PANACEA: PAN Alimentary Cancer Exhaled breath Analysis

Background In the UK, there are over 75,000 new cases annually of gastrointestinal cancers (oesophageal, gastric, pancreatic, liver and colorectal). The overall 5-year survival for these cancers is poor and even lower in deprived areas.

Symptoms related to gastrointestinal cancers are non-specific, therefore the decision to refer for investigations is challenging. Currently, the cancer yield of urgent and non-urgent referral pathways is 4.4-5.0% and 0.1-1.7% respectively.

Breath analysis offers a simple, quick and non-invasive method to detect volatile organic compounds (VOCs) in breath that are specific to gastrointestinal cancers. The triage test would maximise patient compliance, particularly in certain ethnic groups and deprived areas.

Research questions (i) Can we validate VOCs in the detection of multi-gastrointestinal cancers? (ii) How well does a single breath test perform in the detection of multi-gastrointestinal cancers? (iii) What is the optimal strategy to implement the breath test in primary care? (iv) Would a triage breath test reduce costs in NHS diagnostic pathways?

Methods Multicentre clinical study [WP1]: At least 8,000 individuals with suspected cancer, referred from primary care along upper and lower gastrointestinal cancer pathways, will be recruited from 40 centres.

We aim to have 256 cancers and 6,144 controls with complete dataset (reliable breath data and results of reference test).

Breath samples will be collected on thermal desorption tubes which will be analysed using gas chromatography-mass spectrometry.

We will examine diagnostic accuracy of the breath test to detect cancer and estimate the most likely cancer from upper and lower gastrointestinal referral pathways.

Stakeholder engagement [WP2]: Views of key stakeholders will be captured through interviews, workshops and digital platforms and their feedback will be integrated into strategic decision-making, public engagement and awareness campaigns.

Implementing breath test in primary care [WP3]: Multiple implementation models will be co-designed and tested for breath test delivery in primary care. Process evaluation will be conducted across three sites to determine the strengths and weaknesses of the models. Guidance on best practice in breath test delivery for primary care will be developed.

Health economics [WP4]: A cost-effectiveness and budget impact analysis will be performed to understand the affordability and financial impact on the NHS. Deliverables ? Multi-outcome prediction model to identify gastrointestinal cancers with the highest probability; ? Comprehensive plan to integrate breath testing into the NHS, which impacts health inequalities; ?

Implementation guidance for scaling-up the optimal primary care breath test pathway; ? A cost-effective breath test to detect gastrointestinal cancers in the NHS. Timelines ? Trial set-up at sites: (M0-6) October 2024 – March 2025; ? Patient recruitment and conduction of WPs: (M7-24) April 2025 – September 2026; ?

Data analysis and final report: (M25-30) October 2026 – March 2027.

Anticipated impact and dissemination The non-invasive breath test will provide direct patient benefit through earlier and accurate detection of gastrointestinal cancers, along with higher patient acceptability. Ensuring timely referral will translate to curative treatment and improved long-term survival.

Outcomes will be disseminated via conference presentations, publications, our public advisory group (PAG), charities, our research website and social media.