Abstract 1266P
Background
Pleural effusion (PE) which is often seen in advanced lung cancer patients has been one of the promising sources of liquid biopsy. However, the difference between PE, plasma and tumor tissue profiling as well as associated clinical significance are not yet fully explored.
Methods
Data from 164 patients with advanced lung cancer for whom molecular profiling of their tumor tissues and PE-derived cell-free DNA (PE-cfDNA) was available were studied. Data of other sample types, including 153 matched plasma and 63 PE cell sediment DNA (PE-sDNA) were also included for analysis, with a focus on the discrepancies of molecular alterations between different sample types.
Results
Compared to PE sediment (PE-sDNA) and plasma cell-free DNA (cfDNA), PE supernatant (PE-cfDNA) displayed advantages in mutation detections including mutant allele frequency, numbers of shared mutations with tumor tissues(PE-sDNA 43%, plasma-cfDNA 43%, PE-cfDNA 65%). The discrepancies between PE-cfDNA and tumor tissue in high in several genes, including SMARCA4, PIK3CA, ERBB2, KM T2A, ALK and NF1. For clinically actionable mutations, the concordance rate between PE-cfDNA and tumor tissue is 87%. Eleven patients showed only PE-derived actionable mutations and four patients (three EGFR T790M and one BRAF V600E) benefited from PE-cfDNA-guided targeted therapies (osimertinib, dabrafenib and trametinib). Meanwhile, PE-cfDNA recapitulated mutations of diverse tissue origins and provided more mutational information under the circumstance that tumor tissue or tumor tissue of different origins were unavailable. The combination of tumor tissue and PE-cfDNA profiling increased positive detection rates of patients by 6% compared to tumor tissue alone.
Conclusions
The PE-cfDNA-based liquid biopsy overcomes tumor heterogeneity and displays better performance in gene alterations characterization than PE-sDNA and plasma-cfDNA. PE-cfDNA together with tumor tissue profiling optimizes comprehensively genomic profiling of lung cancer patients, which may be important for selecting patients for better treatment management.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences.
Funding
The study was supported by National Key R&D Program of China (Grant No. 2016YFC1303800, to Q Zhou), the National Natural Science Foundation of China (grant no. 81802298, to Y.S. Li), the Key Laboratory System Project of the Guangdong Science and Technology Department-Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer (grant no. 2012A061400006/2017B030314120, to Y.L. Wu), National Natural Science Foundation (Grant No.81972164, to J.J. Yang) and National Natural Science Foundation of China (Grant No. 81802266, to B.F. Xu).
Disclosure
X. Tong: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. X. Wu: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. D. Zhu: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. Y. Wu: Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Eli Lilly; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Sanofi; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim. All other authors have declared no conflicts of interest.