Lung cancer has a poor prognosis, and recurrence rates of 6-10% per person year occur. Conventional chemotherapy has had limited efficacy in improving the outcomes of non-small cell lung cancer (NSCLC- the most common type of lung cancer) in part because of emergent treatment resistance. Genomic clonal evolution within lung cancers leads to intra-tumour heterogeneity (ITH), and it is now thought that genomically heterogeneous clonal subpopulations are involved in tumour progression and evolutionary treatment resistance. Understanding of this phenomenon in lung cancer is limited, in part because obtaining sequential tumour biopsies is not practical and single biopsies do not confer full information on the entirety of the tumour. Efforts to detect circulating tumour DNA (ctDNA) in blood samples have shown some promise, but in the largest comprehensive study to date (TRACERx) blood performs poorly in the detection of ctDNA in lung adenocarcinoma [19% (11/58 cases)] [1]. A non-invasive method of detecting changes at multiple time points reflecting spatial and temporal tumour heterogeneity is needed. In this study, we will characterise the genomic features of early stage lung adenocarcinoma (ESLADC), using tumour and serial blood and exhaled breath condensate (EBC) samples from 15 ESLADC patients undergoing curative resection. Our aims are: 1. Determination of the intra-tumour heterogeneity of genomic mutations in primary ESLADC tumours at multiple loci within the resected tumour (spatial heterogeneity).
2. Determination of whether EBC can be used to detect spatially homogenous and heterogeneous genomic mutations in ESLADC. 3. Determination of whether EBC is more representative of tumour genomic heterogeneity than the initial diagnostic biopsy and circulating tumour DNA in plasma or can augment blood-based testing
4. Determination of whether EBC can reliably detect reductions in tumour mutations post-complete tumour removal and detect molecular recurrence at or before evidence of disease relapse using serial samples post operatively.