Targeted Molecular Profiling of Circulating Cell-Free DNA in Patients With Advanced Hepatocellular Carcinoma
Darren Cowzer, Jessica White, Joanne F. Chou, Pin‐Jung Chen, Tae‐Hyung Kim, Danny N. Khalil, Imane H. El Dika, Katrina Columna, Amin Yaqubie, Joseph S. Light, Jinru Shia, Hooman Yarmohammadi, Joseph P. Erinjeri, Alice C. Wei, William R. Jarnagin, Richard Kinh Gian, David B. Solit, Marinela Capanu, Ronak Shah, Michael F. Berger, Ghassan K. Abou‐Alfa, James J. Harding
Abstract
PURPOSE: Next-generation sequencing (NGS) of tumor-derived, circulating cell-free DNA (cfDNA) may aid in diagnosis, prognostication, and treatment of patients with hepatocellular carcinoma (HCC). The operating characteristics of cfDNA mutational profiling must be determined before routine clinical implementation. METHODS: This was a single-center, retrospective study with the primary objective of defining genomic alterations in circulating cfDNA along with plasma-tissue genotype agreement between NGS of matched tumor samples in patients with advanced HCC. cfDNA was analyzed using a clinically validated 129-gene NGS assay; matched tissue-based NGS was analyzed with a US Food and Drug Administration-authorized NGS tumor assay. RESULTS: (8%). Higher average variant allele fraction was associated with elevated alpha-fetoprotein, increased tumor volume, and no previous systemic therapy, but did not correlate with overall survival in treatment-naïve patients. CONCLUSION: Tumor mutation profiling of cfDNA in HCC represents an alternative to tissue-based genomic profiling, given the high degree of tumor-plasma NGS concordance; however, genotyping of both blood and tumor may be required to detect all clinically actionable genomic alterations.