This study presents a detailed analysis of long-term survival and critical factors influencing the outcomes of hepatocellular carcinoma patients treated with stereotactic body radiotherapy (SBRT) and transarterial chemoembolization (TACE). Our findings provide reassurance about the potential of the combination of TACE and SBRT as an effective treatment strategy for patients with large liver tumors due to HCC.

A prospective study was conducted on 42 patients with intermediate-stage hepatocellular carcinoma (HCC) at 108 Military Central Hospital between December 2018 and June 2024. Following a single session of TACE, each patient underwent SBRT 1 month later. The SBRT dose ranged from 27.5 to 48 Gy, delivered in 3-5 fractions. The patient survival analysis was conducted using the Kaplan-Meier method while examining prognostic factors influencing survival, which involved log-rank tests and Cox proportional hazards regression analysis.

Among the 42 patients (83.3% male), 34 patients (81.0%) had tumors measuring ≥ 5 cm. The median follow-up period was 32.2 months (4.5-65.1 months). The median overall survival (OS) was 32.6 months, with the respective 1-, 3-, and 5-year OS rates reported as 73.8%, 24.5%, and 19.6%. Furthermore, the median progression-free survival (PFS) was 16.6 months, with corresponding 1- and 3-year PFS rates of 71.4% and 19.0%. Factors linked to improved OS and PFS included AFP levels and treatment response based on Modified RECIST criteria. Additionally, multivariate analysis identified patient age, EQD2, and BED10 as significant predictors of better survival outcomes.

Our study provides evidence supporting the effectiveness and safety of combining TACE and SBRT as a treatment strategy for patients with large liver tumors due to HCC, instilling confidence in the future of HCC treatment. Positive prognostic factors included patient age, EQD2, and BED10.

To explore the clinical value of transcatheter arterial chemoembolization (TACE) using a temperature-sensitive liquid embolic agent for the interventional treatment of primary hepatocellular carcinoma.

The clinical data and follow-up results sourced from the First Affiliated Hospital of Fujian Medical University were retrospectively analyzed from February 2023 to May 2023. Clinical efficacy was assessed through follow-up imaging using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. In addition, adverse reactions and adverse events were observed and classified using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC) version 3.0.

Among the 11 patients analyzed in this study, a total of 41 lesions were identified. The average maximum diameter of the lesions was 3.55 ± 1.88 cm (range: 1.70 cm-6.60 cm). One month postoperatively, the efficacy assessment revealed complete response (CR) in 1 case, partial response (PR) in 9 cases, stable disease (SD) in 1 case, and progression in 0 case. The objective response rate (CR + PR) was 90.91%, and the disease control rate (CR + PR + SD) was 100%. Postoperative adverse reactions were mostly of grade 1-2, including abdominal pain, bloating, fever, nausea, and vomiting.

The use of temperature-sensitive liquid embolic agents loaded with lobaplatin for chemoembolization in the treatment of unresectable primary liver cancer is a safe and effective therapeutic modality.

To develop a decision framework integrating computed tomography (CT) radiomics and clinical factors to guide the selection of transarterial chemoembolization (TACE) technique for optimizing treatment response in non-resectable hepatocellular carcinoma (HCC).

A retrospective analysis was performed on 151 patients [33 conventional TACE (cTACE), 69 drug-eluting bead TACE (DEB-TACE), 49 degradable starch microsphere TACE (DSM-TACE)] who underwent TACE for HCC at a single tertiary center. Pre-TACE contrast-enhanced CT images were used to extract radiomic features of the TACE-treated liver tumor volume. Patient clinical and laboratory data were combined with radiomics-derived predictors in an elastic net regularized logistic regression model to identify independent factors associated with early response at 4-6 weeks post-TACE. Predicted response probabilities under each TACE technique were compared with the actual techniques performed.

Elastic net modeling identified three independent predictors of response: radiomic feature "Contrast" (OR = 5.80), BCLC stage B (OR = 0.92), and viral hepatitis etiology (OR = 0.74). Interaction models indicated that the relative benefit of each TACE technique depended on the identified patient-specific predictors. Model-based recommendations differed from the actual treatment selected in 66.2% of cases, suggesting potential for improved patient-technique matching.

Integrating CT radiomics with clinical variables may help identify the optimal TACE technique for individual HCC patients. This approach holds promise for a more personalized therapy selection and improved response rates beyond standard clinical decision-making.

To perform a systematic literature review of the efficacy of different AI models to predict HCC treatment response to transarterial chemoembolization (TACE), including overall survival (OS) and time to progression (TTP).

This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines until May 2, 2024.

The systematic review included 23 studies with 4,486 HCC patients. The AI algorithm receiver operator characteristic (ROC) area under the curve (AUC) for predicting HCC response to TACE based on mRECIST criteria ranged from 0.55 to 0.97. Radiomics-models outperformed non-radiomics models (AUCs: 0.79, 95 %CI: 0.75-0.82 vs. 0.73, 0.61-0.77, respectively). The best ML methods used for the prediction of TACE response for HCC patients were CNN, GB, SVM, and RF with AUCs of 0.88 (0.79-0.97), 0.82 (0.71-0.89), 0.8 (0.60-0.87) and 0.8 (0.55-0.96), respectively. Of all predictive feature models, those combining clinic-radiologic features (ALBI grade, BCLC stage, AFP level, tumor diameter, distribution, and peritumoral arterial enhancement) had higher AUCs compared with models based on clinical characteristics alone (0.79, 0.73-0.89; p = 0.04 for CT + clinical, 0.81, 0.75-0.88; p = 0.017 for MRI + clinical versus 0.6, 0.55-0.75 in clinical characteristics alone).

Integrating clinic-radiologic features enhances AI models' predictive performance for HCC patient response to TACE, with CNN, GB, SVM, and RF methods outperforming others. Key predictive clinic-radiologic features include ALBI grade, BCLC stage, AFP level, tumor diameter, distribution, and peritumoral arterial enhancement. Multi-institutional studies are needed to improve AI model accuracy, address heterogeneity, and resolve validation issues.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, with a rising incidence. The most common therapeutic choice for HCC is transarterial chemoembolization (TACE). While the standard protocol of TACE adopts cisplatin, the application of cisplatin needs hydration before and after the procedure to alleviate adverse effects on kidney function. Miriplatin, a lipophilic platinum complex, enables the omission of periprocedural hydration compared to cisplatin-based TACE. This study aimed to compare the survival benefit between miriplatin-based TACE and cisplatin-based TACE. Briefly, a retrospective cohort study in a single hospital was designed. Patients with HCC complicated by vascular invasion or distant metastasis were excluded. Background variability was adjusted using a propensity score matching; then, overall survival rates were compared using the Gehan-Breslow-Wilcoxon test. As a result, cisplatin and miriplatin were administered to 166 and 120 patients in TACE procedures. After adjusting baseline characteristics using a propensity score including age, sex, tumor burden, functional hepatic reserve, baseline year, and HbA1c, a pair of 99-patient cohorts was generated. Overall survivals did not differ significantly, despite poorer serum creatinine at baseline (0.89 vs. 0.74 mg/dL, p < 0.0001) and fewer patients being prepared for TACE through prehydration (18 patients vs. 38 ones, p = 0.0025) in the miriplatin group than in the cisplatin group. The median survival time was 1490 days for the miriplatin group and 1,830 days for the cisplatin group (p = 0.4022; ratio = 0.814; 95% confidence interval 0.546-1.215). In conclusion, miriplatin will benefit patients with HCC who cannot tolerate perioperative hydration.

Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumour worldwide. Depending on the stage of the tumour and liver function, a variety of treatment options are indicated. Traditional radiotherapy and chemotherapy are ineffective against HCC; however, the U.S. Food and Drug Administration (FDA) has approved radiofrequency ablation (RFA), surgical resection, and transarterial chemoembolization (TACE) for advanced HCC. On the other hand, liver transplantation is recommended in the early stages of the disease. Tyrosine kinase inhibitors (TKIs) like lenvatinib and sorafenib, immunotherapy and anti-angiogenesis therapy, including pembrolizumab, bevacizumab, tremelimumab, durvalumab, camrelizumab, and atezolizumab, are other treatment options for advanced HCC. Moreover, to maximize outcomes for patients with HCC, the combination of immune checkpoint inhibitors (ICIs) along with targeted therapies or local ablative therapy is being investigated. This review elaborates on the current status of HCC treatment, outlining the most recent clinical study results and novel approaches.

This study aimed to propose a novel approach of lipiodol combined with drug-eluting beads transarterial chemoembolization (Lipiodol-DEB TACE) and to compare the safety and efficacy with DEB-TACE alone for patients with unresectable hepatocellular carcinoma (HCC).

From the database of four centers, the records of patients with HCC who received DEB-TACE or Lipiodol-DEB TACE as initial treatment were retrospectively evaluated. The tumor response was measured based on the Modified Response Evaluation Criteria in Solid Tumors. Overall survival (OS), progression-free survival (PFS) and adverse events (AEs) were compared between two groups.

A total of 244 patients were included with 160 patients receiving DEB-TACE and 84 patients receiving Lipiodol-DEB TACE. Lipiodol-DEB TACE group had higher objective response rate (86.9 % vs. 76.3 %), higher disease control rate (97.6 % vs. 88.8 %), longer median OS (42.6 vs. 25.8 months) and longer median PFS (34.0 vs. 17.0 months) than DEB-TACE group (P < 0.05). There was no significant difference observed in the incidence of AEs between two groups. Cox analysis identified total bilirubin level, maximum tumor diameter, TACE method and portal vein invasion as independent prognostic factors.

Lipiodol-DEB TACE was a safe option and associated with improved tumor response and survival outcome compared to DEB-TACE alone for selected patients with HCC.

Hepatocellular carcinoma (HCC) is one of the most common primary malignancies of the liver and a leading cause for cancer-related deaths worldwide. HCC surveillance aims at early detection. The recommended strategy for screening HCC is biannual ultrasound with or without alpha-fetoprotein. However, this strategy is associated with sub-optimal sensitivity. Abbreviated magnetic resonance imaging (AMRI) is a promising alternative to ultrasound (US) for surveillance of HCC. The data regarding the role of AMRI in HCC screening is evolving. There are different AMRI protocols, each having its merits and disadvantages. In this review, we discuss the need for AMRI, protocols of AMRI and hindrances to widespread adoption of AMRI.

Transcatheter arterial chemoembolization (TACE) is the main treatment for patients with primary hepatocellular carcinoma (PHC) who miss the opportunity to undergo surgery. Conventional TACE (c-TACE) uses iodized oil as an embolic agent, which is easily washed by blood and affects its efficacy. Drug-eluting bead TACE (DEB-TACE) can sustainably release chemotherapeutic drugs and has a long embolization time. However, the clinical characteristics of patients before the two types of interventional therapies may differ, possibly affecting the conclusion. Only a few studies have compared these two interventions using propensity-score matching (PSM).

To analyze the clinical effects of DEB-TACE and c-TACE on patients with PHC based on PSM.

Patients with PHC admitted to Dangyang People's Hospital (March 2020 to March 2024) were retrospectively enrolled and categorized into groups A (DEB-TACE, n = 125) and B (c-TACE, n = 106). Sex, age, Child-Pugh grade, tumor-node-metastasis stage, and Eastern Cooperative Oncology Group score were selected for 1:1 PSM. Eighty-six patients each were included post-matching. Clinical efficacy, liver function indices (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin), tumor serum markers, and adverse reactions were compared between the groups.

The objective response and disease control rates were significantly higher in group A (80.23% and 97.67%, respectively) than in group B (60.47% and 87.21%, respectively) (P < 0.05). Post-treatment levels of aspartate aminotransferase, alanine aminotransferase, and total bilirubin were lower in group A than in group B (P < 0.05), whereas post-treatment levels of albumin in group A were comparable to those in group B (P > 0.05). Post-treatment levels of tumor serum markers were significantly lower in group A than in group B (P < 0.05). Patients in groups A and B had mild-to-moderate fever and vomiting symptoms, which improved with conservative treatment. The total incidence of adverse reactions was significantly higher in group B (22.09%) than in group A (6.97%) (P < 0.05).

DEB-TACE has obvious therapeutic effects on patients with PHC. It can improve liver function indices and tumor markers of patients without increasing the rate of liver toxicity or adverse reactions.

In recent years, significant progress has been made in treatment strategies for intermediate-stage hepatocellular carcinoma (HCC), which is a highly heterogeneous patient population requiring tailored therapies based on tumor characteristics.

We conducted a comprehensive review of treatment approaches for intermediate-stage HCC, highlighting the evolution of treatment options over time. While chemoembolization remains the standard therapy for many patients, it has advanced to include combinations with systemic therapies, known as combination therapy, which is becoming the new standard of care for this group.

Based on our clinical and research experience, combination therapy is increasingly recognized as the preferred first-line treatment for intermediate-stage HCC patients. This approach allows most patients to be candidates for subsequent curative-intent treatments, while a smaller number will require palliative care.

The triple combination of programmed cell death protein-1 (PD-1) inhibitors plus anti-angiogenesis tyrosine kinase inhibitors (TKIs) with or without transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) enhance the effect of treatment for unresectable hepatocellular carcinoma (uHCC). The present study compared the efficacy and safety of PD-1 plus TKI with or without transarterial chemo(embolization) for uHCC.

The meta-analysis was conducted using data acquired from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials.gov from the inception date to December 2023. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CIs) were used to measure the pooled effect. In addition, subgroup analysis was conducted to determine the specific patient population that benefited.

The OS (HR = 0.47; 95% CI: 0.39-0.56, P <  0.05), PFS (HR = 0.52; 95% CI: 0.45-0.60, P < 0.05), and ORR (RR = 1.94; 95% CI: 1.60-2.35, P < 0.05) were significantly better in TACE/HAIC+TKI+PD-1(TACE/HAIC TP) group than TKI+PD-1(TP) group. The incidence of AEs was acceptable.

The triple therapy of TACE/HAIC TP had better efficacy for uHCC than TP, with acceptable security.

PROSPERO, identifier CRD42023475953.

Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC). Hypoxia has proven to be involved in multiple tumor biological processes and associated with malignant progression and resistance to therapy. Transarterial chemoembolization (TACE) is a well-established locoregional therapy for patients with unresectable HCC. However, TACE-induced hypoxia regulates tumor angiogenesis, energy metabolism, epithelial-mesenchymal transition (EMT), and immune processes through hypoxia-inducible factor 1 (HIF-1), which may have adverse effects on the therapeutic efficacy of TACE. Hypoxia has emerged as a promising target for combination with TACE in the treatment of HCC. This review summarizes the impact of hypoxia on HCC tumor biology and the adverse effects of TACE-induced hypoxia on its therapeutic efficacy, highlighting the therapeutic potential of hypoxia-targeted therapy in combination with TACE for HCC.

Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Given the lack of specific recommendations for conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE) in patients having unresectable HCC with tumor infiltrating the common hepatic duct or the first-order branch of the bile ducts (B1-type bile duct invasion; B1-BDI) after biliary drainage, we retrospectively compared the safety and efficacy of DEB-TACE with cTACE in this patient population.

Using data from five tertiary medical centers (January 2017-December 2021), we compared complications, overall survival (OS), time to progression (TTP), and tumor response rate between patients having unresectable HCC with B1-BDI who underwent DEB-TACE or cTACE after successful biliary drainage. X-tile software calculated the pre-TACE total bilirubin (TBil) cutoff value, indicating optimal timing for sequential TACE after drainage. Propensity score matching (PSM) was performed.

The study included 108 patients with unresectable HCC (B1-BDI) who underwent DEB-TACE and 114 who received cTACE as initial treatment. After PSM (n = 53 for each group), the DEB-TACE group had a longer TTP (8.9 vs. 6.7 months, p = 0.038) and higher objective response rate (64.2% vs. 39.6%, p = 0.011) than did the cTACE group, although OS was comparable (16.7 vs. 15.3 months, p = 0.115). The DEB-TACE group exhibited fewer post-procedural increments in the mean albumin-bilirubin score, TBil, and alanine aminotransferase (ALT), along with a significantly lower incidence of serious adverse events within 30 days (hepatic failure, ALT increase, and TBil increase) than the cTACE group (all p < 0.05). The pre-TACE TBil cutoff value was 99 μmol/L; patients with higher values (>99 μmol/L) had poorer OS in both groups (p < 0.05).

DEB-TACE is safe and effective after successful biliary drainage in unresectable HCC with B1-BDI, potentially better than cTACE in terms of liver toxicity, TTP, and ORR. Lowering TBil below 99 μmol/L through successful drainage may create ideal conditions for sequential TACE.

Transarterial chemoembolization (TACE) has become the standard of care for the treatment of intermediate-stage hepatocellular carcinoma (HCC). However, current clinical practice guidelines lack consensus on the best selection of a specific TACE technique. This study aims to compare safety, tumor response, and progression-free survival (PFS) of conventional TACE (cTACE), drug-eluting bead TACE (DEB-TACE), and degradable starch microsphere TACE (DSM-TACE).

This retrospective study included n = 192 patients with HCC who underwent first TACE with unbiased follow-up at 4-6 weeks at our center between 2008 and 2021. Eligibility for TACE was BCLC intermediate stage B, bridging/down-staging (B/D) to liver transplantation (LT), or any other stage when patients were not suitable for resection, LT, local ablation, or systemic therapy. Patients were grouped into three cohorts (n = 45 cTACE, n = 84 DEB-TACE, n = 63 DSM-TACE), and further categorized by TACE indication (B/D or palliative). Liver function and adverse events, response assessed by the modified response evaluation criteria in solid tumors (mRECIST) 4-6 weeks post-TACE and PFS were analyzed.

There were no significant differences in age, gender distribution, BCLC stage, or etiology of liver disease among the three TACE groups, even in the B/D or palliative subgroups. DEB-TACE induced slight increases in bilirubin in the palliative subgroup and in lactate dehydrogenase in the entire cohort 4-6 weeks post-TACE, and more adverse events in the palliative subgroup. DEB-TACE and DSM-TACE showed significantly higher disease control rates (complete and partial response, stable disease) compared to cTACE, especially in the B/D setting (p < 0.05). There was no significant difference in PFS between the groups [median PFS (months): cTACE, 10.0 vs. DEB, 7.0 vs. DSM, 10.0; p = 0.436].

Our study provides valuable perspectives in the decision-making for a specific TACE technique: DEB-TACE and DSM-TACE showed improved tumor response. DEB-TACE showed a prolonged impact on liver function and more side effects, so patients with impaired liver function should be more strictly selected, especially in the palliative subgroup.

Liver cancer, the sixth most common cancer globally and the second-leading cause of cancer-related deaths, presents a critical public health threat. Diagnosis often occurs in advanced stages of the disease, aligning incidence with fatality rates. Given that established treatments, such as stereotactic body radiation therapy and transarterial radioembolization, face accessibility and affordability challenges, the emerging focus on cancer cell metabolism, particularly arginine (Arg) depletion, offers a promising research avenue. Arg-depleting enzymes show efficacy against Arg-auxotrophic cancers, including hepatocellular carcinoma (HCC). Thus, in this review, we explore the limitations of current therapies and highlight the potential of Arg depletion, emphasizing various Arg-hydrolyzing enzymes in clinical development.

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.

Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of its management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the second part of guidelines, focused on the multidisciplinary tumor board of experts and non-surgical treatments of HCC.

The present study investigated the prognostic impact of preoperative serum ferritin (SF) levels on the survival of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Clinicopathological characteristics and laboratory biomarkers of 223 patients with HCC who underwent TACE were retrospectively reviewed. The Kaplan-Meier method was used to calculate the overall survival (OS), and the log-rank test was used to evaluate statistical significance. Univariate and multivariate analyses were performed using Cox proportional hazards regression to evaluate the prognostic impact of SF in these patients. The present findings identified extrahepatic metastases [hazard ratio (HR)=0.490,95%; confidence interval (CI)=0.282-0.843; P=0.010)] and vascular invasion (HR=0.373; 95% CI=0.225-0.619; P<0.0001) as independent prognostic factors for OS. However, preoperative SF levels could not independently predict OS when compared with other prognostic factors (HR=0.810; 95% CI=0.539-1.216; P=0.309). In conclusion, preoperative SF level is an unreliable biochemical predictor of survival in patients with HCC undergoing TACE.