Management Of Hepatocellular Carcinoma Research Articles

Digital Quantitative Detection for Heterogeneous Protein and mRNA Expression Patterns in Circulating Tumor Cells.

Hepatocellular carcinoma (HCC) circulating tumor cells (CTCs) exhibit significant phenotypic heterogeneity and diverse gene expression profiles due to epithelial-mesenchymal transition (EMT). However, current detection methods lack the capacity for simultaneous quantification of multidimensional biomarkers, impeding a comprehensive understanding of tumor biology and dynamic changes. Here, the CTC Digital Simultaneous Cross-dimensional Output and Unified Tracking (d-SCOUT) technology is introduced, which enables simultaneous quantification and detailed interpretation of HCC transcriptional and phenotypic biomarkers. Based on self-developed multi-real-time digital PCR (MRT-dPCR) and algorithms, d-SCOUT allows for the unified quantification of Asialoglycoprotein Receptor (ASGPR), Glypican-3 (GPC-3), and Epithelial Cell Adhesion Molecule (EpCAM) proteins, as well as Programmed Death Ligand 1 (PD-L1), GPC-3, and EpCAM mRNA in HCC CTCs, with good sensitivity (LOD of 3.2 CTCs per mL of blood) and reproducibility (mean %CV = 1.80-6.05%). In a study of 99 clinical samples, molecular signatures derived from HCC CTCs demonstrated strong diagnostic potential (AUC = 0.950, sensitivity = 90.6%, specificity = 87.5%). Importantly, by integrating machine learning, d-SCOUT allows clustering of CTC characteristics at the mRNA and protein levels, mapping normalized heterogeneous 2D molecular profiles to assess HCC metastatic risk. Dynamic digital tracking of eight HCC patients undergoing different treatments visually illustrated the therapeutic effects, validating this technology's capability to quantify the treatment efficacy. CTC d-SCOUT enhances understanding of tumor biology and HCC management.

Triglyceride-glucose index predicts postoperative overall survival in hepatocellular carcinoma: a retrospective cohort study

BackgroundInsulin resistance is important in hepatocellular carcinoma (HCC) carcinogenesis and progression. The triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio or TyG-body mass index (TyG-BMI) are three non-invasive parameters for insulin resistance. However, their prognostic role in HCC patients undergoing hepatectomy remains unclear.Materials and methodsHCC patients who underwent hepatectomy at the Meizhou People’s Hospital from May 2011 to February 2023 were retrospectively explored. Patients were classified into high and low groups based on different TyG, TG/HDL-c, and TyG-BMI indices. The prognostic role of TyG, TG/HDL-c, and TyG-BMI was evaluated using Kaplan–Meier analysis and Cox regression models. A nomogram incorporating significant prognostic factors was constructed and validated.ResultsA lower TyG, lower TG/HDL-c, and lower TyG-BMI were linked to worse overall survival (OS) in HCC patients. Multivariate analysis indicated the TyG index, but not the TG/HDL-c and TyG-BMI index, could independently predict HCC OS. The nomogram incorporating the TNM stage and TyG index demonstrated good calibration, discriminative ability, and clinical benefit for predicting OS in HCC patients.ConclusionsThe TyG index could independently predict HCC OS after hepatectomy in this cohort. The nomogram incorporating the TyG index may aid in the prognosis management of HCC.

Challenges in metastatic hepatocellular carcinoma: beyond tumor stage in guiding treatment.

Extrahepatic metastases in hepatocellular carcinoma (HCC) often signify a poor prognosis. This case details the five-year survival of a patient with HCC and adrenal metastasis managed with an aggressive multimodal approach, including ablation, systemic therapy, and surgical resection. Despite therapeutic advances, metastatic HCC management remains a clinical challenge, underscoring the need for individualized treatment strategies beyond traditional staging systems. Further research is essential to determine the role of surgical resection and other treatment modalities in the metastatic setting.

Interventional Oncology Meets Immuno-oncology: Combination Therapies for Hepatocellular Carcinoma.

The management of hepatocellular carcinoma (HCC) is undergoing transformational changes due to the emergence of various novel immunotherapies and their combination with image-guided locoregional therapies. In this setting, immunotherapy is expected to become one of the standards of care in both neoadjuvant and adjuvant settings across all disease stages of HCC. Currently, more than 50 ongoing prospective clinical trials are investigating various end points for the combination of immunotherapy with both percutaneous and catheter-directed therapies. This review will outline essential tumor microenvironment mechanisms responsible for disease evolution and therapy resistance, discuss the rationale for combining locoregional therapy with immunotherapy, summarize ongoing clinical trials, and report on developing imaging end points and novel biomarkers that are relevant to both diagnostic and interventional radiologists participating in the management of HCC.

Sintilimab Plus Lenvatinib with or Without Radiotherapy for Advanced Hepatocellular Carcinoma with Pulmonary Metastasis.

Hepatocellular carcinoma (HCC) with pulmonary metastasis (PM) significantly worsens prognosis, and current treatment options remain limited. A retrospective study was conducted on HCC patients treated with sintilimab combined with lenvatinib at three hospitals in China between 2020 and 2021. Progression-free survival (PFS), overall survival (OS), and tumor response based on RECIST 1.1 were compared. Treatment safety was assessed by analyzing treatment-related adverse events (TRAEs). Among 144 patients, 105 received sintilimab combined with lenvatinib (S+L), while 39 were treated with radiotherapy combined with sintilimab and lenvatinib (RT+S+L). The RT+S+L group showed superior outcomes in OS (25 months vs 16 months, HR = 0.58, 95% CI = 0.35-0.94, P=0.025) and PFS (14 months vs 6 months, HR = 0.61, 95% CI = 0.40-0.94, P=0.022) compared to the S+L group. Similarly, the RT+S+L group exhibited significantly higher objective response rate (ORR) and disease control rate (DCR) compared to the S+L group (61.5% vs 27.6%, P<0.001; 94.9% vs 76.2%, P=0.011). The most common grade 3/4 TRAEs in the RT+S+L group were hypertension, decreased platelet count, elevated total bilirubin, and proteinuria. Radiotherapy combined with sintilimab and lenvatinib is an effective strategy for treating HCC with pulmonary metastasis. These findings highlight the critical role of radiotherapy in the management of HCC.

Advancing Hepatocellular Carcinoma Management Through Peritumoral Radiomics: Enhancing Diagnosis, Treatment, and Prognosis.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is associated with high mortality rates due to late detection and aggressive progression. Peritumoral radiomics, an emerging technique that quantitatively analyzes the tissue surrounding the tumor, has shown significant potential in enhancing the management of HCC. This paper examines the role of peritumoral radiomics in improving diagnostic accuracy, guiding personalized treatment strategies, and refining prognostic assessments. By offering unique insights into the tumor microenvironment, peritumoral radiomics enables more precise patient stratification and informs clinical decision-making. However, the integration of peritumoral radiomics into routine clinical practice faces several challenges. Addressing these challenges through continued research and innovation is crucial for the successful implementation of peritumoral radiomics in HCC management, ultimately leading to improved patient outcomes.

Deficiency of TET2-mediated KMT2D self-transcription confers a targetable vulnerability in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has become a leading cause of cancer-related mortality worldwide. Conventional therapies tend to exacerbate comorbidities, liver dysfunction, and relapse, rendering an urgent demand for novel strategy for management of HCC. Here, we reported that DNA dioxygenase TET2 collaborates with histone methyltransferase KMT2D to enable transcription of KMT2D and ARID1A in HCC. Mechanistically, KMT2D and ARID1A are the major epigenetic targets of TET2 through RNA-seq analysis. Moreover, KMT2D recruits TET2 to facilitate self-transcription via oxidation of 5-methylcytosine in promoter, thereby maintaining expression of ARID1A. Physiologically, KMT2D was identified as a tumor suppressor and mediates the antitumor effect of vitamin C in HCC. Tumors with depleted KMT2D present growth advantage over control group. Vitamin C is able to impair tumor growth, which is compromised by deficiency of KMT2D. Furthermore, loss of KMT2D sensitizes HCC tumors to cisplatin with reduced tumor weight and high level of DNA damage. Ultimately, TET2-KMT2D axis correlates with prognosis of patients with HCC. Patients with high amounts of TET2 and KMT2D present better outcome. Our findings not only put forth a heretofore unrecognized mechanism underlying cross-talk between TET2 and KMT2D in mediating self-transcription of KMT2D, but also propose a targetable vulnerability for HCC therapy on the basis of TET2-KMT2D axis.

Potential role of predictive models in assessment of liver inflammation in patients with hepatocellular carcinoma: a two-center cohort study

BackgroundHepatic inflammation in patients with hepatocellular carcinoma (HCC) remains unclear. This study aimed to construct a clinically expedient predictive model to grade hepatic inflammation in HCC patients.MethodsThis is a two-center retrospective cohort study of HCC patients comprising Derivation cohort and External Validation cohort of 1201 and 505 patients, respectively. Variables of liver inflammation identified through uni- and multi-variate logistic regression analyses were incorporated into predictive nomograms and applied to Derivation cohort, subject to internal and external validation.ResultsLiver fibrosis severity score, portal hypertension severity, and model for end-stage liver disease-sodium independently predicted hepatic inflammation grade. Performance for distinguishing G1 and non-G1 (≥ G2) patients was good with C-index of 0.810 and 0.817 in Derivation and External Validation cohort, respectively. The nomogram performed poorly to predict grade G2, G3 and G2 + G3, but performed well to predict G4.ConclusionsOur nomogram exhibited good performance for scaling hepatic inflammation (G1 and G4) in HCC, and could be employed as adjunctive diagnostic tools to guide HCC management strategy.

Intratumoral microbiota: an emerging force in diagnosing and treating hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) ranks among the most prevalent types of cancer in the world and its incidence and mortality are increasing year by year, frequently diagnosed at an advanced stage. Traditional treatments such as surgery, chemotherapy, and radiotherapy have limited efficacy, so new diagnostic and treatment strategies are urgently needed. Recent research has discovered that intratumoral microbiota significantly influences the development, progression, and metastasis of HCC by modulating inflammation, immune responses, and cellular signaling pathways. Intratumoral microbiota contributes to the pathologic process of HCC by influencing the tumor microenvironment and altering the function of immune system. This article reviews the mechanism of intratumoral microbiota in HCC and anticipates the future possibilities of intratumoral microbiota-based therapeutic strategies for HCC management. This emerging field provides fresh insights into early diagnosis and personalized approaches for HCC while holding substantial clinical application potential to improve patient outcomes and tailor interventions to individual tumor profiles.

Lessons learned: strategies for implementing and the ongoing use of LI-RADS in your practice.

The establishment of the Liver Imaging Reporting and Data System (LI-RADS) in 2011 provided a comprehensive approach to standardized imaging, interpretation, and reporting of liver observations in patients diagnosed with or at risk for hepatocellular carcinoma (HCC). Each set of algorithms provides criteria pertinent to the various components of HCC management including surveillance, diagnosis, staging, and treatment response supported by a detailed lexicon of terms applicable to a wide range of liver imaging scenarios. Before its widespread adoption, the variability in the terminology of diagnostic criteria and definitions of imaging features led to significant challenges in patient management and made it difficult to replicate findings or apply them consistently. The integration of LI-RADS into the clinical setting has enhanced the efficiency and clarity of communication between radiologists, referring providers, and patients by employing a uniform language that averts miscommunications. LI-RADS has been strengthened with its integration into the American Association for Study of Liver Diseases practice guidelines. We will provide the background on the initial development of LI-RADS and reasons for development to serve as a starting point for conveying the system's benefits and evolution over the years. We will also suggest strategies for the implementation and maintenance of a LI-RADS program will be discussed.

Chinese Expert Consensus on the Whole-Course Management of Hepatocellular Carcinoma (2023 Edition)

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complication of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient's general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.

The Neoangiogenic Transcriptomic Signature Impacts Hepatocellular Carcinoma Prognosis and Can Be Triggered by Transarterial Chemoembolization Treatment.

Background/Objectives: We evaluated the relationship between the neoangiogenic transcriptomic signature (nTS) and clinical symptoms, treatment outcomes, and survival in hepatocellular carcinoma (HCC) patients. Methods: This study prospectively followed 328 patients in the derivation and 256 in the validation cohort (with a median follow-up of 31 and 22 months, respectively). The nTS was associated with disease presentation, treatments administered, and overall survival rates. Additionally, this study investigated how multiple treatments influenced changes in nTS status and alterations in microRNA expression. Results: The nTS was identified in 27.4% of patients, linked to aggressive features like multifocality and elevated alpha-fetoprotein (AFP), a pattern consistent with that of the validation cohort. Most patients in both cohorts received treatment for HCC. nTS+ patients had limited access to, and benefited less from, liver transplantation or radiofrequency ablation (RFA) compared to nTS- patients. By the end, 78.9% had died, with nTS- patients showing better median survival and response to treatments than their nTS+ counterparts, who had lower survival across all treatment types. Among those who received transarterial chemoembolization (TACE), 31.2% (21/80 patients after the initial treatment and another four following a second TACE) transitioned from an nTS- to an nTS+ status. This shift was associated with lower survival and alterations in microRNA expressions related to oncogenic pathways. Conclusions: The nTS markedly influences treatment eligibility and survival in patients with HCC. Notably, the nTS can develop after repeated TACE procedures, significantly impacting patient survival and altering oncogenic microRNA expression patterns. These findings highlight the critical role of the nTS in guiding treatment decisions and prognostication in HCC management.

Integrating molecular, biochemical, and immunohistochemical features as predictors of hepatocellular carcinoma drug response using machine-learning algorithms.

Liver cancer, particularly Hepatocellular carcinoma (HCC), remains a significant global health concern due to its high prevalence and heterogeneous nature. Despite the existence of approved drugs for HCC treatment, the scarcity of predictive biomarkers limits their effective utilization. Integrating diverse data types to revolutionize drug response prediction, ultimately enabling personalized HCC management. In this study, we developed multiple supervised machine learning models to predict treatment response. These models utilized classifiers such as logistic regression (LR), k-nearest neighbors (kNN), neural networks (NN), support vector machines (SVM), and random forests (RF) using a comprehensive set of molecular, biochemical, and immunohistochemical features as targets of three drugs: Pantoprazole, Cyanidin 3-glycoside (Cyan), and Hesperidin. A set of performance metrics for the complete and reduced models were reported including accuracy, precision, recall (sensitivity), specificity, and the Matthews Correlation Coefficient (MCC). Notably, (NN) achieved the best prediction accuracy where the combined model using molecular and biochemical features exhibited exceptional predictive power, achieving solid accuracy of 0.9693 ∓ 0.0105 and average area under the ROC curve (AUC) of 0.94 ∓ 0.06 coming from three cross-validation iterations. Also, found seven molecular features, seven biochemical features, and one immunohistochemistry feature as promising biomarkers of treatment response. This comprehensive method has the potential to significantly advance personalized HCC therapy by allowing for more precise drug response estimation and assisting in the identification of effective treatment strategies.

FBXO family genes promotes hepatocellular carcinoma via ubiquitination of p53

FBXO protein family plays an essential role in the ubiquitination process acting as E3 ligases, which may contribute to the progression of cancers. However, the molecular functions of FBXOs in hepatocellular carcinoma (HCC) remain incompletely understood. Here, we investigated the overlapping genes between the FBXOs and differentially expressed genes (DEGs) of HCC identified by utilizing The Cancer Genome Atlas (TCGA) dataset, then, a prognostic model with effective predictive capacity was constructed based on the uni-cox and LASSO regression analyses. To elucidate the underlying mechanism of the FBXO model genes, KEGG analysis was carried out. Drug metabolism-cytochrome P450 and retinol metabolism were revealed as the potential pathway, which Increased the credibility of subsequent drug prediction research. Meanwhile, patients divided by the prognostic model showed a different immune infiltrating status and we also found FBXO model genes may ubiquitinate P53, inducing TP53 more prone to mutations, thereby promoting the occurrence and development of tumors. Consistent with these findings, the result of immunohistochemistry (IHC) validated an elevated expression of these model genes in HCC tissues than in the adjacent tissues. The primary aim of this investigation is to formulate a prognostic model while exploring the underlying mechanisms associated with FBXO genes in HCC. These findings offer initial research perspectives on the involvement of FBXO genes in HCC and contribute to the discovery of dependable biomarkers for the management, prognostication, and early detection of HCC in patients.

Novel Biomarkers for Early Detection of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally. Most patients present with late diagnosis, leading to poor prognosis. This narrative review explores novel biomarkers for early HCC detection. We conducted a comprehensive literature review analyzing protein, circulating nucleic acid, metabolite, and quantitative proteomics-based biomarkers, evaluating the advantages and limitations of each approach. While established markers like alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, and AFP-L3 remain relevant, promising candidates include circulating tumor DNA, microRNAs, long noncoding RNAs, extracellular vesicle, and metabolomic biomarkers. Multi-biomarker panels like the GALAD score, Oncoguard, and Helio liver test show promise for improved diagnostic accuracy. Non-invasive approaches like urine and gut microbiome analysis are also emerging possibilities. Integrating these novel biomarkers with current screening protocols holds significant potential for earlier HCC detection and improved patient outcomes. Future research should explore multi-biomarker panels, omics technologies, and artificial intelligence to further enhance early HCC diagnosis and management.

Hepatocellular Carcinoma Situation in Indonesia: A Systematic Review of Clinical Staging and Histological Characteristics at the Time of Diagnosis

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. However, systematic data on HCC characteristics in Indonesia are limited. Objective: To summarize the body of literature on the characteristics of HCC in Indonesia. Methods: A comprehensive search was conducted in MEDLINE, ScienceDirect, Scopus, Web of Science, and Google Scholar databases without date restrictions. Clinical studies investigating the characteristics of HCC exclusively in Indonesia were eligible for inclusion. Risk-of-bias assessments were conducted, and results were presented descriptively. Results: Ten studies comprising 1,389 HCC patients were included. The Barcelona Clinic Liver Cancer (BCLC) staging system, reported in 5 studies, revealed a predominance of intermediate to advanced stages (B and C) at diagnosis. Child-Pugh scores, available for 7 studies, indicated variability in liver function, with Child-Pugh A ranging from 12.0% to 85.7%. Hepatitis B virus (HBV) infection was the primary etiological factor, with prevalence ranging from 53.8% to 84.0%. Hepatitis C virus (HCV) infection was less common (1.0% to 25.21%). Non-viral etiologies represented a substantial proportion, reaching up to 37.4% of cases. The mean age at diagnosis ranged from 52.43 to 63.1 years. Conclusion: This review highlights the late-stage presentation of HCC in Indonesia, the predominance of HBV as an etiological factor, and a significant burden of non-viral HCC. The findings underscore the need for improved early detection strategies, strengthened HBV prevention efforts, and increased attention to metabolic risk factors. Regional variations in HCC characteristics suggest the need for tailored approaches to HCC management across different parts of Indonesia.

Incorporating ALBI Grade with Geriatric Nutritional Risk Index Enhances Hepatocellular Carcinoma Risk Stratification

Plain Language SummaryNutritional assessment is often overlooked in hepatocellular carcinoma (HCC) management despite its prognostic value. Geriatric nutritional risk index (GNRI), an objective measure of nutritional status, has shown significant prognostic relevance in HCC. Our research investigates the integration of the albumin-bilirubin (ALBI) grade with the GNRI to enhance prognostic stratification for patients with HCC. Utilizing data from a large nationwide registry cohort of 16,416 HCC patients, we examined the combined impact of ALBI grade and GNRI on overall survival in patients with HCC. Our findings demonstrate that incorporating ALBI grade with GNRI significantly improves risk stratification and provides a more precise prognosis, particularly in patients with preserved liver function (ALBI grade 1/2). Our results underscore the importance of integrating nutritional assessments into HCC management to enhance prognostic accuracy and optimize treatment plans.

Current management of hepatobiliary malignancies between centers with or without a liver transplant program: A multi-society national survey

BackgroundAvailability of liver transplantation (LT) as a treatment for hepatocellular carcinoma (HCC) and other liver malignancies may determine heterogeneity of therapeutic strategies across different centers. AimsTo investigate the practice between hepato-biliary centers without (HB centers) and with a LT program (LT centers), we launched a 38-item web-based national survey, with directors of centers as a target. MethodsThe survey, including 4 clinical vignettes, collected data on their approach to HCC and transplant oncology. ResultsAfter duplicates removal, 75 respondents were considered. Respondents from LT centers (n = 22, 29.3 %) were more in favor of LT in the case of HCC outside Milan criteria (90.9 % vs. 67.9 %, p = 0.037), recurrent HCC (95.5 % vs. 50.9 %, p = 0.002) and other malignancies such as cholangiocarcinoma or neuroendocrine tumors. No significant difference was observed concerning the proportion of centers favorable to LT for unresectable colorectal liver metastases (100 % vs. 88.7 %, p = 0.100). ConclusionThis national survey showed how management of HCC and awareness of transplant oncology may differ between HB and LT centers. Effective networking between HB and LT centers is crucial to provide optimal treatment and access to LT.

Utilization of Microfluidic Droplet-Based Methods in Diagnosis and Treatment Methods of Hepatocellular Carcinoma: A Review.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is associated with high morbidity and mortality. One of the main challenges in the management of HCC is late clinical presentation and thus diagnosis of the disease, which results in poor survival. The pathogenesis of HCC is complex and involves chronic liver injury and genetic alterations. Diagnosis of HCC can be made either by biopsy or imaging; however, conventional tissue-based biopsy methods and serological biomarkers such as AFP have limited clinical applications. While hepatocellular carcinoma is associated with a range of molecular alterations, including the activation of oncogenic signaling pathways, such as Wnt-TGFβ, PI3K-AKT-mTOR, RAS-MAPK, MET, IGF, and Wnt-β-catenin and TP53 and TERT promoter mutations, microfluidic applications have been limited. Early diagnosis is crucial for advancing treatments that would address the heterogeneity of HCC. In this context, microfluidic droplet-based methods are crucial, as they enable comprehensive analysis of the genome and transcriptome of individual cells. Single-cell RNA sequencing (scRNA-seq) allows the examination of individual cell transcriptomes, identifying their heterogeneity and cellular evolutionary relationships. Other microfluidic methods, such as Drop-seq, InDrop, and ATAC-seq, are also employed for single-cell analysis. Here, we examine and compare these microfluidic droplet-based methods, exploring their advantages and limitations in liver cancer research. These technologies provide new opportunities to understand liver cancer biology, diagnosis, treatment, and prognosis, contributing to scientific efforts in combating this challenging disease.

Oncologic outcomes and rates of hepatotoxicity following stereotactic body radiotherapy for hepatocellular carcinoma

Aim: Hepatocellular carcinoma (HCC) localized to the liver has various treatment options, including external beam radiotherapy (EBRT). Despite many prospective and retrospective reports showing excellent local control (LC) and favorable toxicity, EBRT has not been widely adopted in the first-line setting and this may be due to a perceived lack of evidence. This study aims to share a decade of experience with Stereotactic Body Radiotherapy (SBRT) for HCC, leveraging a homogenous treatment technique. Methods: This retrospective study at a single institution included patients with HCC treated with SBRT, with a standardized treatment protocol. Freedom from local progression (FFLP), overall survival (OS), and rates of hepatotoxicity post-treatment using child-pugh (CP) and albumin-bilirubin (ALBI) scores were analyzed. A mixed-effects multivariable analysis (MVA) was also performed to assess various factors’ impact on outcomes. Results: A total of 138 lesions in 106 patients were treated between 2009 and 2020. FFLP was 91% at one year and 86% at three years. OS was 80% and 46% at 1 and 3 years, respectively. Baseline liver function was a significant predictor of FFLP and OS on MVA. CP scores and ALBI grades were stable 3 months after treatment in ≥ 70% of patients. Conclusion: SBRT provides excellent LC and low toxicity for HCC patients. While long-term survival remains challenging, treatment decisions should consider overall clinical status. Multidisciplinary review and forthcoming prospective trial results will further clarify radiotherapy’s role in HCC management.