Journal of Hepatocellular Carcinoma最新文献

Purpose: Amid the era of targeted-immunotherapy for hepatocellular carcinoma (HCC), the selection of second-line therapy following failure of diverse first-line regimens remains inadequately explored. This multicenter study aimed to assess how first-line treatment strategies impact the efficacy and safety of second-line regorafenib-either alone or in combination with PD-1 inhibitors-in patients with unresectable HCC (uHCC). Specifically, we focused on two key populations: patients who failed first-line tyrosine kinase inhibitor (TKI) monotherapy, and a rapidly expanding cohort who progressed after first-line TKI plus PD-1 inhibitor combination therapy, and to address the critical clinical dilemma of whether to continue immunotherapy in the second line.

Patients and methods: This retrospective study enrolled 288 uHCC patients from five centers, stratified into two cohorts based on first-line therapy: 126 patients with first-line TKI monotherapy (Pre-Monotherapy cohort) and 162 with first-line TKI+PD-1 combination therapy (Pre-Combination cohort). All received second-line regorafenib alone or with PD-1 inhibitors. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included progression-free survival (PFS),objective response rate (ORR), disease control rate (DCR), and safety.

Results: In the Pre-Monotherapy cohort, regorafenib plus PD-1 significantly improved outcomes versus regorafenib alone: mPFS (10.5 vs 4.7 months, p<0.001), mOS (18.9 vs 14.0 months, p=0.003), ORR (29.69% vs 4.84%, p<0.001), and DCR (89.06% vs 67.74%, p=0.004). In the Pre-Combination cohort, no significant differences were observed in PFS (9.2 vs 6.3 months, p=0.062), OS (16.2 vs 13.2 months, p=0.13), ORR (22.33% vs 15.25%, p=0.276), or DCR (82.52% vs 74.58%, p=0.227).

Conclusion: Second-line regorafenib plus PD-1 inhibitors yields significant clinical benefits in uHCC patients who failed first-line TKI monotherapy. However, in those who progress following first-line TKI plus PD-1 inhibitor therapy, continuing immunotherapy in the second line confers no additional efficacy, underscoring the need to explore alternative strategies. This study provides the first evidence-based guidance for the unmet clinical scenario of "first-line targeted-immunotherapy failure", highlighting the importance of precision sequential therapy tailored to first-line regimens.

Purpose: Hepatocellular carcinoma (HCC) remains challenges in treatment, particularly when tumors are unresectable and huge. This study aimed to assess the safety and efficacy of combining transarterial chemoembolization (TACE) with hepatic arterial infusion chemotherapy (HAIC) for this patient population.

Patients and methods: A retrospective review was conducted on patients with unresectable huge HCC (>10 cm) who received either TACE-HAIC or TACE as initial regional treatment from January 2020 to December 2023. Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated by propensity score matching (PSM).

Results: Among the 242 patients included, 132 received TACE-HAIC and 110 received TACE. After PSM, 77 matched pairs were analyzed. The TACE-HAIC group had significantly higher objective response (74.0% vs 58.4%, P = 0.040) and disease control rates (93.5% vs 72.7%, P = 0.001) than the TACE group. TACE-HAIC therapy also led to longer PFS (median: 12.3 vs 7.4 months, P < 0.001) and prolonged OS (median: 26.8 vs 20.4 months, P = 0.006). Stratified analysis showed that patients in Barcelona Clinical Liver Cancer stage C had longer survival benefits in the TACE-HAIC group (median PFS: 10.5 vs 5.6 months, P < 0.001; median OS: 24.5 vs 19.8 months, P = 0.013). Among grade 3/4 adverse events, liver abscesses (P = 0.018) were more common in the TACE group.

Conclusion: Compared to TACE alone, TACE-HAIC therapy presented an acceptable safety profile, and offered improved local efficacy and prolonged survival benefits in patients with unresectable huge HCC (> 10 cm).

Objective: This study aims to develop a CT-based radiomics nomogram for preoperative prediction of vessels encapsulating tumor clusters (VETC) and patient prognosis in hepatocellular carcinoma (HCC).

Patients and methods: The retrospective, single-center study included 231 (77 VETC+ and 154 VETC-) HCC patients who underwent preoperative CT scan, and were randomly divided into training and validation cohorts at a 7:3 ratio. Radiomics features were extracted from CT images during the plain, arterial and venous phases. These features were then selected using the Least Absolute Shrinkage and Selection Operator (LASSO). Predictive factors were chosen through univariate and multivariate logistic regression. A prognostic nomogram integrating clinical factor and radiomics features was developed and validated. The model's predictive accuracy was systematically evaluated using the area under the receiver operating characteristic curve (AUC), while calibration curves assessed agreement between predicted and observed outcomes. To quantify clinical utility, decision curve analysis (DCA) was implemented. Furthermore, the model's prognostic performance for postoperative disease-free survival (DFS) was examined through Kaplan-Meier analysis.

Results: The nomogram integrating four radiomics features and alpha-fetoprotein (AFP) exhibited robust predictive performance, with AUC values of 0.782 (95% confidence interval [CI]: 0.708-0.856) in the training cohort and 0.755 (95% CI: 0.628-0.882) in the validation cohort. Calibration curves demonstrated excellent agreement between predicted and observed outcomes in both cohorts. DCA revealed significant clinical utility of the nomogram. Additionally, the model-stratified VETC+ HCC patients showed significantly worse DFS compared to VETC- counterparts (log-rank p = 0.035).

Conclusion: The CT-based radiomics nomogram, integrating radiomics features and AFP, provides a non-invasive and reliable tool for predicting VETC and stratifying prognosis in HCC patients.

Purpose: This study aimed to evaluate the association of tumor compression in the hepatic or portal vein with the presence of microvascular invasion (MVI) and satellite nodules in patients with hepatocellular carcinoma (HCC).

Patients and methods: HCC patients at the Barcelona Clinic Liver Cancer (BCLC) stages 0-A who underwent a radical liver resection in our hospitals from January 2016 to December 2022 were collected. The tumor compression of the portal or hepatic vein in individual patients was analyzed by preoperative imaging and postoperative pathology. Their MVI, satellite nodules, overall survival (OS), and recurrence-free survival (RFS) were analyzed, and the potential risk factors for the MVI and satellite nodules of patients were analyzed by univariable and multivariable logistic analyses.

Results: A total of 390 patients were included with 333 male and 263 patients <60 years old. Of them, 51 (13.1%) HCC patients had tumor venous compression, which was not significantly associated with OS and RFS, but significantly related to higher positive rates of MVI and satellite nodules than those without tumor-venous compression (MVI, 51.0% vs 36.6%, P = 0.025; satellite nodules, 19.6% vs 9.1%, P = 0.023). Tumor venous compression was an independent risk factor for the development of MVI (OR = 1.902, 95% CI: 1.049-3.447; P = 0.034) and satellite nodules (OR = 2.871, 95% CI: 1.277-6.458; P = 0.011).

Conclusion: Preoperative tumor venous compression is an independent predictor of MVI and satellite nodules in HCC patients at BCLC stages 0-A and may serve as an imaging biomarker for determining the resection margin and treatment planning.

Radiation therapy is one of the main methods of tumor treatment, with over 50% of patients opting for it during treatment. The optimal regimen of radiation therapy aims to increase the dose in the target area while decreasing the dose in normal tissue. Radiotherapy for liver tumors has seen significant development in recent years. Despite the technological progress and improved accuracy of radiotherapy, the path of radiation reaching the target area still passes through normal tissues. Although there is tolerance doses as a reference parameter for normal liver exposure in planning, radiation damage still occurs. In addition, when combination of radiation therapy with chemotherapy, targeted therapy and immunotherapy has been widely used in recent years, the occurrence of RILD still affects the implementation of other treatment programs. In this review, latest research results of RILD are discussed to better understand the mechanism and provide research directions for optimizing radiotherapy.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and is increasingly diagnosed in younger populations. Conventional biopsy techniques can be invasive and may not accurately capture tumor heterogeneity. Liquid biopsy, analyzing circulating tumor DNA (ctDNA), offers a minimally invasive and dynamic alternative for detecting genetic alterations critical to early diagnosis and personalized treatment strategies.

Methods: We analyzed serum-derived ctDNA from 20 HCC patients to identify genetic variants using next-generation sequencing (NGS). Mutations in key oncogenes and tumor suppressor genes (eg, KIT, FGFR1, FGFR3, EGFR, BRAF, FBXW7) were evaluated for their association with clinical outcomes, including tumor size, metastasis, and overall survival. Statistical analyses were performed using SPSS (v.30), with survival curves assessed via the Kaplan-Meier method.

Results: Of the 20 patients (mean age 64.8±13.1 years), 35% had detectable ctDNA mutations. The most frequently observed alterations were in KIT (28.6% of ctDNA-positive patients), followed by FGFR1, FGFR3, EGFR, BRAF, and FBXW7. Patients harboring FGFR1 and FGFR3 mutations exhibited the poorest survival (3 and 7 months, respectively). Conversely, one patient with a BRAF mutation showed prolonged survival (60 months), and KIT mutations were linked to comparatively better outcomes. Overall, ctDNA-positive patients demonstrated shorter mean survival (22.5 months) than ctDNA-negative patients (35.7 months).

Conclusion: Liquid biopsy-detected genetic alterations correlate with clinical outcomes in HCC, underscoring the prognostic value of ctDNA analysis. Mutations in FGFR1 and FGFR3 were associated with aggressive disease, suggesting these pathways as potential therapeutic targets. Integrating liquid biopsy with other diagnostic modalities may enhance personalized management and improve prognosis for patients with HCC.

Objective: Anoikis is an anchorage-dependent programmed cell death implicated in multiple pathological processes of cancers; however, the prognostic value of anoikis-related genes (ANRGs) in hepatocellular carcinoma (HCC) remains unclear. Our study aims to develop an ANRGs-based prediction model to improve prognostic assessment in HCC patients.

Methods: The RNA-seq profile was performed to estimate the expression of ANRGs in HCC patients. The univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis were applied in the model construction to predict the prognosis in terms of differentially expressed ANRGs in the Cancer Genome Atlas (TCGA) training cohort. The TCGA test cohort and the International Cancer Genome Consortium (ICGC)-originated cohort were set to verify the predictive capacity. Nomogram was built on the basis of risk score (RS), gender, age, grade, and T_stage, with the hope of extending the predictive ability of ANRGs to evaluate the HCC prognosis. The expression of differentially expressed ANRGs was assessed in HCC cell lines and orthotopic tumor-bearing mice.

Results: Six ANRGs (ANXA5, BIRC5, BSG, DAP3, SKP2 and CDKN3) demonstrated the critical prognostic significance in HCC patients. The prognostic RS model on the basis of these ANRGs was capable of properly predicting 1-, 3-, and 5-year survivals. The Kaplan-Meier results displayed the increased death and decreased survival in the high-risk group. The RS acted as the independent factor for the survival evaluation. Our nomogram model was able to directly reflect the survival probabilities of each patient, which was confirmed through various validations. The transcription and translation of six ANRGs were significantly enhanced in HCC cell lines and tumor tissues.

Conclusion: Despite the lack of mechanistic validation, our anoikis-linked RS model serves as a promising tool for predicting HCC prognosis in clinical practice, and provides valuable insights into the decision of individualized therapeutic approaches.

Purpose: To evaluate the efficacy and safety of different doses of bevacizumab combined with atezolizumab in patients with unresectable hepatocellular carcinoma.

Methods: A retrospective analysis was conducted on clinical data from patients receiving Atezo-Bev therapy at our institution. Patients were stratified into standard-dose (SD) and low-dose (LD) groups based on bevacizumab dosage. Comparative analyses evaluated antitumor efficacy and adverse events (AEs) incidence.

Results: A total of 63 patients were included (SD group: n=32; LD group: n=31). Baseline characteristics showed no significant differences between the groups. Median overall survival (OS) was 22.0 months in the SD group and 19.3 months in the LD group, while median progression-free survival (PFS) was 8.0 months and 6.9 months, respectively. No statistically significant differences were observed in OS or PFS between the two groups (P=0.276 and P=0.297, respectively). However, the incidence of bevacizumab-related AEs was lower in the LD group compared to the SD group.

Conclusion: Compared to low-dose bevacizumab combined with atezolizumab, the standard-dose regimen did not demonstrate significant superiority in OS or PFS. Additionally, the low-dose combination may lead to fewer AEs.

Purpose: Transarterial chemoembolization (TACE) may cause gut dysbiosis by increasing portal vein pressure. However, its association with clinical outcomes remains unknown. We hypothesized that gut microbiota composition and diversity are associated with treatment response and prognosis in patients with hepatocellular carcinoma (HCC) undergoing TACE.

Patients and methods: This single-center, prospective cohort study included 96 adult HCC patients treated with TACE from April 2021 to November 2023. Fecal samples were collected before TACE (P0), one day (P1), and one month (P2) after TACE. Fecal 16S rRNA taxonomy was analyzed to evaluate microbial diversity, composition, and dynamic changes at each time point. The primary outcome was the association between the initial response to TACE and changes in microbial diversity and composition.

Results: Out of the total participants, 63 (65.6%) were responders and 33 (34.4%) were non-responders. Responder stool samples had higher alpha-diversity than those of non-responders at baseline (median Shannon index: 4.26 vs 4.09), albeit not reaching statistical significance, and a higher abundance of short-chain fatty acid (SCFA)-producing bacteria at all time points. Alpha-diversity significantly decreased one day after TACE (P < 0.05 for P1 vs P0) and tended to recover one month later in the responders, albeit without statistical significance for P2 vs P0. Regarding beta-diversity, there were some changes in both responders and non-responders during the post-TACE period, albeit with different patterns. A low abundance of Roseburia cecicola (HR, 3.44; 95% CI, 1.10-10.8) and Dialister_uc (HR, 3.90; 95% CI, 1.32-11.6; both P < 0.05) at baseline was associated with worse overall survival.

Conclusion: Specific SCFA-producing bacteria, such as Roseburia cecicola and Dialister_uc, were associated with treatment response and survival after TACE in patients with HCC, suggesting a potential prognostic role of the gut microbiome.

[This corrects the article DOI: 10.2147/JHC.S520318.].