Search

Abstract Background Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. CompARE is designed to test alternative approaches to intensified treatment for these patients to improve survival. Methods CompARE is a pragmatic phase III, open-label, multicenter randomised controlled trial with an adaptive multi-arm, multi-stage design and an integrated QuinteT Recruitment Intervention. Eligible OPC patients include those with human papillomavirus (HPV) negative, T1–T4, N1–N3 or T3–4, N0, or HPV positive N3, T4, or current smokers (or ≥ 10 pack years previous smoking history) with T1–T4, N2b–N3. CompARE was originally designed with four arms (one control [arm 1] and three experimental: arm 2—induction chemotherapy followed by arm 1; arm 3—dose-escalated radiotherapy plus concomitant cisplatin; and arm 4—resection of primary followed by arm 1). The three original experimental arms have been closed to recruitment and a further experimental arm opened (arm 5—induction durvalumab followed by arm 1 and then adjuvant durvalumab). Currently recruiting are arm 1 (control): standard treatment of 3-weekly cisplatin 100 mg/m2 or weekly 40 mg/m2 with intensity-modulated radiotherapy using 70 Gy in 35 fractions ± neck dissection determined by clinical and radiological assessment 3 months post-treatment, and arm 5 (intervention): one cycle of induction durvalumab 1500 mg followed by standard treatment then durvalumab 1500 mg every 4 weeks for a total of 6 months. The definitive and interim primary outcome measures are overall survival time and event-free survival (EFS) time, respectively. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complication rates, and cost-effectiveness. The design anticipates that after approximately 7 years, 84 required events will have occurred to enable analysis of the definitive primary outcome measure for this comparison. Planned interim futility analyses using EFS will also be performed. Discussion CompARE is designed to be efficient and cost-effective in response to new data, emerging new treatments or difficulties, with the aim of bringing new treatment options for these patients. Trial registration ISRCTN ISRCTN41478539 . Registered on 29 April 2015

IntroductionEvolution of a patient-reported symptom-based risk stratification system to redesign the suspected head and neck cancer (HNC) referral pathway (EVEREST-HN) will use a broad and open approach to the nomenclature and symptomatology. It aims to capture and utilise the patient reported symptoms in a modern way to identify patients’ clinical problems more effectively and risk stratify the patient.MethodThe review followed the PRISMA checklist for scoping reviews. A search strategy was carried out using Medline, Embase and Web of Science between January 1st 2012 and October 31st 2023. All titles, abstracts and full paper were screened for eligibility, papers were assessed for inclusion using predetermined criteria. Data was extracted pertaining to the aims, type of study, cancer type, numbers of patients included and symptoms, presenting complaints or signs and symptoms.ResultsThere were 9,331 publications identified in the searches, following title screening 350 abstracts were reviewed for inclusion and 120 were considered for eligibility for the review. 48 publications met the eligibility criteria and were included in the final review. Data from almost 11,000 HNC patients was included. Twenty-one of the publications were from the UK, most were retrospective examination of patient records. Data was extracted and charted according to the anatomical area of the head and neck where the symptoms are subjectively and objectively found, and presented according to lay terms for symptoms, clinical terms for symptoms and the language of objective clinical findings.DiscussionSymptoms of HNC are common presenting complaints, interpreting these along with clinical history, examination and risk factors will inform a clinician’s decision to refer as suspected cancer. UK Head and Neck specialists believe a different way of triaging the referrals is needed to assess the clinical risk of an undiagnosed HNC. EVEREST-HN aims to achieve this using the patient history of their symptoms. This review has highlighted issues in terms of what is considered a symptom, a presenting complaint and a clinical finding or sign.

Objectives This study aims to assess the feasibility to perform transoral robotic surgery (TORS) with a new robotic platform, the Versius Surgical System (CMR Surgical, UK) in a preclinical cadaveric setting in accordance to stage 0 of the IDEAL-D framework.Design IDEAL stage 0 preclinical assessment of the Versius Robotic System in TORS in human cadavers.Setting All procedures were performed in a simulated operating theatre environment at a UK surgical training centre.Participants 11 consultant head and neck surgeons from the UK, mainland Europe and the USA took part in TORS procedures on six human cadavers.Interventions 3 key index procedures were assessed that represent the core surgical workload of TORS: lateral oropharyngectomy, tongue base resection and partial supraglottic laryngectomy.Main outcome measures The primary outcome was the successful completion of each surgical procedure. Secondary outcomes included the optimisation of system setup, instrumentation and surgeon-reported outcomes for feasibility of each component procedural step.Results 33 cadaveric procedures were performed and 32 were successfully completed. One supraglottic laryngectomy was not fully completed due to issues dividing the epiglottic cartilage with available instrumentation. Surgeon-reported outcomes met the minimal level of feasibility in all procedures and a consensus that it is feasible to perform TORS with Versius was reached. Available instrumentation was not representative of other robotic platforms used in TORS and further instrument optimisation is recommended before wider dissemination.Conclusions It is feasible to perform TORS with the Versius Surgical System (CMR Surgical) within a pre-clinical cadaveric setting. Clinical evaluation is needed and appropriate with the system. Further instrument development and optimisation is desirable.

Introduction Between 2009/2010 and 2019/2020, England witnessed an increase in suspected head and neck cancer (sHNC) referrals from 140 to 404 patients per 100 000 population. 1 in 10 patients are not seen within the 2-week target, contributing to patient anxiety. We will develop a pathway for sHNC referrals, based on the Head and Neck Cancer Risk Calculator. The evolution of a patient-reported symptom-based risk stratification system to redesign the sHNC referral pathway (EVEREST-HN) Programme comprises six work packages (WPs). This protocol describes WP1 and WP2. WP1 will obtain an understanding of language to optimise the SYmptom iNput Clinical (SYNC) system patient-reported symptom questionnaire for sHNC referrals and outline requirements for the SYNC system. WP2 will codesign key elements of the SYNC system, including the SYNC Questionnaire, and accompanying behaviour change materials.Methods and analysis WP1 will be conducted at three acute National Health Service (NHS) trusts with variation in service delivery models and ensuring a broad mixture of social, economic and cultural backgrounds of participants. Up to 150 patients with sHNC (n=50 per site) and 15 clinicians (n=5 per site) will be recruited. WP1 will use qualitative methods including interviews, observation and recordings of consultations. Rapid qualitative analysis and inductive thematic analysis will be used to analyse the data. WP2 will recruit lay patient representatives to participate in online focus groups (n=8 per focus group), think-aloud technique and experience-based codesign and will be analysed using qualitative and quantitative approaches.Ethics and dissemination The committee for clinical research at The Royal Marsden, a research ethics committee and the Health Research Authority approved this protocol. All participants will give informed consent. Ethical issues of working with patients on an urgent cancer diagnostic pathway have been considered. Findings will be disseminated via journal publications, conference presentations and public engagement activities.

Objective Coronary CT angiography (CCTA) permits both qualitative and quantitative analysis of atherosclerotic plaque and may be a suitable risk modifier in assessing patients at intermediate risk of atherosclerotic cardiovascular disease. We sought to determine the association of plaque components with long-term major adverse cardiovascular events (MACEs) in asymptomatic intermediate-risk patients, compared with conventional coronary artery calcium (CAC) score.Methods 100 intermediate-risk patients underwent double-blinded CCTA. Follow-up was conducted at 10 years and data were cross-referenced with the National Death Index. The primary outcome was MACE, which was a composite of death, acute coronary syndrome (ACS), revascularisation and stroke.Results The median time from CCTA to follow-up was 9.5 years. 83 patients completed follow-up interview and mortality data were available on all 100 patients. MACE occurred in 17 (20.5%) patients, which included 2 (2%) deaths, 8 (10%) ACS, 3 (4%) strokes and 5 (6%) revascularisation procedures. 47 (57%) patients had mixed plaque, which was predictive of MACE (OR 4.68 (95% CI 1.19 to 18.5) p=0.028). The burden of non-calcified and mixed plaque, defined by non-calcified plaque segment stenosis score, was also a predictor of long-term MACE (OR 1.59 (95% CI 1.18 to 2.13) p=0.002). Neither calcified plaque (OR 3.92 (95% CI 0.80 to 19.3)) nor CAC score (OR 1.01 (95% CI 0.999 to 1.02)) was associated with long-term MACE.Conclusion The presence and burden of mixed plaque on CCTA is associated with an increased risk of long-term MACE among asymptomatic intermediate-risk patients and is a superior predictor to CAC score.

Single point eddy covariance measurements of the Earth’s surface energy budget frequently identify an imbalance between available energy and turbulent heat fluxes. While this imbalance lacks a definitive explanation, it is nevertheless a persistent finding from single-site measurements; one with implications for atmospheric and ecosystem models. This has led to a push for intensive field campaigns with temporally and spatially distributed sensors to help identify the causes of energy balance non-closure. Here we present results from the Chequamegon Heterogeneous Ecosystem Energy-balance Study Enabled by a High-density Extensive Array of Detectors 2019 (CHEESEHEAD19)—an observational experiment designed to investigate how the Earth’s surface energy budget responds to scales of surface spatial heterogeneity over a forest ecosystem in northern Wisconsin. The campaign was conducted from June–October 2019, measuring eddy covariance (EC) surface energy fluxes using an array of 20 towers and a low-flying aircraft. Across the domain, energy balance residuals were found to be highest during the afternoon, coinciding with the period of surface heterogeneity-driven mesoscale motions. The magnitude of the residual varied across different sites in relation to the vegetation characteristics of each site. Both vegetation height and height variability showed positive relationships with the residual magnitude. During the seasonal transition from latent heat-dominated summer to sensible heat-dominated fall the magnitude of the energy balance residual steadily decreased, but the energy balance ratio remained constant at 0.8. This was due to the different components of the energy balance equation shifting proportionally, suggesting a common cause of non-closure across the two seasons. Additionally, we tested the effectiveness of measuring energy balance using spatial EC. Spatial EC, whereby the covariance is calculated based on deviations from spatial means, has been proposed as a potential way to reduce energy balance residuals by incorporating contributions from mesoscale motions better than single-site, temporal EC. Here we tested several variations of spatial EC with the CHEESEHEAD19 dataset but found little to no improvement to energy balance closure, which we attribute in part to the challenging measurement requirements of spatial EC.