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

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

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

BACKGROUND: Local treatment may function synergistically with immunotherapy and targeted agents. This study aimed to assess the effectiveness and safety of transcatheter arterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and programmed death-1 (PD-1) inhibitors in patients with initially unresectable hepatocellular carcinoma (uHCC).
METHODS: A retrospective study was conducted on patients diagnosed with initially uHCC who received combined treatment of TACE-HAIC combined with TKIs and PD-1 inhibitors from July 2020 to February 2023. The primary endpoints were overall survival (OS) and progression free survival (PFS) and adverse events (AEs). Objective response rate (ORR), disease control rate (DCR) and conversion surgery rate (CSR), whereas the secondary endpoints.
RESULTS: After screening, a total of 62 patients were selected for this study. The overall median OS was 18.2 (95% CI 16.24-20.16) months and median PFS was 9.2 (95% CI 7.24-11.16) months. Based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and RECIST v1.1 criteria, ORR was 67.7% (42/62), and the DCR was 90.3% (56/62), the CSR was 27.4% (17/62). The most common treatment-emergent adverse events (TEAEs) were transaminitis (56.4%, 35/62), nausea and vomiting (43.5%, 27/62), thrombocytopenia (37.1%, 23/62), abdominal pain (33.9%, 21/62), and fever (33.9%, 21/62).
CONCLUSIONS: TKIs combined with PD-1 inhibitors plus TACE-HAIC therapy represents an effective and tolerable treatment option in patients with uHCC. Patients undergoing surgery after combination therapy may have survival benefits.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

Interventional chemotherapy is a common operation in the clinical treatment of liver cancer. The aim of this study was to investigate the expression and molecular mechanism of serum miR-4746-5p in liver cancer patients before and after interventional chemotherapy. The levels of miR-4746-5p and CDKN1C in serum samples from liver cancer patients were detected using real-time fluorescence quantitative polymerase chain reaction. Receiver operating characteristic curves revealed the diagnostic value of miR-4746-5p in tumors. Differences in clinical indicators between liver cancer patients and healthy controls were assessed using Pearson correlation analysis. Luciferase reporter gene assays confirmed the targeted interaction between miR-4746-5p and CDKN1C. In vitro cellular assays were validated by Cell Counting Kit-8, Transwell assay, and chemoresistance assay. Serum miR-4746-5p levels were increased in liver cancer patients but were downregulated after chemotherapy intervention. CDKN1C expression showed the opposite trend. Low levels of miR-4746-5p mediated cell growth and metastasis by targeting and negatively regulating CDKN1C expression, while silencing CDKN1C restored cell activity. Inhibition of miR-4746-5p reduced chemoresistance, while downregulation of CDKN1C affected cell sensitivity. miR-4746-5p may be a potential therapeutic factor for liver cancer diagnosis and interventional chemotherapy.

(1) Background: HBV-DNA is an essential clinical indicator of primary hepatocellular carcinoma (HCC) prognosis. Our study aimed to investigate the prognostic implication of a low load of HBV-DNA in HCC patients who underwent local treatment. Additionally, we developed and validated a nomogram to predict the recurrence of patients with low (20-100 IU/mL) viral loads (L-VL). (2) Methods: A total of 475 HBV-HCC patients were enrolled, including 403 L-VL patients and 72 patients with very low (<20 IU/mL) viral loads (VL-VL). L-VL HCC patients were randomly divided into a training set (N = 282) and a validation set (N = 121) at a ratio of 7:3. Utilizing the Lasso-Cox regression analysis, we identified independent risk factors for constructing a nomogram. (3) Results: L-VL patients had significantly shorter RFS than VL-VL patients (38.2 m vs. 23.4 m, p = 0.024). The content of the nomogram included gender, BCLC stage, Glob, and MLR. The C-index (0.682 vs. 0.609); 1-, 3-, and 5-year AUCs (0.729, 0.784, and 0.783, vs. 0.631, 0.634, the 0.665); calibration curves; and decision curve analysis (DCA) curves of the training and validation cohorts proved the excellent predictive performance of the nomogram. There was a statistically significant difference in RFS between the low-, immediate-, and high-risk groups both in the training and validation cohorts (p < 0.001); (4) Conclusions: Patients with L-VL had a worse prognosis. The nomogram developed and validated in this study has the advantage of predicting patients with L-VL.

UNASSIGNED: A common treatment strategy for individuals with multifocal hepatocellular carcinoma (HCC) who are not candidates for surgical resection is transarterial chemoembolization (TACE). Combining TACE with 125I seed insertion (ISI) may offer a means of enhancing therapeutic efficacy. The purpose of this study was to compare the therapeutic efficacy of TACE administered with and without ISI for the treatment of multifocal HCC.
UNASSIGNED: The data from the two centers were analyzed retrospectively. The present study involved 85 consecutive patients with multifocal HCC who underwent TACE between January 2018 and December 2021. Of these patients, 43 were in the combined group, receiving TACE with ISI, and 42 were in the TACE-only group, receiving TACE without ISI. Comparisons of treatment outcomes were made between these groups.
UNASSIGNED: No significant differences in baseline data were observed between these groups of patients. Higher rates of complete (60.5% vs. 33.3%, P = 0.016) and total (93.0% vs. 61.9%, P = 0.001) responses were evident in the combined group compared to the TACE-only group. Median progression-free survival (PFS, 13 vs. 10 months, P = 0.014) and overall survival (OS, 22 vs. 17 months, P = 0.035) were also significantly longer in the combined group than in the TACE-only group. Using a Cox regression analysis, risk variables associated with shorter PFS and OS included Child-Pugh B status (P = 0.027 and 0.004) and only TACE treatment (P = 0.011 and 0.022).
UNASSIGNED: In summary, these findings suggest that, as compared to TACE alone, combining TACE and ISI can enhance HCC patients\' treatment outcomes and survival.

Hepatitis B surface antigen (HBsAg) clearance is associated with improved long-term outcomes and reduced risk of complications. The aim of our study was to identify the effects of levels of HBsAg in HCC patients undergoing TACE and sequential ablation. In addition, we created a nomogram to predict the prognosis of HCC patients with high levels of HBsAg (≥1000U/L) after local treatment.
This study retrospectively evaluated 1008 HBV-HCC patients who underwent TACE combined with ablation at Beijing Youan Hospital and Beijing Ditan Hospital from January 2014 to December 2021, including 334 patients with low HBsAg levels and 674 patients with high HBsAg levels. The high HBsAg group was divided into the training cohort (N=385), internal validation cohort (N=168), and external validation cohort (N=121). The clinical and pathological features of patients were collected, and independent risk factors were identified using Lasso-Cox regression analysis for developing 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 in the training and validation cohorts. Patients were classified into high-risk and low-risk groups based on the risk scores of the nomogram.
After PSM, mRFS was 28.4 months (22.1-34.7 months) and 21.9 months (18.5-25.4 months) in the low HBsAg level and high HBsAg level groups (P<0.001). The content of the nomogram includes age, BCLC stage, tumor size, globulin, GGT, and bile acids. The C-index (0.682, 0.666, and 0.740) and 1-, 3-, and 5-year AUCs of the training, internal validation, and external validation cohorts proved good discrimination of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classification of patients with high HBsAg levels into low-risk and high-risk groups according to the risk of recurrence. There was a statistically significant difference in RFS between the two groups in the training, internal validation, and external validation cohorts (P<0.001).
High levels of HBsAg were associated with tumor progression. The nomogram developed and validated in the study had good predictive ability for patients with high HBsAg levels.

OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.