Volatile Organic Compounds as Breath Biomarkers in Squamous Oesophageal Neoplasms (ViSON)

Oesophageal Squamous Cell Carcinoma (OSCC) is a cancer of the food pipe that affects around 2000 patients in the UK every year. It is often detected at an advanced stage, resulting in poor survival (5-year survival less than 20%). Early detection can improve survival (5-year survival >70%). Therefore, early detection is vital to improving survival.

There are no national screening guidelines, and an endoscopy (A camera test to look at the food pipe) is the only available test to detect OSCC.

Early detection of OSCC is challenging for many reasons. Firstly, early disease symptoms are non-specific, which patients often overlook. Secondly, 'Alarm' symptoms such as weight loss, difficulty swallowing or vomiting blood are signs of advanced stage. Lastly, endoscopy is an invasive test with associated risks and significant discomfort.

The investigators propose to develop a breath test for patients with non-specific symptoms. Breath testing has the ideal characteristics for a triage test because it is non-invasive, simple to perform, cost-effective and highly acceptable to patients. The test is based on identifying volatile organic compounds (VOCs, small molecules) that are produced by the cancer and released in breath.

The breath test will be offered by General Practitioners (GPs) to patients with non-specific symptoms. Those who test positive will be referred for an urgent camera test, and those who test negative can be reassured.

Study Overview

• Status: Recruiting
• Conditions: Oesophageal Squamous Cell Carcinoma; Oesophageal Cancer
• Intervention / Treatment: Other: Exhaled breath sampling

Detailed Description

In this prospective multicentre case-control study, the investigators will recruit a total of 518 patients. These will be divided into the following groups:

1. Cancer group (n=259): Patients with treatment naive, histopathology confirmed OSCC.
2. Control group (n=259): Patients who have undergone or are undergoing an upper gastrointestinal (GI) endoscopy as part of their investigation for upper GI symptoms and are found to have either - (i) A normal upper GI tract or (ii) Benign upper GI disease.

Eligible and willing participants will be asked to provide two breath samples by exhaling into single-use breath collection bags. Using a custom designed gas sampling pump, the breath VOCs will be transferred onto thermal desorption (TD) tubes at a controlled flow rate. When the participants' breath sampling is complete, room air (Blank) samples will be taken onto additional TD tubes using the same process.

Once collected, the TD tubes will be transported to Imperial College London (The Hanna lab), where they will be analysed.

• Study Type: Observational
• Enrollment (Estimated): 518

Contacts and Locations

• Study Contact: Name: Sameera Sharma, MBBS; MRCS; Phone Number: 07576583519; Email: vison@imperial.ac.uk

Study Locations

• United Kingdom
  • Cardiff, United Kingdom
    • Not yet recruiting
    • Cardiff And Vale University Health Board
    • Principal Investigator: Tarig Abdelrahman
  • Cardiff, United Kingdom
    • Not yet recruiting
    • Velindre NHS Trust
    • Principal Investigator: Betsan Thomas
  • Coventry, United Kingdom
    • Recruiting
    • University Hospitals Coventry and Warwickshire NHS Trust
    • Principal Investigator: Martin Scott-Brown
  • Leicester, United Kingdom
    • Recruiting
    • University Hospitals of Leicester NHS Foundation Trust
    • Principal Investigator: Alex Boddy
  • Liverpool, United Kingdom
    • Recruiting
    • The Clatterbridge Cancer Centre NHS Foundation Trust
    • Principal Investigator: Alia Alchawaf
  • Liverpool, United Kingdom
    • Not yet recruiting
    • Liverpool University Hospitals NHS Foundation Trust
    • Principal Investigator: Andrew Moore
  • Luton, United Kingdom
    • Not yet recruiting
    • Bedfordshire Hospitals NHS Foundation Trust
    • Principal Investigator: Periyathambi Jambulingam
  • Newcastle, United Kingdom
    • Recruiting
    • Newcastle Upon Tyne Hospitals NHS Trust
    • Principal Investigator: Shajahan Wahed
  • Norwich, United Kingdom
    • Recruiting
    • Norfolk and Norwich University Hospitals NHS Foundation Trust
    • Principal Investigator: Bhaskar Kumar
  • Oxford, United Kingdom
    • Recruiting
    • Oxford University Hospitals NHS Trust
    • Principal Investigator: Somnath Mukherjee
  • Portsmouth, United Kingdom
    • Not yet recruiting
    • Portsmouth Hospitals University NHS Trust
    • Principal Investigator: Philip Pucher
  • Greater London
    • London, Greater London, United Kingdom, W12 0NN
      • Recruiting
      • Imperial College Healthcare NHS Trust
      • Contact: George Hanna, PhD; FRCS; Phone Number: 02033122124; Email: g.hanna@imperial.ac.uk
      • Contact: Sameera Sharma, MBBS; MRCS; Phone Number: 07576583519; Email: ssharma@ic.ac.uk
  • Hull
    • Cottingham, Hull, United Kingdom
      • Recruiting
      • Hull University Teaching Hospitals NHS Trust
      • Principal Investigator: Terence Lo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with treatment naïve OSCC will be identified via the weekly multidisciplinary team (MDT) meetings (OSCC group). Patients undergoing an OGD for upper GI symptoms will be identified using the National Health Services (NHS) trust booking systems (Control group).

Description

Inclusion Criteria: Participants with all the following characteristics will be eligible for inclusion in the study:

1. Cancer cohort (n=259): Patients with treatment naïve, histopathology confirmed OSCC.

2. Control cohort (n=259): Patients who have undergone or are undergoing an endoscopy (OGD) as part of their investigation for upper GI symptoms and are found to have either:

   • A normal upper gastrointestinal tract
   • Benign upper gastrointestinal disease

Exclusion Criteria: Participants with the following characteristics will not be eligible for inclusion in the study:

1. Received some form of treatment (chemotherapy, radiotherapy, immunotherapy, endoscopic resection, or surgery) for OSCC
2. History of another cancer in the last five years
3. Non-squamous cell oesophageal cancer
4. Barrett's oesophagus (with or without dysplasia)
5. Previous oesophageal or gastric resection
6. Unable to provide written consent or lack capacity.
7. Pregnant women

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
OSCC group; Patients with histopathology confirmed, treatment naive OSCC	Other: Exhaled breath sampling; Participants will maintain a clear fluid diet for a minimum of 6 hours prior to breath collection. Participants will be asked to provide a breath sample by exhaling into single-use breath collection bags. Using a custom designed gas sampling pump, the breath VOCs will be transferred onto TD tubes at a controlled flow rate. This breath sampling procedure will be repeated once. When the participants' breath sampling is complete, room air (Blank) samples must be taken onto additional TD tubes using the same procedure. The TD tubes will be sealed with long-term storage caps using the CapLok Tool.
Non-cancer controls; Patients who are undergoing an endoscopy for non-specific upper gastrointestinal (GI) symptoms and are shown to have either: A healthy upper GI tract; Benign upper gastrointestinal disease	Other: Exhaled breath sampling; Participants will maintain a clear fluid diet for a minimum of 6 hours prior to breath collection. Participants will be asked to provide a breath sample by exhaling into single-use breath collection bags. Using a custom designed gas sampling pump, the breath VOCs will be transferred onto TD tubes at a controlled flow rate. This breath sampling procedure will be repeated once. When the participants' breath sampling is complete, room air (Blank) samples must be taken onto additional TD tubes using the same procedure. The TD tubes will be sealed with long-term storage caps using the CapLok Tool.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To develop a breath test for detection of OSCC	The investigators hypothesise that breath VOCs in OSCC are unique and different to those in non-cancer patients. Replicate breath samples will be analysed by two independent assays using different Thermal Desorption - Gas Chromatography - Time of Flight Mass Spectrometry (TD-GC-TOF-MS) instruments. One assay will use a mid-polar, and the other a polar column stationary phase for optimal determination of VOC chemical classes. The samples will then be recollected and analysed by two-dimensional (2D) TD-GC-TOF-MS for robust VOC identification. Confirming the identity of the top VOCs driving the model will provide chemical validation. Data obtained will be used to refine the model using molecular network analysis. Statistical methods will estimate the probability of OSCC as a function of measured VOCs. Calibrations and method validation will be used to assess and correct for discrimination.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effects of known confounding variables on the target VOCs in OSCC	To develop this clinical triage test, the investigators will use logistic regression modelling. They will assess the linearity of relationships between OSCC risk and continuous variables and explore categorical variables and two-way interactions. Inclusion of patient characteristics (e.g., age, gender, alcohol use and smoking), clinical variables (e.g., symptoms) and VOCs in the model will be determined using a combination of statistical significance (Wald p<0.05), size of the model coefficients and clinical opinion, drawing on contemporary methods for clinical prediction rules. The investigators will use model reduction techniques such as the LASSO (least absolute shrinkage and selection operator) or Harrell's step-down approach to prevent over-fitting. They will also assess optimism. If there is missing data, the investigators will apply multiple imputation techniques.	36 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Norfolk and Norwich University Hospitals NHS Foundation Trust; University Hospitals, Leicester; Liverpool University Hospitals NHS Foundation Trust; Cardiff and Vale University Health Board; NHS Tayside; Newcastle-upon-Tyne Hospitals NHS Trust; East and North Hertfordshire NHS Trust; Portsmouth Hospitals NHS Trust; Hull University Teaching Hospitals NHS Trust; The Christie NHS Foundation Trust; Oxford University Hospitals NHS Trust; Imperial College Healthcare NHS Trust; University Hospital Plymouth NHS Trust; University Hospitals Coventry and Warwickshire NHS Trust; Velindre NHS Trust; University Hospitals of Derby and Burton NHS Foundation Trust; NHS Highlands; The Clatterbridge Cancer Centre NHS Foundation Trust; Maidstone & Tunbridge Wells NHS Trust; Bradford Teaching Hospitals NHS Foundation Trust; Bedfordshire Hospitals NHS Foundation Trust; North Cumbria University Hospitals NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 24, 2023
• First Submitted That Met QC Criteria: December 5, 2023
• First Posted (Actual): December 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Oesophageal cancer; Early detection; Volatile organic compounds; Breath biomarker; Oesophageal squamous cell cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Neoplasms; Esophageal Neoplasms
• Other Study ID Numbers: 23SM8534

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No