JCSE01.05 Biomarkers and Liquid Biopsy for Early Detection of Lung Cancer

Abstract

The analysis of circulating DNA released by tumor cells, frequently known as liquid biopsy, provides a convenient and noninvasive way for the assessment of cancers. The most common application of liquid biopsy is to guide the choice of treatment in lung cancers. The detection of EGFR mutations in the plasma of patients with advanced lung cancers is useful for predicting the response to EGFR TKI treatment. Because of its noninvasive nature and quick turn-around time, liquid biopsy has been proposed to be a first line investigation for the assessment of EGFR mutational status. Another potential application of liquid biopsy is for the screening of early cancers. However, there is a lack of information regarding the biological feasibility of this approach as it is unclear if a small tumor would release sufficiently large amount of DNA into the circulation to allow early detection of the cancer. In this regard, we used nasopharyngeal cancer (NPC) as a model to address this biological question. As NPC is closely related to Epstein-Barr virus infection, we developed plasma EBV DNA as a marker for NPC. From 2013 to 2016, we screened over 20,000 asymptomatic men for NPC using a sensitive plasma EBV DNA assay. Subjects with positive test results were further investigated with nasal endoscopy and MRI. Through this arrangement, we identified 34 cases of NPC and almost half of them had stage I disease. Compared with historical cohorts, patients identified by screening had much improved progression-free survivial with a hazard ratio of 0.1. This study clearly demonstrates that a small early cancer can release sufficiently large amount of DNA into the circulation to allow sensitive detection by liquid biopsy. To apply these results to non-viral-associated cancers, we developed a generic cancer test based on copy number aberrations and altered methylation in plasma DNA. This test successfully detect various types of cancers, including lung cancer. cancer screening, EGFR testing, liquid biopsy