Development of a clinical prediction model using volatile organic compounds as breath biomarkers in squamous oesophageal neoplasms: ViSON, protocol for a multicentre case–control study in UK NHS hospitals
Sameera Sharma, James Murray, Aaron Parker, Sara Jamel, Stefan Antonowicz, Adele Phillips, Elaine Bailey, Lyn Fox, Christine Plant, Valerio Converso, James K Ellis, Somnath Mukherjee, Bhaskar Kumar, Terence Lo, Shajahan Wahed, Alia Alchawaf, Andrew R Moore, Alex Boddy, Martin Scott-Brown, Betsan Thomas, Tarig Abdelrahman, Philip H Pucher, Ahmed El-Sharkawy, Samantha Forner, John Wayman, Ahmed Elshaer, David Chan, Stephen Mcnally, Russell Petty, Pradeep Patil, Neel Bhuva, Jambulingam Periyathambi, Lubna Bhatt, Ravinder Vohra, Linda Sharples, George B HannaIntroduction
Oesophageal squamous cell carcinoma (OSCC) accounts for more than 85% of the global burden of oesophageal cancer, resulting in 500 000 deaths annually. In the UK, over two-thirds of OSCC cases are diagnosed at an advanced stage, with a 5-year overall survival of less than 20%. Breath-based triage tests are feasible, acceptable and show proof of concept for earlier cancer detection.
Methods and analysis
The Volatile Organic Compounds as Breath Biomarkers in Squamous Oesophageal Neoplasms (ViSON) study is a multicentre case–control study powered to estimate breath test performance with 90% sensitivity and 80% specificity. A total of 518 participants (259 with OSCC and 259 non-cancer controls) will be recruited via a network of participating National Health Service trusts. Participants will provide exhaled breath samples, which will be stored on Thermal Desorption tubes and transported to the central laboratory for processing and analysis using gas chromatography-mass spectrometry. A clinical prediction model will be developed using logistic regression with cross-validation and bootstrap methods to mitigate overfitting. Model performance will be evaluated using discrimination, calibration and accuracy. Decision curve analysis will assess clinical utility.
Ethics and dissemination
The ViSON study received ethical approval from the London – Riverside Research Ethics Committee (23/PR/1300) from the Health Research Authority (HRA) and the Health and Care Research Wales (HCRW) to conduct study procedures in England and Wales. A Scotland-wide review was approved on 24 January 2024. The results of the study will be presented at national and international conferences, and a lay summary will be developed with the patient and public involvement representatives and shared using the online website, social media accounts and charity newsletters.
Trial registration number