. CONCLUSIONS:LYSA demonstrates the feasibility and acceptability of an ePRO-led survivorship approach, with potential HRQOL and symptom benefits, warranting a powered efficacy trial.

BACKGROUND:The development and use of core outcome sets (COSs) have the potential to inform best practice in healthcare treatment options by facilitating data synthesis across studies. In surgical oncology, eight cancer-specific COSs exist, and these overlap in content. The development of a meta-COS that includes the core outcomes from existing cancer data sets would be applicable, as a minimum, across all cancer types in surgical oncology for use in effectiveness trials and clinical practice. METHODS:The process of developing a meta-COS included identification of the existing COS and their discussion with 3 different stakeholder focus groups (surgeons/oncologists, other healthcare professionals, and patients and carers). Outcomes were identified through a review of the literature and registered clinical trials. Stakeholders representing healthcare professionals (surgeons/oncologists and others) were recruited from national societies, regional cancer networks, and local trial centres, whereas patients and carers were recruited using independent representative organizations. The aim was to include at least two individuals from each group for the ten common cancers requiring surgery. These ten cancer types were regarded as the commonest based on global incidence in World Cancer Research Fund data. An agreed-upon list of outcomes was scored in a two-round online Delphi survey (March-May 2025). The results of this survey were discussed and ratified at an online consensus meeting (June 2025) by Delphi participants who completed both rounds, members of the stakeholder groups, and patients. The 80% threshold defined consensus. RESULTS:Forty-five participants completed both survey rounds, and 15 participated in the consensus meeting. Of 317 outcomes initially identified, 35 were discussed with stakeholders, 32 were scored in Delphi rounds, and consensus was achieved on eight core outcomes to include in the surgical oncology meta-COS: overall survival, disease-free survival, disease-specific survival, death related to surgery, delay to further treatment, completeness of tumour removal, overall quality of life, and serious adverse events. CONCLUSION:This meta-COS for surgical oncology offers a standard set of outcomes to be used in surgical oncology studies and clinical practice, regardless of cancer type.

Extracellular vesicles (EVs) are versatile transporters of genetic cargo with enormous potential in the therapeutic setting. Scalable production of EVs, and routes to overcome rapid clearance are required. Biocompatible hydrogels may support precise, localized delivery of EVs to target sites. This study aimed to establish sustained production of EVs in a scalable 3D dynamic bioreactor and to fabricate hydrogels using tyramine-modified hyaluronic acid (HA-TA) to study EV integration and release patterns. MDA-MB-231 cells transduced with lentiviral GFP fused with CD63, were cultured in a 20kD dynamic hollow fiber bioreactor and GFP-EVs harvested over five weeks. GFP-EVs were characterized by Nanoparticle Tracking Analysis(NTA), Western Blot(WB) and Transmission Electron Microscopy(TEM). Tyramine modified hyaluronic acid(HA-TA) hydrogels were formulated via enzymatic crosslinking using hydrogen peroxide and horseradish peroxidase, to investigate EV release patterns in static and dynamic conditions. Hydrogel swelling was recorded at 1-72 hrs and hydrogels were loaded with GFP-EVs to assess distribution and release by Scanning Electron Microscopy(SEM) and NTA respectively. GFP-EV uptake was assessed by confocal microscopy. Longitudinal GFP expression was demonstrated in transduced cells and released EVs throughout bioreactor culture. TEM and NTA demonstrated successful isolation of EVs of 30-200 nm in size with intact lipid bilayers (average 4x109 EVs/harvest). Initial harvests exhibited subpopulations of larger EVs, which disappeared upon serum withdrawal. WB verified the presence of EV markers CD63, TSG101, and CD81. HA-TA hydrogels were successfully formed and swelling assays revealed the requirement for higher concentrations of HA-TA and crosslinkers for scaffold stability and continued swelling. GFP-EVs were successfully incorporated into the hydrogels with variable release patterns observed over time, depending on EV concentration and hydrogel formulation. EV clusters in hydrogels were visualized by SEM. Investigation of GFP-EV release patterns under static and dynamic conditions highlighted a significant increase in release under fluid flow conditions. Efficient transfer of released EVs to recipient cells was also demonstrated in vitro. The data demonstrate the potential for scalable production of engineered EVs in serum free conditions and subsequent incorporation into HA-TA hydrogels for sustained release. These biocompatible hydrogels hold promise for tuneable delivery of therapeutic EVs in a variety of disease settings. ### Competing Interest Statement The authors have declared no competing interest.

Understanding locoregional recurrence (LRR) risk is important in breast cancer, as it relates directly to breast cancer-associated mortality. Individualised LRR risk estimation should inform treatment and surveillance strategies. Increased mammographic breast density has been identified as a risk factor for the development of breast cancer. However, the precise relationship between mammographic density and breast cancer LRR remains unclear. To perform a systematic review and relative risk meta-analysis to explore the assocation between breast mammographic density and breast cancer LRR. A systematic review was performed as per PRISMA guidelines. Mammographic breast density (MBD) was classified as BI-RADs A-B (breast density < 50

Hyperparathyroidism (HPT) is a common and significant complication of chronic kidney disease (CKD). Both parathyroidectomy and cinacalcet, are used routinely in an effort to manage this cohort. Unfortunately, there remains no guideline consensus on how best to combine these treatments into an effective strategy. We look to assess the efficacy of these interventions and identify factors predicting recurrence and the development of post-operative complications. We also examine changes in our practice nationally following the arrival of cinacalcet as an alternative or an abridge to definitive surgical management. This was a nationwide study. We conducted a retrospective analysis of a prospectively maintained database. All patients who underwent a parathyroidectomy as management of secondary or tertiary HPT between 1999 and 2023 were included. A control group of patients managed with cinacalcet were also included. Our cohort included 155 patients managed with parathyroidectomy and 203 patients treated with cinacalcet. Pre-operative Alkaline phosphatase > 200 IU/L was predictive of hungry bone syndrome (HBS) on univariate (P = 0.003) and multivariate (P = 0.002) analysis, whilst a PTH > 1000 pg/ml (P = 0.012) was also predictive of HBS on univariate analysis. In an attempt to identify an optimal PTH cut off to trigger surgical referral we found mean serum PTH levels were significantly higher at 5 years in the cohort of patients who had a PTH > 1000 pg/ml prior to surgical intervention (39 ± 32 Vs 374 ± 544, P = 0.045). Our findings re-emphasise the efficacy and safety of parathyroid surgery in the management of renal HPT and suggest earlier surgical referral may improve the incidence of post-operative HBS and recurrent HPT.

Background Understanding outcomes of surgery performed with curative intent for different cancer types allows comparisons to be made provided consistent outcomes are selected and measured. At present core outcome sets (COS) that represent the minimum outcomes measured and reported in any clinical trial for a given condition exists for six of the ten most prevalent cancer types but it is uncertain whether this can be used to inform the development of a meta-COS (core outcome set) for any cancer type requiring a surgical operation with curative intent. This paper describes our study protocol to develop a meta-COS for surgical oncology. Methods Three stages of work will be conducted : (1) identification of a long list of outcomes including adverse events from previously published COS, a review of outcomes from trials registered with ClinicalTrials.gov, and focus groups with key stakeholders (inclusive of cancer patients having undergone surgery with curative intent for cancer or carers of such patients); (2) a two-round online Delphi survey including clinicians, patients or carers, and allied health professionals (such as dietitians, specialist nurses, physiotherapists, occupational health workers) to prioritise the outcomes; (3) an online consensus meeting using to agree on the final meta-COS. Discussion The meta-COS for surgical oncology trials will ensure that a selection of relevant outcomes will be available for use in all research studies for any cancer type requiring a surgical intervention. Registration This study titled “A meta-Core Outcome Set (COS) for surgical oncology” is registered on the COMET (Core Outcome Measures in Effectiveness Trials) Initiative database. (https://www.comet-initiative.org/Studies/Details/3252).

Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY (MEthods for LOcalization of Different types of breast lesions) is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com). MELODY is a prospective intergroup cohort study which enrolls female and male patients requiring breast-conserving surgery and image-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study is being conducted in 30 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Financial support was provided by Endomag, Merit Medical, Sirius Medical and Hologic. Citation Format: Maggie Banys-Paluchowski, Nina Ditsch, Thorsten Kühn, James Harvey, Nuh Zafer Canturk, Neslihan Cabioglu, Tove Filtenborg Tvedskov, Lina Pankratjevaite, Maria Luisa Gasparri, Dawid Murawa, Jai Min Ryu, Oreste Davide Gentilini, Rosa Di Micco, Mah Muneer Khan, Aoife Lowery, Natalia Krawczyk, Steffi Hartmann, Isabel T. Rubio, Antonio J. Esgueva, Jana de Boniface, Andreas Karakatsanis, Rajiv V. Dave, Shelley Potter, Ashutosh Kothari, Walter Paul Weber, Güldeniz Karadeniz Cakmak, Markus Hahn, Michael Patrick Lux, Marjolein Smidt, Bahadir M. Gulluoglu, Michaelis Kontos, Florentina Peintinger, Lia Pamela Rebaza, Maria Antónia Vasconcelos, Mariana Correia, Sarah Nietz, Francois Malherbe, Severine Alran, Khaled Mohammad Abdelwahab, Veronica Yamila Fabiano, Svs Deo, Yazan Masannat, Katharina Jursik, Bilge Aktas Sezen, Meldoy Study Group. MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4 / iBRA-NET, NCT 05559411) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-12-16.

Introducción Para la mayoría de las enfermedades malignas, la infusión intravenosa (IV) es el método principal de administración de medicamentos sistémicos contra el cáncer. Cada día se realizan más de un millón de IV en todo el mundo. Un análisis de alcance reveló recientemente una brecha importante en la literatura con respecto a los aspectos clínicos de la selección, inserción y, en particular, de la capacitación y la educación de los profesionales con respecto a los dispositivos de acceso vascular (DAV). Por esta razón, estamos llevando a cabo una encuesta cuantitativa en toda Europa para conocer las prácticas existentes entre los proveedores de atención sanitaria con respecto a los DAV utilizados para la terapia sistémica contra el cáncer, en un esfuerzo por responder algunas de estas preguntas. Métodos El presente artículo metodológico detalla los pasos dados por un equipo de investigación especializado en acceso vascular para realizar una encuesta europea a gran escala. Aunque el tema de la encuesta son las prácticas clínicas con DAV para la administración de terapia sistémica contra el cáncer, el objetivo de este artículo es transmitir algunas reflexiones en relación con: a) el proceso paso a paso para diseñar un cuestionario de alta calidad; b) el alcance, la calidad y el impacto de la participación del paciente (patient and public involvement, PPI) en el diseño de una encuesta; c) las metodologías utilizadas para cuantificar la validez aparente y de contenido de un cuestionario, y d) las experiencias adquiridas en relación con las prácticas de difusión y participación de las partes interesadas. Conclusión Este artículo destaca algunos de los conocimientos adquiridos al integrar e interactuar con PPI en diversas fases de la investigación clínica. También presenta estrategias viables para supervisar un gran equipo global de colaboradores y explica las muchas técnicas empleadas para mejorar la validez y precisión de la encuesta.