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NCT Number: NCT06169163

Volatile Organic Compounds as Breath Biomarkers in Squamous Oesophageal Neoplasms

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.

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Key information

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Imperial College Healthcare NHS Trust, London, Greater London, United Kingdom

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About this study

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

  • Cancer group (n=259): Patients with treatment naive, histopathology confirmed OSCC.
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

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

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

Treatment and study plan

exhaled breath sampling

Other

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.

Primary outcomes

  1. To develop a breath test for detection of OSCC

    Time frame: 36 months

    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.

Secondary outcomes

  1. To evaluate the effects of known confounding variables on the target VOCs in OSCC

    Time frame: 36 months

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Sameera Sharma, MBBS; MRCS

CONTACT

[email protected]

07576583519

Sponsors and collaborators

Lead sponsor

Imperial College London

Other

Collaborators

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

Registry information

Acronym: ViSON

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Dec 13, 2023
Registry last updated
May 2, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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