The Christie Hospital

SummaryTeenage and young adult (TYA) patients undergoing allogeneic stem cell transplant have distinct psychosocial needs, yet they are poorly represented in research and their outcomes are not well understood. This study uses prospectively collected data from the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT) registry to explore UK transplant practice and outcomes for TYA patients (aged 16–24) in this healthcare setting, alongside children (aged 1–15) and adults (aged 25–39), transplanted for acute leukaemia (including lymphoblastic, acute lymphoblastic leukaemia [ALL], and myeloid, acute myeloid leukaemia [AML]). Nine hundred and forty TYA patients, transplanted between 1999 and 2018, are included, representing 87% of all UK activity during the study period. On adjusted analyses, overall survival after transplant for ALL worsened from children, through TYA, to adults; survival for patients with AML was similar across age groups. Non‐relapse mortality was not significantly worse in TYA patients compared with children (p = 0.117 in ALL, p = 0.379 in AML). The risk of chronic graft‐versus‐host disease (GvHD) was strongly correlated with age, with rates in the TYA group much closer to those seen in adults. While a graft‐versus‐leukaemia effect may be suppressing relapse, the high rate of GvHD represents an unmet need in this group, who are at a crucial juncture in their personal, educational and social development.

173 Background: Sarcopenia is common in advanced prostate cancer and worsened by androgen deprivation therapy (ADT). Routine staging CT scans provide an opportunity to screen for sarcopenia. The STAMPEDE trials have demonstrated treatment intensification beyond ADT improve cancer outcomes; however, benefits are heterogeneous. This study investigates CT-derived skeletal muscle index (SMI), a validated marker of total muscle mass, as a prognostic and predictive biomarker in the STAMPEDE docetaxel and ARPI trials. Methods: Men with newly diagnosed non-metastatic high-risk (M0) and metastatic (M1) hormone-sensitive prostate cancer (HSPC) with available staging CT imaging in the STAMPEDE docetaxel or ARPI trials were included. These trials compared standard of care (SOC) with addition of docetaxel ± zoledronic acid (ZA) or abiraterone acetate with prednisolone (AAP) ± enzalutamide (Enz). SMI (cm²/m²) was calculated as mean muscle area divided by height squared. Outcomes were overall survival (OS) in M1 patients and metastasis-free survival (MFS) in M0. Prognostic utility of SMI was evaluated in Kaplan–Meier analyses and Cox regression models. Predictive value was assessed by comparing hazard ratios of the treatment effect in Cox models for high vs low SMI cohorts. Likelihood ratio tests were used to identify treatment-SMI interactions. Continuous predictive effects were examined using multivariable fractional polynomial interaction (MFPI) models. Results: 2,267 patients (1,578 M1, 689 M0) met inclusion criteria. The median SMI was 47.2cm²/m² (IQR 42-52) in M1 patients and 48.2cm²/m² (IQR 44-54) in M0. SMI and CHAARTED burden were identified as independent prognostic biomarkers in M1 patients, with a 10 cm²/m² increase in SMI associated with a 15% reduction in risk of death (HR 0.85, 95% CI 0.79–0.92, p<0.001). SMI was not an independent prognostic biomarker in M0 patients. SMI was identified as an independent predictive biomarker of MFS benefit upon addition of AAP±Enz in M0 patients; high SMI cohorts had greater MFS benefit from addition of AAP±Enz compared with the low SMI cohort (HR 0.44 [0.3-0.66] vs 0.59 [0.38-0.91]). Likelihood ratio tests confirmed that adding a treatment-SMI interaction improved prediction of treatment benefit (χ²: 4.67, p=0.03). MFPI modelling demonstrated a significant MFS benefit with addition of AAP±Enz in M0 patients (χ²=9.95, p=0.006) with increasing SMI, however this benefit was observed in the range of 41-63 cm 2 /m 2 only. 20% of our cohort lay outside this range (13% lower, 7% higher) and did not observe MFS benefit from addition of AAP±Enz to SOC. Conclusions: SMI is an independent prognostic biomarker in trial patients with de novo metastatic HSPC. SMI is predictive of improved MFS with addition of AAP±Enz to SOC in M0 disease. Further research is required to validate our findings in real-world cohorts.

Meningiomas, benign central nervous system tumors, express progesterone and estrogen receptors. Their proliferation has been associated with hormonal and demographic factors, including female sex, obesity, and race. Prior studies on oral contraceptive pill (OCP) use and meningioma risk have been limited in their analysis of the modifying effects of race, obesity, and polycystic ovary syndrome (PCOS). To assess the association between combined OCP use and meningioma development, and to assess how race, obesity, and PCOS influence this relationship. Retrospective cohort study using aggregated electronic health record data in Epic Cosmos. Women aged 13-50 from 2005 to 2023 with and without combined OCP use were identified. Patients with history of radiation, neurofibromatosis 2, progestin-only contraceptive use, and hormone replacement therapy were excluded. The cohort was then stratified by PCOS status, obesity, and race. Combined OCP users saw a 40% lower risk of meningioma compared to non-users. PCOS was associated with a bidirectional effect on meningioma risk, modified by obesity. Among patients with obesity, those with PCOS had a 30% lower risk of developing meningioma compared to those without PCOS. Among non-obese patients, those with PCOS had a 108% greater risk of developing meningioma compared to those without PCOS. After adjusting for both PCOS and obesity, women with a history of combined OCP usage had 42% reduced odds of developing meningioma. When stratified by race, combined OCP use was associated with 47% decreased risk in White patients, 34% lower risk in Black patients, and 28% lower risk in Asian patients. Controlling for race overall, combined OCP use remained significantly protective, with 43% reduced odds of meningioma development. Findings suggest a potential protective association between combined OCP use and meningioma that remained significant after controlling for obesity, PCOS status, and race. Additionally, this study found that meningioma risk in patients with PCOS differed based on obesity status.

Background:Patients with epithelial ovarian cancer (EOC) receiving neoadjuvant platinum-based chemotherapy (NACT) who remain ineligible for complete interval cytoreductive surgery (ICS) due to poor chemosensitivity (CA-125 KELIM™ score <1.0) have a poor prognosis (~20% 5-year survival). A weekly dose-dense carboplatin–paclitaxel regimen may improve outcomes in this high-risk subgroup.Objectives:To demonstrate the superiority of a salvage weekly dose-dense carboplatin–paclitaxel regimen over continuation of the standard 3-weekly regimen in poor-prognosis EOC patients after 3–4 cycles of standard NACT.Design:SALVOVAR is a pragmatic, open-label, multicenter, international, randomized phase III trial.Methods and analysis:Patients with stages III–IV high-grade EOC are eligible if they present (1) an unfavorable standardized KELIM score <1.0, and (2) a disease not amenable to complete ICS after 3–4 cycles of standard 3-weekly carboplatin–paclitaxel. Patients are randomized (1:1) to either the experimental arm (dose-dense carboplatin AUC5 day 1 plus paclitaxel 80 mg/m2 on days 1, 8, and 15, every 3 weeks) or the control arm (continuation of the standard regimen) for 3 cycles. Bevacizumab use is allowed at investigator discretion. Stratification factors include planned bevacizumab administration, BRCA mutation status, and KELIM strata. The two co-primary endpoints are (1) improvement in late complete cytoreduction rates (from 5% in the control arm to 20% in the experimental arm), and (2) overall survival (target hazard-ratio, 0.61). Total 250 patients will be randomized. Secondary endpoints include objective response rate, progression-free survival, and safety. Additional planned analyses include quality-of-life, cost-effectiveness, surgical standardization, human sciences, and biology studies.Ethics:The protocol was approved by the national ethics committee and health authorities.Discussion:SALVOVAR will evaluate whether chemotherapy densification improves outcomes in poorly chemosensitive advanced EOC. If positive, this pragmatic strategy could be implemented in large-scale studies, independent of resource setting.Trial registration:ClinicalTrials.gov NCT06476184 (June-2024). Available at: https://clinicaltrials.gov/study/NCT06476184

Breast cancer (BC) is the world's most prevalent cancer and can affect almost any post-pubertal woman. Early detection is associated with improved survival, and most high-income countries have adopted population-based screening programs to enhance early detection and survival although significant differences in screening age, methodology, and frequency exist. BC is known to be a heritable disease, with a small percentage of women having pathogenic variants in moderate or high-risk genes. However, Polygenic Risk Scores (PRS) incorporate many low penetrance single nucleotide polymorphisms (SNPs) and are the most powerful tool to help stratify women based on their personalized BC risk. PRS are particularly useful if incorporated into established risk prediction models (RPM). Risk stratification using PRS-containing RPMs can guide eligibility for enhanced screening and prevention programmes. This review discusses the role PRS plays in personalized risk prediction screening and prevention approaches as some of the challenges to their use.

Robotic surgery in England is undergoing rapid expansion, with projected growth from 70,000 procedures in 2023-24 to over 500,000 annually by 2035. This shift not only affects surgical technology but redefines perioperative roles - particularly bedside assistance. Despite growing attention from national initiatives such as Getting It Right First Time, regulatory clarity remains lacking. The scope and responsibilities of bedside assistants - a role often conflated with surgical assistance - vary significantly depending on professional background and qualifications. Without clear governance, perioperative practitioners may face liability risks, and patients are left exposed to inconsistent practice. This viewpoint highlights the urgent need for perioperative bodies such as The Association for Perioperative Practice and the Perioperative Care Collaborative to lead the development of national guidance specific to bedside assistance in robotic surgery. Doing so is essential to ensure safe practice, appropriate delegation, and professional accountability in this evolving surgical landscape.

Testicular torsion is a time-sensitive urological emergency in which delays in diagnosis and treatment can lead to testicular loss. Despite advances in healthcare delivery, delayed presentation and management remain common worldwide and contribute to significant morbidity. This scoping review aimed to explore trends in presentation, diagnosis, and surgical management of testicular torsion across healthcare settings; identify and categorise the causes of delays; assess the impact of these delays on outcomes; highlight predictive factors influencing salvage; and map gaps in the literature to inform future research and interventions. The review was conducted in accordance with the Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. PubMed, Scopus, and Google Scholar were searched for studies published between 2010 and 2025. Eligible studies were original peer-reviewed research articles reporting on delays, predictive factors, or outcomes of testicular torsion. Data were charted on study characteristics, delays, predictive factors, and surgical outcomes. Ten studies were included, representing 1,910 patients with acute scrotal pain, of whom 1,529 had confirmed torsion. Delays in presentation and diagnosis were multifactorial, arising from patient-related, diagnostic, and system-level barriers. Salvage rates varied from 12% to 82%, with an overall salvage rate of 41.5% and orchidectomy rate of 58.5%. Outcomes were closely linked to timing of surgery, with salvage highest within six hours of symptom onset and declining sharply thereafter. Predictive factors included symptom duration, degree of torsion, age, and imaging findings. None of the studies reported long-term functional outcomes. Delays remain the most important determinant of outcome in testicular torsion. Findings are consistent with international guidelines emphasising urgent exploration within six hours. Improved patient education, streamlined referral pathways, and institutional preparedness are essential to reduce preventable testicular loss. Future research should prioritise long-term outcomes and the evaluation of system-level interventions.