Validating breath analysis for the case finding of pleural mesothelioma and lung cancer in at risk populations.

Approximately 75% of patients with lung cancer present with advanced disease and hence, have a bad prognosis. For those with stage 1 disease, the chance of cure is up to 70%. Therefore, companion diagnostics, which may aid identification of those with early stage lung cancer, will play an important role in future screening programs. It is assumed that lung cancer starts as an intrapulmonary nodule, before expanding and spreading to loco-regional lymph nodes and resulting in distant metastases. Because all cancer cells are characterized by an uncontrolled growth that changes their metabolism, the detection of the resulting metabolites may be a novel diagnostic tool to differentiate between early stage lung cancer among incidental pulmonary nodules. Subsets of these metabolites are volatile and are exhaled as so-called volatile organic compounds (VOCs). Analysis of those VOCs suggests they differ between patients with advanced lung cancer and healthy controls. This study aims to validate the use of a high-throughput breath analysis technique in a population of patients who present with an incidental pulmonary nodule. This study will be a case-control study. Six hundred consecutive patients with various underlying conditions and in whom a pulmonary nodule is found on CT scan performed in the course of their illness, will be invited to participate and will be asked to provide a breath sample prior to the diagnostic procedures –if any- for this nodule. Breath sampling is a non-invasive procedure that will require the patient to breath normally into a facemask for 10 minutes to collect 2.5L of breath. The resulting samples will be analysed by Field Asymmetrical Ion Mobility Spectrometry (FAIMS). The resulting VOC profiles will be used to generate a diagnostic algorithm in order to try to differentiate between benign and malignant nodules. The results of this study will provide detailed insights into the accuracy of the test for the detection of early stage lung cancer in incidentally found pulmonary nodules and will form the base for a subsequent study in a population at high risk for the development of lung cancer ((ex-)smokers of at least 15 pack years with emphysema). If sufficiently accurate for early stage disease, analysis of breath VOCs could help implement large-scale screening for lung cancer, significantly decreasing the morbidity and mortality of the disease.

Keywords:LUNG CANCER

Disciplines:Morphological sciences, Oncology, Respiratory medicine