Journal of Hepatocellular Carcinoma最新文献

{"title":"A Phase 1a/1b Study of Fostroxacitabine Bralpamide (Fostrox) Monotherapy in Hepatocellular Carcinoma and Solid Tumor Liver Metastases.","authors":"Ruth Plummer, Alastair Greystoke, Gregory Naylor, Debashis Sarker, A N M Kaiser Anam, Hans Prenen, Laure-Anne Teuwen, Eric Van Cutsem, Jeroen Dekervel, Beate Haugk, Thomas Ness, Sujata Bhoi, Malene Jensen, Tom Morris, Pia Baumann, Niclas Sjögren, Karin Tunblad, Hans Wallberg, Fredrik Öberg, Thomas R Jeffry Evans","doi":"10.2147/JHC.S481410","DOIUrl":"10.2147/JHC.S481410","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate safety, preliminary efficacy, pharmacokinetics, and pharmacodynamics, of fostroxacitabine bralpamide (fostrox, MIV-818), a novel oral troxacitabine nucleotide prodrug designed to direct exposure to the liver, while minimizing systemic toxicity.</p><p><strong>Patients and methods: </strong>Fostrox monotherapy was administered in an open-label, single-arm, first-in-human, phase 1a/1b study, in patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, or solid tumor liver metastases. The first part (1a) consisted of intra/inter-patient escalating doses (3 mg to 70 mg) QD for up to 5 days, and the second part (1b), doses of 40 mg QD for 5 days, in 21-day cycles. Safety and tolerability were evaluated by the Safety Review Committee, and efficacy was assessed every 6 weeks with CT or MRI using RECIST 1.1 and mRECIST.</p><p><strong>Results: </strong>Nineteen patients were treated with fostrox. Most common adverse events (AEs) were hematological and increased AST. Grade 3 treatment related AEs (TRAE) were seen in 53% of the patients, with transient neutropenia and thrombocytopenia as the most common. No grade 5 AE was observed. Recommended Phase 2 dose of fostrox was 40 mg QD for 5 days in 21-day cycles. Preliminary efficacy showed a clinical benefit rate in the liver of 53% and stable disease (SD) as best response in 10 patients. Liver targeting with fostrox was confirmed with higher exposure of troxacitabine and its metabolites in liver compared to plasma. Systemic exposure of fostrox was generally low with troxacitabine as main analyte. Biopsies demonstrated tumor-selective, drug-induced DNA damage.</p><p><strong>Conclusion: </strong>The phase 1a/1b monotherapy study of fostrox, in patients with liver tumors, showed a tumor selective effect in the liver and that 40 mg QD for 5 days in 21-day cycles is safe and tolerable. Safety and preliminary efficacy in patients with advanced HCC supports clinical development of fostrox in combination with other modes of action in HCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"2033-2047"},"PeriodicalIF":4.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multisequence MRI-Based Radiomic Features Combined with Inflammatory Indices for Predicting the Overall Survival of HCC Patients After TACE.","authors":"Maoting Zhou, Peng Zhang, Qi Mao, Yue Shi, Lin Yang, Xiaoming Zhang","doi":"10.2147/JHC.S481301","DOIUrl":"10.2147/JHC.S481301","url":null,"abstract":"<p><strong>Objective: </strong>To develop a model for predicting the overall survival (OS) of hepatocellular carcinoma (HCC) patients after transarterial chemoembolization (TACE) on the basis of multisequence MRI radiomic features and clinical variables.</p><p><strong>Methods: </strong>The DCE-MRI and clinical data of 116 HCC patients treated with TACE for the first time were retrospectively analyzed. The included patients were randomly divided into training and validation cohorts at a ratio of 7:3. Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors that affect the OS of patients with HCC after TACE. Radiomic features were extracted from the sequences of FS-T2W images and arterial-phase (A) and portal venous-phase (P) axial DCE-MR images. The LASSO method was used to select the best radiomic features. Logistic regression was used to establish a radiomic model of each sequence, a joint model of MRI features (M model) combined the radiomic features of all the sequences, and a radiomic-clinical model (M-C model) that integrated the radiomic signatures and clinically independent predictors. The diagnostic performance of each model was evaluated as the area under the receiver operating characteristic (ROC) curve (AUC).</p><p><strong>Results: </strong>The Child-Turcotte-Pugh (CTP) score and neutrophil-to-lymphocyte ratio (NLR) -platelet-to-lymphocyte ratio (PLR) were found to be independent risk factors that affect the OS of patients with HCC treated with TACE. The AUCs of the FS-T₂WI, A, P, M, and M-C models for predicting the OS of HCC patients after TACE treatment were 0.779, 0.803, 0.745, 0.858 and 0.893, respectively, in the training group and 0.635, 0.651, 0.644, 0.778 and 0.803, respectively, in the validation group. The M-C model had the best predictive performance.</p><p><strong>Conclusion: </strong>Multiparameter MRI-based radiomic features may be helpful for predicting OS after TACE treatment in HCC patients. The inclusion of clinical indicators such as inflammation scores can improve the predictive performance.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"2049-2061"},"PeriodicalIF":4.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognosis of Neoadjuvant HAIC and Lenvatinib Followed by Surgery versus Direct Resection for Resectable or Borderline Resectable Hepatocellular Carcinoma: A Real-World Study.","authors":"Yuan Shi, Kai Chen, Xinlin Li, Xiaodong Li, Xu Feng, Xinhua Wu, Shiguai Qi, Zhengrong Shi","doi":"10.2147/JHC.S480852","DOIUrl":"10.2147/JHC.S480852","url":null,"abstract":"<p><strong>Purpose: </strong>This research aims to compare the efficacy of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) combined with Lenvatinib (Len) to direct liver resection (LR) in patients with resectable or borderline resectable hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>This retrospective study included 154 patients with hepatocellular carcinoma (HCC) treated at the a large-scale hepatocellular carcinoma Research Center between March 2019 and June 2023. Patients were assigned to one of two groups: 63 received neoadjuvant hepatic arterial infusion chemotherapy (HAIC) combined with Lenvatinib followed by liver resection (HAIC+Len→LR), while 91 received direct liver resection (LR). The primary outcomes assessed were median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and adverse events (AEs).</p><p><strong>Results: </strong>Patients in the HAIC+Len→LR group demonstrated significantly longer median overall survival (mOS) (40.1 months vs 35.9 months, P=0.001) and median progression-free survival (mPFS) (32.8 months vs 23.8 months, P=0.0023) compared to the LR group. Preoperative complete response (CR) to HAIC was associated with better median duration of response (mDOR) and mOS compared to partial response (PR) (not reached vs 28.9 months, P=0.006; 40.0 vs 29.1 months, P=0.037). Subgroup analysis revealed no significant difference in OS or PFS between the HAIC+Len→LR and LR groups in early Barcelona Clinic Liver Cancer (BCLC) stages. However, in late BCLC stages, the HAIC+Len→LR group exhibited significantly improved OS and PFS (HR 0.471, P=0.016; HR 0.551, P=0.022). Treatment-related grade ≥3 adverse events were comparable between the two groups.</p><p><strong>Conclusion: </strong>For patients with resectable or marginally resectable HCC in the intermediate to advanced stages of BCLC, surgery after neoadjuvant HAIC+Len may offer improved long-term prognosis.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"2063-2076"},"PeriodicalIF":4.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Indicator Changes in Hepatocellular Carcinoma Undergoing TACE Plus ICIs and Anti-VEGF Antibodies/TKIs: A Prognostic Biomarker Analysis.","authors":"Xiao-Yang Xu, Ze Wang, Chen-You Liu, Hao-Dong Wu, Ze-Xin Hu, Yu-Ying Lin, Shuai Zhang, Jian Shen, Bin-Yan Zhong, Xiao-Li Zhu","doi":"10.2147/JHC.S487472","DOIUrl":"10.2147/JHC.S487472","url":null,"abstract":"<p><strong>Objective: </strong>To explore changing trends in circulating immune indicators of hepatocellular carcinoma (HCC) undergoing TACE plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/TKIs and to elucidate the relationship between immune response and tumor prognosis.</p><p><strong>Materials: </strong>This single-center retrospective study included patients with unresectable HCC undergoing TACE plus ICIs and anti-VEGF antibodies/TKIs from March 11, 2019, to February 15, 2024. Peripheral blood samples were collected at baseline and every cycle, from which blood cell counts and immune indicators were analyzed. The primary outcome was the objective response rate (ORR) at the first evaluation. According to the first evaluation based on mRECIST, patients were classified into PD, SD, and OR groups for analysis. Further subgroup analysis was performed on the OR group based on whether experiencing progression after the first evaluation. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The neutrophil-to-lymphocyte ratio (NLR) was measured by the complete blood count. Simple linear regression was employed to examine the dynamic trends.</p><p><strong>Results: </strong>A total of 63 patients were enrolled, with an ORR of 55.6% and a disease control rate (DCR) of 87.3% at the first evaluation. The median overall survival (mOS) was 27.5 months (95% CI: 22.5-32.5 months). In the OR group (n=35), more active immune responses, expressed in a decrease in CD3^-CD19⁺ (<i>p</i>=0.004), CFB (<i>p</i>=0.027), NLR (<i>p</i><0.001) and an increase in Ig λ (<i>p</i>=0.010), Ig κ (<i>p</i>=0.037), Ig A (<i>p</i>=0.005), Ig G (<i>p</i>=0.006), were related to better prognosis, while similar patterns seen in the OR-nPD subgroup. Concurrently, no significant differences were noted in the PD group (n=8).</p><p><strong>Conclusion: </strong>The combination therapy may modify the tumor microenvironment of HCC. Changing trends in circulating immune indicators and NLR can serve as potential biomarkers for predicting tumor response and guiding clinical treatment.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"2019-2032"},"PeriodicalIF":4.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transarterial Chemoembolization Combined with Microwave Ablation in Elderly Patients with Recurrent Medium or Large Hepatocellular Carcinoma.","authors":"Chuxiao Zhang, Yuelan Qin, Yangguang Song, Yingying Liu, Xiaodong Zhu","doi":"10.2147/JHC.S455411","DOIUrl":"10.2147/JHC.S455411","url":null,"abstract":"<p><strong>Purpose: </strong>There are insufficient data about the optimal treatment for older patients with recurring medium or large hepatocellular carcinoma (HCC). The study intended to assess the effect of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) in an elderly cohort through a retrospective analysis.</p><p><strong>Methods: </strong>From 2011 to 2018, a cohort of individuals (age ≥70 years) with recurrent HCC tumors ranging from 3.1 cm to 7 cm underwent either a combination treatment of TACE and MWA (n = 43) or surgical intervention (n = 33). Using the Inverse Probability of Treatment Weighting (IPTW) technique, factors of disease-free survival (DFS), overall survival (OS), and rates of major adverse events were analyzed, retrospectively.</p><p><strong>Results: </strong>The group that underwent surgery had a greater history of alcohol use before treatment (<i>P</i>= 0.001), as well as a higher Barcelona Clinic Liver Cancer (BCLC) stage for the primary tumor before treatment (<i>P</i>= 0.014) and a higher primary tumor location before treatment (<i>P</i>= 0.045). The TACE-MWA group had DFS rates of 86.2%, 68.8%, and 60.4% at 1, 3, and 5 years, while the surgery group had rates of 53.0%, 42.2%, and 25.8% at the same time points. In the TACE-MWA treatment group, survival rates at 1 year, 3 years, and 5 years post-treatment were recorded as 93.0%, 80.8%, and 65.7%, respectively, while in the surgery group, they were 62.7%, 46.9%, and 42.6%. In the univariate analysis using IPTW, the type of treatment was found to have a significant correlation with disease progression (hazard ratio [HR] 0.41, 95% CI 0.20-0.86, <i>P</i>=0.017). IPTW multivariate analysis showed that treatment modality (HR, 0.35; 95% CI, 0.17 to 0.79; <i>P</i>= 0.011) was the only significant prognostic factor for OS.</p><p><strong>Conclusion: </strong>In elderly patients with recurrent 3.1 cm≤ HCC ≤ 7 cm, TACE-WMA was superior to surgery in the respects of DFS and OS.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"2005-2017"},"PeriodicalIF":4.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognosis of Patients with Hepatocellular Carcinoma Treated with TACE: A New Score Combining Alpha-Fetoprotein and Des-γ-Carboxy Prothrombin.","authors":"Shang-Yu Lu, Han-Yao Sun, Yan Zhou, Xi Luo, Sheng Liu, Wei-Zhong Zhou, Hai-Bin Shi, Wei Yang, Wei Tian","doi":"10.2147/JHC.S481393","DOIUrl":"10.2147/JHC.S481393","url":null,"abstract":"<p><strong>Purpose: </strong>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).</p><p><strong>Patients and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1979-1992"},"PeriodicalIF":4.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Atezolizumab Plus Bevacizumab Combined with Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Real-World Study.","authors":"Xiao Shen, Jin-Xing Zhang, Jin Liu, Sheng Liu, Hai-Bin Shi, Yuan Cheng, Qing-Qiao Zhang, Guo-Wen Yin, Qing-Quan Zu","doi":"10.2147/JHC.S478604","DOIUrl":"10.2147/JHC.S478604","url":null,"abstract":"<p><strong>Purpose: </strong>Transarterial chemoembolization (TACE), when used in combination with immunotherapy and antiangiogenic therapy, has been shown to have synergistic anticancer effects. The aim of this study was to further assess the efficacy and safety of TACE combined with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC) in the real world.</p><p><strong>Methods: </strong>Between August 2021 and September 2023, clinical information was collected from consecutive HCC patients who received treatment via TACE-Atezo/Bev at four tertiary institutions. This study evaluated the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) as outcomes. Predictors for OS and PFS were also analyzed. Treatment-related adverse events (TRAEs) were recorded and assessed.</p><p><strong>Results: </strong>Ninety-two patients were enrolled in this study, with a median follow-up duration of 14.1 months. The ORRs based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) and RECIST 1.1 criteria were 54.3% and 41.3%, respectively. The median OS and PFS of the patients were 15.9 months [95% confidence interval (CI), 14.5-17.2 months] and 9.1 months (95% CI, 7.4-10.8 months), respectively. Multivariate analyses revealed that the Eastern Cooperative Oncology Group score and neutrophil‒lymphocyte ratio were independent risk factors for OS, whereas tumor size and extrahepatic metastasis were independent risk factors for PFS. Grade 3/4 TRAEs occurred in 16.3% (15/92) of the patients and were controlled conservatively.</p><p><strong>Conclusion: </strong>The combination of Atezo/Bev with TACE demonstrated acceptable synergistic therapeutic effects and manageable safety profiles in patients with unresectable HCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1993-2003"},"PeriodicalIF":4.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy(HAIC) Combined with PD-1 Inhibitors for Advanced Hepatocellular Carcinoma with Macrovascular Invasion: A Multicenter Propensity Score Matching Analysis.","authors":"Fengtao Zhang, Sheng Zhong, Qiming Wei, Haiming Zhang, Honglei Hu, Bicheng Zeng, Xiang Zheng","doi":"10.2147/JHC.S483824","DOIUrl":"10.2147/JHC.S483824","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the efficacy and safety of HAIC combined with programmed cell death protein-1 (PD1) inhibitors in MVI-positive advanced hepatocellular carcinoma(HCC).</p><p><strong>Methods: </strong>From September 2017 to May 2019, we retrospectively collected the clinical data from three medical centers in China pertaining to patients diagnosed with BCLC C stage HCC with MVI and receiving treatment with a combination of HAIC and PD-1 inhibitors treatment or HAIC alone, and we compared the efficacy of HAIC combined with PD-1 inhibitors and HAIC monotherapy. Propensity score matching(PSM) was utilized to adjust for baseline differences between groups. Survival outcomes and tumor response rate were used to assess survival benefits, while the incidence of adverse events was used to evaluate safety.</p><p><strong>Results: </strong>After screening for eligibility, 489 patients diagnosed with HCC and concomitant MVI were enrolled. Of these, 173 patients received treatment combining HAIC with PD-1 inhibitors, while 316 patients underwent HAIC monotherapy. After PSM adjustment, the combination therapy group demonstrate superior survival outcomes. Median overall survival(OS) and progression free survival(PFS) were 31.8 months and 10.8 months, respectively, significantly higher than those in the monotherapy group (OS: 10.0 months; PFS: 6.1 months; both P<0.0001). Moreover, ORR and DCR remained significantly elevated in the combination therapy group (ORR: 44.3% vs 20.4%, P<0.0001; DCR: 89.8% vs 82.0%, P=0.041). Safety profiles indicated no significant differences in adverse event rates between the two treatment groups, encompassing both overall and grade-specific assessments.</p><p><strong>Conclusion: </strong>Compared to HAIC alone, the combination of HAIC with PD-1 inhibitors represents a more promising and effective approach for patients with HCC complicated by macrovascular invasion.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1961-1978"},"PeriodicalIF":4.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incomplete Thermal Ablation-Induced FOXP4-Mediated Promotion of Malignant Progression in Liver Cancer via NDST2.","authors":"Weijun Wan, Yunjing Pan, Jinshu Pang, Xiumei Bai, Lipeng Li, Tong Kang, Jiamin Chen, Rong Wen, Dongyue Wen, Hong Yang, Yun He","doi":"10.2147/JHC.S476612","DOIUrl":"10.2147/JHC.S476612","url":null,"abstract":"<p><strong>Purpose: </strong>The explosive progression of residual hepatocellular carcinoma (HCC) following incomplete thermal ablation is challenging, and the underlying mechanisms require further exploration. We investigated the mechanism by which Forkhead box P4 (FOXP4) promotes the malignant transformation of residual HCC cells through N-deacetylase and N-sulfotransferase 2 (NDST2) after incomplete thermal ablation.</p><p><strong>Methods: </strong>The clinical significance of FOXP4 and NDST2 in HCC was evaluated using big data analysis. FOXP4 expression was detected in clinical samples of HCC. The gene expression levels in an in vitro heat-stressed HCC cell model were determined using quantitative real-time PCR (RT-qPCR) and Western blotting. The effects of the genes on heat-stressed HCC cells were investigated using Cell Counting Kit-8 (CCK-8), scratch, Transwell migration, and invasion assays. Additionally, the regulatory relationship between FOXP4 and NDST2 was validated using the Cleavage Under Targets and Tagmentation (CUT&Tag) experiments and phenotypic assays.</p><p><strong>Results: </strong>High FOXP4 expression was correlated with liver cancer occurrence and development. In the heat-stressed HCC cell model, downregulating FOXP4 inhibited cancer cell progression. Besides, there was a positive association between FOXP4 and NDST2 in liver cancer. Suppressing FOXP4 reduced NDST2 expression in the heat-stressed HCC cells. Furthermore, reducing NDST2 expression weakened the biological behavior of heat-stressed HCC cells.</p><p><strong>Conclusion: </strong>FOXP4 and NDST2 are crucial in the incomplete thermal ablation of residual cancer. FOXP4 might regulate the biological progression of residual HCC after incomplete thermal ablation through NDST2.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1945-1959"},"PeriodicalIF":4.2,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Growth Pattern and Intra- and Peritumoral Radiomics Combined for Prediction of Initial TACE Outcome in Patients with Primary Hepatocellular Carcinoma.","authors":"Jiaying Li, Minhui Zhou, Yahan Tong, Haibo Chen, Ruisi Su, Yinghui Tao, Guodong Zhang, Zhichao Sun","doi":"10.2147/JHC.S480554","DOIUrl":"https://doi.org/10.2147/JHC.S480554","url":null,"abstract":"<p><strong>Purpose: </strong>Non-invasive methods are urgently needed to assess the efficacy of transarterial chemoembolization (TACE) and to identify patients with hepatocellular carcinoma (HCC) who may benefit from this procedure. This study, therefore, aimed to investigate the predictive ability of tumor growth patterns and radiomics features from contrast-enhanced magnetic resonance imaging (CE-MRI) in predicting tumor response to TACE among patients with HCC.</p><p><strong>Patients and methods: </strong>A retrospective study was conducted on 133 patients with HCC who underwent TACE at three centers between January 2015 and April 2023. Enrolled patients were divided into training, testing, and validation cohorts. Rim arterial phase hyperenhancement (Rim APHE), tumor growth patterns, nonperipheral washout, markedly low apparent diffusion coefficient (ADC) value, intratumoral arteries, and clinical baseline features were documented for all patients. Radiomics features were extracted from the intratumoral and peritumoral regions across the three phases of CE-MRI. Seven prediction models were developed, and their performances were evaluated using receiver operating characteristic (ROC) and decision curve analysis (DCA).</p><p><strong>Results: </strong>Tumor growth patterns and albumin-bilirubin (ALBI) score were significantly correlated with tumor response. Tumor growth patterns also showed a positive correlation with tumor burden (r = 0.634, P = 0.000). The Peritumor (AUC = 0.85, 0.71, and 0.77), Clinics_Peritumor (AUC = 0.86, 0.77, and 0.81), and Tumor_Peritumor (AUC = 0.87, 0.77, and 0.80) models significantly outperformed the Clinics and Tumor models (P < 0.05), while the Clinics_Tumor_Peritumor model (AUC = 0.88, 0.81, and 0.81) outperformed the Clinics (AUC = 0.67, 0.77, and 0.75), Tumor (AUC = 0.78, 0.72, and 0.68), and Clinics_Tumor (AUC = 0.82, 0.83, and 0.78) models (P < 0.05 or 0.053, respectively). The DCA curve demonstrated better predictive performance within a specific threshold probability range for Clinics_Tumor_Peritumor.</p><p><strong>Conclusion: </strong>Combining tumor growth patterns, intra- and peri-tumoral radiomics features, and ALBI score could be a robust tool for non-invasive and personalized prediction of treatment response to TACE in patients with HCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1927-1944"},"PeriodicalIF":4.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}