Safety and efficacy of hepatic arterial infusion chemotherapy with raltitrexed and oxaliplatin post-transarterial chemoembolization for unresectable hepatocellular carcinoma

Objective:To investigate the safety,efficacy,and prognostic factors of hepatic arterial infusion chemotherapy(HAIC)with raltitrexed and oxaliplatin post-transarterial chemoembolization(TACE)for unresectable hepatocellular carcinoma(uHCC).Methods:Thirty-seven patients with uHCC who received HAIC with raltitrexed and oxaliplatin post-TACE between June 2014 and December 2016 at our hospital were recruited.The primary endpoint was overall survival(OS),and secondary endpoint was progression-free survival(PFS).The overall response rate(ORR)was evaluated using the modified Response Evaluation Criteria in Solid Tumors.Toxicity was assessed according to the Common Terminology Criteria for Adverse Events(v4.0).The OS and prognostic factors were analyzed using the Kaplan-Meier method,log-rank test,and Cox regression models.Results:Three(8.1%)patients achieved complete response,17(46.0%)patients achieved partial response,and the ORR was54.0%.The median OS and median PFS were 19.0 months and 12.0 months,respectively.The common toxicities included grade 3-4 increased aspartate aminotransferase levels(8/37,21.6%),grade 1-2 hyperbilirubinemia(75.7%,28/37),nonspecific abdominal pain and fever,and grade 2-3 thrombocytopenia(18.9%,7/37);no patients developed grade 3-4 neutropenia.Univariate analysis showed that the tumor diameter(≤50 mm,p=0.028),Barcelona Clinic Liver Cancer(BCLC)stage(p=0.012),hepatitis B virus DNA level(p=0.033),and derived neutrophil-to-lymphocyte ratio(dNLR;derived neutrophils/leukocytes minus neutrophils)(p=0.003)were predictive factors for prognosis.Multivariate analysis showed that patients with BCLC stage B disease(p=0.029)and dNLR<2 before therapy(p=0.004)had better prognosis.Conclusions:HAIC with raltitrexed and oxaliplatin post-TACE is a safe and efficacious therapy for patients with uHCC;in particular,those with BCLC stage B and dNLR<2 have better prognosis.

Efficacy of 5-Fluorouracil and High-Concentration Cisplatin Suspended in Lipiodol by Short-Term Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

Background: Since advanced hepatocellular carcinoma (HCC) is potentially fatal, and patients’ quality of life (QOL) often deteriorates during their treatment, improving the prognosis and QOL of patients given chemotherapy is very important. In addition, cost-effective treatments are highly desirable when chemotherapy must be given repeatedly. The aim of this study was to evaluate the efficacy and usefulness of 5-fluorouracil (5-FU) and high-concentration cisplatin by short-term hepatic arterial infusion chemotherapy (3-day FPL) in advanced HCC patients. Methods: Thirty patients with unresectable advanced HCC were enrolled. The patients underwent hepatic arterial infusion chemotherapy via the implanted port system with 5-FU on days 1 - 3 and a fine-powder formulation of cisplatin in suspended pre-warmed lipiodol on day 2 every 4 to 10 weeks. Tumor response was assessed one month later with CT. Results: All patients had evidence of portal vein invasion (Vp2-4). Four patients achieved a complete response (CR), 8 patients achieved a partial response (PR), and 7 patients had stable disease (SD). The median progression-free survival (PFS) and overall survival (OS) were 198 days and 452 days, respectively. The OS was significantly longer in the successful disease control group (CR, PR, and SD) than in the progressive disease group (P < 0.005). Conclusions: Three-day FPL was effective and tolerable in advanced HCC patients due to its shorter time of administration than conventional FP therapy. Therefore, repetitive 3-day FPL appears useful and contributes to improving the prognosis and QOL of patients with advanced HCC. In addition, this protocol is a cost-effective treatment.

Advances in Conversion Therapy for Primary Unresectable Hepatocellular Carcinoma

Primary liver cancer is one of the most common malignant tumours in the world, and according to statistics, about half of liver cancers occur in China, which seriously threatens the lives and health of people around the world, especially in China. Hepatocellular carcinoma is the most common type, accounting for about 90 per cent of primary liver cancers. Most patients are asymptomatic in the early stage and fail to pay attention to it. Most of the patients are in the middle or late stage when they are first diagnosed, and only 20% - 30% of them can receive radical hepatectomy. Patients are through the treatment to make the tumour shrinkage and downstaging, to achieve the condition of resectable, that is, the conversion treatment. Conversion therapy has great potential for development and has now become an indispensable treatment for intermediate and advanced hepatocellular carcinoma. However, there are various treatment options for conversion therapy, no uniform guidelines to guide clinical selection, and the overall conversion rate is still low, so it is particularly important to explore appropriate conversion therapy options. This article mainly describes the existing conversion therapies, hoping to provide help and ideas for exploring the best conversion therapies in the future.

RALOX-HAIC联合免疫检查点抑制剂及靶向药物治疗中晚期肝癌的疗效分析

目的:探讨雷替曲塞+奥沙利铂方案肝动脉灌注化疗(RALOX-HAIC)联合免疫及靶向药物三联治疗中晚期肝细胞癌(hepatocellular carcinoma,HCC)的疗效与安全性。方法:回顾性分析2020年6月至2021年12月收治于南方医科大学南方医院39例行RALOX-HAIC联合靶免治疗的中晚期HCC患者,以首次HAIC治疗为起点,以患者疾病进展、死亡、不可耐受不良反应为终点,按照RECIST 1.1标准进行疗效评估,随访时间截至2022年10月。主要研究终点为客观缓解率(objective response rate,ORR),次要研究终点为疾病控制率(disease control rate,DCR)、中位无进展生存期(median progression-free survival,mPFS)、中位总生存期(median overall survival,mOS)及安全性。结果:ORR为41.0%,DCR达87.2%,m PFS为7.3个月(95%CI:5.0~9.6),mOS为14.6个月(95%CI:10.8~18.5),其中1例患者成功转化行手术治疗后完全缓解至今。常见的不良反应有HAIC术后发热、腹痛;化疗药物引起的骨髓抑制;肝功能异常、高血压、手足综合征等,无治疗相关死亡事件发生。结论:RALOX-HAIC联合免疫检查点抑制剂及靶向药物治疗中晚期HCC的DCR高,安全性良好,不良反应可耐受,为后续前瞻性临床研究奠定了基础。

免疫及靶向药物联合肝动脉灌注化疗治疗晚期肝癌的回顾性分析

目的:探讨免疫及靶向药物联合肝动脉灌注化疗术(hepatic arterial infusion chemotherapy,HAIC)治疗晚期肝细胞癌(hepatocellular carcinoma,HCC)的疗效与安全性。方法:回顾性分析2021年4月至2022年4月天津医科大学肿瘤医院收治的34例行HAIC联合信迪利单抗及贝伐珠单抗生物类似物治疗的晚期HCC患者,以首次治疗为起点,以患者死亡、疾病进展及不可耐受的不良反应为终点,按照实体肿瘤的疗效评价(mRECIST)1.1标准进行疗效评估,随访截至2023年4月。主要研究终点为客观缓解率(objective response rate,ORR),次要研究终点为疾病控制率(disease control rate,DCR)、总生存期(overall survival,OS)、无复发生存期(disease-free survival,DFS)、手术转化率及安全性。结果:ORR为52.9%,DCR可达到85.3%,手术转化利率为41.1%。部分缓解(partial response,PR)组1年OS及DFS分别为94.4%、50.0%;病变稳定(stable disease,SD)+病变进展(progressive disease,PD)组患者1年OS及DFS分别为66.7%、25.0%,两组差距均有统计学意义(P=0.002及P=0.013)。常见的不良反应有恶心呕吐(38.2%)、高血压(32.4%)及血小板减少(29.4%)等,无治疗相关死亡事件发生。结论:HAIC联合信迪利单抗及贝伐珠单抗生物类似物治疗晚期HCC的客观缓解率高,安全性良好,为后续临床试验的开展奠定了基础。

肝细胞癌的抗血管生成免疫联合介入治疗:肝动脉灌注化疗与化疗栓塞疗效的比较

目的:旨在比较抗血管生成免疫治疗联合肝动脉灌注化疗(hepatic artery infusion chemotherapy,HAIC)与联合肝动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)治疗肝细胞癌的有效性和安全性。方法:回顾性分析天津医科大学肿瘤医院2019年1月至2020年12月收治93例肝细胞癌病人,B期18例,C期75例。男74例,女19例,中位年龄57(27~78)岁。50例行抗血管生成免疫联合TACE(TACE组)治疗,43例行抗血管生成免疫联合HAIC(HAIC组)治疗。采用实体肿瘤疗效评价标准RECIST1.1评估疗效。主要观察终点为客观反应率和疾病控制率,次要观察终点为中位无进展生存期及中位总生存期。结果:HAIC组客观反应率和疾病控制率显著高于TACE组(客观反应率:72.09%比44.00%,P=0.006;疾病控制率:88.37%比60.00%,P=0.002)。HAIC组及TACE组的中位随访时间分别为12.13个月及11.95个月。截至随访,TACE组中位无进展生存期11.83个月(95%CI:4.36~19.31个月),中位总生存期17.93个月(95%CI:11.80~24.06个月),而HAIC组均未到达中位无进展生存期和总生存期。两组无进展生存期及总生存期差异有统计学意义(P=0.017,P=0.007)。结论:针对进展期肝细胞癌,抗血管生成免疫联合HAIC相比联合TACE在疾病控制和生存上获益更大,不良反应相对可控,安全性好。

肝动脉灌注化疗联合全身化疗作为一线和非一线治疗不可切除肝转移患者的疗效对比(英文)

Objective: The combination of hepatic arterial chemotherapy(HAIC) and systemic chemotherapy(SYC) has potential effect on colorectal cancer(CRC) patients with unresectable hepatic metastasis. The aim of this retrospective study was to investigate the efficacy and safety of this combined therapeutic regimen on Chinese patients based on single institute experiences. Methods: All 54 patients of this retrospective analysis were diagnosed with CRC with unresectable liver metastasis and received combined HAIC and SYC. Among the patients, 23 of them received HAIC plus SYC when they developed liver metastases as first-line treatment(Group 1), and 31 patients received HAIC plus SYC as non-first-line treatment(Group 2). The different efficacy in two groups was analyzed by SPSS 19.0. Results: The overall response rate(ORR) were 52.2% and 25.8% respectively in Groups 1 and 2(P = 0.047), and the disease control rate(DCR) were 65.2% and 35.5% respectively in Groups 1 and 2(P = 0.031). The median progression-free survival(PFS) were 6.8 and 3.3 months(P = 0.002), the median hepatic progression-free survival(H-PFS) were 8.8 and 3.7 months(P = 0.001), and the median overall survival(OS) were 18.8 and 13.7 months(P = 0.121) in Groups 1 and 2, respectively. No fatal reaction was observed and no significant difference of adverse reaction was found in two groups. Grade 3/4 toxic effects included neutropenia(9.7% in Group 2 only), gastrointestinal reaction(8.7% in Group 1 and 6.5% in Group 2), stomatitis(6.5% in Group 2 only) and hyperbilirubinemia(4.3% in Group 1 only). Conclusion: HAIC combined with SYC showed promising efficacy and safe profiles on CRC patients with unresectable liver metastases.