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Liver Cancer, November 18 2025 | https://doi.org/10.1159/000549565 Clinical feasibility of ctDNA in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Sohyun Hwang^a,†, Dong Jun Shin^b,†, Beodeul Kang^c,†, Haeyoun Kang^a, Sung Hwan Lee^d, Jung Sun Kim^c, Je-Gun Joung^b,e, Suyog Jain^f, Steven Olsen^f, Lars Becker^g, Richard S. Finn^h, Josep M. Llovet^i,j,k, Gwangil Kim^a,*, Chan Kim^c,*, and Hong Jae Chon^c,*

^aDepartment of Pathology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
^bDepartment of Biomedical Science, College of Life Science, CHA University School of Medicine, Seongnam, Republic of Korea
^cDepartment of Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
^dDepartment of Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
^eDepartment of Biomedical Informatics, CHA University School of Medicine, Seongnam, Republic of Korea
^fDepartment of Medical Affairs, Guardant Health AMEA, Singapore 138543, Singapore
^gF. Hoffmann-La Roche Ltd., Basel, Switzerland
^hDivision of Hematology-Oncology, Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
ⁱMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
^jLiver Cancer Translational Research Group, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.
^kInstitució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain.

^†These authors contributed equally to this work.
Corresponding Author: Gwangil Kim, MD; Chan Kim, MD, PhD; Hong Jae Chon, MD, PhD

Abstract

Introduction: The development of targeted therapies and immune checkpoint inhibitors for advanced hepatocellular carcinoma (HCC) reinforces the need for individualized treatment. However, precision medicine is hindered by the lack of mandatory tissue biopsy for genomic profiling in HCC. Liquid biopsy enables genomic profiling of circulating tumor DNA (ctDNA), which could compensate for the lack of tissue-based analysis. This study evaluated the concordance between ctDNA and tumor tissue genomic profiling and its feasibility in advanced HCC treated with atezolizumab plus bevacizumab (atezo/bev).

Methods: This cohort study prospectively collected pretreatment plasma samples from 130 patients with advanced HCC who underwent tissue-based sequencing before systemic therapy from June 2020 to October 2022. Tumor tissue sequencing was performed using the Oncomine Comprehensive Assay, and ctDNA sequencing was conducted using Guardant360.

Results: ctDNA variants revealed 72.6% (69/95; 95% CI, 62.9%-80.6%) sensitivity and 75.0% (69/92; 95% CI, 65.3%-82.7%) positive predictive value compared to tumor tissue. With an interval of ≤30 days between ctDNA and tumor tissue sampling, the sensitivity increased to 96.3% (26/27; 95% CI, 81.7%-99.3%). In patients treated with first-line atezo/bev, maximum variant allele frequency (maxVAF) of ctDNA was strongly correlated with survival outcomes even after adjustment for clinicogenomic variables.

Conclusion: In advanced HCC, ctDNA-based genotyping demonstrated clinically acceptable concordance with tissue-based profiling, providing a reliable alternative when tissue samples are limited. Additionally, ctDNA maxVAF demonstrated independent prognostic value in patients treated with first-line atezo/bev. Liquid biopsy using ctDNA can help address challenges associated with limited tissue-based genomic profiling in advanced HCC.

논문정보

형식Research article
게재일2025년 11월 (BRIC 등록일 2025-11-20)
연구진국내 연구진
분야 의약학 > 종양의학

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