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

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 cutoff values for cfD)NA 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 (IC) 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 cfD)NA 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.