Whole Exome Sequencing of Cell-Free DNA for Early Lung Cancer: A Pilot Study to Differentiate Benign From Malignant CT-Detected Pulmonary Lesions

Conclusions: This study suggests a potential role for cfDNA for the early identification of lung cancer in patients with CT-detected pulmonary lesions. Importantly, a substantial number of somatic variants in healthy patients with benign pulmonary nodules were also found. Such “benign” variants, while largely unexplored to date, have widespread relevance to all liquid biopsies if cfDNA is to be used accurately for cancer detection. Introduction Lung cancer is the leading cause of cancer-related death in the United States (1). Most patients present with advanced disease with limited cure potential. The National Lung Screening Trial (NLST) demonstrated a 20% relative reduction in cancer mortality with lung cancer screening with low-dose computerized tomography (LDCT) compared to radiography (1). However, CT poses limitations; namely, the high incidence of indeterminate pulmonary nodules (IPNs). Over 24% of NLST participants in the CT arm had IPNs, and the majority (>96%) were false positive (1). IPNs are also common in routine clinical radiology, with frequency up to 60%. Patients with IPNs often require long-term sequential imaging and/or biopsy to establish diagnosis (2). There has been growing interest in plasma cell free DNA (cfDNA), or “liquid biopsy,” for cancer diagnosis and surveillance (2, 3). cfDNA is thought to be released into circulation by necrotic or apotpic cells, and is frequently present at higher quantities in ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research