Circulating tumor DNA is a potential prognostic risk factor of recurrence in patients with hepatocellular carcinoma treated by liver transplantation.

Abstract

e16196 Background: Liver transplantation (LT) is one of the most effective therapeutic strategies for hepatocellular carcinoma (HCC), however, tumour recurrence after LT often leads to poor outcomes. At present, clinical characteristic profile, imaging diagnosis as well as level of serum biomarkers prior to LT could predict the prognosis in HCC patients treated by LT. However, the sensitivity and specificity of these biomarkers are limited, highlighting the crucial need to identify novel biomarkers. Previous clinical studies have shown that postoperative circulating tumor DNA (ctDNA) can be used as a predictive biomarker for the risk of recurrence in stage I-III solid tumor. This study aimed at investigating the relationship between the level of ctDNA and the probability of recurrence in HCC patients treated by LT. Methods: HCC patients receiving LT treatment were enrolled. Peripheral blood samples before LT and available matched tissue samples were collected. Targeted sequencing of 328 cancer-related genes were conducted. The clinicopathologic data of the patients was retrospectively analyzed. The predictive efficiency for recurrence after LT of different clinicopathologic parameters and ctDNA were accessed. Results: A total of 45 patients were enrolled, including 42 males (93%) and 3 females (7%), with a median age of 51 (range 31-76 years). Thirty-five patients (78%) had detectable ctDNA before LT while gene alterations were identified in tumor tissue of all the patients. Larger tumor size (> 5cm), cirrhosis, portal vein tumor thrombus (PVTT) and elevated AFP level (≥400ng/ml) prior to LT were associated with higher percentage of positive ctDNA (94% vs 73%, 84% vs 75%, 88% vs 79%, 88% vs 76%, respectively). Patients with micro-vessel invasion (MVI) had higher ctDNA abundance (maxVAF, P < 0.05). Interestingly, after over 3 years’ follow-up, clinical factors including MVI, PVTT, BCLC stage, maximum tumor diameter and serum AFP failed to predict disease free survival (DFS) and overall survival (OS). In contrast, the recurrence rate was remarkably augmented (48.6% vs 0%) and the median DFS was significantly decreased (390 days vs not reached, p< 0.05) in patients with detectable ctDNA. Conclusions: In conclusion, ctDNA could be a potential biomarker to sensitively predict the recurrence in patients with HCC treated by LT, which may help to improve the post-transplant management of these patients.

Cell-Free DNA as a Surveillance Tool for Hepatocellular Carcinoma Patients after Liver Transplant

“…Another study, performed on ten patients, found a complete correlation between ctDNA detection and the recurrence of HCC [85]. Jiang et al, in a study with 45 HCC patients, found the same correlation, with an increased recurrence rate for patients with detectable ctDNA (48.6% vs. 0%) [86].…”

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

“…In HCC, Wang et al (2020) showed a reduced RFS with post-operative ctDNA assessed according to a panel of four hotspot genomic mutations in TP53 (G747T), CTNNB1 (A121G, C133T), and TERT (c.-124C>T) [ 30 ]. In the setting of liver transplant for unresectable primary liver cancer, larger scale studies by Huang et al (2023) [ 23 ] and Jiang et al (2022) [ 31 ] again display higher recurrence rates in patients with positive post-transplant ctDNA and decreased disease-free survival.…”

“…At a minimum, pre- and post-LT testing should be pursued when using tissue-agnostic testing in order to obtain a pre-transplant comparison. With expanding evidence supporting the use of ctDNA testing in liver cancers [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], the optimization of protocols effective at addressing the concerns regarding donor-derived alterations is warranted in future studies.…”

Liver Transplantation for Hepatocellular Carcinoma: A Narrative Review and A Glimpse into The Future

“…They noted that clinical factors such as BCLC stage, maximum tumor diameter, and serum AFP were ineffective predictors of disease-free and overall survival. However, patients with detectable ctDNA experienced a significantly increased recurrence rate and diminished median disease-free survival [32]. All these studies showed that CTC and ctDNA correlated very well with the risk of recurrence and survival.…”

“…However, patients with detectable ctDNA experienced a significantly increased recurrence rate and diminished median DFS. 32 All these studies showed that CTC and ctDNA correlated very well with the risk of recurrence and survival. Further studies on the CTC, ctDNA, or other molecular biology markers represent a novel strategy to measure tumor burden.…”