Plasma Cell-Free DNA as a Predictive Marker after Radiotherapy for Hepatocellular Carcinoma

Yonsei Med J. 2018 Jun;59(4):470-479. doi: 10.3349/ymj.2018.59.4.470.

Abstract

Purpose: Cell-free DNA (cfDNA) is gaining attention as a novel biomarker for oncologic outcomes. We investigated the clinical significance of cfDNA in hepatocellular carcinoma (HCC) patients treated with radiotherapy (RT).

Materials and methods: Fifty-five patients with HCC who received RT were recruited from two prospective study cohorts: one cohort of 34 patients who underwent conventionally fractionated RT and a second of 21 patients treated with stereotactic body radiation therapy. cfDNA was extracted and quantified.

Results: In total, 30% of the patients had multiple tumors, 77% had tumors >2 cm, and 32% had portal vein tumor thrombus. Optimal cut-off values for cfDNA levels (33.65 ng/mL and 37.25 ng/mL, before and after RT) were used to divide patients into low-DNA (LDNA) and high-DNA (HDNA) groups. The pre-RT HDNA group tended to have more advanced disease and larger tumors (p=0.049 and p=0.017, respectively). Tumor response, intrahepatic failure-free rates, and local control (LC) rates were significantly better in the post-RT LDNA group (p=0.017, p=0.035, and p=0.006, respectively).

Conclusion: Quantitative analysis of cfDNA was feasible in our cohorts. Post-RT cfDNA levels were negatively correlated with treatment outcomes, indicating the potential for the use of post-RT cfDNA levels as an early predictor of treatment responses and LC after RT for HCC patients.

Keywords: Biomarkers; cell-free DNA; hepatocellular carcinoma; radiotherapy; treatment; tumor.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / radiotherapy*
  • Cell-Free Nucleic Acids / blood*
  • Cell-Free Nucleic Acids / genetics*
  • Circulating Tumor DNA / blood*
  • DNA
  • Female
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / radiotherapy*
  • Male
  • Middle Aged
  • Portal Vein
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • Circulating Tumor DNA
  • DNA