CRUK Early Diagnosis Research Conference

The aim of the Cancer Research UK Early Diagnosis Research Conference is to cover a broad range of early diagnosis themes including primary care, clinical decision support tools, emergency presentations and screening. Further information.

Our poster on the LuCID Study for early detection of lung cancer was well received.

Poster title: Early detection of lung cancer through analysis of exhaled volatile organic compounds; The LuCID study

Rationale

A major factor determining prognosis of patients with lung cancer is the stage at diagnosis. Almost 70% of patients have advanced disease and a poor prognosis when they present to clinic. Five-year survival for stage IV patients is only a few percent whereas for stage 1a treated with surgery it is 70%.

The LuCID study (Lung Cancer Indicator Detection) aims to evaluate the use of breath biomarker analysis to detect lung cancer earlier.

At the basis of each cancer lie genetic changes that drive uncontrolled growth. Downstream alterations in RNA and proteins result in altered metabolites that reflect these oncogenic mutations.  These metabolites are naturally excreted by cells and their volatile fraction diffuses into the airways either directly from the tissue or from the blood in the alveoli.  Volatile organic compounds (VOCs) are constantly exhaled and therefore have potential to be non-invasive biomarkers for early detection of lung cancer and play a role in the evaluation of indeterminate pulmonary nodules.

Methods

LuCID is an international, multi-centre cohort collaborative study sponsored by Owlstone Medical currently running at 12 hospitals across Europe (ClinicalTrials.gov ID NCT02612532). The study focuses on evaluating breath VOCs in all patients with a clinical suspicion of lung cancer to reflect the real-life heterogeneity that is observed in clinic. Using tidal breathing, patients breathe into the ReCIVA breath collector device for approximately 7 minutes to collect both bronchial enriched and end-tidal breath fractions in duplicate. The ReCIVA stores these breath samples on sorbent tubes containing activated carbon that stabilizes the VOCs.  The VOCs are analysed by Gas Chromatography Mass Spectrometry (GC-MS) and Owlstone’s Field Asymmetric Ion Mobility Spectrometry (FAIMS) Platform. GC-MS analysis will provide detailed insight into the chemical nature of the VOCs but is less suited for translation to clinical practice. However, the corresponding features identified by the FAIMS sensor allow potential implementation of the test into both primary and secondary care.

The study has an adaptive trial design that will evaluate the accuracy of the breath test against criteria that have been pre-defined based on health economic analysis. This involves analysing the features identified from the breath samples according to a 3 step approach involving method building, internal and external blinded validation.

The study will report the accuracy of breath analysis for the detection of lung cancer in patients with a clinical suspicion of having lung cancer and specifically for the sub-population of patients with indeterminate nodules. The LuCID study will lay the foundation for a subsequent screening study in a high-risk population evaluating clinical deployment of the test. Involving up to 3,000 patients, the LuCID study is evaluating a new modality for non-invasive breath testing incorporating novel FAIMS technology that could enable early detection of lung cancer aimed at reducing lung cancer morbidity and mortality.

Lead Investigator: Dr Robert Rintoul, Papworth Hospital Trust

Other Investigators: Dr Marc van der Schee, Dr Mamta Ruparel, Jasper Boschman, Rob Smith, Russell Parris, Billy Boyle, Duncan Apthorp, Simon Kitchen, Professor Sam Janes, Prof Hubertus Wirtz, Lisa Richardson, Dr Liz Fuller, Dr Seamus Grundy, Professor David Baldwin, Dr Philip Crosbie, Dr Anjani Prasad, Dr Mohammed Haris, Dr Andy Barlow, Dr Lori Calvert, Dr Andrew Wight.