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

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

• Park S
• Lee EJ
• Rim CH
• Seong J

• KMID: 2410901
• DOI: http://doi.org/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.

Keyword

Biomarkers; tumor; cell-free DNA; hepatocellular carcinoma; radiotherapy; treatment

MeSH Terms

Biomarkers
Carcinoma, Hepatocellular*
Cohort Studies
DNA*
Humans
Plasma*
Portal Vein
Prospective Studies
Radiotherapy*
Thrombosis
Biomarkers
DNA

Figure

• 

  Fig. 1 Mean cfDNA (ng/mL) and 95% confidence interval before and after radiotherapy according to treatment response. A positive response was defined as a complete response or partial response. A negative response was defined as stable disease or progressive disease. RT, radiotherapy; cfDNA, cell-free DNA.

• 

  Fig. 2 Kaplan-Meier estimates of survival. (A) OS, (B) PF rate, (C) IHFF rate, and (D) LC rate according to post-RT cell-free DNA levels. OS, overall survival; PF, progression-free; IHFF, intrahepatic failure-free; LC, local control; RT, radiotherapy; LDNA, low DNA; HDNA, high DNA.

• 

  Fig. 3 Subgroup analysis of the two study cohorts. (A) IHFF rate and (B) LC rate for patients who received concurrent chemoradiotherapy. (C) IHFF rate and (D) LC rate for patients who received stereotactic body radiotherapy. IHFF, intrahepatic failure-free; LC, local control; RT, radiotherapy; LDNA, low DNA; HDNA, high DNA.

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