Journal of Hepatocellular Carcinoma最新文献

Purpose: This study aimed to develop a novel nomogram to predict recurrence-free survival (RFS) for microvascular invasion (MVI)-negative hepatocellular carcinoma (HCC) patients after curative resection.

Patients and methods: A total of 143 pathologically confirmed MVI-negative HCC patients were analyzed retrospectively. Baseline MRI features and inflammatory markers were collected. We used univariable and multivariable Cox regression analysis to identify the independent risk factors for RFS. And we established a nomogram based on significant MRI features and inflammatory marker. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve were used to evaluate the predictive accuracy and discriminative ability of the nomogram. The decision curve analysis (DCA) was performed to validate the clinical utility of the nomogram.

Results: In multivariate Cox regression analysis, neutrophil-to-lymphocyte ratio (NLR) (P = 0.018), tumor size (P = 0.002), and tumor capsule (P = 0.000) were independent significant variables associated with RFS. Nomogram with independent factors was developed and achieved a good C-index of 0.730 (95% confidence interval [CI]: 0.656-0.804) for predicting RFS. In ROC analysis, the areas under curve of the nomogram for 1-, 3- and 5-year RFS prediction were 0.725, 0.784 and 0.798, respectively. The risk score calculated by nomogram could divide MVI-negative HCC patients into high-risk group or low-risk group (P < 0.0001). DCA analysis revealed that the nomogram could increase net benefit and exhibited a wider range of threshold probabilities by the risk stratification than the independent risk factors in the prediction of MVI-negative HCC recurrence.

Conclusion: The nomogram prognostic model based on MRI features and NLR for predicting RFS showed high accuracy in MVI-negative HCC patients after curative resection. It can help clinicians make treatment decisions for MVI-negative HCC patients and identify high-risk patients for timely intervention.

Background: Radiotherapy offers potential benefits for patients with hepatocellular carcinoma (HCC); however, the distinct role of intraoperative radiotherapy (IORT) during narrow-margin hepatectomy remains inadequately defined. This study aims at assessing the safety and effectiveness of IORT for centrally located HCCs during narrow-margin hepatectomy.

Methods: This single-center, retrospective research incorporated 659 patients with centrally located HCCs. After applying exclusion criteria, 607 patients remained and were divided into two groups: IORT integrated with liver resection (IORT+LR, 54 patients) and mere liver resection (LR, 553 patients). Propensity score matching (PSM) was performed to balance baseline characteristics. Post PSM, surgical outcomes, long-term recurrence, survival rates and adverse events were analyzed.

Results: A total of 54 patients were successfully matched, without significant differences upon baseline characteristics (standardized mean difference, SMD <0.15). Post-matching analysis revealed that overall survival (OS) and disease-free survival (DFS) were notably improved in the IORT+LR group (P =0.027 and 0.015, respectively). Multivariate Cox regression identified IORT as an independent prognostic factor for better DFS and OS. Among the 108 patients included after matching, 57 experienced HCC recurrence, 23 in the IORT group and 34 in the LR group, showing a clear difference in recurrence rates (P =0.034). Also, there were no apparent differences in mild/severe complications between IORT and RT groups (96.3% vs 98.2%, P =0.558, respectively).

Conclusion: IORT is an effective and well-tolerated therapy for HCC patients. The combination of narrow-margin hepatectomy and IORT enhances patient prognosis, with IORT identified as an independent prognostic factor.

Background: Maximum diameter and number are the main parameters of tumor burden in hepatocellular carcinoma (HCC). Tumor burden score (TBS) shows its distinguished ability to stratify patients with HCC undergoing transcatheter arterial chemoembolization (TACE). However, the prognostic accuracy of TBS in HCC undergoing liver resection and its association with the BCLC stage has not been well evaluated.

Methods: A total of 3044 treatment-naïve HCC patients from six independent medical centers undergoing liver resection were retrospectively analyzed. Survival analyses were conducted by plotting Kaplan-Meier curves and the Log rank test. We further investigated whether the tumor burden score was a feasible subclassification criterion across the BCLC stage. Then, we also used TBS to identify HCC patients beyond BCLC criteria who could benefit most from surgical resection. Finally, univariate and multivariate cox analysis was used to determine independent prognostic predictors.

Results: About 44.2% (n=1343) of patients had low TBS, 38.8% (n=1182) had intermediate TBS and 17% (n=519) had high TBS. Overall survival (OS) and recurrence-free survival deteriorated incrementally with increasing TBS (P<0.0001). Subgroup analysis indicated that there was a significant survival difference among the three TBS groups across the BCLC stage (P<0.0001). Low TBS group of patients beyond BCLC criteria reported acceptable outcomes compared to intermediate TBS group patients within BCLC criteria, even better than high TBS group (5-year OS: 64.3%, 69.8%, and 56.3%). Finally, low TBS was identified as an independent protective prognostic factor.

Conclusion: Tumor burden score is a feasible and reliable prognostic tool for prognosis prediction and clinical decisions.

Introduction: While several systemic therapies are available for unresectable hepatocellular carcinoma (uHCC), there is a lack of granular real-world evidence to support the efficacy and safety of these therapies. The REFINE study evaluated safety and effectiveness of regorafenib in a global population under real-world practice conditions. This sub-analysis describes the safety and effectiveness of regorafenib among the United States (US) subset of patients in the REFINE study relative to patients in the non-US subset.

Materials and methods: REFINE was an international, prospective, multicenter observational study. Eligible patients were those with uHCC for whom a decision to treat with regorafenib had already been made. The primary study endpoint was the frequency of documented treatment-emergent adverse events (TEAEs). Additional endpoints included overall survival and progression-free survival. Groups were compared descriptively.

Results: Of 1005 patients, 65 were from the US and 940 were from other countries. 91% of patients in the US subset (n=59) and 92% in the non-US subset (n=862) experienced ≥1 TEAE. Common adverse events (AEs) included gastrointestinal disorders, fatigue, and hand-foot skin reaction. Median overall survival for patients in the US subset was 11.4 months (interquartile range [IQR]: 4.7-25.4) and 13.2 months (IQR: 5.8-26.3) in the non-US subset. Median progression-free survival was 3.4 months (IQR: 2.4-6.1) for patients in the US subset and 3.9 months (IQR: 2.2-8.5) in the non-US subset.

Conclusion: Regorafenib was associated with similar safety and effectiveness outcomes for patients in the US and non-US subsets of the REFINE study. Differences in the incidence of certain AEs may be due to differences in treatment management between study sites or baseline disease status. These findings are consistent with the phase 3 RESORCE trial and corroborate the safety and effectiveness of regorafenib as a subsequent-line treatment in US patients with uHCC.

Purpose: Liver venous deprivation (LVD; simultaneous portal vein embolization and hepatic vein embolization) has been the latest surgical strategy for rapid future liver remnant (FLR) hypertrophy. The aim of this study was to assess the feasibility, safety, and efficacy of simultaneous LVD following hepatic arterial chemoembolization (TACE-LVD) before major hepatectomy for hepatocellular carcinoma (HCC).

Patients and methods: A retrospective analysis of the outcomes of 23 HCC patients who underwent TACE-LVD at our center between October 2019 and October 2023 was conducted. An assessment of postoperative complications, FLR volume, liver function, and tumor response was performed.

Results: All patients successfully underwent TACE-LVD. No other serious complications occurred except in 1 patient who underwent puncture drainage due to excessive pleural effusion. Following TACE-LVD, transaminase levels peak two days before rapidly decreasing and return to preoperative levels within one week. The ratio of FLR to standardized liver volume increased from 35.9% (interquartile range [IQR], 8.6) to 46.4% (IQR, 8.2), with a mean degree of hypertrophy and kinetic growth rate of 13.2% (IQR, 5.4) and 4.4% (IQR, 1.8) per week, respectively. At the first assessment after TACE-LVD, most patients exhibited sufficient FLR for hepatectomy, except for 4 patients with cirrhosis. The modified response evaluation criteria for solid tumor assessment revealed a disease control rate of 95.7%, with only 1 patient (Barcelona Clinic Liver Cancer stage C) developing intrahepatic disease progression.

Conclusion: TACE-LVD seems to be a feasible, safe, and effective strategy for rapid FLR hypertrophy. Moreover, TACE-LVD may be a therapeutic choice if insufficient FLR hypertrophy precludes resection. This strategy warrants further exploration.

Background: Salvage liver transplantation is promising for hepatocellular carcinoma(HCC) recurrence post-ablation but is significantly affected by recurrence beyond Milan Criteria (RBM).

Materials and methods: A retrospective cohort study of potentially transplantable HCC patients undergoing ablation between 2007 and 2017 assessed median time to recurrence beyond Milan Criteria(TRBM) via Kaplan-Meier curves and predictive capacity of recurrence and RBM for overall survival(OS) via Receiver Operating Characteristic Curves, and identified independent risk factors for TRBM and RBM via Cox and binary logistic regression models.

Results: We enrolled 191 potentially transplantable patients with early-stage HBV-related HCC ≤3 cm who underwent ablation. During a median follow-up of 7.64 years, HCC recurrence occurred in 126 patients(65.9%), with RBM 86 patients(45.0%). The median TRBM was 10.54 years. Cumulative survival rates without RBM at 3, 5, 8, 10, and 13 years were 77.3%, 65.9%, 56.5%, 51.0%, and 37.6%, respectively. Multivariable analysis identified older age, C-reactive protein(CRP)≥1.81 mg/L, and platelet(PLT)≤80×10⁹/L as independent risk factors for TRBM. Also, cirrhosis, CRP≥1.81 mg/L and PLT≤80×10⁹/L were identified as independent risk factors of the occurrence of RBM. Elevated Platelet-CRP Score(PCS), integrating CRP and PLT, correlated significantly with an increased incidence of RBM and a more aggressive phenotype, characterized by vascular invasion or metastatic dissemination (P<0.05). Notably, RBM was a superior predictive indicator for OS compared to recurrence (P<0.05).

Conclusion: When using ablation as a bridge to liver transplantation for solitary HBV-related early HCC (≤3 cm), it is crucial first to identify key preoperative features, including high CRP, low PLT, cirrhosis, and older age.

Background & aims: Dual-phenotype hepatocellular carcinoma (DPHCC) is discernible from classical HCC (CHCC) in its morphology and is characterized by the co-expression of both CHCC and cholangiocyte markers. This study aimed to clarify the difference between DPHCC and CHCC after surgery.

Methods: Patients with HCC after surgery were collected. The clinical characteristics, patterns of recurrence, and survival outcomes of patients with DPHCC and CHCC were compared. Multivariate analyses were used to determine the independent risk factors that influence the prognosis of patients.

Results: Patients with DPHCC (n = 141) account for 26% of the total patients (n = 541). Compared to patients with CHCC, patients with DPHCC are significantly associated with incomplete capsules, microvascular invasion, and poor differentiation (all P < 0.05). Compared to patients with CHCC, the 5-year overall survival (OS) (56% vs 43%) and recurrence-free survival (RFS) (35% vs 28%) are lower in patients with DPHCC. Meanwhile, among patients with tumor recurrence after surgery, patients with DPHCC have a higher proportion of advanced-stage tumors, and extrahepatic metastasis (all P < 0.05). Moreover, multivariate analysis showed that DPHCC is an independent risk factor for both OS (HR 1.399, 95% CI 1.061-1.845, P = 0.017) and RFS (HR 1.313, 95% CI 1.033-1.669, P = 0.026).

Conclusion: DPHCC, an aggressive HCC subtype with poor differentiation and high invasiveness, shows inferior RFS and OS post-liver resection compared to CHCC. Clinicians' recognition and addressing of its unique challenges can improve DPHCC patients' prognosis and QoL.

Purpose: To develop and validate a predictive model for predicting six-month outcome by integrating pretreatment MRI features and one-month treatment response after TACE.

Methods: A total of 108 patients with 160 hCCs from a single-arm, multicenter clinical trial (NCT03113955) were analyzed and served as the training cohort. An external multicenter dataset (ChiCTR2100046020) consisting of 63 patients with 99 hCCs served as the test dataset. Radiomics model was constructed based on the selected features from pretreatment MR images. Univariate and multivariate logistic regression analysis of clinical and radiological factors were used to identify the independent predictors for the 6-month treatment response. A combined model was further constructed by incorporating one-month treatment response, selected clinical and radiological factors and radiomics signature.

Results: Among all the clinical and radiological features, only corona enhancement and one-month treatment response were selected. The combined model, named TRACE model (Treatment response at 1 month, RAdiomics and Corona Enhancement), with AUCs of 0.91 (training cohort) and 0.84 (test cohort). The TRACE model demonstrated a significantly higher AUC than the radiomics model (P = 0.001). High-risk and low-risk groups stratified by using the TRACE model also exhibited significant differences in overall survival (OS) (P < 0.001). In contrast, none of the published scoring systems, including ART, SNACOR or ABCR score, demonstrated significant differences between the risk groups in OS prediction.

Conclusion: The TRACE model exhibited favorable predictive capability for six-month TACE response, and holds potential as a marker for long-term survival outcomes.

Purpose: To assess the activity and toxicity of hepatic arterial infusion chemotherapy (HAIC)+tislelizumab+lenvatinib (HAIC+tisle+len) in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) type IV (Vp4 hCC) in a real-world context.

Methods: Fifty-five patients, with Vp4 hCC receiving HAIC+tisle+len therapy from April 2021 to December 2022, were analyzed retrospectively. Data on patient characteristics, adverse events (AEs), treatment, and survival were collected. Outcomes were disease control rate (DCR), overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and treatment-related AEs (TRAEs).

Results: As of December 20, 2023, the median follow-up was 17.5 months (95% confidence interval [CI]: 14.7-22.5). The ORR was 52.7% (3 complete response [CR], 26 partial response [PR]) as per RECIST v1.1 and 65.5% (12 CR, 24 PR) as per mRECIST. The DCR was 94.5% using both RECIST v1.1 and mRECIST. The median PFS and the median OS were 8.0 months (95% CI: 6.2-12.3) and 16.7 months (95% CI: 12.0-not reached), respectively. Additionally, PFS was independently predicted only by the best tumor response. In patients with the best tumor response (PR or CR), the median PFS was 11.7 months (95% CI: 8.02-not reached) by mRECIST and 15.4 months (95% CI: 7.39-not reached) by RECIST v1.1. Hypertension (14.5%), decreased albumin levels (10.9%) and anorexia (9.1%) were the most frequently observed grade 3-4 TRAEs.

Conclusion: HAIC+tisle+len regimen demonstrated a promising efficacy and favorable safety for patients with HCC and Vp4, providing valuable real-world evidence to complement the trial data for Vp4 hCC.

Objective: Artesunate can inhibit the proliferation of various tumor cells and has practical value in developing anti-tumor drugs. However, its biological activity against hepatocellular carcinoma is weak. The efficacy of its anti-tumor effect needs to be improved.

Methods: 11 compounds of three types were designed and synthesized. Their antitumor activity was detected by MTT assay in vitro and subcutaneous xenograft model in vivo. Then, DCFH-DA probe detection and NAC intervention experiments were used to detect ROS levels. The ferroptosis inhibitor (Liproxstatin-1) was used to study the effect of compound 6c in inducing ferroptosis. Western blot was used to observe the expression of apoptosis-related proteins. The ability of 6c to induce apoptosis was detected by Annexin V-FITC/PI double staining and Hoechst 33342 staining experiment. The effect of 6c on cycle arrest was detected by flow cytometry. Molecular simulations of several hybrids with vascular endothelial growth factor receptor 2 (VEGFR-2) and Transferrin receptor protein 1 (TFR1) were performed using MOE molecular docking software.

Results: A series of new artemisinin-4-(4-substituted phenoxy) pyridine derivatives were synthesized and their anticancer activities were tested in three lines of hepatocellular carcinoma (HCC) cells. Among the hybrid hits with anticancer activity, a representative 6c compound increased the reactive oxygen species (ROS) level in hepatocellular carcinoma cells and activated mitochondrial apoptosis and ferroptosis, leading to cell cycle arrest at G2/M phase. Molecular docking shows the binding of 6c compound to oncogenic vascular endothelial growth factor receptor 2 (VEGFR-2) and Transferrin receptor protein 1 (TFR1) that are overexpressed in malignant epithelial tumors.

Conclusion: Taken together, our identification of the promising compound 6c may hold developmental potential for therapy of hepatocellular carcinoma.