Abstract 4669: Prognostic value of postoperative circulating tumor DNA in patients with resectable hepatocellular carcinoma

Abstract Background: Hepatocellular carcinoma (HCC) is endemic in Asia, particularly Vietnam due to the prevalence of hepatitis B virus infection. Liver resection is the first-line treatment but prognosis remains poor with a high relapse rate. Current methods including imaging and serum tumor biomarkers have suboptimal accuracy to monitor tumor burden and predict relapse. Method: In this prospective study, sixty HCC patients who were eligible for curative-intent liver resection were recruited. Genomic DNA isolated from primary tumor tissues and paired white blood cells were subjected to targeted sequencing of 95 cancer-related genes to profile tumor-derived mutations. Top-ranked mutations specific to each individual were then used to track the presence of circulating tumor DNA (ctDNA) in serial plasma samples. Results: The most frequently mutated genes in our cohort were TP53 (42.4%), TERT promoter (39.0%), CTNNB1 (23.7%), and AXIN1 (22.0%). TP53 R249S was the major hotspot found in 8.5% of the patients. Mutations in TERT promoter were significantly more prevalent in hepatitis C- than hepatitis B- infected patients, while CTNNB1 was not mutated in those with no virus infection. On average, 4 mutations were selected to track ctDNA in plasm samples. Pre-operative detection rate of ctDNA was 96.6%, higher than AFP (57.6%). Post-operative ctDNA positivity, both at the landmark time point and during surveillance, was the strongest independent predictor of disease-free survival (HR: 17.9, 95% CI: 5.9 - 54.1, p<0.001). ctDNA detection could predict clinical relapse with sensitivity and specificity of 82.8% and 96.0% respectively, and the lead time of up to 7.3 months. This outperformed all serum tumor biomarkers: AFP, AFP-L3, and PIVKA-II. Conclusion: Our simplified and cost-effective assay enabled longitudinal ctDNA monitoring for early relapse detection and predict disease-free survival in HCC patients. This study also provided the first mutation spectrum of Vietnamese HCC that could be helpful to uncover the multifactorial etiology of the disease. Citation Format: Van-Anh Nguyen Hoang, Dao Nguyen Vinh, Giang Hoang Vu, Duy Sinh Nguyen, Hoa Giang, Hoai-Nghia Nguyen, Lan N. Tu. Prognostic value of postoperative circulating tumor DNA in patients with resectable hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4669.