ArticleCancers2022
Circulating Cell-Free DNA Profiling Predicts the Therapeutic Outcome in Advanced Hepatocellular Carcinoma Patients Treated with Combination Immunotherapy.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Efficacy and safety of immune checkpoint inhibitors for hepatocellular carcinoma patients with macrovascular invasion or extrahepatic spread: a systematic review and meta-analysis of 54 studies with 6187 hepatocellular carcinoma patients.Cancer immunology, immunotherapy : CII · 2023Pooled it
- Clinical Feasibility of Circulating Tumor DNA in Patients with Advanced Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab.Liver cancer · 2026Article
- Microbiome-Immune Interactions as Determinants of Checkpoint Inhibitor Efficacy in Hepatocellular Carcinoma.International journal of molecular sciences · 2026Review
- Circulating cfDNA CD86 methylation is associated with durable response to atezolizumab-bevacizumab in hepatocellular carcinoma.Hepatology international · 2026Article
- Acquired Genetic Variants, Not Tumor Mutation Burden, Drive Resistance to Immunotherapy in Hepatocellular Carcinoma.Liver cancer · 2026Article
- WNT-β-catenin signalling in hepatocellular carcinoma: from bench to clinical trials.Nature reviews. Gastroenterology & hepatology · 2026Review
- Tumor-based biomarkers and circulating tumor DNA for precision medicine in advanced hepatocellular carcinoma.Clinical and molecular hepatology · 2026Review
- Tissue and blood-based predictive biomarkers in hepatocellular carcinoma immunotherapy: synthesis of 2023-2026 evidence and a proposed clinical integration framework.Frontiers in oncology · 2026Review
- Discontinuing Immune Checkpoint Inhibitor-Based Therapy After Complete Response in Unresectable Hepatocellular Carcinoma: Evidence, Bias, and a Research Framework.Journal of hepatocellular carcinoma · 2026Review
- AI-integrated single-cell multi-omics decodes the hepatocellular carcinoma metabolism-immune axis: a new strategy for precision therapeutic targeting.Frontiers in oncology · 2026Review
- Clinical management of liver cancer patients with immune checkpoint inhibitors treatment.Hepatic oncology · 2025Review
- Article
- Noninvasive prediction of the clinical benefit of immunotherapy in hepatocellular carcinoma.Journal of gastroenterology · 2025Review
- Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Review
- Emerging Trends in Neoadjuvant Immunotherapy for Hepatocellular Carcinoma: A Focus on Liver Transplant Candidates.Cancer reports (Hoboken, N.J.) · 2025Review
- Role of Liquid Biopsy for Early Detection, Prognosis, and Therapeutic Monitoring of Hepatocellular Carcinoma.Diagnostics (Basel, Switzerland) · 2025Review
- The bile duct and liver cancer: ON-treatment surveillance of tumor evolution and response to systemic treatment (BILLIONSTARS) study.BMC cancer · 2025Observational
- Navigating the complexities: challenges and opportunities in conversion therapy for advanced hepatocellular carcinoma.Clinical and experimental medicine · 2025Review
- The evolving landscape of biomarkers for systemic therapy in advanced hepatocellular carcinoma.Biomarker research · 2025Review
- Alpha-fetoprotein combined with initial tumor shape irregularity in predicting the survival of patients with advanced hepatocellular carcinoma treated with immune-checkpoint inhibitors: a retrospective multi-center cohort study.Journal of gastroenterology · 2025Article
Corrections and comments
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Authors and funding
24 authors at 8 institutions in 2 countries.
Funding
Abstract
Combination immunotherapy with anti-programmed cell death1-ligand1 (PD-L1) and anti-vascular endothelial growth factor (VEGF) antibodies has become the standard treatment for patients with unresectable HCC (u-HCC). However, limited patients obtain clinical benefits. Cell-free DNA (cfDNA) in peripheral blood contains circulating tumor DNA (ctDNA) that reflects molecular abnormalities in tumor tissue. We investigated the potential of cfDNA/ctDNA as biomarkers for predicting the therapeutic outcome in u-HCC patients treated with anti-PD-L1/VEGF therapy. We enrolled a multicenter cohort of 85 HCC patients treated with atezolizumab and bevacizumab (Atezo/Bev) between 2020 and 2021. Pretreatment plasma was collected, and cfDNA levels were quantified. Ultradeep sequencing of cfDNA was performed with a custom-made panel for detecting mutations in 25 HCC-related cancer genes. We evaluated the association of cfDNA/ctDNA profiles and clinical outcomes. Patients with high plasma cfDNA levels showed a significantly lower response rate and shorter progression-free survival and overall survival (OS) than those with low cfDNA levels. ctDNA detected in 55% of HCC patients included the telomerase reverse transcriptase (TERT) promoter in 31% of these patients, tumor protein 53 (TP53) in 21%, catenin beta 1 (CTNNB1) in 13% and phosphatase and tensin homolog (PTEN) in 7%. The presence or absence of ctDNA did not predict the efficacy of Atezo/Bev therapy. Twenty-six patients with a TERT mutation had significantly shorter OS than those without. The presence of a TERT mutation and alpha-fetoprotein (AFP) ≥ 400 ng/mL were independent predictors of poor OS according to multivariate Cox proportional hazard analysis and could be used to stratify patients treated with Atezo/Bev therapy based on prognosis. In conclusion, pretreatment cfDNA/ctDNA profiling may be useful for predicting the therapeutic outcome in u-HCC patients treated with anti-PD-L1/VEGF therapy.
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