P1.01-21 Sputum Can Serve as an Alternative Source for Liquid Biopsy in Patients with Lung Cancer

With the advancements in the development of targeted therapy, the detection of actionable mutations has become routine practice in diagnosing lung cancer, especially in non-small cell lung cancer (NSCLC). Due to its non-invasiveness and great accessibility, plasma-based mutation profiling, with a sensitivity of approximately 70%, is widely used in clinical settings. Profiling using other body fluids have been actively explored. In this study, we investigated the potential of sputum obtained from non-small cell lung cancer (NSCLC) patients for mutation profiling. We performed capture-based ultra-deep targeted sequencing on matched Falin-Fixed Paraffin-Embedded (FFPE), plasma and sputum samples of 11 treatment-naïve NSCLC patients using a panel consisting of 168 lung cancer-related genes. Among the 11 patients, with a median age of 57, 8 were diagnosed with adenocarcinoma and 3 with squamous cell carcinoma. In addition, 4 patients were classified with central types and the other 7 were classified with peripheral types. Five of them were non-smokers and the remaining were smokers. Three of them were females and 8 were males. All patients were diagnosed with advanced disease (stage III or IV). Collectively, we identified 52, 40 and 33 mutations from FFPE, plasma and sputum samples, respectively. Using FFPE samples as a reference, both plasma and sputum had an overall concordance rate of 61.5%. If only actionable classic driver mutations were considered, the concordance rate increased to 91% for sputum and 82% for plasma. Profiling of sputum revealed 8 patients with classic lung cancer driver genes: 4 patients with EGFR mutation, 1 with ALK rearrangements, 2 with KRAS mutation, and 1 with ERBB2 mutation. The ERBB2 mutation revealed by sputum was not detected from the corresponding plasma sample. Furthermore, our study revealed that the allelic fractions (AFs) from sputum were significantly higher than AFs from plasma samples (p=0.039). For smokers, the difference of AFs between sputum and plasma was more significant (p<0.001). Furthermore, among the mutations which were detected from both sputum and plasma, 92% mutations had higher AF in sputum. In contrast, for non-smokers, only 29% of mutations had higher AF in sputum. Our data revealed for non-smokers, two media had comparable AFs (p=0.273). Our study demonstrated that sputum from advanced stage NSCLC patients is an alternative media for mutation profiling. Potentially, it may serve as a better source for mutation profiling than plasma in smokers. Larger studies are needed to confirm our findings.