The efficacy of adding programmed death-1 (PD-1) inhibitors to transcatheter arterial chemoembolization (TACE) combined with apatinib for advanced hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the efficacy of incorporating PD-1 inhibitors into TACE combined with apatinib.

Relevant literature on TACE combined with apatinib plus PD-1 inhibitors for advanced HCC was searched in PubMed, Cochrane Library, Embase, and Web of Science databases. Trial sequential analysis (TSA) was conducted to minimize randomization errors and assess whether the meta-analysis provided conclusive evidence.

Six studies involving 1,452 patients were included. Compared with the TACE combined with apatinib treatment group (T-A), TACE combined with apatinib plus PD-1 inhibitors (T-A-P) significantly prolonged overall survival (OS) (Hazard Ratio [HR] 2.22, 95% Confidence Interval [CI] 1.93-2.56; p < 0.001) and progression-free survival (PFS) (HR 2.36, 95% CI 2.01-2.77; p < 0.001), while also improving the objective response rate (ORR) (risk ratios [RR] 1.60, 95% CI 1.20-2.14; p < 0.001) and disease control rate (DCR) (RR 1.06, 95% CI 1.00-1.12; p < 0.001). TSA results indicated that additional studies were required to confirm the significance of DCR. Prognostic analysis identified treatment regimen and extrahepatic metastasis as common independent risk factors for OS and PFS. The incidence of adverse events in the T-A-P treatment group was comparable to that in the T-A treatment group.

Adding PD-1 inhibitors to TACE combined with apatinib significantly prolonged OS and PFS, particularly in patients without extrahepatic metastases. It also improved ORR and DCR in patients with HCC.

Proliferative hepatocellular carcinoma (HCC) is an aggressive phenotype associated with unfavorable clinical outcomes. Predicting the preoperative subtype of HCC can aid in the development of individualized treatment. We retrospectively recruited 180 HCC patients who underwent hepatic resection and established a CT-based radiomics model for predicting proliferative HCCs. The evaluation of tumor response to transarterial chemoembolization therapy and progression-free survival (PFS) according to the radiomics model was further performed in internal (n = 54) and external (n = 80) outcome cohorts. In our study, 98 of 180 (54%) patients were confirmed to have proliferative HCCs. The radiomics model comprising 9 radiomic features and exhibited good performance for predicting proliferative HCCs. The nomogram integrated radiomics and serum α-fetoprotein level showed good calibration and discrimination in both the training cohort (AUC = 0.848) and the validation cohort (AUC = 0.825). Predicted proliferative HCCs (high radiomics scores) were associated with lower response rate (P < 0.05) and worse PFS (P < 0.05) compared to predicted non-proliferative HCCs in outcomes cohorts. We linked radiomics model to gene expression, unveiling that activated/immature B cells and tertiary lymphoid structures were downregulated in the high radiomics group. The proposed CT radiomics model exhibited good performance for identifying proliferative HCCs, which may facilitate clinical decision-making. Our findings suggest a potential correlation between proliferative HCC and immunosuppressive tumor microenvironment.

There is still no noninvasive, automated, and accurate model for guiding physicians in the decision-making of transarterial chemoembolization combined with microwave ablation (TACE-MWA) in intermediate-stage hepatocellular carcinoma (HCC).

To develop a prognostic score based on the tumor burden and radiomic features for the prediction of the long-term survival of patients with intermediate-stage HCC after TACE-MWA.

From June 2008 to October 2022, a total of 2189 consecutive patients from seven tertiary-care hospitals with intermediate-stage HCC who received initial TACE combined with MWA were enrolled. Among them, 2189 were divided into training cohort (N = 1753), and internal test cohort (N = 436) in a single center, and 316 patients were assigned to external test cohort in another 6 centers. A prognostic scoring system was constructed using tumor burden and radiologic features (TBR) and compared with conventional predicting systems.

In training cohort, multivariate Cox regression analysis suggested that tumor burden (hazard ratio (HR), 0.693; 95% confidence interval (CI): 0.505, 0.814; 1 point per 1.0 increase, p = 0.024), radiologic features (HR, 0.349; 95% CI: 0.236, 0.517; p < 0.001), and alpha-fetoprotein (HR, 1.629; 95% CI: 1.280, 2.073; p < 0.001) were independent prognostic factors for OS. A prognostic model that comprises TBR was built, which showed significantly higher AUC values than other clinical stagings in all three cohorts. Moreover, the TBR score provided greater net benefit across the range of reasonable threshold probabilities than other models. Based on cutoff values of 32 and 74 centiles of the TBR score, the cohort was divided into low-, middle-, and high-risk strata, which provide consistent performance in survival discrimination across different patient subgroups.

The TBR score serves as an efficient instrument for risk stratification, guiding the course of adjuvant targeted and immunotherapies for HCC patients undergoing TACE-MWA combined treatment.

A retrospective, multi-institutional study.

Background/Objectives: The Barcelona Clinic Liver Cancer (BCLC) staging system for hepatocellular carcinoma (HCC) was updated in 2022 to refine patient stratification, particularly in patients with intermediate-stage (BCLC B) HCC. Although transarterial chemoembolization (TACE) remains a key treatment for these patients, there is no prognostic model for survival outcomes based on the pretreatment factors of patients who meet the updated 2022 BCLC indications for TACE. The aim of this study was to develop a pretreatment risk model predicting overall survival (OS) in patients with intermediate-stage HCC and reclassified as candidates for TACE according to the updated 2022 BCLC criteria. Methods: This retrospective study included 658 HCC patients treated with first-line TACE according to the updated BCLC 2022 guidelines. Pretreatment factors such as the Child-Pugh score, tumor burden (up-to-11 criteria), bilobar tumor involvement, and serum alpha-fetoprotein (AFP) levels were analyzed. Cox proportional hazards models were used to identify significant predictors of OS, with these factors subsequently incorporated into a risk prediction model. Results: Significant predictors of OS included Child-Pugh score ≥ 7, bilobar tumor involvement, beyond up-to-11 criteria, and AFP ≥ 400 ng/mL. A risk model was developed using these factors, stratifying patients into low-, intermediate-, and high-risk groups. The median OS in the low-, intermediate-, and high-risk groups was 53, 35, and 21 months, respectively. Conclusions: The proposed pretreatment risk prediction model may be useful for predicting OS and guiding TACE candidacy in intermediate-stage HCC patients based on the updated 2022 BCLC guidelines.

An effective model for risk stratification and prognostic assessment of early hepatocellular carcinoma (HCC) patients following microwave ablation (MWA) is lacking in clinical practice. The aim of this study is to develop and validate a prognostic model specifically for these patients.

Between January 2008 and December 2018, 345 treatment-naïve patients with HCC conforming to the Milan criteria who underwent MWA were enrolled and randomly assigned to the training (n=209) and validation (n=136) cohorts. The nomogram model was constructed based on the predictors assessed by the multivariate Cox proportional hazards model and validated. Predictive accuracy and discriminative ability were further evaluated and compared with other prognostic models.

After a median follow-up of 59.0 months, 52.5% (187/356) of the patients had died. Prognostic factors for overall survival (OS) were α-fetoprotein (AFP), albumin-bilirubin (ALBI) score, platelets, and ablation margins, which generated the nomograms. The nomogram model consistently achieved good calibration and discriminatory ability with a concordance index of 0.64 (95% confidence interval (CI): 0.59-0.69) and 0.69 (95% CI: 0.63-0.75) in both the training and validation cohorts. The performance of the nomogram model also outperformed other prognostic models. By using the nomogram model, the patient population could be correctly divided into low- and high-risk strata presenting significantly different median OS of 105.0 (95% CI: 84.1-125.9) months, and 45.0 (95% CI: 28.0-62.0) months, respectively.

The nomogram model based on AFP, PLT, ablation margins, and ALBI score was a simple visualization model that could stratify patients with early-stage HCC after MWA and predict individualized long-term survival with favorable performance.

To assess tumor progression in patients with hepatocellular carcinoma (HCC) without macrovascular invasion who underwent treatment with conventional transarterial chemoembolization (cTACE) based on microvascular invasion (MVI) risk within 2 years.

This retrospective investigation comprised adult patients with HCC who had either liver resection or cTACE as their first treatment from January 2016 to December 2021. A predictive model for MVI was developed and validated using preoperative clinical and MRI data from patients with HCC treated with liver resection. The MVI predictive model was applied to patients with HCC receiving cTACE, and differences in tumor progression between the MVI high- and low-risk groups were examined throughout 2 years.

The MVI prediction model incorporated nonsmooth margin, intratumoral artery, incomplete or absent tumor capsule, and tumor DWI/T2WI mismatch. The area under the receiver operating characteristic curve (AUC) for the prediction model, in the training cohort, was determined to be 0.904 (95% CI, 0.862-0.946), while in the validation cohort, it was 0.888 (0.782-0.994). Among patients with HCC undergoing cTACE, those classified as high risk for MVI possessed a lower rate of achieving a complete response after the first tumor therapy and a higher risk of tumor progression within 2 years.

The MVI prediction model developed in this study demonstrates a considerable degree of accuracy. Patients at high risk for MVI who underwent cTACE treatment exhibited a higher risk of tumor progression within 2 years.

The optimal prognostic assessment for patients with hepatocellular carcinoma (HCC) after drug-eluting bead transarterial chemoembolization (DEB-TACE) remains unclear. This study aimed to propose a novel staging system in comparison with the current staging systems for HCC following DEB-TACE.

From four centers, patients with HCC undergoing DEB-TACE as the initial therapy were retrospectively included and classified into training and validation sets. Multivariable regression was used to determine the independent prognostic factors in the training set. A novel staging system incorporating the independent factors was proposed and externally validated in terms of discrimination and calibration compared to other staging systems in both sets.

The training and validation sets included 335 and 99 patients, respectively. Multivariable regression revealed independent factors including alpha-fetoprotein level, aspartate aminotransferase to lymphocyte count ratio index, maximum tumor diameter, Child-Pugh class, and portal vein invasion. The novel prognostic staging system, named PADCA, was proposed and outperformed other staging systems with the highest C-index, area under the curve, Wald test value, clinical benefit, and the lowest Akaike information criterion in the training and validation sets.

The PADCA staging system has a superior prognostic predictive ability compared to the current staging systems. PADCA can assist clinicians in screening out the patients most likely to derive benefit from DEB-TACE and guiding the formulation of therapy and follow-up strategy.

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.

Post-transarterial chemoembolization liver failure (PTLF) is a potentially fatal complication of transarterial chemoembolization (TACE). Accurate preoperative prediction of PTLF is crucial for improving patient outcomes. This study aimed to develop and validate a prediction model based on the functional liver imaging score (FLIS) to assess the risk of PTLF.

A total of 156 patients underwent Gadoxetic acid-enhanced MRI within four weeks before TACE. Two radiologists, unaware of the clinical data, independently assessed FLIS on hepatobiliary phase images to quantitatively assess liver function. Univariate and multivariate logistic regression analyses identified independent predictors of PTLF. A nomogram was developed and subjected to internal validation through bootstrap resampling of 1000 samples. The model's performance was conducted through the area under the curve (AUC), Hosmer-Lemeshow test, calibration curves, and decision curve analysis (DCA). P< 0.05 was considered statistically significant.

PTLF occurred in 37.2% of patients (58/156). Significant differences were observed in factors such as portal vein thrombosis, albumin, aspartate transaminase, international normalized ratio (INR), model for end-stage liver disease scoring, albumin-bilirubin score, and FLIS. Multivariate analysis showed FLIS, portal vein thrombosis, and INR as independent predictors. The model achieved an AUC of 0.759, with 87.8% specificity and 56.9% sensitivity, and demonstrated good calibration (χ² = 7.101, P=0.526). Calibration curves and DCA confirmed its clinical utility.

This FLIS-based prediction model performs well in predicting PTLF, potentially serving as a practical clinical tool.

Cytokeratin 19 (CK19)-positive HCC is a subtype of hepatocellular carcinoma (HCC) with poor biological behavior and resistance to different treatments including transarterial chemoembolization (TACE). The current study aimed to investigate the predictive value of serum CK 19 fragment 21-1 (CYFRA 21-1) and serum CK 19 fragment 2G2 (CK 19-2G2) for TACE response in patients with hepatitis C virus (HCV)-related HCC.

This prospective study assessed the pretreatment serum CYFRA 21-1 and CK 19-2G2 levels in 64 patients with HCV-related naïve HCC who underwent TACE to predict 1-year overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Additionally, 40 healthy individuals were included as controls. Pretreatment alpha-fetoprotein (AFP) was also measured for comparison.

After exclusions, 60 patients completed TACE sessions, and the 1-year OS was 52%, and ORR post TACE was 71.8%. HCC patients with elevated levels of CYFRA 21-1, CK 19-2G2, or baseline AFP measuring ≥400 ng/ml have decreased 1-year OS and PFS after TACE. Serum CK19-2G2 was an independent predictor of 1-year OS using multivariate hazard regression analysis. Pretreatment normal serum CYFRA 21-1 levels (P = 0.047), serum AFP measuring <400 ng/ml (P = 0.016), and lower AST (P = 0.002) were independent predictors of ORR to TACE using multivariate logistic regression analysis. The predictive ability of pretreatment elevated serum CYFRA 21-1, AFP measuring ≥400 ng/ml, AFP + CYFRA 21-1, AFP + CK 19-2G2, or AFP + CYFRA 21-1+ CK19-2G2 to predict nonresponse (progressive disease) to TACE (area under the curve = 0.795, 0.690, 0.830, 0.725, and 0.850, respectively).

This study demonstrated that incorporating the measurement of serum CYFRA 21-1 or CK19-2G2 levels, along with AFP, during the initial diagnosis can aid in predicting poor 1-year OS, PFS, and ORR to TACE in patients with HCV-related HCC.

Stereotactic body radiation therapy (SBRT) is an emerging treatment for hepatocellular carcinoma (HCC), which provides excellent local control (LC) and prolongs overall survival (OS). However, in current guidelines, transcatheter arterial chemoembolization (TACE) has been proposed as a key treatment option for patients with early- and intermediate-stage HCC, whereas SBRT is not. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials and retrospective studies using the propensity score (PS) to compare the outcomes of SBRT and TACE for HCC in a balanced manner. We systematically searched the PubMed, Cochrane, EMBASE, and Web of Science databases to identify randomized controlled trials and studies comparing SBRT and TACE using PS analysis. The hazard ratios (HRs) for OS and LC were pooled. The heterogeneity between the data collected from these studies was also assessed. SBRT led to a comparable OS (HR: 0.83; 95 % confidence interval (CI): 0.52-1.34; p = 0.44) to TACE, and significantly improved LC (HR: 0.25; 95 % CI: 0.09-0.67; p = 0.006). Considerable heterogeneity was observed in the HR of OS and LC. Although there was no significant difference in the rate of grade 3 or higher toxicities between TACE and SBRT, or between studies, liver toxicity was identified as a common adverse event associated with both SBRT and TACE. Compared to TACE, SBRT showed a comparable OS and improved LC without serious toxicity. Therefore, SBRT should be considered an effective treatment option for various stages of HCC, depending on the tumor factors and pretreatment liver function.

Current prognostic models for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) are not extensively validated and widely accepted. We aimed to develop and validate a continuous model incorporating tumor burden and biology for individual survival prediction and risk stratification.

Overall, 4,377 treatment-naive candidates for whom TACE was recommended, from 39 centers in five countries, were enrolled and divided into training, internal validation, and two external validation datasets. The novel model was developed using a Cox multivariable regression analysis and compared with our original 6-and-12 model (the largest tumor size [ts, centimetres] + tumor number [tn]) and other available models in terms of predictive accuracy.

The proposed model, named the '6-and-12 model 2.0', was generated as 'ts + tn + 1.5×log10 alpha-fetoprotein (AFP)', showed good discrimination (C-index 0.674) and calibration (Hosmer-Lemeshow test p = 0.147), and outperformed current existing models. An easy-to-use stratification was proposed according to the different AFP levels (≤100, 100-400, 400-2,000, 2,000-10,000, 10,000-40,000, and >40,000 ng/ml) along with the corresponding tumor burden cutoffs (8/14, 7/13, 6/12, 5/11, 4/10, and any tumor burden); that is, if the AFP level was 400-2,000 ng/ml, the stratification should be low-(≤6)/intermediate-(6-12)/high-risk (>12) strata. Hence, it could divide the patients into three distinct risk categories with a median overall survival of 45.0 (95% CI, 40.1-49.9), 30.0 (95% CI, 26.1-33.9), and 15.4 (95% CI, 13.4-17.4) months (p <0.001) from low-risk to high-risk strata, respectively. These findings were confirmed in validation and subgroup analyses.

The 6-and-12 model 2.0 significantly improved individual outcome predictions and better stratified the candidates recommended for TACE; thus, this model could be used in both clinical practice and trial design.

In this international multicentre study, we developed and internally and externally validated a novel outcome prediction model for candidates with HCC who would be ideal for TACE. The model, called the 6-and-12 model 2.0, was based on 4,377 patients from 39 centers in five countries. The model offers individualized outcome prediction, outperforming the original 6-and-12 model score and other existing metrics across all datasets and subsets. Based on different levels of alpha-fetoprotein (AFP) and corresponding cut-offs of tumor burden, patients could be stratified into three risk strata with significantly different survival prognoses, which could provide a referential framework to control study heterogeneity and define the target population in future trial designs.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide and lacks biomarkers for personalized therapy. Herein, it is reported that MCB1 could be a novel oncofetal protein that is upregulated in the preneoplastic lesions and serum of early HCC patients. Functional studies reveal that MCB1 modulated p53 protein degradation to promote T-IC generation and drive HCC initiation. Furthermore, the MCB1/p53 axis is shown to determine the responses of hepatoma cells to conventional chemotherapeutics and predict transcatheter arterial chemoembolization (TACE) benefits in patients. Importantly, MCB1 can mediate sorafenib/lenvatinib resistance by downregulating two essential drug targets fibroblast growth factor receptor 1 (FGFR1) and vascular endothelial growth factor receptor 3 (VEGFR3) expression in a proteasome-dependent manner. Patient-derived tumor organoids (PDOs), patient-derived xenografts (PDXs), and patient cohorts analysis suggested that MCB1 levels in HCCs may determine the distinct responses to conventional therapeutics and targeted drugs. Furthermore, treatment of targeted drugs-resistant HCC with adeno-associated virus (AAV) targeting MCB1 or a proteasome inhibitor restores targeted drug response, suggesting their clinical significance in HCC combinational therapy. In conclusion, these findings demonstrate that MCB1 could act as a driver for HCC initiation, a contributor to drug resistance, and a biomarker for individualized HCC therapy.

The goal of this study was to compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with targeted therapy and PD-(L)1 blockade (triple therapy), either sequentially (SE) or simultaneously (SI), in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC).

From January 1, 2018, to June 1, 2022, 575 patients with BCLC stage C HCC who underwent SE or SI triple therapy were retrospectively enrolled. Propensity score matching (PSM; 1:1) was performed to eliminate possible confounder imbalances across cohorts. We used the Kaplan-Meier method and a log-rank test to compare the overall survival (OS) and progression-free survival (PFS) rates between the SI and SE groups. The tumor response and the incidence of adverse events (AEs) were reported. After PSM, 182 patients in each of the two groups were matched. The median OS in the SI group was significantly longer than that in the SE group (28.8 vs. 16.1 months; P = 0.002), and the median PFS was significantly improved in the SI versus SE group (9.6 vs. 7.0 months; P = 0.01). The objective response rate based on the mRECIST was higher in the SI group (58% vs. 37%; P < 0.001). The total incidences of grade 3-4 AEs were 111/182 (60.9%) and 128/182 (70.3%) in the SE and SI groups, respectively. No grade 5 AEs were reported in either group.

Simultaneous HAIC plus targeted therapy and PD-(L)1 blockade significantly improved outcomes compared to the sequential regimen in patients with BCLC stage C HCC, with no unexpected AEs.

The patients who received hepatic arterial infusion chemotherapy combined with targeted therapy and PD-(L)1 blockade simultaneously have a better prognosis than those who received it sequentially.

Transarterial chemoembolization (TACE) is recommended as a palliative treatment for patients of the B stage of the Barcelona Clinic Liver Cancer (BCLC) classification.

To identify clinical, biological, and radiological predictors of survival in patients undergoing TACE and develop a pre-therapeutic prognostic score.

191 adult cirrhotic patients treated for HCC with TACE at the University Hospital (UH) of Clermont-Ferrand (France) from 2007-2017 were retrospectively included. We investigated the impact of baseline liver function, patient characteristics, and tumor burden on overall survival and developed a prognostic score.

Patients had a median age of 66 years and 126 patients were Child A. The AFP-DIAM score distinguishes two groups with a significant difference in survival time (median OS 28.3 months in patients with a score = 0 versus 17.7 months in patients with a score > 0). AFP-DIAM was validated on an external cohort, is well calibrated, and has the best discrimination capacity (C-index) as compared to NIACE, HAP, STATE, and SIX TO TWELVE. AFP-DIAM and SIX TO TWELVE are the more easy-to-use scores. When AFP-DIAM and the SIX TO TWELVE scores were tested in the same statistical model, results confirmed a better AFP-DIAM performance.

The AFP-DIAM is an easy-to-use score which allows to distinguish two groups with different prognosis before the first TACE session. Its use could provide further support to BCLC system to guide the therapeutic strategy of patients with HCC.

Hepatocellular carcinoma (HCC) represents a significant global health problem, requiring precise prognostic tools for optimal treatment stratification. This study aimed to develop a new risk prediction score, called AD score, based on the serum markers alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), to offer an objective and accurate preoperative assessment of HCC in patients undergoing transarterial chemoembolization (TACE).

This was a retrospective study that included 295 HCC patients who were subjected to TACE (training set, n=147; testing set, n=148). Serum AFP and DCP levels were log-transformed to construct the AD score. Multivariate Cox regression analysis on cirrhosis subgroups validated the objectivity of the model. Performance comparison of established models (Child Pugh, BCLC, ALBI, Up-to-seven, Six-and-twelve, Four and seven, HAP score, mHAP-II, FAIL-T score), was assessed through time-dependent receiver operating characteristic (ROC) curves and risk stratification.

The AD score, incorporating lgAFP and lgDCP, demonstrated superior predictive accuracy than the existing models. Time-dependent ROC curve revealed the consistent superiority of the AD score over a 5-year period. The risk stratification into low, intermediate, and high group based on the AD score showed a significant survival difference in both training and testing set.

For HCC patients undergoing TACE, the AD score serves as an objective and straightforward prognostic tool, enhancing predictive accuracy and showcasing its clinical utility. It demonstrates potential significance as a crucial addition to preoperative risk assessment for TACE.

Transarterial chemoembolization (TACE) plus molecular targeted therapies has emerged as the main approach for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). A robust model for outcome prediction and risk stratification of recommended TACE plus molecular targeted therapies candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients.

A retrospective analysis was conducted on 384 patients with HCC and PVTT who underwent TACE plus molecular targeted therapies at 16 different institutions. We developed and validated a new prognostic score which called ABPS score. Additionally, an external validation was performed on data from 200 patients enrolled in a prospective cohort study.

The ABPS score (ranging from 0 to 3 scores), which involves only Albumin-bilirubin (ALBI, grade 1: 0 score; grade 2: 1 score), PVTT(I-II type: 0 score; III-IV type: 1 score), and systemic-immune inflammation index (SII,<550 × 1012: 0 score; ≥550 × 1012: 1 score). Patients were categorized into three risk groups based on their ABPS score: ABPS-A, B, and C (scored 0, 1-2, and 3, respectively). The concordance index (C-index) of the ABPS scoring system was calculated to be 0.802, significantly outperforming the HAP score (0.758), 6-12 (0.712), Up to 7 (0.683), and ALBI (0.595) scoring systems (all P < 0.05). These research findings were further validated in the external validation cohorts.

The ABPS score demonstrated a strong association with survival outcomes and radiological response in patients undergoing TACE plus molecular targeted therapy for HCC with PVTT. The ABPS scoring system could serve as a valuable tool to guide treatment selection for these patients.

With continuous advancements in interventional radiology, considerable progress has been made in transarterial therapies for hepatocellular carcinoma (HCC) in recent years, and an increasing number of research papers on transarterial therapies for HCC have been published. In this editorial, we comment on the article by Ma et al published in the recent issue of the World Journal of Gastro intestinal Oncology: "Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC". We focus specifically on the current research status and future directions of transarterial therapies. In the future, more studies are needed to determine the optimal transarterial local treatment for HCC. With the emergence of checkpoint immunotherapy modalities, it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.

Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown efficacy for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, whether DEB-TACE is superior to conventional TACE (cTACE) remains unclear.

This randomized controlled trial aimed to compare the efficacy and safety of DEB-TACE versus cTACE in treating HCC with PVTT.

The study was conducted at a tertiary care center in Southeast China. HCC patients with PVTT were randomized at a 1:1 ratio into the DEB-TACE or cTACE groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and the incidence of adverse events (AEs). An independent review committee assessed the radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). AEs were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Systemic therapies were not restricted.

Between September 2018 and July 2020, 163 patients were randomized to undergo DEB-TACE ( n =82) or cTACE ( n =81). Nine patients were excluded, and 154 patients were included in the final analysis; the median age was 55 years (range, 24-78 years), and 140 (90.9%) were male. The median PFS in the DEB-TACE group was 6.0 months (95% CI, 5.0-10.0) versus 4.0 months (95% CI, 3.0-5.0) in the cTACE group (hazard ratio, 0.63; 95% CI, 0.42-0.95; P =0.027). The DEB-TACE group showed a higher response rate [51 (66.2%) vs. 36 (46.8%); P =0.0015] and a longer median OS [12.0 months (95% CI, 9.0-16.0) vs. 8.0 months (95% CI, 7.0-11.0), P =0.039] than the cTACE group. Multivariate analysis showed that the treatment group, ALBI score, distant metastasis and additional TKIs were the four independent prognostic factors correlated with PFS. In addition, the treatment group, PVTT group and combination with surgery were independently associated with OS. AEs were similar in the two groups, and postembolization syndrome was the most frequent AE.

DEB-TACE is superior to cTACE in treating HCC patients with PVTT, demonstrating improved PFS and OS with an acceptable safety profile, and may thus emerge as a promising treatment strategy for HCC patients with PVTT.

Chinese Clinical Trial Registry ChiCTR1800018035.

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.

Although methods in diagnosis and therapy of hepatocellular carcinoma (HCC) have made significant progress in the past decades, the overall survival (OS) of liver cancer is still disappointing. Machine learning models have several advantages over traditional cox models in prognostic prediction. This study aimed at designing an optimal panel and constructing an optimal machine learning model in predicting prognosis for HCC. A total of 941 HCC patients with completed survival data and preoperative clinical chemistry and immunology indicators from two medical centers were included. The OCC panel was designed by univariate and multivariate cox regression analysis. Subsequently, cox model and machine-learning models were established and assessed for predicting OS and PFS in discovery cohort and internal validation cohort. The best OCC model was validated in the external validation cohort and analyzed in different subgroups. In discovery, internal and external validation cohort, C-indexes of our optimal OCC model were 0.871 (95% CI, 0.863-0.878), 0.692 (95% CI, 0.667-0.717) and 0.648 (95% CI, 0.630-0.667), respectively; the 2-year AUCs of OCC model were 0.939 (95% CI, 0.920-0.959), 0.738 (95% CI, 0.667-0.809) and 0.725 (95% CI, 0.643-0.808), respectively. For subgroup analysis of HCC patients with HBV, aged less than 65, cirrhosis or resection as first therapy, C-indexes of our optimal OCC model were 0.772 (95% CI, 0.752-0.792), 0.769 (95% CI, 0.750-0.789), 0.855 (95% CI, 0.846-0.864) and 0.760 (95% CI, 0.741-0.778), respectively. In general, the optimal OCC model based on RSF algorithm shows prognostic guidance value in HCC patients undergoing individualized treatment.

To develop a model based on whole-liver radiomics features of pre-treatment enhanced MRI for predicting the prognosis of hepatocellular carcinoma (HCC) patients undergoing continued transarterial chemoembolization (TACE) after TACE-resistance.

Data from 111 TACE-resistant HCC patients between January 2014 and March 2018 were retrospectively collected. At a ratio of 7:3, patients were randomly assigned to developing and validation cohorts. The whole-liver were manually segmented, and the radiomics signature was extracted. The tumor and liver radiomics score (TLrad-score) was calculated. Models were trained by machine learning algorithms and their predictive efficacies were compared.

Tumor stage, tumor burden, body mass index, alpha-fetoprotein, and vascular invasion were revealed as independent risk factors for survival. The model trained by Random Forest algorithms based on tumor burden, whole-liver radiomics signature, and clinical features had the highest predictive efficacy, with c-index values of 0.85 and 0.80 and areas under the ROC curve of 0.96 and 0.83 in the developing cohort and validation cohort, respectively. In the high-rad-score group (TLrad-score > - 0.34), the median overall survival (mOS) was significantly shorter than in the low-rad-score group (17 m vs. 37 m, p < 0.001). A shorter mOS was observed in patients with high tumor burden compared to those with low tumor burden (14 m vs. 29 m, p = 0.007).

The combined radiomics model from whole-liver signatures may effectively predict survival for HCC patients continuing TACE after TACE refractoriness. The TLrad-score and tumor burden are potential prognostic markers for TACE therapy following TACE-resistance.

Transarterial chemoembolization (TACE) represent the standard of therapy for non-operative hepatocellular carcinoma (HCC), while prediction of long term treatment outcomes is a complex and multifactorial task. In this study, we present a novel machine learning approach utilizing radiomics features from multiple organ volumes of interest (VOIs) to predict TACE outcomes for 252 HCC patients. Unlike conventional radiomics models requiring laborious manual segmentation limited to tumoral regions, our approach captures information comprehensively across various VOIs using a fully automated, pretrained deep learning model applied to pre-TACE CT images. Evaluation of radiomics random survival forest models against clinical ones using Cox proportional hazard demonstrated comparable performance in predicting overall survival. However, radiomics outperformed clinical models in predicting progression-free survival. Explainable analysis highlighted the significance of non-tumoral VOI features, with their cumulative importance superior to features from the largest liver tumor. The proposed approach overcomes the limitations of manual VOI segmentation, requires no radiologist input and highlight the clinical relevance of features beyond tumor regions. Our findings suggest the potential of this radiomics models in predicting TACE outcomes, with possible implications for other clinical scenarios.

We explored the role of tumor size and number in the prognosis of HCC patients who underwent ablation and created a nomogram based on machine learning to predict the recurrence.

A total of 990 HCC patients who underwent transcatheter arterial chemoembolization (TACE) combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were prospectively enrolled, including 478 patients with single small HCC (S-S), 209 patients with single large (≥30mm) HCC (S-L), 182 patients with multiple small HCC (M-S), and 121 patients with multiple large HCC (M-L). S-S patients were randomized in a 7:3 ratio into the training cohort (N=334) and the validation cohort (N=144). Lasso-Cox regression analysis was carried out to identify independent risk factors, which were used to construct a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves. Patients in the training and validation cohorts were divided into low-risk, intermediate-risk, and high-risk groups based on the risk scores of the nomogram.

The median recurrence-free survival (mRFS) in S-S patients was significantly longer than the S-L, M-S, and S-L patients (P<0.0001). The content of the nomogram includes age, monocyte-to-lymphocyte (MLR), gamma-glutamyl transferase-to-lymphocyte (GLR), International normalized ratio (INR), and Erythrocyte (RBC). The C-index (0.704 and 0.71) and 1-, 3-, and 5-year AUCs (0.726, 0.800, 0.780, and 0.752, 0.761, 0.760) of the training and validation cohorts proved the excellent predictive performance of the nomogram. Calibration curves the DCA curves showed that the nomogram had good consistency and clinical utility. There were apparent variances in RFS between the low-risk, intermediate-risk, and high-risk groups (P<0.0001).

S-S patients who underwent ablation had the best prognosis. The nomogram developed and validated in the study had good predictive ability for S-S patients.

The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with atezolizumab and bevacizumab (Atez/Bev). However, no large sample size studies have reported the application of the CRAFITY score among HCC patients undergoing transarterial chemoembolization (TACE) in conjunction with lenvatinib. This research aims to assess the prognostic role of the CRAFITY score in the context of individuals with HCC receiving TACE in combination with lenvatinib.

This retrospective analysis encompassed 314 individuals diagnosed with HCC who underwent the combination of TACE and lenvatinib at two medical facilities in China from August 2019 to August 2022 (comprising a training cohort of n = 172 and a validation cohort of n = 142). We investigated the prognostic values of overall survival (OS), progression-free survival (PFS), disease control rate, and objective response rate in the training cohort based on the CRAFITY scores. Furthermore, the predictive capacity of the model was corroborated through validation using an external cohort.

We included 174 and 142 patients treated with TACE plus lenvatinib in the training and validation cohorts, correspondingly. PFS and OS differed across all three groups in all training and validation cohorts, based on the CRAFITY score (p < 0.001). In both cohorts, the CRAFITY score effectively predicted tumor response (p < 0.001). Moreover, among the 121 patients who received TACE, lenvatinib, and immunotherapy, the CRAFITY score showed promising predictive efficacy in PFS and OS.

The CRAFITY score, utilizing C-reactive protein and alpha-fetoprotein values, emerges as a dependable and pragmatic instrument for forecasting the effectiveness of TACE plus lenvatinib in individuals with unresectable HCC. This scoring system holds the potential to assist oncologists in making informed clinical decisions.

To compare the efficacy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICI) versus TKIs plus ICIs (TKI-ICI) for unresectable hepatocellular carcinoma (HCC) with first- or lower-order portal vein tumor thrombosis (PVTT).

A retrospective study was performed in HCC patients with first- or lower-order PVTT receiving TKIs (Lenvatinib or sorafenib) plus ICIs (camrelizumab, sintilimab, or atezolizumab) with or without TACE from four institutions between January 2019 and January 2022. Propensity score-based method was performed to minimize bias by confounding factors. Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups.

After inverse probability of treatment weighting, two balanced pseudopopulations were created: 106 patients in the TACE-TKI-ICI group and 109 patients in the TKI-ICI group. The objective response rate was higher in the TACE-TKI-ICI group (50.9% vs. 28.4%, P < 0.001). The median PFS and OS were significantly longer in the TACE-TKI-ICI group than in the TKI-ICI group (PFS: 9.1 vs. 5.0 months, P = 0.005; OS: 19.1 vs. 12.7 months, P = 0.002). In Cox regression, TACE-TKI-ICI treatment was an independent predictor of favorable OS. Treatment-related grade 3/4 AEs were comparable between the two groups (22.6% vs. 17.9%, P = 0.437).

TACE-TKI-ICI therapy contributed to better tumor control, PFS and OS than TKI-ICI therapy in unresectable HCC patients with first- or lower-order PVTT.

The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy.

Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores.

Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes.

Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.

This study aims to establish a prognostic nomogram for patients who underwent transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC) after hepatectomy.

Patients who underwent TACE for recurrent early- and middle-stage HCC after hepatectomy between 2009.01 and 2015.12 were included. Enrolled patients were randomly divided into training (n=345) and validation (n=173) cohorts according to a computer-generated randomized number. Independent factors for overall survival (OS) were determined and included in the nomogram based on the univariate and multivariate analyses of the training group. The nomogram was validated and compared to other prognostic models. Discriminative ability and predictive accuracy were determined using the Harrell C index (C-index), area under the receiver operating characteristic curve (AUROC), and calibration curve.

The final nomogram was established based on four parameters including resection-to-TACE time interval, recurrent tumor diameter, recurrent tumor number, and AFP level. The C-indexes of the nomogram for predicting OS were 0.67 (95% CI 0.63-0.70) and 0.71 (95% CI 0.68-0.74) in the training and validation cohort respectively. The AUROCs for predicting the 1-year, 2-year and 3-year OS based on the nomogram were also superior to those of the other models. The calibration curve for 3-year survival showed a high congruence between the predicted and actual survival probabilities. According to the scores calculated by the nomogram, patients were stratified into three subgroups: high-risk (scoring ≥53 points), middle-risk (scoring ≥26 and <53 points), and low-risk (scoring <26 points) subgroups with a median OS of 10.1 (95% CI 0.63-0.70), 20.3 (95% CI 17.5-22.5) and 47.0 (95% CI 34.2-59.8) months, respectively.

The proposed nomogram served as a new tool to predict individual survival in patients who underwent TACE for recurrent HCC after hepatectomy, with favorable performance and discrimination. For high-risk patients, treatment should be optimized beyond TACE alone based on the nomogram.

Transarterial chemoembolization (TACE) is widely performed as a major treatment for hepatocellular carcinoma (HCC) patients, and there is a need to stratify patients for whom the most benefit from the treatment. This study aimed to develop a refined prediction model for overall survival (OS) in patients undergoing TACE as a first-line treatment in a large cohort and validate its performance.

A total of 2,632 patients with HCC of Barcelona Clinic Liver Cancer stage A or B who underwent TACE between 2008 and 2017 were enrolled. The patients were randomly assigned to a training cohort (n = 1,304) or a validation cohort (n = 1,328). Independent predictors of OS were used to develop a prediction model.

The median age of patients in the entire cohort was 63 years, with the majority having hepatitis B virus (56.6%) and being classified as Child-Pugh class A (82.4%). We developed a new prognostic model, called the TACE-prognostic (TP) score, based on tumor burden (sum of the largest tumor diameter and tumor number), alpha-fetoprotein, and Albumin-Bilirubin grade. Patients were classified into five risk groups according to TP scores, with median survival significantly differentiated in both training and validation cohorts (P < 0.001). The new model consistently outperformed other currently available models in both the training and validation cohorts.

This newly developed TP scoring system has the potential to be a useful tool in identifying ideal candidates of TACE and predicting OS with favorable performance and discrimination. However, further external validation is needed to confirm its effectiveness.

Patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) may have varied outcomes based on their liver function and tumor burden diversity. This study aims to assess the prognostic significance of the tumor burden score (TBS) in these patients and develop a prognostic model for their overall survival.

The study involved a retrospective analysis of 644 newly diagnosed HCC patients undergoing TACE treatment. The individuals were assigned randomly to a training cohort (n = 452) and a validation cohort (n = 192). We utilized a multivariate Cox proportional risk model to identify independent preoperative predictive factors. We then evaluated model performance using the area under the curve (AUC), consistency index (c-index), calibration curve, and decision curve analysis (DCA) methods.

The multivariate analysis revealed four prognostic factors associated with overall survival: Tumor Burden Score, Tumor Extent, Types of portal vein invasion (PVI), and Child-Pugh score. The total score was calculated based on these factors. The model demonstrated strong discriminative ability with high AUC values and c-index, providing high net clinical benefits for patients. Based on the model's scoring results, patients were categorized into high, medium, and low-risk groups. These results were validated in the validation cohort.

The tumor burden score shows promise as a viable alternative prognostic indicator for assessing tumor burden in cases of HCC. The new prognostic model can place patients in one of three groups, which will estimate their individual outcomes. For high-risk patients, it is suggested to consider alternative treatment options or provide the best supportive care, as they may not benefit significantly from TACE treatment.

To summarize current evidence about the influence of body composition on the prognosis of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) treatment.

Public databases were systematically searched to identify relevant studies published from the inception of the database up to May 2023. Studies that evaluated the association between body composition and clinical outcomes in HCC patients who underwent TACE were included. A pre-designed table was applied to summarize relevant information. Meta-analysis was performed to estimate the association of body composition with overall survival.

Fourteen studies were included in this review, including 3631 patients (sample size range: 56-908, median 186). All body composition measurements (including skeletal muscle area, visceral and subcutaneous adipose area, and bone mineral density) were based on computer tomography. The commonly used parameter was skeletal muscle index at 3rd lumbar vertebra level (8/14). Three studies evaluated the correlations of body composition changes with the prognosis after TACE. Most studies (12/14) identified body composition parameters as an independent indicator for overall survival, progression-free survival, and treatment response rate. The hazard ratio of different body composition parameters ranged from 1.01 to 2.88, and hazard ratio of body composition changes ranged from 1.88 to 5.93. The pooled hazard ratio of sarcopenia for overall survival was 1.38 (95 %CI: 1.20-1.58).

Body composition seems to be an important prognostic factor for a poorer clinical outcome after TACE treatment in patients with hepatocellular carcinoma. Future prospective studies with a larger sample size are required to confirm these findings.

This study has been prospectively registered at the PROSPERO platform (https://www.crd.york.ac.uk/prospero/) with the registration No. CRD42022345602.