Abstract 1273P
Background
Sputum has attracted attention as a potential medium for detecting genomic abnormalities in early-stage lung cancer. Recent progress in advanced non-small cell lung cancer (aNSCLC) has highlighted plasma as a promising alternative. In this study, we investigated the feasibility of mutation profiling with sputum from aNSCLC patients.
Methods
Matched tissue (TIS), plasma (PLA) and sputum supernatant (SPU) were collected from 71 treatment-naïve aNSCLC patients. Capture-based targeted sequencing of all three biopsies was performed with a panel of 520 cancer-related genes. Detection rate was defined as the proportion of patients with any identified genomic aberration.
Results
The cohort had a median age of 59 (range 20-79) with mostly men (54/71). Fifty-six patients had adenocarcinoma (LUAD) and 15 had squamous cell carcinoma (LUSC). Detection rates between SPU and PLA were comparably (67.6% vs 70.4%, p = 0.86) but were both significantly lower than that of TIS (96.8%, p < 0.001). For SPU, detection rates were significantly higher in LUSC than in LUAD (93.3% vs 60.7%, p = 0.03) and in centrally than in peripherally located tumors (79.5% vs 53.6%, p = 0.047). Detection rates using SPU was higher than using PLA in centrally located tumors (79.5% vs 61.5%, p = 0.14) but lower in peripherally located tumors (53.6% vs 85.7%, p = 0.02). Next, with TIS as gold standard, we compared the sensitivity of detecting established NSCLC driver alterations. SPU and PLA achieved respective sensitivity of 48% and 63% overall, and 59% for both in centrally located tumors. Importantly, SPU enabled more sensitive detection than PLA in the entire cohort and in centrally located tumors for altered KRAS and ALK but less sensitive for EGFR mutations in both populations. Detection of aberrant MET, however, appeared difficult for both biopsies (0/3 for both). In addition, tumor mutation burden estimates from SPU and PLA were highly correlated (Pearson r = 0.78).
Conclusions
Our study demonstrated that for aNSCLC patients, sputum supernatant showed comparable performance as plasma in genomic profiling. Sputum is a viable alternative liquid biopsy, especially for analyzing most actionable driver mutations in patients with centrally located tumors or LUSC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Qiu: Financial Interests, Personal, Member, The author was an employee of Burning Rock Biotech during the conduct of the study: Burning Rock Biotech. J. Xiang: Financial Interests, Personal, Member, The author was an employee of Burning Rock Biotech during the conduct of the study: Burning Rock Biotech. Z. Chen: Financial Interests, Personal, Member, The author was an employee of Burning Rock Biotech during the conduct of the study: Burning Rock Biotech. X. Zou: Financial Interests, Personal, Member, The author was an employee of Burning Rock Biotech during the conduct of the study: Burning Rock Biotech. All other authors have declared no conflicts of interest.