The Christie School of Oncology: Christie Research Publications Repository
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Radiotherapy for oesophageal cancer in the United Kingdom: patterns of practice and quality indicators
No full textAims: There is limited guidance relating to the provision of radiotherapy for patients with oesophageal cancer. Given this, we sought to assess variation in patterns of care in the UK and to devise quality improvement metrics to support future treatment standardisation. Materials and Methods: We undertook a cross-sectional survey using a bespoke online survey to explore geographical variation in radiotherapy use for oesophageal cancer across the United Kingdom (UK) National Health Service (NHS). These data were combined with an observational registry analysis using the National Disease Registration Service Radiotherapy Dataset to explore temporal variation in radiotherapy utilization from January 2020 - June 2024. Results: Survey responses were received from 75% (n = 45/60) of UK centres. These demonstrate considerable variation in the interpretation of radiotherapy indications, particularly in the non-curative setting, as well as in radiotherapy technique; with, for instance, one third (n = 15/45) of centres reporting that they do not use motion management strategies for lower third or junctional tumours. Induction chemotherapy use differs between centres and by concurrent regimen, with 93-96% (n = 42-43/45) of centres using induction treatment prior to concurrent platinum/fluoropyrimidine and 56-62% (n = 25-28/45) using it prior to concurrent platinum/taxane. Post-treatment surveillance and follow-up measures also differed with little evidence for more intensive surveillance in patients fit for salvage resection. Most centres reported the use of intensity modulated or volumetric arc therapy (IMRT/VMAT) for radical plans, which was supported by NDRS data demonstrating that the median proportion of patients in each centre treated using IMRT/VMAT increased from 60% (range 14.3-10 0%) in January-June 2020 to 91.7% (range 16.7-10 0%) in January-June 2024. Conclusions: There is substantial variation in the radiotherapy-based care of patients with oesophageal cancer in the UK. Formal national guidance is required to build on the quality metrics outlined here. (c) 2025 The Author(s). Published by Elsevier Ltd on behalf of The Royal College of Radiologists. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)
The breast cancer risk assessment pathway in England: a systems analysis of current challenges and ways to improve
No full textBACKGROUND: In England, NICE guidance recommends enhanced screening and prevention for women at increased breast cancer risk. This study aimed to map current risk assessment pathways for women under 50, explore existing challenges and opportunities for improvement, and assess the healthcare system's capacity and readiness for potential systemic change. METHODS: Informed by the systems engineering framework and the Consolidated Framework for Implementation Research, we conducted semi-structured interviews and a post-interview questionnaire. Participants were 29 healthcare professionals and policy stakeholders across England with relevant expertise spanning all stages of the breast cancer risk assessment and management pathway. They were purposefully recruited through the research team's networks and by using the snowball method. Data were analysed by using thematic analysis. Questionnaire data were analysed descriptively. RESULTS: Participants discussed the challenges of the current pathway and consistently described it as fragmented, with access often influenced more by ethnicity, geographic and socioeconomic factors than by clinical need. Participants identified six key areas where reform is needed, including a standardised national service, developing digital and flexible tools, a shift towards being proactive, division of responsibilities, a need for funding and strengthening skills in risk assessment. CONCLUSIONS: This study demonstrates challenges, variation and missed opportunities in care within the current pathway for breast cancer risk assessment and management in women under 50. The readiness of the system to change is clear, and recommendations are made to support systemic reform, which could contribute to the development of a more standardised, proactive and equitable breast cancer risk assessment and management pathway
Current landscape, successes, and key challenges in cancer vaccine clinical trials acrossthe UK
No full textMaintaining oxaliplatin therapy after hypersensitivity reactions: real-world experience with a desensitisation protocol
No full textHypersensitivity reactions (HSRs) to oxaliplatin occur in 7-25% of patients and pose a significant clinical challenge, particularly for individuals who otherwise benefit from oxaliplatin-based therapy. Although evidence supporting its efficacy remains limited, drug desensitisation protocols (DDPs) involving stepwise dose escalation have been adopted in clinical practice. This study describes the experience of a tertiary cancer centre with oxaliplatin desensitisation, focusing on recurrence of HSRs and treatment completion rates. A retrospective observational study was conducted at a comprehensive cancer centre between October 2019 and January 2024. Clinicopathological characteristics and oncological outcomes were examined for patients with gastrointestinal malignancies who received oxaliplatin-based chemotherapy using a DDP. Sixty-six patients underwent oxaliplatin desensitisation (median age 60 years; 55% female). Most had colorectal cancer (CRC) (n = 35, 53%) or upper gastrointestinal malignancies (n = 26, 39%); 85% (n = 56) were treated with palliative intent. The median number of oxaliplatin cycles prior to the first HSR was six (range 1-26). CAPOX (53%) and FOLFOX (42%) were the most common regimens associated with HSRs. Patients received a median of three cycles within the DDP (range 1-19). Most (76%) remained on their original systemic anti-cancer therapy without premature treatment modification. Sixteen patients (24%) experienced a recurrent HSR; however, 55 patients (83%) successfully completed their intended treatment. Outcomes during the desensitisation period included: no evidence of disease in eight patients (seven treated in the adjuvant setting), treatment response in 26 patients, and disease progression in 32 patients. Oxaliplatin desensitisation is feasible and enables most patients to continue systemic therapy, with low rates of treatment discontinuation and acceptable oncological outcomes. This approach should be considered for eligible patients who experience oxaliplatin-related HSRs to maintain access to effective chemotherapy
Pathological features, differential diagnosis, prognosis, and diagnostic challenges in the classification of penile squamous neoplasia
No full textApproximately 50% of penile squamous cell carcinomas are of the usual (conventional) type, resembling their counterparts in the skin or other organs. The remaining half comprises a heterogeneous group of histological variants, some of which exhibit highly distinctive morphological features. Current classification models recognize more than 14 subtypes of penile squamous cell carcinoma. Pathological guidelines recommend histological subtyping of penile carcinomas in diagnostic reports. This practice is clinically significant because specific subtypes carry distinct prognostic implications. However, diagnostic challenges may arise in certain cases due to overlapping histological features. While most subtypes of penile intraepithelial neoplasia (PeIN) are readily identifiable, a subset of cases presents diagnostic challenges. A notable example is distinguishing benign condylomas from low grade minimally atypical warty PeIN. Among invasive carcinomas, the most significant diagnostic difficulties arise in classifying verruciform tumours, due to their overlapping morphological features. Warty carcinomas may simulate giant condylomas; verrucous carcinoma may simulate giant condylomas or Papillary NOS carcinomas. Conversely, this tumour may be confused with low grade warty carcinomas. With some experience, histological classification using H&E stain is possible in about 70% of the cases. The remainder 30%, however, presents diagnostic difficulties even for experienced pathologists. The use of immunostaining and HPV genotyping are crucial aids in the differential diagnosis. By describing and illustrating in detail their morphological features, suggesting treatment options, and emphasizing diagnostic difficulties in the differential diagnosis, we aimed to assist our colleagues in improving their penile neoplasia classification skills
CD40-CD40L inhibition attenuates platelet-neutrophil interaction and neutrophil extracellular trap release in primary antiphospholipid syndrome
No full textOBJECTIVES: Neutrophil extracellular traps (NETs) are increasingly recognised for their role in primary antiphospholipid syndrome (PAPS) pathogenesis. Herein, we examined underlying mechanisms driving NET formation and the thrombogenic effects of NETs in patients with PAPS, along with potential inhibitors. METHODS: We examined NET release in PAPS, asymptomatic antiphospholipid autoantibodies (aPLs) carriers, and healthy controls (HCs) as well as NET-bound proteins by immunofluorescence, immunoblotting, quantitative polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA). We assessed platelet-neutrophil aggregates by flow cytometry (CD61/CD66b staining) and autophagy using LC3B immunofluorescence and immunoblotting. Immunofluorescence was performed in paraffin-embedded kidney, skin ulcer, and endoarterial thrombus tissues from patients with PAPS. Suppression of NET release via CD40-CD40L inhibition was tested in in vitro and venous thrombosis mouse models. RESULTS: Neutrophils from patients with PAPS exhibited increased NET release compared with asymptomatic aPL carriers and HCs. NETs from patients with PAPS expressed tissue factor (TF) that induced thrombin generation in platelet-poor plasma from HCs. aPL induced in vitro intracellular TF expression in HC neutrophils. TF-expressing NETs were abundant in the kidney, skin ulcer, and endoarterial thrombus tissues from patients with PAPS, and colocalised with fibrinogen. NET release in PAPS neutrophils was driven by aPL-mediated platelet activation, subsequent platelet-neutrophil interaction, and autophagy induction. CD40-CD40L blockade reduced platelet activation, autophagy, and NET formation in patients with PAPS. In a mouse model, inhibition of CD40-CD40L reduced neutrophil-platelet aggregates and myeloperoxidase (MPO)-DNA complexes in mouse peripheral blood, and the presence of NETs in the formed thrombi. CONCLUSIONS: Targeting the platelet-neutrophil/autophagy/TF-expressing NETs axis by CD40-CD40L inhibition attenuates thromboinflammation in PAPS and should be explored as a potential therapeutic target
Procedures of data merging in precision cancer medicine: the PRIME-ROSE project
No full textBACKGROUND AND PURPOSE: As more interventional clinical trials in Precision Cancer Medicine (PCM) are introduced, molecular descriptions of tumours have led to multiple subtypes, even within common tumour types. Therefore, the main limitation of these trials is the small number of eligible patients to assess the clinical benefit. The PRIME-ROSE project addresses this limitation by pooling data from multiple European Drug Rediscovery Protocol (DRUP)-like clinical trials, such that slowly accruing cohorts are accelerated. To achieve this task, a well-documented commonly approved procedure for data merging needs to be established. Patient/material and methods: Data sharing is achievable when there is an organisation that includes people from different disciplines who can navigate institutional and country-specific information and governance requirements. Furthermore, alignment of all the study procedures are needed before data are shared. Next, the process of merging data requires harmonisation and standardisation. Implementation of the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) facilitates future data aggregation. RESULTS: By aggregating data from European DRUP-like clinical trials, cohorts are completed that were unable to do so in stand-alone studies. Since initiation, the PRIME-ROSE project monitors over 300 cohorts across more than 20 treatments encompassing over 1,000 patients. At least 20 cohorts have progressed after interim analysis. INTERPRETATION: Data sharing across European trials is feasible and enhances the advancements of PCM studies. The methodologies developed in the PRIME-ROSE project provide a foundation for future data integration efforts in PCM clinical trials, underscoring the viability of conducting robust trials in a global context
Three versus 6 months of adjuvant oxaliplatin-fluoropyrimidine chemotherapy for colorectal cancer: final results of SCOT-an international, randomized, phase III, noninferiority trial
No full textAdjuvant chemotherapy for colorectal cancer (CRC) with oxaliplatin and fluoropyrimidine was traditionally given for 6 months but is associated with cumulative peripheral neuropathy. The SCOT study (ISRCTN59757862) was an international, randomized, phase III, noninferiority trial investigating treatment reduction from 6 to 3 months. It originally reported noninferior disease-free survival with reduced toxicity and improved quality of life for 3 months of treatment in 6,088 patients. Here, we report overall survival (OS) with 38 months of additional follow-up. Patients with high-risk stage II and stage III CRC were assigned (1:1) to receive 3 or 6 months of either capecitabine and oxaliplatin (CAPOX) or infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX; bolus and infused fluorouracil with oxaliplatin) that were selected before random assignment. With a median of 113 months follow-up and 1,255 OS events, 5-year OS for 3 versus 6 months of treatment was 82.4% in both groups (hazard ratio, 0.96; 95% CI, 0.8 to 1.07), proving noninferiority of 3 months of treatment. Noninferiority of 3 months of treatment for OS was also shown in 1,087 patients with rectal cancer. The duration effect is regimen-dependent with noninferiority shown for CAPOX but not for FOLFOX. In summary, SCOT has shown noninferiority for OS with 3 months of adjuvant chemotherapy treatment, which should be recommended for most patients
