Locoregional therapies play a fundamental role in the treatment of patients with early and intermediate and locally advanced hepatocellular carcinomas. With encouraging recent advances in immunotherapy-based systemic therapies, locoregional therapies are being both promoted and challenged by new systemic therapy options. Combined locoregional and systemic therapies might enhance treatment outcomes compared with either option alone. This Series paper summarises the existing data on locoregional and systemic therapies for hepatocellular carcinoma, and discusses evidence from studies investigating their combination with a focus on their synergistic efficacy and safety.

Histotripsy is a novel, noninvasive, nonionizing, and nonthermal approach that uses focused ultrasound waves to treat liver tumors. This technology received a de novo Food and Drug Administration grant in late 2023. This study aimed to provide the first report on post-trial real-world clinical safety data.

Safety outcomes within 30 days of histotripsy were collected after obtaining Food and Drug Administration clearance (December 22, 2023 to July 26, 2024). All centers that performed histotripsy were invited to participate in this study. Complications requiring treatment were graded using the Clavien-Dindo classification and Comprehensive Complication Index (CCI).

A total of 295 patients underwent histotripsy for 510 tumors at 18 centers. The treated liver tumor types included colorectal metastases (n = 140), neuroendocrine tumors (n = 46), hepatocellular carcinomas (n = 31), pancreatic tumors (n = 30), and breast metastases (n = 26). The most common numbers of tumors treated per procedure were 1 (n = 170), 2 (n = 69), and 3 (n = 37). All 8 liver segments were treated for tumors. Safety data were available for 230 patients from 9 centers. Of note, 12 of 230 patients (5.2%) experienced complications of any grade. Most patients (9 [75%]) had minor cases (Clavien-Dindo grade ≤ II). The median and mean CCIs were 0.00 (IQR, 0.00-0.00) and 0.00 (95% CI, 0.00-0.75). All 3 major complications (Clavien-Dindo grade > II [1.3%]) were death due to disease progression. All 3 patients underwent histotripsy with palliative intent for known advanced intra- and extrahepatic diseases.

To the best of our knowledge, this is the first study to report on the real-world therapeutic use of histotripsy for liver tumors. Histotripsy was well tolerated, with few overall complications and rare serious complications, indicating a safety profile that compares favorably with that of other liver-directed and surgical therapies for the treatment of liver tumors. Long-term follow-up data, including oncologic outcomes, were collected.

HCC is the fourth leading cause of cancer-related mortality with increasing incidence worldwide. Historically, treatment for early disease includes liver transplantation, surgical resection, and/or other local therapies, such as thermal ablation. As a result of technical advances and high-quality prospective data, the use of definitive external beam radiotherapy with ablative doses has emerged. Intermediate-stage disease has been generally addressed with arterially directed therapies (eg, chemoembolization or radioembolization) and external beam radiotherapy, while advanced stages have been addressed by systemic therapy or best supportive care. The role of each local/locoregional therapy has rapidly evolved in the context of novel pharmacotherapies, including immunotherapies and antiangiogenic agents. The combinations, indications, and timing of treatments vary widely among specialties and geographies. Here, we aim to synthesize the best quality evidence available regarding the efficacy and safety of different liver-directed modalities, with a focus on recent prospective clinical data of external beam radiotherapy within the context of other available liver-directed therapies across Barcelona Liver Classification (BCLC) stages.

Transcatheter arterial chemoembolization (TACE) has been combined with immune checkpoint inhibitor (ICI)-based systemic therapies for unresectable hepatocellular carcinoma (uHCC) with promising efficacy. However, whether the addition of TACE to the combination of ICI and tyrosine kinase inhibitor (TKI) (ICI+TKI+TACE) is superior to ICI+TKI combination therapy is still not clear. Thus, this study compares the efficacy of ICI+TKI+TACE triple therapy and ICI+TKI doublet therapy in patients with uHCC.

uHCC patients treated with either ICI+TKI+TACE triple therapy or ICI+TKI doublet therapy were retrospectively recruited between January 2016 and December 2021 at Eastern Hepatobiliary Surgery Hospital. The patients from ICI+TKI+TACE group and ICI+TKI group were further subjected to propensity score matching (PSM). The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS) and objective response rate (ORR). Post-progression survival (PPS) as well as treatment-related adverse events (TRAEs) were also assessed.

A total of 120 patients were matched. The median PFS was 8.4 months in ICI+TKI+TACE triple therapy group versus 6.6 months in ICI+TKI doublet therapy group (HR 0.72, 95%CI 0.48-1.08; p=0.115). Similar results were obtained in term of OS (26.9 versus 24.2 months, HR 0.88, 95% CI 0.51-1.52; p=0.670). The ORR in the triple therapy group was comparable with that in the doublet therapy group (16.6% versus 21.6%, p=0.487). Further subgroup analysis for PFS illustrated that patients without previous locoregional treatment (preLRT) (10.5 versus 3.7 months, HR 0.35 [0.16-0.76]; p=0.009), without previous treatment (10.5 versus 3.5 months, HR 0.34 [0.14-0.81]; p=0.015) or treated with lenvatinib (14.8 versus 6.9 months, HR 0.52 [0.31-0.87]; p=0.013) can significantly benefit from triple therapy compared with doublet therapy. A remarkable interaction between treatment and preLRT (p=0.049) or TKIs-combined (p=0.005) was also detected in term of PFS. Post progression treatment significantly improved PPS in both groups. The incidence of TRAEs was comparable between two groups.

The addition of TACE to ICI+TKI combination therapy did not result in a substantial improvement in efficacy and prognosis of patients. However, in selected uHCC patients (without preLRT or treated with lenvatinib as combination), ICI+TKI+TACE triple therapy may remarkably improve PFS.

Hepatocellular carcinoma (HCC) is increasing in prevalence globally, and cure remains limited with non-operative treatment. Surgical intervention, through resection or transplantation, offers a potential for cure for select patients. However, many patients present with advanced or unresectable disease, and recurrence rates remain high. Recent advances in systemic therapies, particularly immune checkpoint inhibitors, have demonstrated promise in treating unresectable HCC and as adjuvant therapy. Evidence from adjuvant trials highlights the synergistic potential of combined liver-directed and systemic therapies. These findings have ignited growing interest in neoadjuvant therapy across various scenarios: (1) as a bridging strategy while awaiting transplantation, (2) for downstaging disease to enable transplantation, (3) for converting unresectable disease to a resectable state, or (4) as neoadjuvant treatment in operable cases. Early-stage trials of neoadjuvant therapy in resectable HCC have reported promising outcomes. To realize the potential of neoadjuvant treatment for HCC, thoughtfully designed, adequately powered, multi-center clinical trials are essential.

Locoregional therapies (LRTs), including transarterial embolization (TAE), transarterial chemoembolization (TACE), and transarterial radioembolization (TARE), have become integral in the management of hepatocellular carcinoma (HCC) in recent decades and continue to shape evolving treatment strategies. While their role in liver tumor management is well established, their potential for treating extrahepatic malignancies is gaining increasing attention. Notably, growing research has highlighted the promising applications of TAE, TACE, and TARE in extrahepatic cancers such as glioblastoma (GBM), soft tissue sarcomas (STSs), prostate cancer (PCa), pancreatic cancer, and renal cell carcinoma (RCC). This review aims to explore these novel applications, providing a comprehensive summary of the current literature, examining clinical outcomes, and discussing future directions for integrating these techniques into broader oncologic treatment strategies.

A systematic literature review was conducted focusing on LRTs such as TAE, TACE, and TARE in extrahepatic malignancies. Studies published between May 1998 and December 2024 were included, emphasizing outcomes in GBM, STS, PCa, pancreatic cancer, and RCC. Data extraction prioritized clinical outcomes, safety profiles, and procedural efficacy.

LRTs demonstrated significant potential in managing extrahepatic malignancies, with TAE, TACE, and TARE showing promising results in palliative management and tumor control. Across studies, these therapies exhibited varying degrees of success in improving progression-free survival and overall survival, with minimal systemic toxicity.

The expanding application of LRTs in extrahepatic malignancies highlights their transformative potential in interventional oncology. By offering targeted, minimally invasive treatment options, these modalities bridge critical gaps in managing tumors refractory to conventional therapies. Future research should focus on standardizing protocols, optimizing patient selection, and exploring combination therapies to maximize their clinical efficacy.

Embolic and ablative locoregional therapies (LRTs) for hepatocellular carcinoma are widely used to cure, bridge, or downstage patients for more definitive therapies. Common ablative therapies include microwave ablation and radiofrequency ablation, while embolic options include transarterial chemoembolization and 90Y transarterial radioembolization. While these therapies can be highly effective for the appropriate stage of disease, LRTs can suffer from a high rate of posttreatment recurrences. Considerations for administration of specific therapies include disease burden and underlying liver function. Recent data on concomitant or adjuvant systemic therapy, with LRT, have the potential to improve disease control and improve outcomes in this high-risk patient population.

Hepatocellular carcinoma (HCC) persists as a leading cause of cancer-related mortality, often diagnosed at advanced stages with limited treatment options. Locoregional therapies (LRTs) are crucial in HCC management, playing significant roles in neoadjuvant and palliative treatments, among others. However, the unique disease background of HCC necessitates multidisciplinary and integrated treatment strategies. The therapeutic landscape for advanced HCC has been significantly broadened by the advent of combined therapies, presenting multiple approaches aimed at improving long-term survival, which remains a critical challenge. This review offers a comprehensive overview of major LRTs for HCC, highlighting recent technological advancements and exploring the challenges and limitations in their application, and presents the latest developments in combination therapies, including combinations between different LRTs and their integration with systemic treatments. Additionally, we outline future directions for the development of integrated treatment modalities for advanced HCC.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is associated with high morbidity and mortality rates. The aims of this study were to investigate the immune-promoting action of nucleolar and spindle-associated protein 1 (NUSAP1) and identify an immunotherapy target for HCC. The Cancer Genome Atlas (TCGA) was used to analyze interaction molecules and immune correlation. The interaction between NUSAP1 and SHC binding and spindle associated 1 (SHCBP1) was examined. The role of the SHCBP1/Janus kinase 2/signal transducer and activator of transcription 3 (SHCBP1/JAK2/STAT3) pathway in this process was explored. After co-culture with HCC cell lines, the differentiation of peripheral blood mononuclear cells (PBMCs) into dendritic cells (DC) was evaluated by measuring the expression of surface factors CD1a and CD86. Pathological tissues from 50 patients with HCC were collected to validate the results of cell experiments. The expression levels of CD1a and CD86 in tissues were also determined. The results show that NUSAP1 interacted with SHCBP1 and was positively correlated with DC. In HCC cell lines, an interaction was observed between NUSAP1 and SHCBP1. It was verified that NUSAP1 inhibited the JAK2/STAT3 phosphorylation pathway by blocking SHCBP1. After co-culture, the levels of CD1a and CD86 in PBMC were elevated. In the clinical specimens, CD1a and CD86 expression levels were significantly higher in the high-NUSAP1 group versus the low-NUSAP1 group. In Summary, NUSAP1 enhanced immunity by inhibiting the SHCBP1/JAK2/STAT3 phosphorylation pathway and promoted DC generation and HCC apoptosis. NUSAP1 may be a target of immunotherapy for HCC.

Drug-eluting microsphere transarterial chemoembolization (DEM-TACE) reduces systemic exposure to chemotherapeutic drugs compared with conventional TACE but permanently occludes the embolized vessels, potentially obviating the possibility of re-treatment with TACE. Temporary embolization by resorbable BioPearl™ microspheres might facilitate subsequent re-treatments. We herein describe the trial protocol of BIOPEARL-ONE, a prospective, single-arm, multicenter, post-market clinical follow-up study. The primary objectives are technical success and safety following the use. DEM-TACE with doxorubicin-loaded BioPearl™ for unresectable hepatocellular carcinoma (HCC). The secondary objectives are tumor response, duration of response, progression-free survival, and survival rate at 18 months. Fifty patients with HCC nodules smaller than 5 cm and within the up-to-7 criteria will be enrolled.Clinical Trial Registration: NCT05911633.

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.

Hepatic metastases are a major cause of morbidity and mortality for patients with cancer. Apart from curative resection, which offers patients the potential for long-term survival, an array of locoregional therapies, with limited evidence of improving survival, are used to treat them. The authors use examples from the realm of gastrointestinal cancer, largely focusing on the experience of patients with neuroendocrine cancer, hepatobiliary cancer, and colorectal cancer, to suggest that current systemic therapies offer, at minimum, similar survival outcomes for patients compared with these locoregional approaches.

Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease is increasing. Biannual liver ultrasonography and serum α-fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.g., cirrhosis, chronic HBV). Alternative surveillance tools such as blood-based biomarker panels and abbreviated magnetic resonance imaging (MRI) are being investigated. Multiphasic computed tomography or MRI is the standard for HCC diagnosis, but histological confirmation should be considered, especially when inconclusive findings are seen on cross-sectional imaging. Staging and treatment decisions are complex and should be made in multidisciplinary settings, incorporating multiple factors including tumor burden, degree of liver dysfunction, patient performance status, available expertise, and patient preferences. Early-stage HCC is best treated with curative options such as resection, ablation, or transplantation. For intermediate-stage disease, locoregional therapies are primarily recommended although systemic therapies may be preferred for patients with large intrahepatic tumor burden. In advanced-stage disease, immune checkpoint inhibitor-based therapy is the preferred treatment regimen. In this review article, we discuss the recent global epidemiology, risk factors, and HCC care continuum encompassing surveillance, diagnosis, staging, and treatments.

Systemic therapy for hepatocellular carcinoma has evolved from sorafenib to now include immune checkpoint blockade, either atezolizumab/bevacizumab or durvalumab/tremelimumab, and soon to include camrelizumab/rivoceranib and nivolumab/ipilimumab. Second-line therapy remains predominantly either a multikinase inhibitor or ramucirumab. Areas of development include testing immune checkpoint-based regimens in the adjuvant setting after surgery, ablation, or transarterial embolization. Also of interest are studies for patients with Child-Pugh B liver function and adding new checkpoint molecules to the current standard platforms.

Type II diabetes mellitus (T2DM) has been found to increase the mortality of patients with hepatocellular carcinoma (HCC). Therefore, this study aimed to establish and validate a machine learning-based explainable prediction model of prognosis in patients with HCC and T2DM undergoing transarterial chemoembolization (TACE).

The prediction model was developed using data from the derivation cohort comprising patients from three medical centers, followed by external validation utilizing patient data extracted from another center. Further, five predictive models were employed to establish prognosis models for 1-, 2-, and 3-year survival, respectively. Prediction performance was assessed by the receiver operating characteristic (ROC), calibration, and decision curve analysis curves. Lastly, the SHapley Additive exPlanations (SHAP) method was used to interpret the final ML model.

A total of 636 patients were included. Thirteen variables were selected for the model development. The final random survival forest (RSF) model exhibited excellent performance in the internal validation cohort, with areas under the ROC curve (AUCs) of 0.824, 0.853, and 0.810 in the 1-, 2-, and 3-year survival groups, respectively. This model also demonstrated remarkable discrimination in the external validation cohort, achieving AUCs of 0.862, 0.815, and 0.798 in the 1-, 2-, and 3-year survival groups, respectively. SHAP summary plots were also created to interpret the RSF model.

An RSF model with good predictive performance was developed by incorporating simple parameters. This prognostic prediction model may assist physicians in early clinical intervention and improve prognosis outcomes in patients with HCC and comorbid T2DM after TACE.

Transcatheter arterial chemoembolization (TACE) is a proven and widely accepted treatment option for hepatocellular carcinoma and it is recommended as first-line non-curative therapy for BCLC B/intermediate HCC (preserved liver function, multifocal, no cancer-related symptoms) in patients without vascular involvement. Different types of TACE are available nowadays, including TAE, c-TACE, DEB-TACE, and DSM-TACE, but at present there is insufficient evidence to recommend one TACE technique over another and the choice is left to the operator. This review then aims to provide a comprehensive overview of the current literature on indications, types of procedures, safety, and efficacy of different TACE treatments.

Hepatocellular carcinoma is the sixth most common tumor and the third leading cause of cancer death worldwide. It ranks fourth in the spectrum of malignant tumor incidence and second in the order of death from major malignant tumors in China. Hepatocellular carcinoma is a complex ecosystem containing non-tumor cells (mainly immune-related cells), and its immunotherapy can stimulate the recognition of specific tumor antigens, inhibit the proliferation of cancer cells, and produce over-memory lymphocytes, which can prevent recurrence. So, immunotherapy of hepatocellular carcinoma is increasingly becoming a research hotspot in liver cancer treatment. With the intensive research in recent years, great progress has been made in immunotherapy for hepatocellular carcinoma, including immune checkpoint inhibitors, pericyte therapy, vaccination, and antiviral therapy. In addition, the study found that the therapeutic effect of combination therapy was enhanced compared to monotherapy. This review summarizes the most prominent immunotherapies currently available for the clinical treatment of patients with HCC and the main opportunities and challenges facing HCC research.

Diabetes is prevalent among patients with hepatocellular carcinoma (HCC) and is associated with a poor prognosis. Although the hypoglycemic drug metformin has shown antitumor effects, its potential positive effect on patients with HCC and diabetes undergoing transarterial chemoembolization (TACE) remains unclear. Therefore, this study aimed to investigate the efficacy and safety of metformin in patients with HCC and type II diabetes who are receiving TACE.

This retrospective study involved 372 consecutive patients with HCC and type II diabetes across three medical centers between January 2014 and June 2021. All patients underwent TACE. Propensity score matching (PSM) was used to reduce selection bias. Cox proportional hazards regression was employed to compare all-cause death between the metformin and nonmetformin groups while competing risk regression was performed to assess cancer-specific death.

Among 372 patients included in the study, 208 patients (177 male patients and 31 female patients) with a mean age of 59.6 (10.3) years received metformin, and 164 patients (139 male patients and 25 female patients) with a mean age of 60.3 (10.0) years did not. Before PSM, patients with metformin had significantly longer median overall survival (mOS) and median progression-free survival (mPFS) than those without metformin (mOS: 34 months, 95% CI: 25.6-42.4 vs. 20 months, 95% CI: 15.3-24.7; P <0.001; mPFS: 11 months, 95% CI: 9.3-12.7 vs. 8 months, 95% CI: 5.9-10.1; P <0.001). Similar results were observed after PSM. Multivariate regression analysis indicated that metformin was associated with a reduced risk of all-cause mortality (HR: 0.589, 95% CI: 0.454-0.763; P <0.001) and tumor progression (HR: 0.667, 95% CI: 0.526-0.845; P =0.001) before PSM. After excluding deaths related to other factors, metformin continued to demonstrate a reduction in cancer-specific mortality risk among the patients. Subgroup analysis further revealed that patients using metformin had lower all-cause mortality risk and tumor progression risk than those without metformin in most subgroups. Adverse event evaluation suggested that metformin could lead to elevated nausea incidence.

Metformin may confer survival benefits to patients with HCC and type II diabetes undergoing TACE. Metformin may simultaneously address multiple aspects of treatment in these patients.

To assess the effectiveness of transarterial bland embolization (TAE) compared with transarterial chemoembolization (TACE) therapy in the treatment of patients with intermediate-stage hepatocellular carcinoma (HCC).

Two thousand two hundred ninety-seven patients with intermediate-stage HCC were screened, and 1,461 patients who underwent TAE or TACE as the first-choice treatment were retrospectively analyzed and baseline matched according to the 2 treatment methods. Subgroup analysis was performed among patients according to the Up-to-7 criteria. The primary endpoint was overall survival (OS).

A total of 1,461 patients with HCC who underwent TAE or TACE were included; 730 patients underwent TACE and 731 underwent TAE. The patients in the TAE group exhibited poorer liver function and a significantly higher rate of hepatitis B infection (P < .001) compared with the TACE group. After propensity score matching, 504 well-matched pairs of patients with intermediate-stage HCC were selected for analysis. Univariate analysis showed that TACE significantly prolonged patient survival compared with TAE (P < .001). The 1-, 2-, and 3-year OS rates were 74.3%, 57.1%, and 44.4% and for the TACE group and 58.3%, 32.4%, and 21.7% for the TAE group, respectively. Multivariate analysis showed a hazard ratio of 0.517 (95% CI, 0.442-0.605; P < .001) for the TACE approach over the TAE approach for OS. The TACE group had a significantly higher overall response rate than the TAE group (35% vs 26%; P = .024).

TACE resulted in higher response rate and longer OS compared with TAE as the initial treatment for intermediate-stage HCC.

Primary liver cancers are tumors that develop from different liver cells. Hepatocellular carcinoma (HCC), which develops from hepatocytes, accounts for approximately 75-85% of primary liver cancers.HCC is the 6th leading cause of cancer worldwide and the 3rd leading cause of cancer-related death. Its incidence is low in northern Europe, but high in sub-Saharan Africa and the Far East, where both hepatotropic viruses and exposure to mycotoxins are. It complicates cirrhosis in over 90% of cases and is predominantly male.The prevalence of HCC is increasing due to improved diagnostic techniques and criteria, but also to the persistence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in adults. A worldwide increase in the incidence of steatopathy makes it the leading cause of liver disease worldwide, associated with alcohol abuse and/or steatohepatitis associated with metabolic dysfunction (MASH), including type 2 diabetes.Chronic hepatotropic viral infections, cirrhosis and chemical carcinogens combine to produce an annual incidence of 2-5% of hepatocellular carcinoma arising from cirrhosis. This justifies biannual surveillance of known cirrhosis, without which late diagnosis limits therapeutic options.Major advances have been made in curative treatment (liver transplantation, surgery, radiodestruction) and palliative treatment (chemo- or radioembolization, sorafenib chemotherapy or immunotherapy), depending on how early HCC is diagnosed (size, number of hepatic or extrahepatic lesions) and the severity of underlying liver disease and associated comorbidities.

Camrelizumab and rivoceranib together provide a new first-line treatment approach for unresectable hepatocellular carcinoma (HCC). Meanwhile, transarterial chemoembolization (TACE) is an effective method for the local control of the HCC. The study compared the clinical benefit and safety between TACE with camrelizumab-rivoceranib and camrelizumab-rivoceranib alone for Barcelona Clinic Liver Cancer (BCLC)-C HCC patients.

This multi-center retrospective analysis included continuous BCLC-C HCC patients who received camrelizumab-rivoceranib with TACE and camrelizumab-rivoceranib alone from January 2020 to December 2022. The therapeutic response, progression-free survival (PFS), safety, and overall survival (OS) were compared. The quantitative data were compared via the t-test or Mann-Whitney U-test. Comparison of the categorical data was done by chi-square or Fisher's exact tests. The comparison of PFS with OS was compared by Log rank test. A Multivariate Cox regression test was utilized to identify risk variables for both PFS and OS.

 This analysis comprised 132 BCLC-C HCC patients who received camrelizumab-rivoceranib alone (n = 74) or combined treatment (n = 58). The combined group displayed higher partial response (44.8% vs 21.6%, p = 0.004) and total response (55.2% versus 36.5%, p = 0.032) rates than camrelizumab-rivoceranib alone group. The median PFS (13.5 months vs 10.3 months, p = 0.046) and OS (22.8 months vs 18.4 months, p = 0.041) for the combined group was significantly longer relative to the camrelizumab-rivoceranib alone group. Additional risk factors, excluding the therapy option, were a higher alpha-fetoprotein level and Eastern Cooperative Oncology Group performance status. The incident rates of camrelizumab-rivoceranib-related advents were comparable between combined and camrelizumab-rivoceranib alone groups (46.3% vs 51.4%, p = 0.572). The combined group contained 33 patients (56.9%) who experienced temporary post-embolization symptoms.

For BCLC-C HCC patients, TACE may significantly increase the therapeutic effectiveness of camrelizumab-rivoceranib without increasing the risk of camrelizumab-rivoceranib-related complications.

Hepatocellular carcinoma (HCC) is a type of malignant tumor with high morbidity and mortality. Untimely treatment and high recurrence are currently the major challenges for HCC. The identification of potential targets of HCC progression is crucial for the development of new therapeutic strategies.

Bioinformatics analyses have been employed to discover genes that are differentially expressed in clinical cases of HCC. A variety of pharmacological methods, such as MTT, colony formation, EdU, Western blotting, Q-PCR, wound healing, Transwell, cytoskeleton F-actin filaments, immunohistochemistry (IHC), hematoxylin-eosin (HE) staining, and dual-luciferase reporter assay analyses, were utilized to study the pharmacological effects and potential mechanisms of ribonucleotide reductase regulatory subunit M2 (RRM2) in HCC.

RRM2 expression is significantly elevated in HCC, which is well correlated with poor clinical outcomes. Both in vitro and in vivo experiments demonstrated that RRM2 promoted HCC cell growth and metastasis. Mechanistically, RRM2 modulates the EMT phenotype of HCC, and further studies have shown that RRM2 facilitates the activation of the TGF-β/Smad signaling pathway. SB431542, an inhibitor of TGF-β signaling, significantly inhibited RRM2-induced cell migration. Furthermore, RRM2 expression was correlated with diminished survival in HBV-associated HCC patients. RRM2 knockdown decreased the levels of HBV RNA, pgRNA, cccDNA, and HBV DNA in HepG2.2.15 cells exhibiting sustained HBV infection, while RRM2 knockdown inhibited the activity of the HBV Cp, Xp, and SpI promoters.

RRM2 is involved in the progression of HCC by activating the TGF-β/Smad signaling pathway. RRM2 increases HBV transcription in HBV-expressing HCC cells. Targeting RRM2 may be of potential value in the treatment of HCC.

Hepatocellular carcinoma (HCC) is one of the most common forms of primary liver cancer worldwide. Herein, we present a review article that provides a broad overview of the current landscape of HCC, including the etiology, potential risk factors, and molecular pathways that can serve as potential therapeutic targets. The risk factors tend to vary depending on the geographic distribution; hepatitis B-induced cirrhosis and HCC occur more frequently in Asia and Sub-Saharan Africa, whereas metabolic disorders are the culprits in Western Europe and the Americas. The exact molecular alterations that drive hepatocarcinogenesis have yet to be elucidated; however, a complex interplay exists between oxidative stress and chronic inflammation. Diagnostic modalities such as tri-phasic MRI or CT also have distinct patterns for HCC, which aid significantly in diagnosis. Furthermore, the review aims to highlight treatment strategies, including transplantation, locoregional radiation therapies, and interventional radiological techniques such as chemotherapy or radioembolization. Finally, systemic therapies will be discussed, taking advantage of molecular pathways that influence cellular proliferation and survival as well as immunotherapy.

Active bleeding is a clinical emergency that often requires swift action driven by efficient communication. Extravasation of intravenous (IV) contrast on computed tomography (CT) is a hallmark of active hemorrhage. This can be seen on exams performed for a variety of indications and can occur anywhere in the body. As both traumatic and non-traumatic etiologies of significant blood loss are clinical emergencies, exams demonstrating active bleeding are often performed in emergency departments and read by emergency radiologists. Prompt communication of these findings to the appropriate emergency medicine and surgical providers is crucial. Although many types of active hemorrhage can be managed by interventional radiology techniques, endoscopic and surgical management or clinical observation may be appropriate in certain cases. To facilitate optimal care, it is important for emergency radiologists to understand the scope of indications for embolization of bleeding by interventional radiologists (IR) and when an IR consultation is warranted. Similarly, timely comprehensive diagnostic radiology reporting including pertinent positive and negative findings tailored for IR colleagues can expedite the appropriate intervention.

The purpose of this study is to compare the efficacy and safety of transarterial chemoembolization (TACE) alone with transarterial chemoembolization combined with the arterial infusion of bevacizumab (TACE + Bev) in patients with unresectable hepatocellular carcinoma (uHCC).

A retrospective analysis was conducted on 446 uHCC patients treated with TACE or TACE + Bev between January 2021 and March 2023. The study evaluated objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events in both treatment groups.

Finally, the TACE group comprised 295 patients, and the TACE + Bev group comprised 151 patients. Patients in the TACE + Bev group exhibited significantly prolonged median PFS (7.9 months vs. 10.3 months, P = 0.013) and median OS (16.1 months vs. 21.4 months, P = 0.041), improved ORR (26.8% vs. 37.7%, P = 0.017) and DCR (71.5% vs. 80.8%, P = 0.033) compared to the TACE group. Multifactorial Cox analysis identified alpha-fetoprotein (AFP) > 400 ng/ml as an independent prognostic factor for PFS and OS. Meanwhile, portal vein cancer thrombosis and distant metastasis are poor prognostic factors for OS. The overall incidence of adverse events was similar between the two groups.

In comparison with the TACE group, the TACE + Bev group demonstrated efficacy in improving outcomes for patients with uHCC with a manageable safety profile.

Hepatocellular carcinoma (HCC) is a common and deadly cancer, often diagnosed at advanced stages, limiting surgical options. Transcatheter arterial chemoembolization (TACE) is a primary treatment for inoperable and involves the use of drug-eluting microspheres to slowly release chemotherapy drugs. However, patient responses to TACE vary, with some experiencing tumor progression and recurrence. Traditional TACE uses agents like oil-based drug emulsions and polyvinyl alcohol particles, which can permanently block blood vessels and increase tumor hypoxia. Additionally, TACE can suppress the immune system by reducing immune cell numbers and function, contributing to poor treatment outcomes. New approaches, like TACE using degradable starch microspheres and hydrogel-based materials, offer the potential to create different tumor environments that could improve both safety and efficacy. In our research, we developed a composite hydrogel (IF@Gel) made of Poloxamer-407 gel and Fe3O4 nanoparticles, loaded with idarubicin, to use as an embolic material for TACE in a rat model of orthotopic HCC. We observed promising therapeutic effects and investigated the impact on the tumor immune microenvironment, focusing on the role of immunogenic cell death (ICD). The composite hydrogel demonstrated excellent potential as an embolic material for TACE, and IF@Gel-based TACE demonstrated significant efficacy in rat HCC. Furthermore, our findings highlight the potential synergistic effects of ICD with anti-PD-L1 therapy, providing new insights into HCC treatment strategies. This study aims to provide improved treatment options for HCC and to deepen our understanding of the mechanisms of TACE and tumor environment regulation.

The awareness of anatomical variations of hepatic arteries and celiac trunk is very important in interventional radiology, liver transplant and intra-abdominal oncologic surgeries. Radiology plays an important role in the identification of these variants non-invasively. Digital subtraction angiography was the gold standard for their identification. Computed tomography (CT) angiography non-invasively provides detailed knowledge of various anatomical vascular variations. This pictorial review highlights the role of multidetector computed tomography (MDCT) in the identification of celiac trunk-hepatic arterial system variations and clinical consequences.

We assessed the diagnostic advantage of dual-energy computed tomography (DECT) over single-energy computed tomography (SECT) to evaluate lipiodol accumulation in target lesions following transcatheter arterial chemoembolization (TACE).

TACE was performed in 10 rabbits in whom the VX2 tumor was implanted in their left liver lobes. The miriplatin-lipiodol mixture was injected into the common hepatic artery. All rabbits were sacrificed 2 days after TACE, and the liver was harvested. CT was performed using both single-energy and dual-energy scan modes. The specimen was stained with Oil Red O to evaluate lipiodol accumulation; this was considered the reference standard. Mutual information (MI) was used to evaluate the significance of radiological-pathological correlation. Estimated iodine content values on iodine material density images were compared with actual values obtained using mass spectroscopy.

Mean MI values were 0.69, 0.32, 0.83, 0.72, 0.65, and 0.58 for single-energy scan; iodine density images; and virtual monoenergetic images for energy levels of 40, 60, 80, and 100 keV, respectively. The MI value of the monochromatic image (40 keV) was the highest among all sequences. However, this was not significant compared with the single-energy scan (p = 0.81). A significant correlation was observed between the estimated and actual values of iodine content (Pearson's product moment coefficient = 0.70, p = 0.023).

More accurate and quantitative lipiodol evaluation in targeted tumors after TACE can be achieved by applying DECT rather than SECT.

Locoregional treatment with transarterial chemoembolization (TACE) or hepatic artery infusion chemotherapy (HAIC) and systemic targeted immunotherapy with tyrosine kinase inhibitors (TKI) and programmed cell death protein-1 (PD-1) inhibitors in the treatment of unresectable hepatocellular carcinoma (uHCC) have achieved promising efficacy. The retrospective study aimed to evaluate the efficacy and safety of TACE and HAIC plus TKI with or without PD-1 for uHCC.

From November 2020 to February 2024, the data of 44 patients who received TACE-HAIC + TKI + PD-1 (THKP group) and 34 patients who received TACE-HAIC + TKI (THK group) were retrospectively analyzed. Primary outcomes were overall survival (OS) and progress-free survival (PFS), and secondary outcomes were objective response rate (ORR), disease control rate (DCR), conversion rates, and adverse events (AEs).

A total of 78 patients were recruited in our single-center study. The patients in THKP group had prolonged median OS [25 months, 95% confidence interval (CI) 24.0-26.0 vs 18 months, 95% CI 16.1-19.9; p = 0.000278], median PFS [16 months, 95% CI 14.1-17.9 vs 12 months 95% CI 9.6-14.4; p = 0.004] and higher ORR (38.6% vs 23.5%, p = 0. 156) and DCR (88.6% vs 64.7%, p = 0.011) compared with those in THK group. Multivariate analysis showed that treatment option and alpha-fetoprotein (AFP) level were independent prognostic factors of OS and PFS. The frequency of AEs were similar between the two groups.

The THKP group had better efficacy for uHCC than the THK group, with acceptable safety.

Current embolic agents in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) encounter instability and easy leakage, discounting TACE efficacy with residual HCC. Moreover, clinical TACE aggravates hypoxia and pro-metastatic microenvironments, rendering patients with HCC poor prognosis.

Herein, we developed Zein-based embolic agents that harness water-insoluble but ethanol-soluble Zein to encompass doxorubicin (DOX)-loaded mesoporous hollow MnO2 (HMnO2). The conditions and capacity of HMnO2 to generate reactive oxygen species (ROS) were assayed. Mechanical examinations of Zein-HMnO2@DOX were performed to evaluate its potential as the embolic agent. In vitro experiments were carried out to evaluate the effect of Zein-HMnO2@DOX on HCC. The subcutaneous HCC mouse model and rabbit VX2 HCC model were established to investigate its anti-tumor and anti-metastasis efficacy and explore its potential anti-tumor mechanism.

The high adhesion and crosslinking of Zein with HMnO2@DOX impart Zein-HMnO2@DOX with strong mechanical strength to resist deformation and wash-off. Zein gelation and HMnO2 decomposition in response to water and acidic tumor microenvironment, respectively, enable continuous DOX release and Fenton-like reaction for reactive oxygen species (ROS) production and O2 release to execute ROS-enhanced TACE. Consequently, Zein-based embolic agents outperform clinically-used lipiodol to significantly inhibit orthotopic HCC growth. More significantly, O2 release down-regulates hypoxia inducible factor (HIF-1α), vascular endothelial growth factor (VEGF) and glucose transporter protein 1 (GLUT1), which thereby re-programmes TACE-aggravated hypoxic and pro-metastatic microenvironments to repress HCC metastasis towards lung. Mechanistic explorations uncover that such Zein-based TACE agents disrupt oxidative stress, angiogenesis and glycometabolism pathways to inhibit HCC progression.

This innovative work not only provides a new TACE agent for HCC, but also establishes a new strategy to ameliorate TACE-aggravated hypoxia and metastasis motivation against clinically-common HCC metastasis after TACE operation.

Excellent Young Science Fund for National Natural Science Foundation of China (82022033); National Natural Science Foundation of China (Grant No. 82373086, 82102761); Major scientific and technological innovation project of Wenzhou Science and Technology Bureau (Grant No. ZY2021009); Shanghai Young Top-Notch Talent.

As the third leading cause of cancer-related deaths worldwide, hepatocellular carcinoma (HCC) represents a significant global health challenge. This paper provides an introduction and comprehensive review of transarterial radioembolization (TARE) with Yttrium-90 (Y90), a widely performed transcatheter procedure for HCC patients who are not suitable candidates for surgery. TARE involves the targeted delivery of radioactive microspheres to liver tumors, offering a promising treatment option for managing HCC across various stages of the disease. By evaluating Y90 TARE outcomes across early, intermediate, and advanced stages of HCC, the review aims to present a thorough understanding of its efficacy and safety. Additionally, this paper highlights future research directions focusing on the potential of combination therapies with systemic and immunotherapies, as well as personalized treatments. The exploration of these innovative approaches aims to improve treatment outcomes, reduce adverse events, and provide new therapeutic opportunities for HCC patients. The review underscores the importance of ongoing research and clinical trials to optimize TARE further and integrate it into comprehensive HCC treatment paradigms.

Liver cancer is one of the most prevalent malignant tumors worldwide. According to the Barcelona Clinic Liver Cancer staging criteria, clinical guidelines provide tutorials to clinical management of liver cancer at their individual stages. However, most patients diagnosed with liver cancer are at advanced stage; therefore, many researchers conduct investigations on targeted therapy, aiming to improve the overall survival of these patients. To date, small-molecule-based targeted therapies are highly recommended (first line: sorafenib and lenvatinib; second line: regorafenib and cabozantinib) by current the clinical guidelines of the American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network. Herein, we summarize the small-molecule-based targeted therapies in liver cancer, including the approved and preclinical therapies as well as the therapies under clinical trials, and introduce their history of discovery, clinical trials, indications, and molecular mechanisms. For drug resistance, the revealed mechanisms of action and the combination therapies are also discussed. In fact, the known small-molecule-based therapies still have limited clinical benefits to liver cancer patients. Therefore, we analyze the current status and give our ideas for the urgent issues and future directions in this field, suggesting clues for novel techniques in liver cancer treatment.