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An Oxidative Stress-Related Prognostic Signature Predicts Treatment Response and Outcomes for Hepatocellular Carcinoma After Transarterial Chemoembolization. 与氧化应激相关的预后特征可预测经动脉化疗栓塞术后肝细胞癌的治疗反应和疗效
IF 4.2 3区 医学 Q2 ONCOLOGY Pub Date : 2024-08-13 eCollection Date: 2024-01-01 DOI: 10.2147/JHC.S465592
Hui Ma, Ting Yu, Zhong-Chen Li, Lan Zhang, Rong-Xin Chen, Zheng-Gang Ren

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.

目的:氧化应激在促进肿瘤耐缺氧和耐化疗药物方面发挥着关键作用。然而,氧化应激相关基因(OSRGs)在经动脉化疗栓塞(TACE)治疗的肝细胞癌(HCC)中的预后作用尚未得到充分探讨:我们使用了GSE104580队列中的转录组数据,其中包含标记为TACE治疗应答者或非应答者的患者,以确定与TACE应答相关的差异表达OSRGs(TR-OSRGs)。我们在 HCC 患者训练队列(TCGA-LIHC)中使用最小绝对缩减和选择操作者 Cox 和逐步 Cox 回归分析,根据 TR-OSRGs 创建了 TR-OSRG 预后特征。我们在两个接受 TACE 治疗的 HCC 患者外部队列(GSE14520-TACE 和 ZS-TACE-37)中验证了这一预后特征。最后,我们基于 Cox 回归分析构建了一个预后提名图模型,用于预测 HCC 患者的生存概率:结果:我们创建了 TR-OSRG 预后特征,并证明它是治疗反应和 TACE 治疗后 HCC 结局的可靠独立预后因素。基于该特征的风险评分与肿瘤分期和分级相关。风险评分较高的患者的肿瘤样本显示出更多的免疫细胞浸润,免疫检查点基因的表达也显著增加。我们还根据TR-OSRG预后特征和临床参数为HCC患者制定了一个提名图;该提名图是预测患者生存期的一个有用的定量分析工具:结论:TR-OSRGs特征在预测接受TACE治疗的HCC患者的治疗反应和预后方面表现良好。
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引用次数: 0
Clinical Therapy: HAIC Combined with Tyrosine Kinase Inhibitors and Programmed Cell Death Protein-1 Inhibitors versus HAIC Alone for Unresectable Hepatocellular Carcinoma 临床疗法:HAIC联合酪氨酸激酶抑制剂和程序性细胞死亡蛋白-1抑制剂与单用HAIC治疗无法切除的肝细胞癌比较
IF 4.1 3区 医学 Q2 ONCOLOGY Pub Date : 2024-08-12 DOI: 10.2147/jhc.s470345
Baokun Liu, Lujun Shen, Wen Liu, Zhiyong Zhang, Jieqiong Lei, Zhengguo Li, Qinquan Tan, Hengfei Huang, Xingdong Wang, Weijun Fan
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.

Keywords: hepatocellular carcinoma, TKIs, PD-1, HAIC, combination therapy
目的:大多数新诊断的肝细胞癌(HCC)仍属于无法切除的病例。目前,酪氨酸激酶抑制剂(TKIs)和程序性细胞死亡蛋白-1(PD-1)抑制剂的联合治疗已成为主流治疗方法。根据多项临床指南,强烈建议将局部治疗作为uHCC的主要治疗选择。本研究旨在探讨肝动脉灌注化疗(HAIC)与TKIs和PD-1抑制剂联合治疗uHCC的安全性和有效性:2015年至2020年间,208名HCC患者接受了HAIC单独治疗或HAIC与TKIs和PD-1抑制剂联合治疗。比较两组患者的总生存期(OS)、无进展生存期(PFS)和最佳治疗反应。研究采用倾向评分匹配法(PSM)来减少混杂偏倚:在入组患者中,116 名患者(55.8%)接受了联合治疗,92 名患者(44.2%)接受了单药 HAIC 治疗。两组患者的基线特征相似。经过PSM筛选,选出了82对匹配度较高的肝癌患者;联合治疗组的总体反应率呈上升趋势,优于单用HAIC组。与单用HAIC相比,联合治疗组的OS和PFS危险比(HRs)分别为0.47(95% CI,0.322- 0.687;p< 0.001)和0.58(95% CI,0.397- 0.848;p=0.005):关键词:肝细胞癌;TKIs;PD-1;HAIC;联合治疗
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引用次数: 0
Genetic Variants in p53 Pathway Genes Affect Survival of Patients with HBV-Related Hepatocellular Carcinoma p53 通路基因的遗传变异影响 HBV 相关肝细胞癌患者的存活率
IF 4.1 3区 医学 Q2 ONCOLOGY Pub Date : 2024-08-12 DOI: 10.2147/jhc.s459792
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
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.

Keywords: hepatocellular carcinoma, hepatitis B virus, p53 signaling pathway, genetic variants, survival
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
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引用次数: 0
Endoplasmic Reticulum Membrane Protein Complex Regulates Cancer Stem Cells and is Associated with Sorafenib Resistance in Hepatocellular Carcinoma 内质网膜蛋白复合物调控癌症干细胞并与肝细胞癌的索拉非尼耐药性有关
IF 4.1 3区 医学 Q2 ONCOLOGY Pub Date : 2024-08-09 DOI: 10.2147/jhc.s474343
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.

背景:肝细胞癌(HCC)仍然是癌症相关死亡的主要原因,这凸显了对新型治疗靶点的需求。本研究旨在阐明内质网膜蛋白复合物亚基 1(EMC1)在 HCC 进展中的作用及其治疗潜力:方法:分析公开的测序数据和活检标本,评估EMC在HCC中的临床价值和功能。体外实验验证了EMC的功能,多重免疫荧光分析检验了EMC相关的索拉非尼耐药机制。在 HCC 细胞系中敲除 EMC1 的表达,然后进行细胞活力、伤口愈合和跨孔迁移试验。在小鼠模型中评估了肿瘤生长和对索拉非尼治疗的反应。代谢组分析评估了 TCA 循环的变化:结果:EMC基因在HCC中异常表达,EMC1的高表达与较差的存活率相关。破坏 EMC1 可增强 HCC 细胞对索拉非尼的敏感性,降低细胞活力,增加细胞凋亡,减小肿瘤大小和重量。EMC1 维持了癌细胞的干性,并促进了 M2 巨噬细胞的浸润。代谢组学分析显示 TCA 循环发生了显著变化,表明 EMC1 在 HCC 代谢重编程中的作用。重要的是,EMC1与索拉非尼耐药性高度相关,这可能与CTNNB1突变或激活有关:结论:EMC1 在调节 HCC 的索拉非尼耐药性方面起着关键作用。结论:EMC1 在调节 HCC 索拉非尼耐药中起着关键作用,靶向 EMC1 可提高 HCC 治疗效果。
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引用次数: 0
Impact of Type of Lenvatinib Resistance on Prognosis and Second-Line Regimen in Patients with Virus-Associated HCC 伦伐替尼耐药类型对病毒相关性 HCC 患者预后和二线治疗方案的影响
IF 4.1 3区 医学 Q2 ONCOLOGY Pub Date : 2024-08-08 DOI: 10.2147/jhc.s476439
Yijie Zhang, Jin Lei, Huaxing Ma, Shi Zuo
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 &gt; 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&lt; 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":null,"pages":null},"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}
引用次数: 0
Radiotherapy with Targeted Therapy or Immune Checkpoint Inhibitors for Hepatocellular Carcinoma with Hepatic Vein and/or Inferior Vena Cava Tumor Thrombi. 放疗联合靶向治疗或免疫检查点抑制剂治疗伴有肝静脉和/或下腔静脉瘤栓的肝细胞癌。
IF 4.2 3区 医学 Q2 ONCOLOGY Pub Date : 2024-08-05 eCollection Date: 2024-01-01 DOI: 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.

目的:本研究评估了肝静脉瘤栓(HVTT)和/或下腔静脉瘤栓(IVCTT)肝细胞癌(HCC)患者接受放疗(RT)联合全身治疗的临床疗效:本院确定了接受 RT 的 HVTT 和/或 IVCTT HCC 患者。计划靶体积的处方剂量为30-65 Gy,肿瘤总体积的处方剂量为40-65 Gy。如果患者有远处转移的高风险或已经出现远处转移,则同时使用靶向治疗和免疫检查点抑制剂。RT 结束后,在 1、3、6 和 12 个月时进行随访,此后 3 至 6 个月进行随访。记录客观反应率(ORR)、总生存期(OS)、无进展生存期(PFS)和毒性:34名患者于2016年1月至2021年9月期间回顾性入组。大多数患者同时接受了靶向治疗(70.6%)和/或RT后治疗(79.4%)。现场ORR和疾病控制率分别为79.4%和97.1%。1年的OS率为77.6%,2年的OS率为36.3%(中位OS为15.8个月)。中位 PFS 和中位现场 PFS 分别为 4.2 个月和未达标。1年的PFS和现场PFS率分别为24.6%和79.2%,2年的PFS和现场PFS率分别为19.7%和72.0%。甲胎蛋白水平>1000 ng/mL是OS较差的重要预后因素(HR,5.674;95% CI,1.588-20.276;P=0.008);场内完全/部分反应是OS较好的重要预后因素(HR,0.116;95% CI,0.027-0.499;P=0.004)。首次衰竭最常见的部位是肺(13/34 例患者,38.2%),其次是肝(7/34 例患者,20.6%)。在随访期间,没有患者出现辐射诱发的肝病或肺栓塞:结论:在治疗HVTT和IVCTT的HCC患者时,将RT和全身治疗相结合是安全有效的。
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引用次数: 0
Dynamic Changes of Neutrophil-to-Lymphocyte Ratio on Predicting Response of Immune Checkpoint Inhibitors Plus Targeted Therapies for Unresectable Hepatocellular Carcinoma. 中性粒细胞与淋巴细胞比值的动态变化对预测免疫检查点抑制剂加靶向疗法治疗不可切除肝细胞癌反应的影响
IF 4.2 3区 医学 Q2 ONCOLOGY Pub Date : 2024-08-05 eCollection Date: 2024-01-01 DOI: 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.

背景和目的:免疫检查点抑制剂(ICIs)加靶向治疗的多种方案是不可切除肝细胞癌(uHCC)一线治疗的常用处方。在此,我们旨在研究中性粒细胞与淋巴细胞比值(NLR)的动态变化与肿瘤对 ICIs 和靶向疗法联合治疗 uHCC 的反应之间的相关性:这项回顾性研究共纳入了61例接受ICIs和靶向疗法治疗的uHCC患者。评估治疗前和治疗后3-6周的NLR,计算动态NLR变化(ΔNLR)。多变量逻辑回归和 Cox 回归模型分别用于探讨动态 NLR 变化与肿瘤反应或无进展生存期(PFS)之间的关系。此外,我们还评估了甲胎蛋白(AFP)变化与动态 NLR 变化相结合与单独 AFP 变化相结合的预测效果:结果:接受进展性疾病(PD)治疗的患者在治疗后3-6周的NLR和ΔNLR显著增加,而基线NLR在不同肿瘤反应之间无显著差异。治疗后 NLR 和 AFP 的增加都是进展期的独立预测因素(NLR 增加:OR,2.28;95% AFP;OR,2.28;95% NLR;OR,2.28):OR,2.28;95% CI,1.47-3.88,P <0.001;AFP 增高:OR,1.46;95% CI,1.47-3.88,P <0.001:OR,1.46;95% CI,1.03-2.17,P = 0.043),并与更差的 PFS 相关(NLR 增加:HR,4.08;95% CI,1.03-2.17,P = 0.043):HR,4.08;95% CI,1.99-8.36,P<0.001;AFP 增高:HR,2.10;95% CI,1.99-8.36,P<0.001:HR,2.10;95% CI,1.04-4.24,P = 0.039)。接受者操作特征曲线(ROC)和净再分类指数(NRI)显示,动态NLR和AFP变化的组合在预测PD(AUC:0.83 vs 0.68,P = 0.034;NRI:0.340,P = 0.048)和PFS(AUC:0.80 vs 0.70,P = 0.166;NRI:0.431,P = 0.042)方面优于单独的AFP变化:结论:NLR的动态变化可能是预测ICIs加靶向疗法对uHCC治疗反应的有效指标。
{"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":null,"pages":null},"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}
引用次数: 0
Additional Hepatic Arterial Infusion Chemotherapy to Sorafenib Was Cost-Effective for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis 在索拉非尼基础上进行肝动脉灌注化疗治疗肝细胞癌伴有主要门静脉肿瘤血栓形成具有成本效益
IF 4.1 3区 医学 Q2 ONCOLOGY Pub Date : 2024-07-30 DOI: 10.2147/jhc.s470470
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.

Keywords: HCC, portal vein tumor thrombosis, sorafenib, HAIC, Cost-effectiveness
目的:与单用索拉非尼相比,索拉非尼和肝动脉灌注化疗(SoHAIC)联合治疗晚期肝细胞癌和主要门静脉肿瘤血栓形成(HCC-Vp3-4)患者可提高总生存率。我们的目的是结合中国医疗支付方的观点,评估索拉非尼与索海克治疗HCC-Vp3-4的成本效益:这项药物经济学研究采用马尔可夫模型评估了索海屈与索拉非尼治疗 HCC-Vp3-4 的成本效益。患者特征来自2017年6月至2019年11月期间进行的试验中的个体,成本和健康价值数据来自已发表的文献。本研究的主要结果指标是增量成本效益比(ICER),它表示每质量调整生命年(QALY)的额外成本。每 QALY 的支付意愿(WTP)阈值设定为 30,492.00 美元。此外,还进行了单向敏感性分析和概率敏感性分析,以验证结果的一致性:在基线方案中,索拉非尼产生了 0.42 QALY,成本为 10,507.89 美元,而 SoHAIC 产生了 1.66 QALY,成本为 32,971.56 美元。将 SoHAIC 与索拉非尼进行比较,每 QALY 的 ICER 为 18,237.20 美元,低于每 QALY 的 WTP 临界值。此外,单向敏感性分析表明,尽管变量存在波动,ICER仍保持在WTP阈值以内。在概率敏感性分析中,考虑到各种参数,SoHAIC在WTP阈值下具有成本效益的概率为98.8%:结论:在此次成本效益评估中,从中国支付方的角度观察,SoHAIC在治疗伴有门静脉肿瘤血栓的HCC方面比索拉非尼更具成本效益:HCC、门静脉肿瘤血栓、索拉非尼、HAIC、成本效益
{"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 &amp;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 &amp;dollar10,507.89, while SoHAIC generated 1.66 QALY at a cost of &amp;dollar32,971.56. When comparing SoHAIC to sorafenib, the ICER was &amp;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":null,"pages":null},"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}
引用次数: 0
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 巴塞罗那诊所肝癌 0-A 期肝细胞癌经皮消融术、开腹或腹腔镜肝切除术的比较:同期广义倾向得分分析
IF 4.1 3区 医学 Q2 ONCOLOGY Pub Date : 2024-07-25 DOI: 10.2147/jhc.s477265
Zhi-Hang Chen, Qian Zhou, Ze-Bin Chen, Wen-Xuan Xie, Zi-Min Song, Shui-Rong Lin, Wei Wang, Shun-Li Shen, Ming Kuang
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.

Keywords: hepatocellular carcinoma, laparoscopic liver resection, generalized propensity score analysis, overlap weighting, clinical outcome
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
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引用次数: 0
Why Liver Cancer Hits Home: Bridging Healthcare Disparities in the Asian American and Pacific Islander Community 肝癌为何 "如影随形":消除亚裔美国人和太平洋岛民社区的医疗差距
IF 4.1 3区 医学 Q2 ONCOLOGY Pub Date : 2024-07-18 DOI: 10.2147/jhc.s467913
Daneng Li, Spencer Cheng, Andrea Wilson Woods, Allyson Luong, Sarah Schiltz, Ruoding Tan, Zeena Huang Chi
Abstract: Asian Americans and Pacific Islanders have an increased risk of developing liver cancer and higher risk of death compared to non-Hispanic White individuals. The role of individual-level risk factors, social determinants of health, and barriers navigating health systems present unique challenges in obtaining liver cancer care for these patients. Additionally, the Asian American and Pacific Islander population is a heterogenous group originating from several different countries and speaking various languages, and they are often underrepresented in cancer clinical trial populations. This article describes the challenges faced by Asian American and Pacific Islander patients with liver cancer from the clinician, research, and patient advocacy perspectives and proposes targeted solutions to reduce healthcare disparities in this group.

Keywords: Asian American and Pacific Islander, health equity, hepatocellular carcinoma, cancer care
摘要:与非西班牙裔白人相比,亚裔美国人和太平洋岛民罹患肝癌的风险更高,死亡风险也更高。个人层面的风险因素、健康的社会决定因素以及在医疗系统中遇到的障碍,为这些患者获得肝癌治疗带来了独特的挑战。此外,亚裔美国人和太平洋岛民是一个异质群体,他们来自多个不同的国家,讲各种语言,在癌症临床试验人群中的代表性往往不足。本文从临床医生、研究和患者权益保护的角度阐述了亚裔美国人和太平洋岛民肝癌患者所面临的挑战,并提出了有针对性的解决方案,以减少这一群体在医疗保健方面的差异:亚裔美国人和太平洋岛民、健康公平、肝细胞癌、癌症护理
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引用次数: 0
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Journal of Hepatocellular Carcinoma
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