Early recurrence detected in hepatocellular carcinoma patients after transcatheter arterial chemoembolization treatment with plasma cell-free DNA

Abstract

Objective Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide with poor prognosis due to the high incidence of recurrence. For patients with advanced HCC, transcatheter arterial chemoembolization (TACE) is the preferred treatment option owing to the minimal invasive clinical treatment with optimum therapeutic outcomes. But, there is a paucity of studies on early detection of residual cancer and relapse that result in the bottleneck of long-term effects after TACE therapy. Patients and methods Using next-generation sequencing platform targeting a panel of 622 cancer-associated genes, we prospectively evaluated the predictive significance of plasma cell-free DNA (cfDNA) to detect minimal residual disease in plasma cfDNA in comparison with DNA obtained from tumor tissue and blood cells of three eligible cases with HCC following TACE therapy. Results The results indicated that the mutational spectrum from plasma cfDNA was consistent with tumor-derived DNA and potentially suggested disease progression. Next, we determined if the dynamic variation of plasma cfDNA could indicate treatment response, the findings suggested that the mutation burden of plasma cfDNA could reveal relapse before alterations in conventional computed tomography imaging and serum α-fetoprotein values. Conclusion The mutation burden in plasma cfDNA may serve as a novel prognostic biomarker by providing early evidence of residual disease and identifying high risk of recurrence in patients with HCC following TACE therapy.

Utility of Liquid Biopsy Analysis in Detection of Hepatocellular Carcinoma, Determination of Prognosis, and Disease Monitoring: A Systematic Review

“…Thirteen studies used CTCs to monitor the response to therapy, [44][45][46]52,108,109,113,119,120,[137][138][139][140] 12 evaluated cfDNA, 58,66,125,126,[141][142][143][144][145][146][147][148] and none evaluated EVs (Table 5).…”

“…140 Few studies examined the effect of post-treatment cfDNA properties on prognosis, and those that did failed to show an association between post-treatment cfDNA and progression-free survival or overall survival. 126,141 Several studies evaluated dynamic changes in cfDNA after therapy 58,143,144,146,148 and found that cfDNA tended to increase at or before the time of disease recurrence/progression more reliably than did AFP. Indeed, 2 studies reported changes in cfDNA mutational profiles preceded radiographic documentation of tumor relapse/progression by up to 8 weeks.…”

“…Indeed, 2 studies reported changes in cfDNA mutational profiles preceded radiographic documentation of tumor relapse/progression by up to 8 weeks. 143,146 It should be noted that all of the studies evaluating cfDNA for monitoring of tumor response were very small (N < 20), and results of some are available only in abstract form.…”

Relationship between plasma cell-free DNA (cfDNA) and prognosis of TACE for primary hepatocellular carcinoma

“…Previously, a study pointed out that the level of cfDNA may be a potential indicator reflecting the prognosis of TACE. However, only 3 PHC patients were included in the study (16). The sample size was small and lacking convincing, and it did not include another potential indicator (cfDNA integrity).…”

Carcinoma of the Liver in Children and Adolescents

“…Advantages of TACE include the delivery of high concentrations of cytotoxic drugs to the tumor center, prolonged intratumoral dwell time of drug, and reduced systemic toxicity. TACE appears to be a safe and effective method in children with unresectable hepatocellular neoplasm and is useful for handling hepatic tumor burden, downstaging, and bridging to OLT (53)(54)(55). Occasionally, pulmonary embolism and thrombosis of some branches of the hepatic artery have been recorded as severe complications.…”