45P Actionable mutations in matched liquid and tissue biopsy next-generation sequencing

Sufficient tumour tissue at diagnosis and recurrence is often suboptimal for comprehensive genomic profiling (CGP) in non-small cell lung cancer (NSCLC). Furthermore, the turnaround time for tumour tissue CGP may impact timely treatment decision-making. However, liquid biopsies may compensate for this shortfall in terms of sample size and turnaround time. Given the limitations of liquid biopsies in detecting actionable alterations, due to insufficient circulating tumour DNA (ctDNA), we, therefore, investigated the accuracy and concordance of ctDNA CGP. Patients were recruited as part of an ongoing multi-centre prospective Precision Oncology Programme in advanced NSCLC, in Hong Kong starting from July 2021. CGP was performed using FDA-approved Foundation One CDx and Foundation One Liquid CDx. The diagnostic accuracy of liquid biopsy was investigated by positive percentage agreement (PPA). The correlation of tumour mutational burden (TMB) was calculated with Pearson correlation. 72 patients with matched liquid and tissue CGPs were analysed. In our cohort, the median age at biopsy was 69. 71% of the ctDNA samples had a tumour fraction score of <1%. Additionally, the average ctDNA TMB and tumour tissue TMB was 5.5 muts/Mb and 6.1 muts/Mb, respectively. 47% (n=35) of patients harboured ESCAT level I actionable mutations. The actionable mutations reported were: ALK fusions (n=1), BRAF V600E (n=2), EGFR L858R (n=17), EGFR Exon 19 deletion (n=13), KRAS G12C (n=1), and MET exon 14 splice site (n=1). The PPA of the reported actionable mutations in our paired cohort was 71%. Conversely, the correlation of TMB between liquid and tumour tissue was 0.56 with a PPA of 60%. Importantly, our study highlights the potential of ctDNA in detecting clinically actionable mutations when tumour biopsies are unavailable. Conversely, ctDNA alone is not adequate in reporting TMB.