Exploring the Evolving Landscape of Stereotactic Body Radiation Therapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) carries significant morbidity and mortality. Management of the HCC requires a multidisciplinary approach. Surgical resection and liver transplantation are the gold standard options for the appropriate settings. Stereotactic body radiation therapy (SBRT) has emerged as a promising treatment modality in managing HCC; its use is more studied and well-established in advanced HCC (aHCC). Current clinical guidelines universally endorse SBRT as a viable alternative to radiofrequency ablation (RFA), transarterial chemoembolisation (TACE), and transarterial radioembolisation (TARE), a recommendation substantiated by literature demonstrating comparable efficacy among these modalities. In early-stage HCC, SBRT primarily manages unresectable tumours unsuitable for ablative procedures such as microwave ablation and RFA. SBRT has been incorporated as a modality to downstage tumours or as a bridge to transplant. In the case of intermediate or advanced HCC, SBRT offers excellent results either as a single modality or adjunct to other locoregional modalities such as TACE/TARE. Recent data from late-stage HCC patients illustrate the effectiveness of SBRT in achieving local tumour control while minimising damage to surrounding healthy liver tissue. It has promising local control of approximately 80-90% in managing HCC. Additional prospective data comparing the efficacy of SBRT with the first-line recommended therapies such as RFA, TACE, and surgery are essential. The standard of care for patients with advanced/metastatic disease is systemic therapy (immunotherapy/tyrosine kinase inhibitors). SBRT, in combination with immune-checkpoint inhibitors, has an immune-modulatory effect that results in a synergistic effect. Recent findings indicate that the combination of immunotherapy and SBRT in HCC is well-tolerated and exhibits synergistic effects. Further exploration of diverse immunotherapy and radiotherapy strategies is essential to identify the appropriate time for combination treatments and to optimise dose and fraction regimens. Prospective, randomised studies are imperative to establish SBRT as the primary treatment for HCC.

A Study on Overcoming Post-TACE Drug Resistance in HCC Based on Controllable Oxygen Release-Magnetic Hyperthermia Therapy.

Drug-eluting bead transcatheter arterial chemoembolization (D-TACE) is one of the first-line treatment for intermediate hepatocellular carcinoma (HCC). However, the dual hypoxia microenvironment, due to inherent tumor hypoxia and TACE-induced hypoxia, triggers drug resistance in HCC. To address this challenge, the study develops multicavitary microspheres capable of encapsulating oxygen and harnessing magnetic hyperthermia to enhance oxygen permeability. The novel multicavitary oxygen-encapsulated magnetothermal drug-eluting microspheres (OTD-Ms) effectively reduce hypoxia-related proteins (HIF-1α, VEGF-A) and drug resistance (P-gp) both in vitro and in vivo. Moreover, these microspheres demonstrate improved TACE efficacy and enhance survival rates in a rabbit VX-2 tumor model, suggesting their potential for HCC treatment.

Transarterial chemoembolization combined with sintilimab and lenvatinib for the treatment of unresectable hepatocellular carcinoma: a retrospective study.

BACKGROUND: The treatment of unresectable hepatocellular carcinoma (uHCC) challenging due to unfulfilled clinical requirements. OBJECTIVE: To evaluate the safety and efficacy of combining transarterial chemoembolization (TACE) with sintilimab and lenvatinib in the treatment of uHCC. METHODS: We retrospectively analyzed the data of patients with uHCC who were treated with a combination of TACE, sintilimab, and lenvatinib between May 2019 and December 2021 at the Chinese PLA General Hospital. Systemic treatment was started 1 week after TACE was performed. Sintilimab was administered intravenously at a dosage of 200 mg every three weeks, and lenvatinib was given orally at dosages of 8 mg or 12 mg daily, contingent upon the weight of the patients. The primary endpoint was the objective response rate (ORR) as per the mRECIST. Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (tr-AEs). RESULTS: A total of 32 patients were enrolled in the study. Among them, 9 patients were classified as Barcelona Clinic Liver Cancer-B (BCLC-B), 23 patients were classified as BCLC-C, 14 patients diagnosed with portal vein tumors, and 12 patients were diagnosed with extra hepatic metastases. The ORR and DCR were 75% and 90.6% respectively, with 4 patients exhibiting (12.5%) complete response, 20 patients exhibiting (62.5%) partial response, 5 patients exhibiting (15.6%) stable disease, and 3 patients exhibiting (9.4%) progressive disease. With a median follow-up time of 19.6 months, the median PFS was 9.9 months, and the median OS was 33.3 months. A total of 31 patients experienced different degrees of tr-AEs, of which 2 were grade 3 tr-AEs. CONCLUSION: The combination therapy of TACE, sintilimab, and lenvatinib demonstrates satisfactory efficacy in the treatment of uHCC with manageable tr-AEs.

Detection of hepatocellular carcinoma feeding vessels: MDCT angiography with 3D reconstruction versus digital subtraction angiography.

BACKGROUND: Accurate detection of Hepatocellular carcinoma (HCC) feeding vessels during transcatheter arterial chemoembolization (TACE) is important for an effective treatment, while limiting non-target embolization. This study aimed to investigate the feasibility and accuracy of pre-TACE three dimensional (3D) CT angiography for tumor-feeding vessels detection compared to DSA. METHODS: Sixty-nine consecutive patients referred for TACE from May 2022 to May 2023 were included. (3D) CT images were reconstructed from the pre-TACE diagnostic multiphasic contrast enhanced CT images and compared with non-selective digital subtraction angiography (DSA) images obtained during TACE for detection of HCC feeding vessels. A "Ground truth" made by consensus between observers after reviewing all available pre-TACE CT images, and DSA and CBCT images during TACE to detect the true feeding vessels was the gold standard. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), accuracy and ROC curve with AUC were calculated for each modality and compared. RESULTS: A total of 136 active HCCs were detected in the 69 consecutive patients included in the study. 185 feeding arteries were detected by 3D CT and DSA and included in the analysis. 3D CT detection of feeding arteries revealed mean sensitivity, specificity, PPV, NPV and accuracy of 91%, 71%, 98%, 36%, and 90%, respectively, with mean AUC = 0.81. DSA detection of feeding arteries revealed mean sensitivity, specificity, PPV, NPV, and accuracy of 80%, 58%, 96.5%, 16.5% and 78%, respectively, with mean AUC = 0.69. CONCLUSIONS: Pre-TACE 3D CT angiography has shown promise in improving the detection of HCC feeding vessels compared to DSA. However, further studies are required to confirm these findings across different clinical settings and patient populations. TRIAL REGISTRATION: This study was prospectively registered at Clinicaltrials.gov with ID NCT05304572; Date of registration: 2-4-2022.

Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma.

Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.

Clinical Efficacy and Safety of transarterial chemoembolization Combined with Targeted Therapy for primary hepatocellular carcinoma.

Objective: To explore the clinical efficacy and safety of transarterial chemoembolization (TACE) combined with targeted therapy for primary hepatocellular carcinoma (PHC). Methods: This was a retrospective study. Retrospective selection of 150 PHC patients admitted to the Renmin Hospital, Hubei University of Medicine January 2019 and June 2021 were included. The patients were divided into the control group and the experimental group according to their treatment regimens. The control group received TACE treatment, while the experimental group received TACE combined with targeted therapy. We analyze the relevant data of two groups of patients and evaluate the clinical efficacy and safety of TACE combined with targeted therapy. Results: The tumor remission rate and control rate in the control group were 41.89% and 75.68%, respectively, while those in the experimental group were 77.63% and 90.79%, with statistically significant differences (p<0.05). The 1-year and 3-year recurrence rates in the control group were 52.71% and 98.65%, respectively, while those in the experimental group were 39.47% and 61.84%, with statistically significant differences (p<0.05). After treatment, the AFP, VEGF, ALT, and AST in the experimental group were significantly reduced compared to the control group (p<0.05). During the treatment period, the incidence and severity of nausea, vomiting, and fever in the experimental group were significantly lower than those in the control group (p<0.05). Conclusion: The clinical efficacy of TACE combined with targeted therapy for PHC is superior to that of TACE alone, with improved disease control rate, improved long-term survival rate, and good safety.

Investigating synergy between beta-blockers and transarterial chemoembolization in the treatment of hepatocellular carcinoma: preliminary data from a propensity matched analysis.

PURPOSE: Favorable clinical outcomes have been reported with the adjunct use of beta-blockers in cancer treatment, hypothetically secondary to their anti-angiogenic/anti-proliferative effects. Hereby, we investigate whether there is synergy between beta-blockers and TACE in the treatment of HCC. METHODS: 36 HCC patients on beta-blockers (mean dose of 48 mg daily) at the time of first-line treatment with TACE at our institution were retrospectively identified out of a cohort of 221 patients between 2008 and 2019. Using propensity scoring, a matched cohort of 36 patients not exposed to beta-blockers was generated based on age, gender, ethnicity, etiology of liver disease, BCLC, child Pugh score, PS/ECOG, cirrhosis, largest mass treated, type of TACE and treated liver segments. Tumor response was assessed at 1st and 2nd post-TACE imaging timepoints (1.4 and 4.1 months on average respectively). Variables were compared using chi-square test and Student's t-test. Kaplan-Meier transplant-free survival plots were generated using IBM® SPSS® software. Cox regression analysis was used to evaluate survival predictors. A p values < 0.05 was considered significant. RESULTS: Comparing the control and beta-blocker cohorts, there were no differences in baseline characteristics, post-TACE imaging timepoints, tumor response or transplant free survival (p > 0.05). Tumor size was found to be a predictor of survival when the two cohorts were combined (p = 0.03). CONCLUSION: Transplant-free survival and HCC response to first-line TACE treatment were similar in the control and beta-blocker groups. Large tumor sizes were associated with higher mortality in combined analysis of the cohorts.

Efficacy and safety of transarterial chemoembolization alone compared to its combination with anlotinib among patients with intermediate or advanced stage hepatocellular carcinoma: a phase II randomized controlled trial.

Background: Anlotinib hydrochloride is a potent oral multitargeted tyrosine kinase inhibitor that targets VEGFR1-3, FGFR1-4, and PDGFR α/ß, demonstrating significant antiangiogenic activity. Transcatheter arterial chemoembolization (TACE) is considered the effective treatment for intermediate/advanced hepatocellular carcinoma (HCC), which remains a major global health challenge. This study evaluated the relative efficacy and safety of combining anlotinib with TACE against the standard TACE monotherapy among patients with intermediate or advanced HCC. Methods: This phase II randomized controlled trial included 38 patients diagnosed with intermediate or advanced HCC. Patients were randomly assigned to receive either TACE in combination with anlotinib or TACE alone. The primary endpoint of the study was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. This trial aimed to determine whether the addition of anlotinib could extend PFS and improve other clinical outcomes compared to TACE alone. Results: The median PFS for patients treated with TACE and anlotinib was significantly longer at 11.04 months compared to 6.87 months in the TACE-alone group [hazard ratio (HR) 0.46; P=0.02], indicating a robust enhancement in disease management. Although the median OS was not reached at the time of analysis, early trends suggest potential improvement. Both treatment groups had comparable ORR and DCR, demonstrating effective disease control. The safety profile of the combined treatment was manageable, with side effects similar in nature to those observed with TACE alone but not significantly more severe, thus maintaining patient quality of life. Conclusions: The addition of anlotinib to TACE appears to provide a safe and effective therapeutic benefit for patients with intermediate or advanced-stage HCC. However, longer follow-up is needed for a more comprehensive efficacy assessment. Trial Registration: ClinicalTrials.gov NCT04066543.

Percutaneous thermal segmentectomy for liver malignancies over 3 cm: mid-term oncological performance and predictors of sustained complete response from a multicentric Italian retrospective study.

INTRODUCTION: Percutaneous thermal segmentectomy is a single-step combination of microwave ablation, performed during arterial occlusion obtained with a balloon micro catheter, followed in the same session by balloon-occluded TACE. The aim of this multicenter retrospective study is to report the mid-term oncological performance of this technique for liver malignancies > 3.0 cm and to identify risk factors for the loss of sustained complete response. METHODS: Oncological results were evaluated with CT or MRI according to m-RECIST (HCC) and RECISTv1.1 (metastasis/intra-hepatic cholangiocarcinoma, iCC) at 1-month, 3-6-month and then at regular-6-month intervals. To identify predictive variables associated with not achieving or losing complete response two mixed-effects multivariable logistic regression models were constructed. RESULTS: Sixty-three patients (40/23, male/female) with primary liver malignancies (HCC = 49; iCC = 4) and metastasis (n = 10) were treated. Median diameter of target lesion was 4.5 cm (range 3.0-7.0 cm). The median follow-up time was 9.2 months. At one-month follow-up, 79.4% of patients presented with a complete response and the remaining 20.6% were partial responders. At the 3-6-month follow-up, reached by 59 of the initial 63 patients, 83.3% showed a sustained complete response, while 10.2% had a partial response and 8.5% a local recurrence. At the last follow-up, 69.8% of the lesions showed a complete response. The initial diameter of the target lesion ≥ 5.0 cm was the only independent variable associated with the risk of failure in maintaining a complete response at 6 months (OR = 8.58, 95% CI 1.38-53.43; P = 0.02). CONCLUSION: Percutaneous thermal segmentectomy achieves promising oncological results in patients with tumors > 3.0 cm, with tumor dimension ≥ 5.0 cm being the only risk factor associated with the failure of a sustained complete response.

Initial Trans-Arterial Chemo-Embolisation (TACE) Is Associated with Similar Survival Outcomes as Compared to Upfront Percutaneous Ablation Allowing for Follow-Up Treatment in Those with Single Hepatocellular Carcinoma (HCC) ≤ 3 cm: Results of a Real-World Propensity-Matched Multi-Centre Australian Cohort Study.

Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation. Patients with a new diagnosis of BCLC 0/A HCC with a single tumour ≤3 cm first diagnosed between 1 January 2016 and 31 December 2020 who received initial TACE or ablation were included in the study. A total of 348 patients were included in the study, with 147 patients receiving initial TACE and 201 patients undergoing upfront ablation. After propensity score matching using key covariates, 230 patients were available for analysis with 115 in each group. There were no significant differences in overall survival (log-rank test p = 0.652) or liver-related survival (log-rank test p = 0.495) over a median follow-up of 43 months. While rates of CR were superior after ablation compared to TACE as a first treatment (74% vs. 56%, p < 0.004), there was no significant difference in CR rates when allowing for further subsequent treatments (86% vs. 80% p = 0.219). In those who achieved CR, recurrence-free survival and local recurrence-free survival were similar (log rank test p = 0.355 and p = 0.390, respectively). Our study provides valuable real-world evidence that TACE when offered with appropriate follow-up treatment is a reasonable initial management strategy in very early/early-stage HCC, with similar survival outcomes as compared to those managed with upfront ablation. Further work is needed to better define the role for TACE in BCLC 0/A HCC.

Feasibility and safety of transarterial chemoembolization in patients with liver cancer via the distal radial approach: a single-center retrospective cohort study.

Background: The femoral artery is the standard route for transarterial chemoembolization (TACE); however, it is negatively associated with the quality of life of patients, and carries an increased risk of deep vein thrombosis in the lower limbs. We employed the distal radial approach to TACE to assess its feasibility and safety. Methods: We conducted a retrospective study at the First Hospital of Jilin University from August 1, 2020 to October 31, 2023. To be eligible for inclusion in the study, the patients had to meet the following main inclusion criteria: (I) have undergone a preoperative imaging (abdominal computed tomography enhancement or magnetic resonance dynamic enhancement) examination, or have a pathologically confirmed diagnosis of primary liver cancer, and a Child-Pugh score of A or B; and (II) have undergone distal radial artery puncture. The primary endpoint of this study was the success rate of distal radial artery puncture. The secondary endpoints were complications and the duration of the puncture. Results: Among the 343 patients with primary liver cancer (of whom 236 were male and 107 were female), a total of 1,315 distal radial artery punctures were attempted. The success rate was remarkably high at 95.13% (1,251/1,315), with only 64 cases requiring an alternative approach due to failed puncture. The average puncture duration was 20±7.43 minutes. No bleeding and hematoma, no arterial dissection and pseudoaneurysm formation were observed on ultrasound, and the radial pulse was palpable in all patients, highlighting the safety of the procedure. Further, no adverse events of vascular occlusion were observed among the 12 patients who received 6 or more punctures, indicating the sustainability of the distal radial artery access under the premise of adequate vascular protection. The development of this technique requires a learning curve of at least 50 cases to break through the learning baseline and be proficient in distal radial artery blind puncture. This may be the reason why many interventional physicians are reluctant to perform this procedure, adapting to the femoral approach with a shorter learning curve. Conclusions: The distal radial artery approach is feasible and safe in hepatic arterial chemoembolization, and should be widely promoted in TACE.

Evaluation of different scoring systems for repeating Transarterial Chemoembolization in Egyptian patients with Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE) have a diverse range of outcomes due to their high degree of heterogeneity. Therefore, different predictive scoring systems have been created to assist in decision-making regarding retreatment with TACE. We compared the predictive capabilities of different scoring systems, such as ART, ABCR, and SNACOR, for prediction of the outcome of subsequent TACE in HCC patients. METHOD: In this retrospective study, the three scoring systems were compared for their capability of predicting the outcome of repeating TACE in 149 HCC patients treated at the National Liver Institute, Egypt, between January 2017 and December 2019. We used the likelihood ratio to select the model with the highest predictive capability for overall survival (OS). RESULTS: According to our data, the amount of tumor, the change in Barcelona Clinic Liver Cancer (BCLC) stage following TACE, and the SNACOR score (with a 95% confidence range for HR 1.0305-1.256 and p-value = 0.0106) were the most predictive variables. It was also shown that the ABCR score was a good predictor of survival (90 patients had an ABCR score ≤ 0 with a P- value <0.0001, 56 patients had 0 < ABCR < 4 with a P-value <0.0001, and the ART score was not useful in predicting OS (P-value = 0.18). CONCLUSION: The SNACOR score is the most predictive score for OS and would be the most helpful scoring system in decision-making regarding retreatment with TACE.

Impact of Microparticle Transarterial Chemoembolization (mTACE) on myeloid-derived suppressor cell subtypes in hepatocellular carcinoma: Clinical correlations and therapeutic implications.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play a pivotal role in immunosuppression and tumor progression in hepatocellular carcinoma (HCC). While various treatments like surgical resection, ablation, and radiotherapy have been studied for their effects on circulating MDSC frequencies in HCC patients, the findings remain inconclusive. Transarterial Chemoembolization (TACE) stands as the standard care for unresectable HCC, with Microparticle TACE (mTACE) gaining prominence for its capacity to induce significant tumor necrosis. However, the immunological ramifications of such pathological outcomes are scarcely reported. METHODS AND RESULTS: This study aims to elucidate the alterations in MDSC subtypes, specifically monocytic MDSCs (mMDSCs) and early-stage MDSCs (eMDSCs), post-mTACE and to investigate their clinical correlations in HCC patients. A cohort comprising 75 HCC patients, 16 liver cirrhosis patients, and 20 healthy controls (HC) was studied. Peripheral blood samples were collected and analyzed for MDSC subtypes. The study also explored the associations between MDSC frequencies and various clinical parameters in HCC patients. The frequency of mMDSCs was significantly elevated in the HCC group compared to liver cirrhosis and HC. Importantly, mMDSC levels were strongly correlated with aggressive clinical features of HCC, including tumor size, vascular invasion, and distant metastasis. Post-mTACE, a marked reduction in mMDSC frequencies was observed, while eMDSC levels remained stable. CONCLUSIONS: Our findings underscore the critical role of mMDSCs in HCC pathogenesis and their potential as a therapeutic target. The study also highlights the efficacy of mTACE in modulating the immunosuppressive tumor microenvironment, thereby opening new avenues for combinatorial immunotherapeutic strategies in HCC management.

Efficacy of doxorubicin and lipiodol therapy by trans-arterial chemoembolization in hepatocellular carcinoma Egyptian patients and relation to genetic polymorphisms.

BACKGROUND: Genetic polymorphisms play a crucial role in predicting treatment efficacy in patients with hepatocellular carcinoma (HCC). This study aims to evaluate the response to Transarterial Chemoembolization (TACE) in relation to the genetic polymorphisms of interleukin 28B (IL28B) and angiopoietin-2 (ANGPT2) in HCC patients. RESEARCH DESIGN AND METHODS: Prospective cohort study conducted on 104 eligible HCC Egyptian patients who underwent TACE using doxorubicin and lipiodol. Genotyping of the IL28B and ANGPT2 genes was performed with laboratory data analysis. RESULTS: At baseline IL28B rs12979860 genotypes C/T, C/C and T/T appeared in 43.9%, 34.6% and 21.5% while ANGPT2 rs55633437 genotypes C/C, C/A and A/A found in 71.03%, 28.04% and 0.93% of patients respectively. After one month of therapy, 51.4% of patients achieved a complete response. There was a significant difference in relation to IL28B rs12979860 genotypes (p = 0.017) whereas ANGPT2 rs55633437 genotypes (p = 0.432) showed no significant difference in patient response after one month of TACE. CONCLUSION: This study demonstrates the effectiveness of TACE in Egyptian HCC patients, as evidenced by low recurrence rates. Furthermore, the IL28B rs12979860 (C/T) gene may be associated with the efficacy and prognosis of TACE treatment in HCC Egyptian patients. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05291338).

Neoadjuvant-Based Triple Therapy for Hepatocellular Carcinoma with Type I/II Portal Vein Tumor Thrombosis.

Purpose: Hepatectomy could provide better survival benefit for hepatocellular carcinoma (HCC) with type I/II portal vein tumor thrombosis (PVTT). However, the postoperative recurrence remains high. We discussed whether neoadjuvant therapy could reduce HCC recurrence for these patients. Patients and Methods: One hundred and thirty-eight resectable HCC with type I-II PVTT were retrospectively included. The neoadjuvant therapy regimens included tyrosine kinase inhibitor (TKI), programmed death 1(PD-1) antibodies and transarterial chemoembolization (TACE). Short-term and long-term outcomes were compared. Propensity score matching (PSM) was performed to minimize the influence of potential confounders. Results: Thirty-three patients underwent neoadjuvant therapy and 105 patients underwent surgery alone. In the neoadjuvant group, 7 (21.2%) patients achieved stable disease, 13 (39.4%) achieved partial response and 13 (39.4%) achieved complete response based on the modified Response Evaluation Criteria in Solid Tumors criterion. By PSM, the neoadjuvant therapy resulted in less microvascular invasion (24.1% vs 50.0%, P=0.021), satellite nodule (6.9% vs 24.1%, P=0.036) and less patients with alpha-fetoprotein>20(ng/mL) (37.9% vs 69.0%, P=0.006). The neoadjuvant therapy reduced tumor recurrence and prolonged survival. Multivariate analysis found that neoadjuvant therapy was an independent protective factor for overall survival and recurrence free survival. Conclusion: Neoadjuvant treatment presents a promising treatment option for HCC patients with type I/II PVTT.

Feasibility and Safety of the Clinical Outcomes of TACE Combined with Lenvatinib and PD-1 Blockades in the Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective Exploratory Study.

Objective: This study aimed to investigate the feasibility of the efficacy and safety of TACE combined with Lenvatinib and PD-1 blockade in HCC with portal vein tumor thrombus (PVTT). Methods: Patients with HCC and PVTT who underwent TACE combined with Lenvatinib and PD-1 blockade as first-line therapy in clinical practice were retrospectively included. All subjects were followed-up regularly to obtain prognostic outcomes. The safety profile observed during the combination therapy was collected and documented. The Log rank test was used for exploratory analysis of prognosis and baseline characteristics and Cox regression analysis was used for multivariate analysis. Results: A total of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockade were included in this study. The best therapeutic response during treatment suggested that 4 patients achieved complete response, 30 patients showed partial response, 25 patients were stable disease, 5 patients had disease progression and 3 patients were not available. Objective response rate of this regimen was 50.7% [95% confidence interval (CI): 38.2-63.2%] and disease control rate was 88.1% (95% CI: 77.8-94.7%). The median progression-free survival of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockades was 9.3 months (95% CI: 5.85-12.75), and the median overall survival was 24.4 months (95% CI: 19.11-29.69). The safety profile highlighted that 65 patients experienced adverse reactions regardless of grade during treatment (97.0%), among whom 34 patients were deemed as grade ≥3 adverse reactions (50.7%). The most common adverse reactions were hypertension, fatigue, abnormal liver function, nausea, vomiting, and diarrhea. Overall adverse reactions were acceptable and controllable. Conclusion: TACE combined with Lenvatinib and PD-1 blockades as first-line therapy for HCC with PVTT demonstrated potential feasibility and encouraging clinical outcomes, providing long-term survival benefits for HCC patients. This conclusion should be confirmed in prospective large-scale clinical trials.

A Patient With Hepatocellular Carcinoma and Lung Metastasis Successfully Underwent Curative Surgery Following the Downstaging Treatment: A Case Report.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Hepatic resection constitutes the major curative treatment option, but a significant proportion of patients are not surgical candidates on initial evaluation. Along with the development of novel therapeutic strategies including targeted therapies and immunotherapies, a few HCCs can achieve tumor downstaging and be curatively resected. A 52-year-old man was diagnosed with HCC with portal vein invasion and extensive pulmonary and lymph node metastasis. Transarterial chemoembolization (TACE) in conjunction with donafenib and sintilimab was given. Primary tumors in the liver largely shrank with almost complete elimination of the lung metastases following treatment. The patient subsequently underwent curative surgery for HCC, and the pathological examination revealed complete necrosis of the tumor. Targeted immunotherapy was continued after surgery and no disease progression was found on the latest follow-up. Advanced HCC with distant metastasis might have an excellent response to combination therapy of TACE with tyrosine kinase-targeted inhibitors and PD-1 blocker, and achieve opportunity for curative surgery. This efficacy may be associated with the remodeling of immune microenvironment and angiogenesis. HCC is extremely heterogeneous, and the response to therapeutics varies among patients. There is a lack of useful biomarkers to predict therapeutic efficacy, which needs further studies.

Efficacy and features of balloon-occluded transarterial chemoembolization for hepatocellular carcinoma: a narrative review.

Background and Objective: Systemic therapy for hepatocellular carcinoma (HCC) is recommended in transarterial chemoembolization (TACE)-refractory and unsuitable cases. In Japan, TACE is broadly classified into conventional TACE (C-TACE), balloon occluded TACE (B-TACE), and drug-eluting beads TACE. However, the type of TACE recommended for TACE-refractory or unsuitable cases has not been elucidated, and a targeted approach for individual cases and appropriate TACE selection is important. B-TACE is considered a valuable therapeutic option in the management of HCC. The technique involves the precise placement of a microcatheter with a balloon into the target hepatic artery, followed by selective occlusion of the hepatic artery, including tumor-feeding vessels, using the balloon. By leveraging the hemodynamic changes resulting from arterial occlusion, B-TACE enables effective accumulation of chemotherapeutic agents within the tumor. Incorporating B-TACE into the treatment strategy for HCC is of utmost importance. Therefore, this article provides an overview of the technique. Methods: A comprehensive review of all available literature in the English language through December 1, 2023 utilizing PubMed was conducted. Key Content and Findings: In the intermediate stage, TACE and systemic therapy play complementary roles, and it is important to select a treatment strategy that considers tumor status and hepatic reserve. However, no study has investigated the various types of TACE in the treatment of such patients. Currently, TACE in Japan is broadly classified into C-TACE, B-TACE, and drug-eluting beads TACE (DEB-TACE). This article outlines the evolution of B-TACE for HCC. We identified retrospective and prospective studies evaluating B-TACE. In this review, we evaluate data on B-TACE for HCC. Conclusions: In the era of systemic therapy, B-TACE may play a complementary and synergy effect role.

Immobilized Drugs on Dual-Mode Imaging Ag2S/BaSO4/PVA Embolic Microspheres for Precise Localization, Rapid Embolization, and Local Antitumor Therapy.

Transcatheter arterial embolization (TAE) in interventional therapy and tumor embolism therapy plays a significant role. The choice of embolic materials that have good biocompatibility is an essential component of TAE. For this study, we produced a multifunctional PVA embolization material that can simultaneously encapsulate Ag2S quantum dots (Ag2S QDs) and BaSO4 nanoparticles (BaSO4 NPs), exhibiting excellent second near-infrared window (NIR-II) fluorescence imaging and X-ray imaging, breaking through the limitations of traditional embolic microsphere X-ray imaging. To improve the therapeutic effectiveness against tumors, we doped the doxorubicin (DOX) antitumor drug into microspheres and combined it with a clotting peptide (RADA16-I) on the surface of microspheres. Thus, it not only embolizes rapidly during hemostasis but also continues to release and accelerate tumor necrosis. In addition, Ag2S/BaSO4/PVA microspheres (Ag2S/BaSO4/PVA Ms) exhibited good blood compatibility and biocompatibility, and the results of embolization experiments on renal arteries in rabbits revealed good embolic effects and bimodal imaging stability. Therefore, they could serve as a promising medication delivery embolic system and an efficient biomaterial for arterial embolization. Our research work achieves the applicability of NIR-II and X-ray dual-mode images for clinical embolization in biomedical imaging.

Vessel-targeted compensation of deformable motion in interventional cone-beam CT.

The present standard of care for unresectable liver cancer is transarterial chemoembolization (TACE), which involves using chemotherapeutic particles to selectively embolize the arteries supplying hepatic tumors. Accurate volumetric identification of intricate fine vascularity is crucial for selective embolization. Three-dimensional imaging, particularly cone-beam CT (CBCT), aids in visualization and targeting of small vessels in such highly variable anatomy, but long image acquisition time results in intra-scan patient motion, which distorts vascular structures and tissue boundaries. To improve clarity of vascular anatomy and intra-procedural utility, this work proposes a targeted motion estimation and compensation framework that removes the need for any prior information or external tracking and for user interaction. Motion estimation is performed in two stages: (i) a target identification stage that segments arteries and catheters in the projection domain using a multi-view convolutional neural network to construct a coarse 3D vascular mask; and (ii) a targeted motion estimation stage that iteratively solves for the time-varying motion field via optimization of a vessel-enhancing objective function computed over the target vascular mask. The vessel-enhancing objective is derived through eigenvalues of the local image Hessian to emphasize bright tubular structures. Motion compensation is achieved via spatial transformer operators that apply time-dependent deformations to partial angle reconstructions, allowing efficient minimization via gradient backpropagation. The framework was trained and evaluated in anatomically realistic simulated motion-corrupted CBCTs mimicking TACE of hepatic tumors, at intermediate (3.0 mm) and large (6.0 mm) motion magnitudes. Motion compensation substantially improved median vascular DICE score (from 0.30 to 0.59 for large motion), image SSIM (from 0.77 to 0.93 for large motion), and vessel sharpness (0.189 mm-1 to 0.233 mm-1 for large motion) in simulated cases. Motion compensation also demonstrated increased vessel sharpness (0.188 mm-1 before to 0.205 mm-1 after) and reconstructed vessel length (median increased from 37.37 to 41.00 mm) on a clinical interventional CBCT. The proposed anatomy-aware motion compensation framework presented a promising approach for improving the utility of CBCT for intra-procedural vascular imaging, facilitating selective embolization procedures.