LAUSR

Introduction: Residual disease detection is a significant clinical need in post-surgery treatment of resectable hepatocellular carcinoma (HCC) patients. Previous NGS-based studies targeting fixed genomic regions had reported that circulating tumor DNA (ctDNA) could provide evidence for prognosis prediction during HCC treatment. However, the sensitivity of methods was limited and could not reach the threshold of minimal residual disease (MRD) test. Here we reported a baseline tissue -informed ctDNA NGS assay, detecting MRD in HCC patients who received hepatectomy and predicted prognosis in MRD positive patients. Methods: The study retrospectively enrolled 200 early-stage HCC patients who received surgical resections. Tumor and normal tissue samples were collected respectively through surgery. Plasma samples were collected 7 days or more post-surgery. In the completed pilot study, samples from 17 patients were tested by a baseline tissue-informed MRD assay (PredicineBEACON). Tumor-specific mutations were identified by whole exon sequencing on baseline tumor and normal tissue samples. For each patient, up to 50 mutations were selected through bioinformatics pipelines for personalized MRD panel design, in combination with a fixed panel of 500 tumor actionable hotspots. The post-surgery plasma samples were then tested for MRD with the panel through ultra-deep sequencing(100,000X). Afterward, genomic tumor fraction proportions were calculated. Results: In the completed pilot study, 12 of 17 patients (70.6%) were called MRD positive based on tests of post-surgery plasma. Among MRD positive patients, 3 were identified as MRD risk high (proportion of tumor fraction≥0.1%) and MRD risk of others were moderate (proportion of tumor fraction<0.1%). The tumor fraction proportion of MRD positive patients varied from 0.013% to 17.84% (median 0.042%). The recurrence free survival (RFS) and overall survival (OS) probabilities were significantly correlated with MRD risk: the median RFS of two groups(risk-high vs. risk-moderate) was 10.1 months vs. 57.4 months (p-value<0.001), while the median OS of two groups (risk-high vs. risk-moderate) was 31.2 months vs. 57.4 months(p-value=0.028). Conclusions: Baseline-informed ctDNA NGS assay showed ultra-sensitive capability of MRD detection on early-stage HCC patients, with outstanding positive rate through plasma samples collected 7 days post-surgery. The MRD risk provided significant prognostic evidence for patient survival and disease relapse. Citation Format: Jie Hu, Haoran Tang, Feng Xie, Yue Zhang, Shidong Jia, Jian Zhou. Tissue-informed ctDNA MRD assay detects post-surgery minimal residual disease in HCC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1020.