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Circulating tumor DNA may predict HCC recurrence

Researchers at Hiroshima University found circulating tumor DNA to be an accurate predictor of hepatocellular carcinoma recurrence within 2 years of liver resection, according to newly published data.

“We uncovered that circulating tumor DNA levels accurately reflect cancer progression and therapy effects on hepatocellular carcinoma,” Atsushi Ono, MD, Hiroshima University, said in a press release. “With further research, the identification of genome profiles through circulating tumor DNA analysis may guide individualized management of hepatocellular carcinoma.”

Ono and colleagues analyzed data of 46 patients with HCC who underwent hepatectomy or liver transplantation between October 2009 and January 2012. The researchers quantified circulating tumor DNA (ctDNA) through the use of assays that targeted somatic rearrangements of each tumor. Exome sequencing also was performed using cell-free DNA paired primary tumor tissue DNA from a patient with recurrent liver cancer after transcatheter arterial chemoembolization (TACE).

“We investigated whether ctDNA levels reflect HC tumor dynamics and could be used as a predictor of poor diagnosis by quantifying each of the cancer-specific genomic arrangements,” the researchers wrote. “We have also investigated whether exome sequencing of cell-free DNA in a patient with liver cancer could identify somatic mutations in cancer tissue.”

Mutations were found in all of the tumors; however, ctDNA was found in only seven of the 46 patients before surgery. The presence of ctDNA was associated with larger tumor size and increased recurrence for HCC within 2 years of liver resection. In addition, ctDNA also increased with disease progression.

The cumulative incidence of recurrence and extrahepatic metastasis in the patients with ctDNA (P = .0102) was worse compared with the patients without ctDNA (P = .0386).

Multivariate analysis showed ctDNA to be an independent predictor of microscopic vascular invasion of the portal vein (OR = 6.1; 95% CI, 1.11-33.33).

In addition, the researchers found 45 nonsynonymous somatic mutations in cell-free DNA after TACE and 71 nonsynonymous somatic mutations in primary tumor tissue by exome sequencing. There were 25 common mutations in both samples, with 83% of mutations identified in the primary tumor also detectable in the cell-free DNA.

“The presence of ctDNA reflects tumor progression, and detection of ctDNA can predict [vascular invasion of the portal vein] and recurrence, especially extrahepatic metastasis within 2 years. Our study demonstrated the usefulness of ctDNA detection and sequencing analysis of cell-free DNA for personalized treatment of liver cancer.” – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.