Outcomes of repeat conventional transarterial chemoembolization in patients with liver metastases.

INTRODUCTION AND OBJECTIVES: Although unlimited sessions of conventional transarterial chemoembolization (cTACE) may be performed for liver metastases, there is no data indicating when treatment becomes ineffective. This study aimed to determine the optimal number of repeat cTACE sessions for nonresponding patients before abandoning cTACE in patients with liver metastases. MATERIALS AND METHODS: In this retrospective, single-institutional analysis, patients with liver metastases from neuroendocrine tumors (NET), colorectal carcinoma (CRC), and lung cancer who underwent consecutive cTACE sessions from 2001 to 2015 were studied. Quantitative European Association for Study of the Liver (qEASL) criteria were utilized for response assessment. The association between the number of cTACE and 2-year, 5-year, and overall survival was evaluated to estimate the optimal number of cTACE for each survival outcome. RESULTS: Eighty-five patients underwent a total of 186 cTACE sessions for 117 liver metastases, of which 30.7 % responded to the first cTACE. For the target lesions that did not respond to the first, second, and third cTACE sessions, response rates after the second, third, and fourth cTACE sessions were 33.3 %, 23 %, and 25 %, respectively. The fourth cTACE session was the optimal number for 2-year survival (HR 0.40; 95 %CI: 0.16-0.97; p = 0.04), 5-year survival (HR 0.31; 95 %CI: 0.11-0.87; p = 0.02), and overall survival (HR 0.35; 95 %CI: 0.13-0.89; p = 0.02). CONCLUSIONS: Repeat cTACE in the management of liver metastases from NET, CRC, and lung cancer was associated with improved patient survival. We recommend at least four cTACE sessions before switching to another treatment for nonresponding metastatic liver lesions.

Neoadjuvant therapy of sequential TACE, camrelizumab, and apatinib for single huge hepatocellular carcinoma (NEO-START): study protocol for a randomized controlled trial.

BACKGROUND: The high recurrence rate after liver resection emphasizes the urgent need for neoadjuvant therapy in hepatocellular carcinoma (HCC) to enhance the overall prognosis for patients. Immune checkpoint inhibitors, camrelizumab combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) apatinib, have emerged as a first-line treatment option for patients with unresectable HCC, yet its neoadjuvant application in combination with transarterial chemoembolization (TACE) in HCC remains unexplored. Therefore, this study aims to investigate the efficacy and safety of sequential TACE, camrelizumab, and apatinib as a neoadjuvant therapy for single, huge HCC. METHODS: This multi-center, open-label randomized phase 3 trial will be conducted at 7 tertiary hospitals. Patients with single huge (≥ 10 cm in diameter), resectable HCC will be randomly assigned in a 1:1 ratio to arm of surgery alone or arm of neoadjuvant therapy followed by surgery. In the neoadjuvant therapy group, patients will receive TACE within 1 week after randomization, followed by camrelizumab (200 mg q2w, 4 cycles), along with apatinib (250 mg qd, 2 months). Patients will receive liver resection after neoadjuvant therapy unless the disease is assessed as progressive. The primary outcome is recurrence-free survival (RFS) at 1 year. The planned sample size of 60 patients will be calculated to permit the accumulation of sufficient RFS events in 1 year to achieve 80% power for the RFS primary endpoint. DISCUSSION: Synergistic effects provided by multimodality therapy of locoregional treatment, TKI, and anti-programmed cell death 1 inhibitor significantly improved overall survival for patients with unresectable HCC. Our trial will investigate the efficacy and safety of the triple combination of TACE, camrelizumab, and apatinib as a neoadjuvant strategy for huge, resectable HCC. TRIAL REGISTRATION: www.chitr.org.cn ChiCTR2300078086. Registered on November 28, 2023. Start recruitment: 1st January 2024. Expected completion of recruitment: 15th June 2025.

Radiomics as a tool for prognostic prediction in transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis.

INTRODUCTION: Transarterial chemoembolization (TACE) is one of the predominant locoregional therapeutic modalities for addressing hepatocellular carcinoma (HCC). However, achieving precise prognostic predictions and effective patient selection remains a challenging pursuit. The primary objective of this systematic review and meta-analysis is to evaluate the efficacy of radiomics in forecasting the prognosis associated with TACE treatment. METHODS: A comprehensive exploration of pertinent original studies was undertaken, encompassing databases of PubMed, Web of Science and Embase. The studies' quality was meticulously evaluated employing the quality assessment of diagnostic accuracy studies 2 (QUADAS-2), the radiomics quality score (RQS) and the METhodological RadiomICs Score (METRICS). Pooled statistics, along with 95% confidence intervals (95% CI), were computed for sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Additionally, a summary receiver operating characteristic curve (sROC) was generated. To discern potential sources of heterogeneity, meta-regression and subgroup analyses were performed. RESULTS: The systematic review incorporated 29 studies, comprising a total of 5483 patients, with 14 studies involving 2691 patients qualifying for inclusion in the meta-analysis. The assessed studies exhibited commendable quality with regard to bias risk, with mean RQS of 12.90 ± 5.13 (35.82% ± 14.25%) and mean METRICS of 62.98% ± 14.58%. The pooled sensitivity was 0.83 (95% CI: 0.78-0.87), specificity was 0.86 (95% CI: 0.79-0.92), PLR was 6.13 (95% CI: 3.79-9.90), and NLR was 0.20 (95% CI: 0.15-0.27). The area under the sROC was 0.90 (95% CI: 0.87-0.93). Significant heterogeneity within all the included studies was observed, while meta-regression and subgroup analyses revealed homogeneous and promising findings in subgroups where principal methodological variables such as modeling algorithms, imaging modalities, and imaging phases were specified. CONCLUSION: Radiomics models have exhibited robust predictive capabilities concerning prognosis subsequent to TACE, thereby presenting promising prospects for clinical translation.

Atezolizumab and bevacizumab plus transarterial chemoembolization and hepatic arterial infusion chemotherapy for patients with high tumor burden unresectable hepatocellular carcinoma: A multi-center cohort study.

BACKGROUND: Though atezolizumab plus bevacizumab (A+B) offer promise for unresectable hepatocellular carcinoma (uHCC) treatment, the response rate remains suboptimal. Our previous studies highlighted the potential of transarterial chemoembolization (TACE) when combined with FOLFOX-based hepatic arterial infusion chemotherapy (HAIC) in HCC treatment. This study aims to evaluate the safety and efficacy of A+B plus TACE-HAIC for high tumor burden uHCC (HTB-uHCC). METHODS: This three-center retrospective study involved 82 HTB-uHCC patients administered with TACE-HAIC followed by A+B. We characterized HTB-uHCC patients as those surpassing the up-to-11 criteria, exhibiting VP 3-4, or presenting extrahepatic metastases. The primary outcomes were the objective response rate (ORR) and progression-free survival (PFS). Secondary outcomes encompassed the incidence of treatment-related adverse events (TRAEs) and overall survival (OS). RESULTS: Employing the mRECIST criteria, the ORR was 62.2 %, wherein 18 (22.0 %) patients achieved complete response, 33 (40.2 %) demonstrated partial response, 21 (25.6 %) maintained stable disease, and 10 (12.2 %) exhibited disease progression. Impressively, 11 (13.4 %) patients were converted to resectable HCC and underwent curative hepatectomy. The median PFS was 10.1 months (95 % CI, 8.4 to NA), and the median OS was still pending. At the one-year mark, the OS and PFS rates were 92.8 % (95 % CI, 86.1 to 100.0) and 42.9 % (95 % CI, 31.3 to 58.7), respectively. 79 (96.3 %) experienced TRAEs, and 39 (47.6 %) had grade 3-4 TRAEs, though no treatment-related death was recorded. CONCLUSIONS: The findings underscore the potential of the A+B and TACE-HAIC combined treatment for HTB-uHCC patients, marking it as a viable therapeutic option, given its potent efficacy and tolerable safety profile.

Prognostic Role of Lymphocyte-to-Monocyte Ratio (LMR) in Patients with Intermediate-Stage Hepatocellular Carcinoma (HCC) Undergoing Chemoembolizations (DEM-TACE or cTACE) of the Liver: Exploring the Link between Tumor Microenvironment and Interventional Radiology.

Inflammation-based scores are biomarkers of the crosstalk between the tumor microenvironment and the immune response. Investigating the intricate relationship between the tumor stromal microenvironment, biomarkers, and the response to transcatheter arterial chemoembolization (TACE) is essential for early identification of TACE refractoriness or failure, providing insights into tumor biology and facilitating personalized therapeutic interventions. This study addresses a dearth of recent literature exploring the prognostic significance of the preoperative LMR in individuals from western countries diagnosed with stage B hepatocellular carcinoma (HCC) undergoing drug eluting microspheres TACE (DEM-TACE) or conventional TACE (cTACE). This international multi-center retrospective analysis included consecutive patients with stage B HCC who underwent TACE from January 2017 to June 2023. The study evaluated the ability of the preoperative LMR to predict complete response (CR), objective response (OR), sustained response duration (SRD) exceeding 6 months, successful downstaging at 6 months, progression-free survival (PFS) at 6 months, and overall survival (OS) at 6 months. The study population included 109 HCC patients and it was divided into low LMR (LMR < 2.24) and high LMR (LMR ≥ 2.24) groups, according to ROC curve analysis to select the optimal LMR cut-off value. High LMR was associated with lower Hepatitis C prevalence, higher absolute lymphocyte count, and a trend toward lower alpha-fetoprotein. The group with high LMRs exhibited superior CR rates (14.9% vs. 0%), overall OR (43.2% vs. 14.3%), and better PFS at 6 months (75.7% vs. 45.7%). The LMR, specifically categorized as <2.24 and ≥2.24, emerged as a robust predictor for treatment response and short-term outcomes in patients with stage B HCC undergoing DEM- or c-TACE.

Efficacy Analysis of PTCD + TACE vs PTCD + Apatinib in the Treatment of HCC with Obstructive Jaundice: A Retrospective Study.

PURPOSE: The aim was to evaluate the safety and effectiveness of PTCD combined with TACE in the treatment of hepatocellular carcinoma with obstructive jaundice and to compare the efficacy of TACE in patients with different levels of bilirubin after PTCD. METHODS: The clinical data of 141 patients with HCC complicated with obstructive jaundice were analyzed retrospectively. The patients underwent PTCD first. When the total bilirubin decreased, the patients received TACE or Apatinib treatment. They were divided into two groups: (1) PTCD+TACE group, N=68; (2) PTCD+Apatinib group, N=73. RESULTS: The PTCD+TACE group had higher ORR and DCR than the PTCD+Apatinib group (57.4% vs 12.3%, p < 0.001;80.9% vs 60.3%, p = 0.010). The mPFS of the PTCD+TACE group was longer than that of the PTCD+Apatinib group (7.1 months vs 3.8 months, p < 0.001). The mOS of the PTCD+TACE group was longer than that of the PTCD+Apatinib group(11.5 months vs 7.7 months, p < 0.001). In the subgroup analysis of the PTCD+TACE group, the results showed that the survival benefits of the groups with total bilirubin <2 times and 2-3 times were greater. CONCLUSION: In patients with HCC and obstructive jaundice, superselective TACE(lipiodol+epirubicin emulsion) significantly prolonged OS and PFS compared with Apatinib after using PTCD to reduce total bilirubin to <100umol/L. Patients whose total bilirubin dropped to ≤3 times of the upper limit of normal value after PTCD had longer OS and PFS than patients >3 times.

Therapeutic analysis of 632 cases treated by transcatheter arterial chemoembolization combined with ablation in hepatocellular carcinoma: A retrospective study.

OBJECTIVES: This study aims to analyze the efficacy of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation (CA) in hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was conducted on 632 patients with HCC at Barcelona Clinic Liver Cancer Staging (BCLC) System stages 0, A, and B from Beijing You'an Hospital affiliated with Capital Medical University. The primary outcomes analyzed were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes included one-, three-, and five-year OS rates among different groups. RESULTS: The median follow-up period for 632 cases identified with HCC was 52.1 months (range: 3-162 months), while 127 patients died during follow-up. The one-, three-, and five-year OS rates were 97.1 %, 89.5 %, and 80.4 %, respectively. Moreover, the one-, three-, and five-year PFS rates were 58.1 %, 29.3 %, and 19.8 %, respectively. Multivariate analysis revealed that the BCLC stages and complete ablation were independent predictors of OS and PFS (all p < 0.05). Subgroup analysis showed no difference in OS rate among TACE-RFA, TACE-MWA, and TACE-CA groups, but TACE-CA showed better efficacy in improving the PFS rate (all p < 0.05). CONCLUSIONS: The combination of TACE and ablation is effective in early-stage HCC and BCLC stage B. Complete ablation and BCLC stages are significant prognostic factors for PFS and OS. Further research, including randomized controlled trials, is needed to validate these findings.

DEB-TACE versus cTACE for unresectable HCC with B1-type bile duct invasion after successful biliary drainage: A propensity score matching analysis.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Effectiveness and safety of brucea javanica oil assisted TACE versus TACE in the treatment of liver cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: The effectiveness and safety of using Brucea javanica oil (BJO) in combination with Transarterial Chemoembolization (TACE) for liver cancer treatment are subjects of debate. This study aims to assess the comparative effectiveness and safety of BJO-assisted TACE versus TACE alone and quantifies the differences between these two treatment methods. Methods: A systematic search was conducted in multiple databases including PubMed, Cochrane, CNKI, and Wanfang, until 1 July 2023. Meta-analysis was conducted, and the results were presented as mean difference (MD), risk ratio (RR), and 95% confidence intervals (CI). Results: The search yielded 11 RCTs, with a combined sample size of 1054 patients. Meta-analysis revealed that BJO-assisted TACE exhibited superior outcomes compared to standalone TACE. Specific data revealed that BJO-assisted TACE improves clinical benefit rate by 22% [RR = 1.22, 95% CI (1.15, 1.30)], increases the number of people with improved quality of life by 32%, resulting in an average score improvement of 9.53 points [RR = 1.32, 95% CI (1.22, 1.43); MD = 9.53, 95% CI (6.95, 12.10)]. Furthermore, AFP improvement rate improved significantly by approximately 134% [RR = 2.34, 95% CI (1.58, 3.46)], accompanied by notable improvements in liver function indicators, with an average reduction of 27.19 U/L in AST [MD = -27.19, 95% CI (-40.36, -14.02)], 20.77 U/L in ALT [MD = -20.77, 95% CI (-39.46, -2.08)], 12.17 µmol/L in TBIL [MD = -12.17, 95% CI (-19.38, -4.97)], and a decrease of 43.72 pg/mL in VEGF [MD = -43.72, 95% CI (-63.29, -24.15)]. Most importantly, there was a 29% reduction in the occurrence of adverse reactions [RR = 0.71, 95% CI (0.60, 0.84)]. Conclusion: These findings indicate that BJO-assisted TACE may be considered as a potentially beneficial treatment option for liver cancer patients when compared to standalone TACE. It appears to contribute to improved treatment outcomes, enhanced quality of life, and potentially reduced adverse reactions, suggesting it warrants further investigation as a promising approach for liver cancer treatment. Systematic Review Registration: identifier CRD42023428948.

Radiomics analysis based on contrast-enhanced MRI for predicting short-term efficacy of drug-eluting beads transarterial chemoembolization in hepatocellular carcinoma.

OBJECTIVE: We developed and validated a clinical-radiomics model for preoperative prediction of the short-term efficacy of initial drug-eluting beads transarterial chemoembolization (D-TACE) treatment in patients with hepatocellular carcinoma (HCC). METHODS: In this retrospective cohort study of 113 patients with intermediate and advanced HCC, 5343 features were extracted based on three sequences of the arterial phase (AP), diffusion-weighted imaging, and T2-weighted images based on contrast-enhanced magnetic resonance imaging, and minimum redundancy maximum correlation and least absolute shrinkage and selection operator (LASSO) regression were applied for feature selection and model construction. Multifactor logistic regression was used to build a clinical-imaging model based on clinical factors and a clinical-radiomics model. The area under the curve (AUC) and calibration curves were used to assess model performance, and the clinical value of the model was analyzed using decision curve analysis. The relationship between the actual and predicted short-term efficacy of the combined model and progression-free survival (PFS) was evaluated using Kaplan-Meier survival curves and log-rank tests. RESULTS: A total of 34 radiomics features were selected by LASSO, and the clinical-radiomics model had the best predictive performance (AUC = 0.902 and AUC = 0.845 for the training and testing sets, respectively), and the model based on AP had the best predictive performance among the four radiomics models (AUC = 0.89 for the training set and AUC = 0.85 for the testing set); the multifactorial logistic regression results showed that microsphere type (p = 0.042) and AP Rad-score (p = 0.01) were associated with short-term efficacy. In addition, a difference in PFS was observed in patients with HCC with different short-term efficacies predicted by the combined model. Moreover, prognosis was better in the objective versus non-objective response group. CONCLUSIONS: The combined clinical-radiomics model is an effective predictor of the short-term efficacy of initial D-TACE in patients with HCC, contributing to clinical and economic benefits for patients.

Immunotherapy in gastric cancer with liver metastasis: Challenges and opportunities.

In this editorial, we review the article by Liu et al published in the World Journal of Gastrointestinal Surgery investigating the efficacy and safety of immunotherapy in patients with gastric cancer (GC) and liver metastasis. GC, the fifth most commonly diagnosed malignancy worldwide, presents a significant challenge due to its multifactorial etiology and a grim prognosis for unresectable or recurrent cases. The advent of immune checkpoint inhibitors (ICIs) has revolutionized oncology; yet liver metastasis has been associated with reduced response rates, progression-free survival, and overall survival in various malignancies. The CheckMate-649 and KEYNOTE-859 trials demonstrated promising results with ICIs in advanced GC, particularly in patients with liver metastasis. However, a meta-analysis of liver metastatic solid tumors revealed worse outcomes with ICIs, highlighting the need for further investigation. While combined therapies, including ICIs with local treatments, show promise in improving outcomes, the nuanced landscape of ICIs in liver metastatic GC necessitates continued research for robust conclusions. The current contradictions in the literature underscore the importance of cautious interpretation and the exploration of tailored approaches to enhance clinical efficacy in this challenging patient population.

Clinical efficacy of Gamma Knife® combined with transarterial chemoembolization and immunotherapy in the treatment of primary liver cancer.

BACKGROUND: This study was designed to investigate the clinical efficacy and safety of Gamma Knife® combined with transarterial chemoembolization (TACE) and immunotherapy in the treatment of primary liver cancer. AIM: To investigate the clinical efficacy and safety of Gamma Knife® combined with TACE and immune-targeted therapy in the treatment of primary liver cancer. METHODS: Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected. All patients underwent Gamma Knife® treatment combined with TACE and immunotherapy. The clinical efficacy, changes in liver function, overall survival (OS), and progression-free survival (PFS) of patients with different treatment responses were evaluated, and adverse reactions were recorded. RESULTS: The last follow-up for this study was conducted on October 31, 2023. Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response (PR) in 27 patients, accounting for 52.94% (27/51); stable disease (SD) in 16 patients, accounting for 31.37% (16/51); and progressive disease (PD) in 8 patients, accounting for 15.69% (8/51). The objective response rate was 52.94%, and the disease control rate was 84.31%. Alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment (all P = 0.000). The median OS was 26 months [95% confidence interval (95%CI): 19.946-32.054] in the PR group and 19 months (95%CI: 14.156-23.125) in the SD + PD group, with a statistically significant difference (P = 0.015). The median PFS was 20 months (95%CI: 18.441-34.559) in the PR group and 12 months (95%CI: 8.745-13.425) in the SD + PD group, with a statistically significant difference (P = 0.002). Common adverse reactions during treatment included nausea and vomiting (39.22%), thrombocytopenia (27.45%), and leukopenia (25.49%), with no treatment-related deaths reported. CONCLUSION: Gamma Knife® combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.

Radiofrequency ablation combined with transcatheter arterial chemoembolization for recurrent liver cancer.

BACKGROUND: The recurrence rate of liver cancer after surgery is high. Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) is an effective treatment for liver cancer; however, its efficacy in recurrent liver cancer remains unclear. AIM: To investigate the clinical effect of TACE combined with RFA in the treatment of recurrent liver cancer. METHODS: Ninety patients with recurrent liver cancer were divided into 2 groups according to treatment plan: Control (RFA alone); and experimental [TACE combined with RFA (TACE + RFA)]. The incidence of increased alanine aminotransferase levels, complications, and other indices were compared between the two groups before and after the procedures. RESULTS: One month after the procedures, the short-term efficacy rate and Karnofsky Performance Status scores of the experimental group were significantly higher than those of the control group (P < 0.05). Alpha-fetoprotein (AFP) and total bilirubin levels were lower than those in the control group (P < 0.05); The overall response rate was 82.22% and 66.67% in the experimental and control groups, respectively; The disease control rate was 93.33% and 82.22% in the experimental and control groups, respectively, the differences are statistically significant (P < 0.05). And there were no statistical differences in complications between the two groups (P > 0.05). CONCLUSION: TACE + RFA was effective for the treatment of recurrent liver cancer and significantly reduced AFP levels and improved various indices of liver function.

Omics-imaging signature-based nomogram to predict the progression-free survival of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization.

BACKGROUND: Enhanced magnetic resonance imaging (MRI) is widely used in the diagnosis, treatment and prognosis of hepatocellular carcinoma (HCC), but it can not effectively reflect the heterogeneity within the tumor and evaluate the effect after treatment. Preoperative imaging analysis of voxel changes can effectively reflect the internal heterogeneity of the tumor and evaluate the progression-free survival (PFS). AIM: To predict the PFS of patients with HCC before operation by building a model with enhanced MRI images. METHODS: Delineate the regions of interest (ROI) in arterial phase, portal venous phase and delayed phase of enhanced MRI. After extracting the combinatorial features of ROI, the features are fused to obtain deep learning radiomics (DLR)_Sig. DeLong's test was used to evaluate the diagnostic performance of different typological features. K-M analysis was applied to assess PFS in different risk groups, and the discriminative ability of the model was evaluated using the C-index. RESULTS: Tumor diameter and diolame were independent factors influencing the prognosis of PFS. Delong's test revealed multi-phase combined radiomic features had significantly greater area under the curve values than did those of the individual phases (P < 0.05).In deep transfer learning (DTL) and DLR, significant differences were observed between the multi-phase and individual phases feature sets (P < 0.05). K-M survival analysis revealed a median survival time of high risk group and low risk group was 12.8 and 14.2 months, respectively, and the predicted probabilities of 6 months, 1 year and 2 years were 92%, 60%, 40% and 98%, 90%,73%, respectively. The C-index was 0.764, indicating relatively good consistency between the predicted and observed results. DTL and DLR have higher predictive value for 2-year PFS in nomogram. CONCLUSION: Based on the multi-temporal characteristics of enhanced MRI and the constructed Nomograph, it provides a new strategy for predicting the PFS of transarterial chemoembolization treatment of HCC.

Transarterial Chemoembolization Treatment Paradigms for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for 90% of liver cancer cases worldwide and is currently the most quickly increasing cause of cancer-related deaths in the United States. The 5-year survival rate for primary liver cancer is estimated to be below 20%, and HCC mortality is expected to increase by 41% by 2040. Currently, surgical resection is the first-line approach to definitive treatment of early-stage HCC. However, the majority of patients present with late-stage, unresectable disease due to the asymptomatic nature of early HCC. For patients who present with unresectable HCC, locoregional therapies such as transarterial chemoembolization (TACE) represent an alternative approach to HCC treatment. TACE is a minimally invasive, catheter-based technique that allows for targeted delivery of chemotherapy to tumor sites while occluding tumor-feeding blood vessels. In appropriately selected patients, outcomes for TACE therapy have been shown to be more favorable than supportive care or conservative management. The increasing incidence and mortality of HCC, in addition to the late-stage presentation of most HCC patients, demonstrates the need to expand the role of locoregional therapies in the treatment of HCC. TACE represents an appealing approach to HCC management, including disease control, palliation, and potentially curative-intent strategies. In this review, we will describe the current utility of TACE in the treatment of HCC, characterize the outcomes of patients treated with TACE across different HCC stages, and outline future applications of TACE in the treatment paradigm.

Biodegradable Microembolics with Nanografted Polyanions Enable High-Efficiency Drug Loading and Sustained Deep-Tumor Drug Penetration for Locoregional Chemoembolization Treatment.

Transarterial chemoembolization (TACE), the mainstay treatment of unresectable primary liver cancer that primarily employs nondegradable drug-loaded embolic agents to achieve synergistic vascular embolization and locoregional chemotherapy effects, suffers from an inferior drug burst behavior lacking long-term drug release controllability that severely limits the TACE efficacy. Here we developed gelatin-based drug-eluting microembolics grafted with nanosized poly(acrylic acid) serving as a biodegradable ion-exchange platform that leverages a counterion condensation effect to achieve high-efficiency electrostatic drug loading with electropositive drugs such as doxorubicin (i.e., drug loading capacity >34 mg/mL, encapsulation efficiency >98%, and loading time <10 min) and an enzymatic surface-erosion degradation pattern (∼2 months) to offer sustained locoregional pharmacokinetics with long-lasting deep-tumor retention capability for TACE treatment. The microembolics demonstrated facile microcatheter deliverability in a healthy porcine liver embolization model, superior tumor-killing capacity in a rabbit VX2 liver cancer embolization model, and stabilized extravascular drug penetration depth (>3 mm for 3 months) in a rabbit ear embolization model. Importantly, the microembolics finally exhibited vessel remodeling-induced permanent embolization with minimal inflammation responses after complete degradation. Such a biodegradable ion-exchange drug carrier provides an effective and versatile strategy for enhancing long-term therapeutic responses of various local chemotherapy treatments.

Relaxin combined with transarterial chemoembolization achieved synergistic effects and inhibited liver cancer metastasis in a rabbit VX2 model.

OBJECTIVE: To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE). MATERIALS AND METHODS: HCCLM3 and Huh-7 cells were adopted to evaluate the effect of tumor proliferation, migration, and invasion after RLX administration in vitro. The rabbit VX2 model was used to evaluate the biosafety, doxorubicin penetration, local tumor response, tumor metastasis, and survival benefit of RLX combined with TACE treatment. RESULTS: RLX did not affect the proliferation, migration, or invasion of HCCLM3 and Huh-7 cells, and the expression of E-cadherin and HIF-1α also remained unchanged while the MMP-9 protein was upregulated in vitro. In the rabbit VX2 model, compared to the normal saline group (NS), RLX group (RLX) and TACE mono-therapy group (TACE), the group that received TACE combined with RLX (TACE + RLX) showed an improved local tumor response and survival benefit. Furthermore, TACE combined with RLX was found to reduce tumor metastasis. This combination therapy reduced the fibrotic extracellular matrix in the tumor microenvironment, allowing for better penetration of doxorubicin, improved infiltration of CD8+ T cells and affected the secretion of cytokines. Additionally, RLX combined with TACE was able to decrease the expression of HIF-1α and PD-L1. The biosafety of TACE combined with RLX was also confirmed. CONCLUSION: RLX synergized with TACE by mitigating the fibrotic extracellular matrix and tumor hypoxic microenvironment, improving the therapeutic effect and inhibiting metastasis during the treatment of liver cancer.

Amount of ascites impacts survival in patients with hepatocellular carcinoma undergoing transarterial chemoembolization advocating for volumetric assessment.

Preliminary work has shown that portal hypertension plays a key role for the prognosis in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Specifically, the presence of ascites appears to be a strong negative predictor for these patients. However, it remains unclear whether different ascites volumes influence prognosis. Therefore, the aim of this work was to investigate the influence of different ascites volumes on survival for patients with HCC undergoing TACE. A total of 327 treatment-naïve patients with HCC undergoing initial TACE at our tertiary care center between 2010 and 2020 were included. In patients with ascites, the fluid was segmented, and the volume quantified by slice-wise addition using contrast-enhanced CT imaging. Median overall survival (OS) was calculated and univariate and multivariate Cox regression analysis has been performed. Ascites was present in 102 (31.9%) patients. Ascites volume as continuous variable was significantly associated with an increased hazard ratio in univariate analysis (p < 0.001) and remained an independent predictor of impaired median OS in multivariate analysis (p < 0.001). Median OS without ascites was 17.1 months, and therefore significantly longer than in patients with ascites (6.4 months, p < 0.001). When subdivided into groups of low and high ascites volume in relation to the median ascites volume, patients with low ascites volume had a significantly longer median OS (8.6 vs 3.6 months, p < 0.001). Ascites in patients with HCC undergoing TACE is strongly associated with a poor prognosis. Our results show that not only the presence but also the amount of ascites is highly relevant. Therefore, true ascites volume as opportunistic quantitative biomarker is likely to impact clinical decision-making once automated solutions become available.

Effectiveness and safety of vascular intervention plus lenvatinib versus vascular intervention alone for hepatocellular carcinoma patients with portal vein tumor thrombus: a retrospective comparative study.

Background: This study aimed to assess the effectiveness and safety of vascular intervention combined with lenvatinib versus vascular intervention alone in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to identify prognostic factors associated with the treatment outcomes. Methods: We conducted a retrospective analysis of data from 92 patients with advanced HCC and PVTT who were treated between February 2016 and February 2023. Among them, 56 patients underwent vascular intervention alone (transarterial chemoembolization, TACE), while 36 patients received vascular intervention (TACE or hepatic arterial infusion chemotherapy [HAIC]) combined with lenvatinib. The primary outcomes included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Survival rates were estimated by the Kaplan-Meier method, and confounders were adjusted using inverse probability of treatment weighting (IPTW). Prognostic factors were determined through the Cox regression model. Results: The median follow-up duration was 20.07 months (interquartile range: 6.41-25.36). The combination therapy group had a significantly longer median PFS (11.00 vs. 5.00 months, P<0.05) and OS (12.91 vs. 6.83 months, P<0.05) in comparison to the monotherapy group, and these findings remained consistent after IPTW matching. Moreover, the combination therapy group showed a higher ORR (55.56% vs. 26.79%, P<0.05) based on mRECIST criteria. Cox multivariate analysis identified extrahepatic metastasis and maximum tumor diameter as risk factors for PFS, while age, tumor number, and maximum tumor diameter influenced OS. Combined treatment emerged as a protective factor for OS. In the combination therapy group, hypertension was the most frequent adverse event, with grade 3 or 4 adverse events occurring rarely. Conclusion: The combination of vascular intervention with lenvatinib has demonstrated improved PFS and OS in advanced HCC patients with PVTT, and its safety profile appears to be acceptable. Adoption of this combined treatment strategy at an earlier stage may enhance patient outcomes.

Efficacy and safety of TACE combined with tyrosine kinase inhibitors and camrelizumab for unresectable hepatocellular carcinoma: A systematic review and meta­analysis.

Transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and camrelizumab (collectively: T-T-C) is a novel treatment strategy for unresectable hepatocellular carcinoma (HCC). The present systematic review and meta-analysis aimed to evaluate the efficacy and safety of T-T-C compared with TACE combined with TKIs only (T-T) in the treatment of patients with unresectable HCC. A systematic literature search was conducted on T-T and T-T-C using PubMed, Embase and the Cochrane Library. Data regarding the clinical outcome, including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs), were independently extracted and analyzed by two researchers using standardized protocols. In total, 7 cohort studies, including 1,798 patients (T-T-C, 838; T-T, 960), were included in the meta-analysis. The results of the present study demonstrated that the T-T-C group had significantly prolonged OS [hazard ratio (HR), 0.38; 95% confidence interval (CI), 0.29-0.50; I2=61.5%; P=0.016)] and PFS (HR, 0.37; 95% CI, 0.30-0.46; I2=44.5%; P=0.109), and showed significantly higher objective response rates [risk ratio (RR), 0.82; 95% CI, 0.69-0.96; I2=25.1%; P=0.237)] and slightly higher disease control rates without a significant difference (RR, 0.96; 95% CI, 0.89-1.03; I2=0.0%; P=0.969). In addition, grade 3/4 AEs were more common in the T-T group, including hypertension (RR, 1.15; 95% CI, 0.85-1.56), vomiting or nausea (RR, 0.88; 95% CI, 0.44-1.76) and pain (RR, 0.74; 95% CI, 0.45-1.21); however, these results were not statistically significant. In conclusion, compared with T-T combination therapy, T-T-C demonstrated a notable advantage in terms of OS, PFS, ORR and DCR in patients with unresectable HCC. For manageable AEs, although the results were not statistically significant, the incidence of AEs in the T-T group was higher than that in the T-T-C group in terms of event probability.