The Christie School of Oncology: Christie Research Publications Repository
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Dose-escalated adaptive radiotherapy for bladder cancer: results of the phase 2 RAIDER randomised controlled trial
No full textBACKGROUND AND OBJECTIVE: Delivering radiotherapy to the bladder is challenging as it is a mobile, deformable structure. Dose-escalated adaptive image-guided radiotherapy could improve outcomes. RAIDER aimed to demonstrate the safety of such a schedule. METHODS: RAIDER is an international phase 2 noncomparative randomised controlled trial (ISRCTN26779187). Patients with unifocal T2-T4a urothelial bladder cancer were randomised (1:1:2) to standard whole bladder radiotherapy (WBRT), standard-dose adaptive radiotherapy (SART), or dose-escalated adaptive radiotherapy (DART). Two fractionation (f) schedules recruited independently. WBRT and SART dose was 55 Gy/20f or 64 Gy/32f, and DART dose was 60 Gy/20f or 70 Gy/32f. For SART and DART, a radiotherapy plan (small, medium, or large) was chosen daily. The primary endpoint was the proportion of patients with radiotherapy-related late Common Terminology Criteria for Adverse Events grade ≥3 toxicity; the trial was designed to rule out >20% toxicity with DART. KEY FINDINGS AND LIMITATIONS: A total of 345 patients were randomised between October 2015 and April 2020: 41/46 WBRT, 41/46 SART, and 81/90 DART patients in the 20f/32f cohorts, respectively. The median age was 72/73 yr; 78%/85% had T2 tumours, 46%/52% had neoadjuvant chemotherapy, and 70%/71% had radiosensitising therapy. The median follow-up was 42.1/38.2 mo. Sixty-six of 77 (86%) 20f and 74 of 82 (90%) 32f participants planned for DART met the mandatory medium plan dose constraints. Radiotherapy-related grade ≥3 toxicity was reported in one of 58 patients (90% confidence interval [CI] 0.1, 7.9) with 20f DART and zero of 56 patients with 32f DART. Two-year overall survival was 77% (95% CI 69, 82) for WBRT + SART and 80% (95% CI 73, 85) for DART (hazard ratio = 0.84, 95% CI 0.59, 1.21, p = 0.4). Thirteen of 345 (3.8%) participants had salvage cystectomy. CONCLUSIONS AND CLINICAL IMPLICATIONS: Grade ≥3 late toxicity was low. DART was safe and feasible to deliver, meeting preset toxicity thresholds. Disease-related outcomes are promising for dose-escalated treatments, with a low salvage cystectomy rate and overall survival similar to that seen in cystectomy cohorts
Long term toxicity results of ACT4 RCT: evaluating reduced dose and standard dose chemoradiotherapy in early-stage anal cancer (ISRCTN:88455282)
No full textTrends in the management of testicular torsion: a scoping review of delays and outcomes
No full textTesticular 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
Surgery or radiotherapy for early-stage cancer study (SORT) target trial protocol: stereotactic ablative radiotherapy (SABR) with curative intent versus surgical resection for early-stage non-small cell lung cancer (NSCLC)
No full textINTRODUCTION: Randomised controlled trials have aimed to assess the effectiveness of stereotactic ablative radiotherapy (SABR) with curative intent versus surgical resection for individuals diagnosed with early-stage non-small cell lung cancer (NSCLC) but have failed to recruit sufficient numbers of patients. Non-randomised studies for early-stage NSCLC have reported mixed outcomes following curative SABR versus surgical resection, but did not fully address confounding by indication. The Surgery Or RadioTherapy for early-stage cancer study (SORT) will assess the comparative effectiveness of SABR with curative intent versus surgical resection for NSCLC with a target trial emulation approach, as this can reduce biases in observational studies that aim to estimate the causal effect of interventions. METHODS AND ANALYSIS: The SORT study will use the National Cancer Registry for individuals diagnosed with early-stage NSCLC in England during 2015-2020 (inclusive) who received SABR with curative intent or surgical resection. These data will be linked to Hospital Episode Statistics, National Radiotherapy Data Set and the Systemic Anti-Cancer Therapy dataset to obtain information on clinical and sociodemographic characteristics and the treatment received. This target trial emulation will define study population eligibility criteria and regimens for SABR with curative intent and surgical resection. We will reduce the risk of residual confounding with instrumental variable analyses that will exploit geographical variation across the National Health Service in England in the use of SABR with curative intent versus surgical resection for early-stage NSCLC. The primary outcome will be 3-year all-cause mortality after treatment initiation. Secondary outcomes will include 3-month, 6-month, 12-month and 24-month all-cause and lung-cancer mortality, time to death, numbers of hospitalisations, incremental costs and incremental cost-effectiveness. ETHICS AND DISSEMINATION: Ethical approval was obtained from the London School of Hygiene and Tropical Medicine Research Ethics Committee (reference number 29 717-1). Results will be disseminated to clinicians, patients, policy-makers and researchers
Identifying pediatric patients at risk of severe hearing impairment after treatment for malignancies of the H&N/ CNS with proton therapy
No full textUK cancer vaccine advance - recognising and realising opportunities
No full textVaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology
Predicting postoperative complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: retrospective cohort study
No full textBACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is an effective but potentially highly morbid treatment option for peritoneal surface malignancies. Adequate risk assessment is fundamental for clinical decision-making and informed patient consent. The aim of this study was to construct a validated nomogram predicting the risk of severe postoperative complications based exclusively on preoperative variables. METHODS: A prospective database of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a single institution between February 1995 and April 2023 was reviewed. The cohort was divided randomly into derivation and validation cohorts (70 : 30). The primary outcome measure was postoperative complications (National Cancer Institute Common Terminology Criteria for Adverse Events grade ≥ 3). Binary logistic regression identified preoperative variables significantly associated with postoperative morbidity. A nomogram was constructed based on the results of the multivariable analysis. The model's performance was evaluated on the validation cohort by receiver operating characteristic curve analysis. RESULTS: A total of 1039 patients were analysed. The majority of the patients were female (58.8%) and the median age was 56 (interquartile range 46-64) years. The postoperative complication rate was 37.7%, and the reoperation rate 12.7%. A nomogram was constructed based on the following predictive factors: age, body mass index, high-grade histology, disease identified in the left upper quadrant and surrounding the stomach and small bowel mesentery on preoperative imaging, preoperative white blood cell count, and Onodera nutritional index score. Receiver operating characteristic curve analysis showed an area under the curve of 0.707 with accurate calibration curves. CONCLUSION: Preoperative variables were selected and included in a simple nomogram predicting the risk of postoperative complications. This nomogram could aid clinicians in decision-making and patients in making informed decisions
Large cell neuroendocrine carcinoma of the lung: results of a UK survey of diagnostic and management strategies
No full textAssessing body composition using auto-segmentations of muscle and subcutaneous adipose tissue in prostate cancer patients receiving magnetic resonance-guided radiotherapy
No full textBackground and purpose: Sarcopenia negatively impacts treatment outcomes in prostate cancer (PCa) patients. With the growing use of magnetic resonance-guided radiotherapy (MRgRT), automated body composition (BC) analysis using deep learning frameworks may allow for early detection of at-risk patients and intervention during treatment. Methods: T2-weighted images were obtained from 71 patients with intermediate-risk PCa who underwent MRgRT using one of three treatment regimens: androgen deprivation therapy (ADT) with 60 Gy in 20 fractions (20# + ADT), ADT with 36.25 Gy in 5 fractions (5# + ADT), or 36.25 Gy in 5 fractions without ADT (5# + noADT). An auto-segmentation model was developed using a 36/9 train-test split with 5-fold cross-validation, implemented with and without a bowel and bone (BB) mask, to delineate muscle and subcutaneous adipose tissue (SAT). Performance was assessed using mean surface distance, 95th percentile Hausdorff distance and Dice similarity coefficient. The model was then applied to quantify muscle, SAT, and intramuscular adipose tissue from images acquired during MRgRT. Results: Performance metrics were similar with and without the BB mask; however, using the mask resulted in a 24 % reduction in failures. At the start of MRgRT, SAT area differed significantly between 20# + ADT and 5# + noADT (p = 0.04), with significant changes across all ROIs observed by treatment end. Conclusion: Routinely acquired MRgRT images can be used for reliable auto-segmentation of BC metrics. Significant differences in BC metrics were found between treatment regimens. This supports their use for sarcopenia detection and adaptive treatment planning