第一部分 血管介入联合仑伐替尼与单独血管介入治疗合并门静脉癌栓的晚期肝细胞癌疗效与安全性研究

目的  本研究旨在评估血管介入治疗联合仑伐替尼对比单独血管介入治疗在伴门静脉癌栓（PVTT）的晚期肝细胞癌（HCC）患者中的疗效及安全性，并明确与治疗结局相关的预后因素。

方法  回顾性分析2016年2月至2023年2月合并PVTT的晚期HCC患者数据。按照治疗方式分组，单独介入组仅接受血管介入治疗（经动脉化疗栓塞术[TACE]），联合治疗组接受血管介入治疗（TACE或肝动脉灌注化疗）联合仑伐替尼口服药物治疗。主要研究终点包括无进展生存期（PFS）、总生存期（OS）及客观缓解率（ORR）。采用Kaplan-Meier法评估两组患者的生存率，并通过逆概率处理加权（IPTW）模型对基线混杂变量进行平衡调整。通过Cox回归模型确定预后因素。

结果  共纳入92例患者，其中单独介入组56例，联合治疗组36例。所有患者的中位随访时间为20.07个月（四分位间距：6.41–25.36）。联合治疗组中位PFS（11.00 vs. 5.00个月，P<0.05）及OS（12.91 vs. 6.83个月，P<0.05）均显著优于单独介入组，且IPTW匹配后结果一致。基于mRECIST标准，联合治疗组ORR更高（55.56% vs. 26.79%，P<0.05）。多因素Cox分析显示，肝外转移与最大肿瘤直径是PFS的独立危险因素，而年龄、肿瘤数目及最大肿瘤直径是OS的独立危险因素。联合治疗是OS的独立保护因素。联合治疗组中高血压为最常见不良事件，3级及以上不良事件发生率低。

结论  血管介入联合仑伐替尼可显著改善伴PVTT晚期HCC患者的PFS及OS，安全性可控，早期应用该联合策略或可提升患者获益。

第二部分 经动脉化疗栓塞术联合替雷利珠单抗和酪氨酸激酶抑制剂治疗中晚期肝细胞癌疗效与安全性研究

目的  经动脉化疗栓塞术（TACE）联合靶向治疗及免疫治疗是中晚期肝细胞癌（HCC）的潜在有效治疗方案。本研究旨在比较TACE联合替雷利珠单抗与酪氨酸激酶抑制剂（TKIs）与单独TACE治疗在该人群中的疗效及安全性。

方法  回顾性分析2017年6月至2023年9月中晚期HCC患者数据。患者分为联合治疗组（接受TACE+替雷利珠单抗+TKIs）和单独介入组（仅行TACE）。主要研究终点为无进展生存期（PFS）；次要研究终点包括客观缓解率（ORR）、疾病控制率（DCR）、总生存期（OS）及安全性。

结果  共纳入62例患者（联合治疗组30例，单独介入组32例），两组基线特征无统计学差异（P>0.05）。中位随访时间为25.4个月（95%置信区间[CI]：18.7–32.0），联合治疗组中位PFS为11.1个月（95%CI：9.6–未达到），显著优于单独介入组的3.8个月（95%CI：0.9–6.7）（风险比，1.95，95%CI：1.08–3.50，P=0.026）。联合治疗组12个月和18个月OS率均高于单独介入组（77% vs 51%；72% vs 47%）。联合治疗组的ORR与DCR亦显著优于单独介入组（ORR：46.7% vs. 18.8%，P=0.014；DCR：96.7% vs. 75.0%，P=0.028）。联合治疗组4例（13.3%）患者获得完全/部分缓解后接受根治性治疗（2例外科切除，2例消融）。不良反应总发生率联合治疗组为86.7%，单独介入组为81.3%；3级及以上不良事件仅见于联合治疗组（10.0%）。

结论  与单独TACE治疗相比，TACE联合替雷利珠单抗及TKIs治疗可能是中晚期HCC安全有效的治疗方案，并有望作为该人群的转化治疗策略选择。

Part Ⅰ Efficacy and safety of vascular intervention plus lenvatinib versus vascular intervention alone for hepatocellular carcinoma patients with portal vein tumor thrombus

Objective This study aimed to assess the efficacy and safety of vascular intervention combined with lenvatinib versus vascular intervention alone in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to identify prognostic factors associated with the treatment outcomes.

Methods We conducted a retrospective analysis of data from patients with advanced HCC and PVTT who were treated between February 2016 and February 2023. The cohort was stratified into dual therapeutic arms: the monotherapy group who underwent vascular intervention alone (transarterial chemoembolization, TACE), the combination therapy group who received vascular intervention (TACE or hepatic arterial infusion chemotherapy) combined with lenvatinib. The primary outcomes included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Survival rates were estimated by the Kaplan-Meier method, and confounders were adjusted using inverse probability of treatment weighting (IPTW). Prognostic factors were determined through the Cox regression model.

Results This study ultimately included 92 eligible participants who were allocated into two therapeutic cohorts: 56 cases receiving monotherapy and 36 cases assigned to the combination group. The median follow-up duration was 20.07 months (interquartile range: 6.41–25.36). The combination therapy group had a significantly longer median PFS (11.00 vs. 5.00 months, P < 0.05) and OS (12.91 vs. 6.83 months, P < 0.05) in comparison to the monotherapy group, and these findings remained consistent after IPTW matching. Moreover, the combination therapy group showed a higher ORR (55.56% vs. 26.79%, P < 0.05) based on mRECIST criteria. Multivariate Cox analysis identified extrahepatic metastasis and maximum tumor diameter as independent risk factors for PFS, while age, tumor number, and maximum tumor diameter influenced OS. Combined treatment emerged as an independent protective factor for OS. In the combination therapy group, hypertension was the most frequent adverse event, with grade 3 or 4 adverse events occurring rarely.

Conclusions The combination of vascular intervention with lenvatinib has demonstrated improved PFS and OS in advanced HCC patients with PVTT, and its safety profile appears to be acceptable. Adoption of this combined treatment strategy at an earlier stage may enhance patient outcomes.

Part Ⅱ Efficacy and safety of transarterial chemoembolization (TACE) plus tislelizumab and tyrosine kinase inhibitors versus TACE for the treatment of intermediate and advanced hepatocellular carcinoma

Objective Transarterial chemoembolization (TACE) combined with targeted therapy and immunotherapy represents a potentially effective treatment for intermediate and advanced hepatocellular carcinoma (HCC). This retrospective cohort analysis compared the efficacy and safety profiles between combination therapy (TACE plus tislelizumab with tyrosine kinase inhibitors [TKIs]) and TACE monotherapy.

Methods Data of patients with intermediate and advanced HCC from June 2017 to September 2023 were retrospectively analyzed. Patients were divided into two groups: the combination therapy group who received TACE plus tislelizumab and TKIs, and the monotherapy group who underwent TACE. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.

Results A total of 62 patients participated in the study, with 30 allocated to the combination therapy group and 32 to the monotherapy group. Baseline characteristics were comparable between the two groups. The average follow-up was 25.4 (95% confidence intervals [CI], 18.7–32.0) months, median PFS were 11.1 (95% CI, 9.6–not reached) months in the combination therapy group and 3.8 (95% CI, 0.9–6.7) months in the monotherapy group (hazard ratio, 1.95 [95% CI, 1.08–3.50], P = 0.026). The 12-month and 18-month OS rates were higher in the combination therapy group than the monotherapy group (77% vs. 51%; 72% vs. 47%). The ORR and DCR were higher in the combination therapy group than the monotherapy group (ORR, 46.7% vs. 18.8%, P = 0.014; DCR, 96.7% vs. 75.0%, P = 0.028). Four patients (13.3%) in the combination therapy group received curative treatments after achieving a complete or partial response, including two undergoing curative hepatic resections and two undergoing ablations. Adverse event (AE) rates were 86.7% (combination therapy group) and 81.3% (monotherapy group) respectively, while grade 3 or higher AE occurred at rates of 10.0% in the combination therapy group in total, with none observed in the monotherapy group.

Conclusion TACE combined with tislelizumab and TKIs is expected to be a safe and effective treatment for intermediate and advanced HCC compared to TACE alone. The combined therapy could be regarded as a considerable option for conversion strategy in this population.