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Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
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Circulating DNA changes are predictive of disease progression after transarterial chemoembolization
David Sefrioui1,2, Vincent Verdier1,2, Céline Savoye-Collet3,4
1UNIROUEN, Inserm 1245, IRON group, Normandie Univ, Rouen, France.
International Journal of Cancer
|October 8, 2021
Summary
Increases in cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) can predict treatment failure. Monitoring these biomarkers alongside imaging helps assess therapeutic response.
Area of Science:
- Oncology
- Molecular Biology
- Medical Imaging
Background:
- Hepatocellular carcinoma (HCC) is a primary liver cancer with limited treatment options for unresectable cases.
- Transarterial chemoembolization (TACE) is a standard treatment for unresectable HCC, but predicting treatment response remains challenging.
- Biomarkers like alpha-fetoprotein (AFP), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA) are being investigated for their role in monitoring HCC treatment.
Purpose of the Study:
- To evaluate the clinical impact of changes in AFP, cfDNA, and ctDNA around the TACE procedure in HCC patients.
- To identify thresholds for cfDNA and ctDNA changes that are associated with progressive disease (PD) after TACE.
- To assess the utility of a combined cfDNA and ctDNA score in predicting PD and progression-free survival (PFS).
Main Methods:
- Prospective monocentric study of 38 patients with unresectable HCC undergoing TACE.
- Collection of blood samples at baseline, Day 2, and 1 month post-TACE for cfDNA and ctDNA quantification.
- Quantification of cfDNA via fluorometry and ctDNA via digital PCR for TERT mutations.
- Radiological assessment using CT/MRI at 1 month and every 3 months post-TACE.
- Receiver operating characteristic (ROC) curve analysis to determine thresholds associated with PD.
Main Results:
- All biomarkers (AFP, cfDNA, ctDNA) initially increased post-TACE (Day 2) and subsequently decreased by 1 month.
- Significant thresholds for PD at 1 month were identified: cfDNA > +31.4% and ctDNA > 0% change from baseline.
- No significant threshold for AFP was found.
- A combined cfDNA and ctDNA score classified patients into high-risk (80% PD) and low-risk (4.3% PD) groups.
- Median PFS was significantly shorter in the high-risk group (1.3 months) compared to the low-risk group (10.3 months).
Conclusions:
- Increases in cfDNA and ctDNA around the TACE procedure are associated with therapeutic failure in HCC.
- cfDNA and ctDNA changes, particularly when combined, show potential as early predictive biomarkers for PD after TACE.
- These molecular markers may offer a valuable adjunct to imaging for monitoring treatment response and guiding clinical decisions in HCC management.
