Tumor-informed circulating tumor DNA assay for surveillance post-liver transplantation in patients with hepatocellular and cholangiocarcinoma.

Background: Liver transplantation (LT) for primary liver cancers achieves excellent patient outcomes, but a minority recur with poor prognosis. Survival may be improved by earlier recurrence detection. This study aims to evaluate the feasibility and performance of a personalized tumor-informed assay utilizing circulating tumor DNA (ctDNA) from peripheral blood for surveillance after LT in patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA). Methods: Here, we test whether a personalized tumor-informed assay utilizing ctDNA from peripheral blood informs post-LT surveillance. Personalized ctDNA assays were employed for surveillance in 38 LT recipients, alongside standard-of-care imaging and peripheral tumor biomarkers [alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9)]. Results: Recurrence was detected radiologically in 6 patients, with positive ctDNA assays in 3 and negative/insufficient to process (ITP) in 3. Nine ITP ctDNA assays were due to insufficient primary tumor tissue. In 31 patients without ITP ctDNA tests, the sensitivity and specificity of ctDNA were 75% [95% confidence interval (CI): 19-99%] and 100% (95% CI: 87-100%). Standard-of-care tumor biomarkers had sensitivity and specificity of 75% (95% CI: 19-99%) and 93% (95% CI: 76-99%), respectively (P>0.99 and P=0.16; McNemar χ Conclusions: This study corroborates the feasibility of ctDNA assays for recurrence surveillance in LT recipients. The results imply that ctDNA assays show promise in confirming recurrence and minimizing the need for invasive biopsy. However, additional prospective studies are needed to confirm ctDNA test utility in surveillance protocols.