Breath Test

Through the HOPE study, the intention would be to determine whether exhaled breath volatile organic compound (VOC) profiles in Primary care differ from Secondary care. The intention would also be to assess intra-subject variability of participants. This would allow us to determine if the results of breath samples are reproducible regardless of whether they are performed in a Primary or Secondary care environment. This would support the clinical translation of breath research outcomes from studies performed in Secondary care, despite the breath test being intended for use in Primary care. The chief investigator of the HOPE study is Professor George Hanna (Head of Department of Surgery and Cancer, and Professor of Surgical Sciences at Imperial College London).

Background: Each year in the United Kingdom there are over 44,000 deaths related to gastrointestinal (gut) cancers that include oesophageal (food pipe), stomach, pancreas, liver and bowel cancers. These cancers are difficult to detect as the symptoms are similar to non-cancer conditions. The delay in suspecting cancer and referral to a camera test (endoscopy) or scans can lead to the growth of cancer. Even with urgent referral only 4 out of every 100 patients are found to have cancer. If diagnosed early, the majority of people can survive gastrointestinal cancer. However, as the disease progresses, the number of people who survive falls significantly. Early diagnosis is therefore key. The proposed solution is a simple breath test for patients with relevant symptoms. Breath testing is quick, acceptable and can be offered directly by a GP. The breath samples are analysed for small molecules called volatile organic compounds. These molecules provide early indicators of gastrointestinal cancer, to identify those who would benefit most from investigations. Picking up gastrointestinal cancers earlier will increase the chances of curing the disease. Aims: breath molecules that are specific to gastrointestinal cancers have been previously identified. The aim is to confirm these molecules and examine the accuracy of the breath test. How to implement the test in primary care will also be studied. Design and Methods: Breath testing will be performed on at least 8,000 patients referred by GPs on suspected gastrointestinal cancer pathways. Patients will be followed up to determine whether they have gastrointestinal cancer or not. The breath test will take place in national NHS hospitals before patients undergo camera tests or scans. The breath test involves them breathing out into a bag allowing the breath to be collected into special tubes. The breath samples in the tubes will be analysed in the local laboratory. Which molecules in patients' breath samples correctly identify cancer will be confirmed. The key members will be engaged with to implement the breath test in primary care and NHS and assess the affordability of the breath test. Patient and public involvement and engagement (PPIE): A diverse PPIE group of 6 members affected by gastrointestinal cancer have identified clear benefits to patients and GPs and provided ways to improve patient recruitment. Work was with charities and appointed a patient representative to the local committee to support dissemination. The results will be disseminated through scientific papers and reports, conference presentations, public-facing areas, social media and cancer charity newsletters.

Upper digestive tract cancer (UDC) is a major disease burden worldwide encompassing all cancers involving the digestive tract (from oral cavity to duodenum). A majority of patients presenting with this disease are diagnosed late and have poor overall survival rates (\<20%). NICE referral guidelines for diagnostic endoscopy are usually associated with late disease. Exhaled breath testing is a non-invasive and acceptable technology utilising mass spectrometry (MS) which has shown promise at diagnosing cancer at an early stage. Previous research has shown that products formed as a result of metabolism can be measured in breath and saliva (biomarkers). This has the ability to accurately identify patients with upper gastrointestinal (UGI) cancers from breath. Our initial pilot data has demonstrated that changes in the breakdown of metabolites release volatile organic compounds (VOC) which can be measured with MS. This data is supported by other patient studies. However no previous study has been performed utilising a non-invasive technique with breath and saliva. Thus the aim of this study is to identify VOCs present in patients with this disease. In this multi-centre study the investigators want to overcome the limitations of previous work by utilising non-invasive samples (breath, saliva and urine) in patients in multiple sites. The investigators aim to conduct a study in patients with UDC and those without. The investigators hope that the results of this study will provide evidence for large scale analysis of patients with this disease, demonstrate the feasibility of this technique and move this valuable test forward into mainstream medical practice. The major advantage of this test is that it is easy to undertake and painless for the patient. This study of products in breath, saliva and urine will be useful for detecting UDC to allow treatment at an early stage, improving overall survival.