Pub Date : 2024-08-20eCollection Date: 2024-01-01DOI: 10.2147/JHC.S479810
Guimin Hou, Feng Zhang, Xielin Feng, Yan Chen, Jinliang Zhang, Haiqing Wang
Purpose: 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.
Patients and methods: 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.
Results: 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.
Conclusion: Neoadjuvant treatment presents a promising treatment option for HCC patients with type I/II PVTT.
目的：肝切除术可为伴有 I/II 型门静脉肿瘤血栓形成（PVTT）的肝细胞癌（HCC）患者带来更好的生存获益。然而，术后复发率仍然很高。我们讨论了新辅助治疗是否能减少这些患者的HCC复发：回顾性纳入138例患有I-II型PVTT的可切除HCC患者。新辅助治疗方案包括酪氨酸激酶抑制剂（TKI）、程序性死亡1（PD-1）抗体和经动脉化疗栓塞（TACE）。对短期和长期疗效进行了比较。为尽量减少潜在混杂因素的影响，进行了倾向评分匹配（PSM）：33名患者接受了新辅助治疗，105名患者接受了单纯手术治疗。根据修改后的实体瘤反应评估标准，新辅助治疗组中有 7 例（21.2%）患者病情稳定，13 例（39.4%）患者部分应答，13 例（39.4%）患者完全应答。通过 PSM，新辅助治疗减少了微血管侵犯（24.1% vs 50.0%，P=0.021）、卫星结节（6.9% vs 24.1%，P=0.036），减少了甲胎蛋白>20（ng/mL）的患者（37.9% vs 69.0%，P=0.006）。新辅助治疗减少了肿瘤复发，延长了生存期。多变量分析发现，新辅助治疗是总生存率和无复发生存率的独立保护因素：结论：新辅助治疗为I/II型PVTT的HCC患者提供了一种前景广阔的治疗方案。
{"title":"Neoadjuvant-Based Triple Therapy for Hepatocellular Carcinoma with Type I/II Portal Vein Tumor Thrombosis.","authors":"Guimin Hou, Feng Zhang, Xielin Feng, Yan Chen, Jinliang Zhang, Haiqing Wang","doi":"10.2147/JHC.S479810","DOIUrl":"10.2147/JHC.S479810","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Patients and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Neoadjuvant treatment presents a promising treatment option for HCC patients with type I/II PVTT.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1581-1595"},"PeriodicalIF":4.2,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055740","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}
Purpose: Oxidative stress plays a critical role in promoting tumor resistance to hypoxia and chemotherapeutic drugs. However, the prognostic role of oxidative stress-related genes (OSRGs) in hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) has not been fully explored.
Methods: We used transcriptome data from the GSE104580 cohort containing patients marked as responders or nonresponders to TACE therapy to identify differentially expressed OSRGs associated with TACE response (TR-OSRGs). We created a TR-OSRG prognostic signature based on TR-OSRGs using least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses in a training cohort of patients with HCC (TCGA-LIHC). We verified this prognostic signature in two external cohorts of patients who received TACE for HCC (GSE14520-TACE and ZS-TACE-37). Finally, we constructed a prognostic nomogram model for predicting survival probability of patients with HCC based on Cox regression analysis.
Results: The TR-OSRG prognostic signature was created and shown to be a robust independent prognostic factor for treatment response and outcomes for HCC after TACE therapy. Risk scores based on this signature correlated with tumor stage and grade. Tumor samples from patients with higher risk scores exhibited more infiltration of immune cells and significantly increased expression of immune checkpoint genes. We also developed a nomogram for patients with HCC based on the TR-OSRG prognostic signature and clinical parameters; this nomogram was a useful quantitative analysis tool for predicting patient survival.
Conclusion: The TR-OSRGs signature exhibited good performance in predicting treatment response and outcomes in patients with HCC treated with TACE.
{"title":"An Oxidative Stress-Related Prognostic Signature Predicts Treatment Response and Outcomes for Hepatocellular Carcinoma After Transarterial Chemoembolization.","authors":"Hui Ma, Ting Yu, Zhong-Chen Li, Lan Zhang, Rong-Xin Chen, Zheng-Gang Ren","doi":"10.2147/JHC.S465592","DOIUrl":"10.2147/JHC.S465592","url":null,"abstract":"<p><strong>Purpose: </strong>Oxidative stress plays a critical role in promoting tumor resistance to hypoxia and chemotherapeutic drugs. However, the prognostic role of oxidative stress-related genes (OSRGs) in hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) has not been fully explored.</p><p><strong>Methods: </strong>We used transcriptome data from the GSE104580 cohort containing patients marked as responders or nonresponders to TACE therapy to identify differentially expressed OSRGs associated with TACE response (TR-OSRGs). We created a TR-OSRG prognostic signature based on TR-OSRGs using least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses in a training cohort of patients with HCC (TCGA-LIHC). We verified this prognostic signature in two external cohorts of patients who received TACE for HCC (GSE14520-TACE and ZS-TACE-37). Finally, we constructed a prognostic nomogram model for predicting survival probability of patients with HCC based on Cox regression analysis.</p><p><strong>Results: </strong>The TR-OSRG prognostic signature was created and shown to be a robust independent prognostic factor for treatment response and outcomes for HCC after TACE therapy. Risk scores based on this signature correlated with tumor stage and grade. Tumor samples from patients with higher risk scores exhibited more infiltration of immune cells and significantly increased expression of immune checkpoint genes. We also developed a nomogram for patients with HCC based on the TR-OSRG prognostic signature and clinical parameters; this nomogram was a useful quantitative analysis tool for predicting patient survival.</p><p><strong>Conclusion: </strong>The TR-OSRGs signature exhibited good performance in predicting treatment response and outcomes in patients with HCC treated with TACE.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1569-1580"},"PeriodicalIF":4.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000095","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}
Purpose: The majority of new diagnoses of hepatocellular carcinoma (HCC) still pertain to unresectable cases. Currently, the combination therapy of tyrosine kinase inhibitors (TKIs) and programmed cell death protein-1 (PD-1) inhibitors has become the mainstream treatment. According to multiple clinical guidelines, it is strongly advised to consider local therapy as the primary treatment choice for uHCC. This research was conducted to examine the safety and effectiveness of combining hepatic arterial infusion chemotherapy (HAIC) with TKIs and PD-1 inhibitors for the treatment of uHCC. Methods: Between 2015 and 2020, 208 HCC patients received HAIC alone or HAIC in combination with TKIs and PD-1 inhibitors. The overall survival(OS), and progression-free survival(PFS) and the best treatment response were compared between the two treatment groups. Propensity score matching (PSM)was used to minimize confounding bias. Results: Among the enrolled patients, 116 patients (55.8%) received combination therapy, while 92 patients (44.2%) received HAIC alone. The baseline characteristics were similar between the two groups. After PSM, 82 pairs of well-matched liver cancer patients were selected; the overall response rate in the combination group trended better than that in the HAIC alone group. The hazard ratios (HRs) for OS and PFS of the combination approach compared to the HAIC-alone approach were 0.47 (95% CI, 0.322– 0.687; p< 0.001) and 0.58 (95% CI, 0.397– 0.848; p=0.005), respectively. Conclusion: For uHCC patients, combination therapy can provide better OS and PFS compared to HAIC alone.
{"title":"Clinical Therapy: HAIC Combined with Tyrosine Kinase Inhibitors and Programmed Cell Death Protein-1 Inhibitors versus HAIC Alone for Unresectable Hepatocellular Carcinoma","authors":"Baokun Liu, Lujun Shen, Wen Liu, Zhiyong Zhang, Jieqiong Lei, Zhengguo Li, Qinquan Tan, Hengfei Huang, Xingdong Wang, Weijun Fan","doi":"10.2147/jhc.s470345","DOIUrl":"https://doi.org/10.2147/jhc.s470345","url":null,"abstract":"<strong>Purpose:</strong> The majority of new diagnoses of hepatocellular carcinoma (HCC) still pertain to unresectable cases. Currently, the combination therapy of tyrosine kinase inhibitors (TKIs) and programmed cell death protein-1 (PD-1) inhibitors has become the mainstream treatment. According to multiple clinical guidelines, it is strongly advised to consider local therapy as the primary treatment choice for uHCC. This research was conducted to examine the safety and effectiveness of combining hepatic arterial infusion chemotherapy (HAIC) with TKIs and PD-1 inhibitors for the treatment of uHCC.<br/><strong>Methods:</strong> Between 2015 and 2020, 208 HCC patients received HAIC alone or HAIC in combination with TKIs and PD-1 inhibitors. The overall survival(OS), and progression-free survival(PFS) and the best treatment response were compared between the two treatment groups. Propensity score matching (PSM)was used to minimize confounding bias.<br/><strong>Results:</strong> Among the enrolled patients, 116 patients (55.8%) received combination therapy, while 92 patients (44.2%) received HAIC alone. The baseline characteristics were similar between the two groups. After PSM, 82 pairs of well-matched liver cancer patients were selected; the overall response rate in the combination group trended better than that in the HAIC alone group. The hazard ratios (HRs) for OS and PFS of the combination approach compared to the HAIC-alone approach were 0.47 (95% CI, 0.322– 0.687; p< 0.001) and 0.58 (95% CI, 0.397– 0.848; p=0.005), respectively.<br/><strong>Conclusion:</strong> For uHCC patients, combination therapy can provide better OS and PFS compared to HAIC alone.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, TKIs, PD-1, HAIC, combination therapy<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"47 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose:P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC. Methods: We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal. Results: We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10– 1.48) and 0.77 (0.66– 0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (Ptrend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells. Conclusion: We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.
目的：P53 是一种与致癌密切相关的抑制基因。然而，p53 信号通路中的遗传变异与乙型肝炎病毒（HBV）相关肝细胞癌（HCC）预后之间的关系仍不清楚。本研究旨在分析 p53 通路相关基因的单核苷酸多态性（SNPs）与 HBV-HCC 患者生存率之间的关系：我们采用 Cox 比例危险度回归分析法，在加性遗传模型中评估了 p53 通路 70 个基因中 4698 个 SNP 与 866 例患者总生存期（OS）之间的关系。在单病灶分析中，采用逐步多变量 Cox 回归分析确定已识别 SNP 的独立效应。我们还利用GTEx和1000基因组计划的数据分析了定量性状位点（eQTL）的表达，并利用RegulomeDB v2.2、3DSNP v2.0、HaploReg v4.2和VannoPortal对SNPs进行了功能预测：我们发现，CD82 rs7925603 A > G和PMAIP1 rs4396625 A > T这两个新型SNP与OS显著独立相关[调整后危险比（HRs）和95%置信区间（CI）分别为1.27（1.10- 1.48）和 0.77（0.66- 0.91）；P = 0.001 和 = 0.002]，并且这些 SNP 的合并风险基因型与 HBV-HCC 患者的 OS 有显著相关性（Ptrend <0.001）。GTEx 数据集中的进一步 eQTL 分析表明，rs7925603 G 等位基因与较低的 CD82 mRNA 表达水平相关，而 rs4396625 T 等位基因与较高的全血细胞中 PMAIP1 mRNA 表达水平相关：我们在 p53 通路中的 CD82 和 PMAIP1 中发现了两个与生存相关的 SNPs，它们可能通过改变 mRNA 表达的机制影响 HBV-HCC 的生存。关键词：肝细胞癌、乙型肝炎病毒、p53 信号通路、遗传变异、存活率
{"title":"Genetic Variants in p53 Pathway Genes Affect Survival of Patients with HBV-Related Hepatocellular Carcinoma","authors":"Liming Qin, Moqin Qiu, Jingmei Tang, Shuyan Liu, Qiuling Lin, Qiongguang Huang, Xiaoxia Wei, Qiuping Wen, Peiqin Chen, Zihan Zhou, Ji Cao, Xiumei Liang, Qian Guo, Cunli Nong, Yizhen Gong, Yuying Wei, Yanji Jiang, Hongping Yu, Yingchun Liu","doi":"10.2147/jhc.s459792","DOIUrl":"https://doi.org/10.2147/jhc.s459792","url":null,"abstract":"<strong>Purpose:</strong> <em>P53</em> is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC.<br/><strong>Methods:</strong> We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal.<br/><strong>Results:</strong> We found that two novel SNPs of <em>CD82</em> rs7925603 A > G and <em>PMAIP1</em> rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10– 1.48) and 0.77 (0.66– 0.91), respectively; <em>P</em> = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (<em>P</em><sub>trend</sub> < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower <em>CD82</em> mRNA expression levels, while the rs4396625 T allele was associated with higher <em>PMAIP1</em> mRNA expression levels in whole blood cells.<br/><strong>Conclusion:</strong> We identified two observed survival-associated SNPs in <em>CD82</em> and <em>PMAIP1</em> in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, hepatitis B virus, p53 signaling pathway, genetic variants, survival<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"3 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuan-Jie Liu, Jing-Xiao Li, Jie-Pin Li, Yi-Dou Hu, Zhi-Bin Ma, Wei Huang, Shen-Lin Liu, Xi Zou
Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for novel therapeutic targets. This study aimed to elucidate the role of endoplasmic reticulum membrane protein complex subunit 1 (EMC1) in HCC progression and its therapeutic potential. Methods: Publicly available sequencing data and biopsy specimens were analyzed to assess EMC’s clinical value and functions in HCC. In vitro experiments validated EMC functions, and multiplex immunofluorescence analysis examined EMC-associated sorafenib resistance mechanisms. EMC1 expression was knocked down in HCC cell lines, followed by cell viability, wound healing, and transwell migration assays. Tumor growth and response to sorafenib treatment were evaluated in mouse models. Metabolomic analysis assessed changes in the TCA cycle. Results: EMC genes were aberrantly expressed in HCC, and high EMC1 expression correlated with poorer survival rates. EMC1 disruption enhanced HCC cells’ sensitivity to sorafenib, reducing cell viability, increasing apoptosis, and decreasing tumor size and weight. EMC1 maintained cancer cell stemness and promoted M2 macrophage infiltration. Metabolomic analysis revealed significant changes in the TCA cycle, indicating EMC1’s role in HCC metabolic reprogramming. Importantly, EMC1 is highly associated with sorafenib resistance, potentially linked to CTNNB1 mutation or activation. Conclusion: EMC1 plays a critical role in regulating the sorafenib resistance in HCC. Targeting EMC1 may improve HCC treatment efficacy.
{"title":"Endoplasmic Reticulum Membrane Protein Complex Regulates Cancer Stem Cells and is Associated with Sorafenib Resistance in Hepatocellular Carcinoma","authors":"Yuan-Jie Liu, Jing-Xiao Li, Jie-Pin Li, Yi-Dou Hu, Zhi-Bin Ma, Wei Huang, Shen-Lin Liu, Xi Zou","doi":"10.2147/jhc.s474343","DOIUrl":"https://doi.org/10.2147/jhc.s474343","url":null,"abstract":"<strong>Background:</strong> Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for novel therapeutic targets. This study aimed to elucidate the role of endoplasmic reticulum membrane protein complex subunit 1 (EMC1) in HCC progression and its therapeutic potential.<br/><strong>Methods:</strong> Publicly available sequencing data and biopsy specimens were analyzed to assess EMC’s clinical value and functions in HCC. In vitro experiments validated EMC functions, and multiplex immunofluorescence analysis examined EMC-associated sorafenib resistance mechanisms. EMC1 expression was knocked down in HCC cell lines, followed by cell viability, wound healing, and transwell migration assays. Tumor growth and response to sorafenib treatment were evaluated in mouse models. Metabolomic analysis assessed changes in the TCA cycle.<br/><strong>Results:</strong> EMC genes were aberrantly expressed in HCC, and high EMC1 expression correlated with poorer survival rates. EMC1 disruption enhanced HCC cells’ sensitivity to sorafenib, reducing cell viability, increasing apoptosis, and decreasing tumor size and weight. EMC1 maintained cancer cell stemness and promoted M2 macrophage infiltration. Metabolomic analysis revealed significant changes in the TCA cycle, indicating EMC1’s role in HCC metabolic reprogramming. Importantly, EMC1 is highly associated with sorafenib resistance, potentially linked to CTNNB1 mutation or activation.<br/><strong>Conclusion:</strong> EMC1 plays a critical role in regulating the sorafenib resistance in HCC. Targeting EMC1 may improve HCC treatment efficacy.<br/><br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"85 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Lenvatinib is the first-line treatment option for patients with advanced hepatocellular carcinoma (HCC); however, the impact of lenvatinib resistance on patient prognosis is unknown. Methods: We recruited all patients with advanced HCC who received first-line lenvatinib treatment between February 2019 and February 2023 at two medical centers in China, according to the selection criteria. The patients were divided into primary and secondary resistance groups based on tumor progression within 3 months. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS). Logistic regression and Cox proportional hazards models were used to explore factors influencing drug resistance and prognosis. The study end points were drug resistance, PFS, and OS. Results: A total of 531 patients met the study criteria, with 169 (31.8%) and 362 (68.2%) patients in the primary and secondary groups, respectively. An alpha-fetoprotein (AFP) concentration > 400 ng/mL was an independent risk factor for primary drug resistance. Patients in the primary group had a significantly shorter median OS (11.0 vs 31.0 months, P< 0.001) than those in the secondary group. The 1-, 2- and 3-year cumulative survival rates in the primary group were 46.3%, 22.2%, and 10.1%, while those in the secondary group were 82.3%, 59.1% and 44.9%, respectively. Compared to tyrosine kinase inhibitor (TKI) monotherapy, longer median PFS (4.0 vs 7.0 months, P=0.008) and OS (11.0 vs 23.0 months, P=0.024) were achieved with the combination of a TKI plus a PD-1 inhibitor as a second-line therapy after lenvatinib resistance. Conclusion: There is a high rate of primary resistance to lenvatinib in patients with HCC and the prognosis for those with primary resistance is poor. TKI combined with PD-1 inhibitors should be preferentially recommended for lenvatinib-resistant patients.
背景：来伐替尼是晚期肝细胞癌（HCC）患者的一线治疗方案，但来伐替尼耐药对患者预后的影响尚不清楚：来伐替尼是晚期肝细胞癌（HCC）患者的一线治疗方案，然而，来伐替尼耐药对患者预后的影响尚不清楚：根据选择标准，我们招募了2019年2月至2023年2月期间在中国两家医疗中心接受来伐替尼一线治疗的所有晚期HCC患者。根据3个月内肿瘤进展情况将患者分为原发性耐药组和继发性耐药组。采用卡普兰-梅耶法计算无进展生存期（PFS）和总生存期（OS）。采用逻辑回归和考克斯比例危险模型探讨影响耐药性和预后的因素。研究终点为耐药性、PFS和OS：共有 531 例患者符合研究标准，其中 169 例（31.8%）和 362 例（68.2%）分别属于初诊组和复诊组。甲胎蛋白（AFP）浓度> 400 ng/mL是原发性耐药的独立风险因素。初治组患者的中位生存期（11.0 个月 vs 31.0 个月，P< 0.001）明显短于复治组。初治组患者的1年、2年和3年累积生存率分别为46.3%、22.2%和10.1%，而复治组患者的1年、2年和3年累积生存率分别为82.3%、59.1%和44.9%。与酪氨酸激酶抑制剂（TKI）单药治疗相比，在来伐替尼耐药后，TKI加PD-1抑制剂联合治疗作为二线治疗，可获得更长的中位PFS（4.0个月 vs 7.0个月，P=0.008）和OS（11.0个月 vs 23.0个月，P=0.024）：结论：来伐替尼在HCC患者中的原发性耐药率很高，原发性耐药患者的预后较差。对于来伐替尼耐药患者，应优先推荐TKI联合PD-1抑制剂。
{"title":"Impact of Type of Lenvatinib Resistance on Prognosis and Second-Line Regimen in Patients with Virus-Associated HCC","authors":"Yijie Zhang, Jin Lei, Huaxing Ma, Shi Zuo","doi":"10.2147/jhc.s476439","DOIUrl":"https://doi.org/10.2147/jhc.s476439","url":null,"abstract":"<strong>Background:</strong> Lenvatinib is the first-line treatment option for patients with advanced hepatocellular carcinoma (HCC); however, the impact of lenvatinib resistance on patient prognosis is unknown.<br/><strong>Methods:</strong> We recruited all patients with advanced HCC who received first-line lenvatinib treatment between February 2019 and February 2023 at two medical centers in China, according to the selection criteria. The patients were divided into primary and secondary resistance groups based on tumor progression within 3 months. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS). Logistic regression and Cox proportional hazards models were used to explore factors influencing drug resistance and prognosis. The study end points were drug resistance, PFS, and OS.<br/><strong>Results:</strong> A total of 531 patients met the study criteria, with 169 (31.8%) and 362 (68.2%) patients in the primary and secondary groups, respectively. An alpha-fetoprotein (AFP) concentration > 400 ng/mL was an independent risk factor for primary drug resistance. Patients in the primary group had a significantly shorter median OS (11.0 vs 31.0 months, P< 0.001) than those in the secondary group. The 1-, 2- and 3-year cumulative survival rates in the primary group were 46.3%, 22.2%, and 10.1%, while those in the secondary group were 82.3%, 59.1% and 44.9%, respectively. Compared to tyrosine kinase inhibitor (TKI) monotherapy, longer median PFS (4.0 vs 7.0 months, P=0.008) and OS (11.0 vs 23.0 months, P=0.024) were achieved with the combination of a TKI plus a PD-1 inhibitor as a second-line therapy after lenvatinib resistance.<br/><strong>Conclusion:</strong> There is a high rate of primary resistance to lenvatinib in patients with HCC and the prognosis for those with primary resistance is poor. TKI combined with PD-1 inhibitors should be preferentially recommended for lenvatinib-resistant patients.<br/><br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"193 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05eCollection Date: 2024-01-01DOI: 10.2147/JHC.S464140
Zhuoran Li, Yirui Zhai, Fan Wu, Dayong Cao, Feng Ye, Yan Song, Shulian Wang, Yueping Liu, Yongwen Song, Yuan Tang, Hao Jing, Hui Fang, Shunan Qi, Ningning Lu, Ye-Xiong Li, Jianxiong Wu, Bo Chen
Purpose: This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies.
Patients and methods: Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30-65 Gy for planning target volume and 40-65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded.
Results: Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level >1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588-20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027-0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up.
Conclusion: Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.
{"title":"Radiotherapy with Targeted Therapy or Immune Checkpoint Inhibitors for Hepatocellular Carcinoma with Hepatic Vein and/or Inferior Vena Cava Tumor Thrombi.","authors":"Zhuoran Li, Yirui Zhai, Fan Wu, Dayong Cao, Feng Ye, Yan Song, Shulian Wang, Yueping Liu, Yongwen Song, Yuan Tang, Hao Jing, Hui Fang, Shunan Qi, Ningning Lu, Ye-Xiong Li, Jianxiong Wu, Bo Chen","doi":"10.2147/JHC.S464140","DOIUrl":"10.2147/JHC.S464140","url":null,"abstract":"<p><strong>Purpose: </strong>This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies.</p><p><strong>Patients and methods: </strong>Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30-65 Gy for planning target volume and 40-65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded.</p><p><strong>Results: </strong>Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level >1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588-20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027-0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up.</p><p><strong>Conclusion: </strong>Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1481-1493"},"PeriodicalIF":4.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11314522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916907","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}
Pub Date : 2024-08-05eCollection Date: 2024-01-01DOI: 10.2147/JHC.S468843
Jianming Yang, Yu Zhang, Yewu Chen, Yang Yang, Yinan Deng
Backgrounds and aims: Multiple regimens of immune checkpoint inhibitors (ICIs) plus targeted therapies are commonly prescribed as first-line treatments for unresectable hepatocellular carcinoma (uHCC). Here, we aimed to investigate the correlation between dynamic changes of neutrophil-to-lymphocyte ratio (NLR) and tumor response to the combination of ICIs and targeted therapies for uHCC.
Methods: Sixty-one patients who received ICIs plus targeted therapies for uHCC were enrolled in this retrospective study. The NLR before and at 3-6 weeks after treatments were assessed to calculate the dynamic NLR changes (ΔNLR). Multivariate logistic regression and Cox regression models were used to explore the relationship between dynamic NLR changes and tumor response or progression-free survival (PFS), respectively. Furthermore, we assessed the predictive effect of alpha-fetoprotein (AFP) changes in combination with dynamic NLR changes compared to AFP changes alone.
Results: The NLR at 3-6 weeks and ΔNLR after treatments significantly increased in patients who underwent progressive disease (PD), while the baseline NLR showed no significant difference between different tumor responses. Increased NLR and AFP after treatments were both independent predictors of PD (For NLR increase: OR, 2.28; 95% CI, 1.47-3.88, P < 0.001; For AFP increase: OR, 1.46; 95% CI, 1.03-2.17, P = 0.043), and correlated with worse PFS (for NLR increase: HR, 4.08; 95% CI, 1.99-8.36, P < 0.001; for AFP increase: HR, 2.10; 95% CI, 1.04-4.24, P = 0.039). The receiver operating characteristic (ROC) curve and net reclassification index (NRI) showed that the combination of dynamic NLR and AFP changes was better than AFP changes alone on predicting PD (AUC: 0.83 vs 0.68, P = 0.034; NRI: 0.340, P = 0.048) and PFS (AUC: 0.80 vs 0.70, P = 0.166; NRI: 0.431, P = 0.042).
Conclusion: Dynamic changes of NLR might be an effective predictor of the therapeutic response to ICIs plus targeted therapies for uHCC.
{"title":"Dynamic Changes of Neutrophil-to-Lymphocyte Ratio on Predicting Response of Immune Checkpoint Inhibitors Plus Targeted Therapies for Unresectable Hepatocellular Carcinoma.","authors":"Jianming Yang, Yu Zhang, Yewu Chen, Yang Yang, Yinan Deng","doi":"10.2147/JHC.S468843","DOIUrl":"10.2147/JHC.S468843","url":null,"abstract":"<p><strong>Backgrounds and aims: </strong>Multiple regimens of immune checkpoint inhibitors (ICIs) plus targeted therapies are commonly prescribed as first-line treatments for unresectable hepatocellular carcinoma (uHCC). Here, we aimed to investigate the correlation between dynamic changes of neutrophil-to-lymphocyte ratio (NLR) and tumor response to the combination of ICIs and targeted therapies for uHCC.</p><p><strong>Methods: </strong>Sixty-one patients who received ICIs plus targeted therapies for uHCC were enrolled in this retrospective study. The NLR before and at 3-6 weeks after treatments were assessed to calculate the dynamic NLR changes (ΔNLR). Multivariate logistic regression and Cox regression models were used to explore the relationship between dynamic NLR changes and tumor response or progression-free survival (PFS), respectively. Furthermore, we assessed the predictive effect of alpha-fetoprotein (AFP) changes in combination with dynamic NLR changes compared to AFP changes alone.</p><p><strong>Results: </strong>The NLR at 3-6 weeks and ΔNLR after treatments significantly increased in patients who underwent progressive disease (PD), while the baseline NLR showed no significant difference between different tumor responses. Increased NLR and AFP after treatments were both independent predictors of PD (For NLR increase: OR, 2.28; 95% CI, 1.47-3.88, P < 0.001; For AFP increase: OR, 1.46; 95% CI, 1.03-2.17, P = 0.043), and correlated with worse PFS (for NLR increase: HR, 4.08; 95% CI, 1.99-8.36, P < 0.001; for AFP increase: HR, 2.10; 95% CI, 1.04-4.24, P = 0.039). The receiver operating characteristic (ROC) curve and net reclassification index (NRI) showed that the combination of dynamic NLR and AFP changes was better than AFP changes alone on predicting PD (AUC: 0.83 vs 0.68, P = 0.034; NRI: 0.340, P = 0.048) and PFS (AUC: 0.80 vs 0.70, P = 0.166; NRI: 0.431, P = 0.042).</p><p><strong>Conclusion: </strong>Dynamic changes of NLR might be an effective predictor of the therapeutic response to ICIs plus targeted therapies for uHCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1495-1505"},"PeriodicalIF":4.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916906","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}
Qi-Feng Chen, Xiong-Ying Jiang, Yue Hu, Song Chen, Jun-Zhe Yi, Sui-Xing Zhong, Jiong-Liang Wang, Ning Lyu, Ming Zhao
Purpose: The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers. Methods: This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at &dollar30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results. Results: In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of &dollar10,507.89, while SoHAIC generated 1.66 QALY at a cost of &dollar32,971.56. When comparing SoHAIC to sorafenib, the ICER was &dollar18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters. Conclusion: In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.
{"title":"Additional Hepatic Arterial Infusion Chemotherapy to Sorafenib Was Cost-Effective for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis","authors":"Qi-Feng Chen, Xiong-Ying Jiang, Yue Hu, Song Chen, Jun-Zhe Yi, Sui-Xing Zhong, Jiong-Liang Wang, Ning Lyu, Ming Zhao","doi":"10.2147/jhc.s470470","DOIUrl":"https://doi.org/10.2147/jhc.s470470","url":null,"abstract":"<strong>Purpose:</strong> The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers.<br/><strong>Methods:</strong> This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at &dollar30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results.<br/><strong>Results:</strong> In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of &dollar10,507.89, while SoHAIC generated 1.66 QALY at a cost of &dollar32,971.56. When comparing SoHAIC to sorafenib, the ICER was &dollar18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters.<br/><strong>Conclusion:</strong> In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.<br/><br/><strong>Keywords:</strong> HCC, portal vein tumor thrombosis, sorafenib, HAIC, Cost-effectiveness<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"262 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141865472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Liver resection and ablation remain the most common therapeutic options for Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC), but there is a lack of evidence to show which is the most suitable therapy. This study aimed to make concurrent multi-arm comparisons of the short-term and long-term outcomes of percutaneous ablation (PA), open (OLR) or laparoscopic liver resection (LLR) for these patients. Patients and Methods: This was a retrospective observational cohort study. A series of generalized propensity score methods for multiple treatment groups were performed to concurrently compare the clinical outcomes of these three treatment options to balance potential confounders. Regression standardization was used to account for hazard of all-cause mortality and recurrence of intergroup differences. Results: Of the 1778 patients included, 1237, 307 and 234 underwent OLR, LLR and PA, respectively. After overlap weighting, which was the optimal adjustment strategy, patients in the minimally invasive group (LLR and PA groups) had few postoperative complications and short postoperative hospital stays (both P < 0.001). The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate were significantly higher in the LLR group when compared with the OLR and PA groups (RFS: 55.6% vs 48.0% vs 30.2%, P < 0.001; OS: 89.1% vs 79.7% vs 84.0%, P = 0.020). Multivariable Cox analysis and regression standardization showed that LLR was an independent factor for better RFS when compared with OLR and PA. In subgroup analysis, the long-term outcomes of patients with BCLC stage A HCC were consistent with the whole population. Conclusion: In the observational study using various covariate adjustment analysis with excellent balance, LLR is not only minimally invasive, but also provides better RFS and equivalent OS for patients with BCLC stage 0-A HCC when compared with OLR and PA.
目的：肝切除术和消融术仍是巴塞罗那临床肝癌（BCLC）0-A期肝细胞癌（HCC）最常见的治疗方案，但目前缺乏证据表明哪种疗法最合适。本研究旨在对这些患者接受经皮消融术（PA）、开腹肝切除术（OLR）或腹腔镜肝切除术（LLR）的短期和长期疗效进行多臂比较：这是一项回顾性观察队列研究。对多个治疗组进行了一系列广义倾向评分法，同时比较这三种治疗方案的临床结果，以平衡潜在的混杂因素。研究采用回归标准化方法计算全因死亡率和组间差异复发的风险：在纳入的 1778 例患者中，分别有 1237 例、307 例和 234 例接受了 OLR、LLR 和 PA 治疗。经过重叠加权（最佳调整策略）后，微创组（LLR 和 PA 组）患者术后并发症少，术后住院时间短（P 均为 0.001）。与 OLR 组和 PA 组相比，LLR 组的 5 年无复发生存率（RFS）和 5 年总生存率（OS）明显更高（RFS：55.6% vs 48.0% vs 30.2%，P < 0.001；OS：89.1% vs 79.7%，P < 0.001）：89.1% vs 79.7% vs 84.0%，P = 0.020）。多变量 Cox 分析和回归标准化显示，与 OLR 和 PA 相比，LLR 是提高 RFS 的独立因素。在亚组分析中，BCLC A期HCC患者的长期预后与整个人群一致：关键词：肝细胞癌；腹腔镜肝切除术；广义倾向评分分析；重叠加权；临床结果
{"title":"Comparisons of Percutaneous Ablation, Open or Laparoscopic Liver Resection for Barcelona Clinic Liver Cancer Stage 0-A Hepatocellular Carcinoma: A Concurrent Generalized Propensity Score Analysis","authors":"Zhi-Hang Chen, Qian Zhou, Ze-Bin Chen, Wen-Xuan Xie, Zi-Min Song, Shui-Rong Lin, Wei Wang, Shun-Li Shen, Ming Kuang","doi":"10.2147/jhc.s477265","DOIUrl":"https://doi.org/10.2147/jhc.s477265","url":null,"abstract":"<strong>Purpose:</strong> Liver resection and ablation remain the most common therapeutic options for Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC), but there is a lack of evidence to show which is the most suitable therapy. This study aimed to make concurrent multi-arm comparisons of the short-term and long-term outcomes of percutaneous ablation (PA), open (OLR) or laparoscopic liver resection (LLR) for these patients.<br/><strong>Patients and Methods:</strong> This was a retrospective observational cohort study. A series of generalized propensity score methods for multiple treatment groups were performed to concurrently compare the clinical outcomes of these three treatment options to balance potential confounders. Regression standardization was used to account for hazard of all-cause mortality and recurrence of intergroup differences.<br/><strong>Results:</strong> Of the 1778 patients included, 1237, 307 and 234 underwent OLR, LLR and PA, respectively. After overlap weighting, which was the optimal adjustment strategy, patients in the minimally invasive group (LLR and PA groups) had few postoperative complications and short postoperative hospital stays (both P < 0.001). The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate were significantly higher in the LLR group when compared with the OLR and PA groups (RFS: 55.6% vs 48.0% vs 30.2%, P < 0.001; OS: 89.1% vs 79.7% vs 84.0%, P = 0.020). Multivariable Cox analysis and regression standardization showed that LLR was an independent factor for better RFS when compared with OLR and PA. In subgroup analysis, the long-term outcomes of patients with BCLC stage A HCC were consistent with the whole population.<br/><strong>Conclusion:</strong> In the observational study using various covariate adjustment analysis with excellent balance, LLR is not only minimally invasive, but also provides better RFS and equivalent OS for patients with BCLC stage 0-A HCC when compared with OLR and PA.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, laparoscopic liver resection, generalized propensity score analysis, overlap weighting, clinical outcome<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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