A comparison of the efficacy of DEB-TACE, radiotherapy combined with lenvatinib or apatinib in the treatment of hepatocellular carcinoma with portal vein tumor thrombus

Abstract

Abstract: Objective To explore the efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE), radiotherapy combined with lenvatinib or apatinib in the treatment of hepatocellular carcinoma with portal vein tumor thrombosis. Methods 72 patients with hepatocellular carcinoma complicated with portal vein thrombosis were randomly divided into an observation group and a control group, with 36 cases in each group. The control group received DEB-TACE, radiotherapy combined with apatinib, while the observation group received DEB-TACE, radiotherapy combined with lenvatinib. After 3 months of treatment, the clinical efficacy, adverse reactions, serum biochemical indicators of liver function, coagulation indicators, tumor markers were compared between the two groups. An 18-month follow-up was conducted to record the primary endpoints, including progression-free survival (PFS) and overall survival (OS). Results The disease control rates of the observation group and the control group were 91.67% and 72.22%, respectively. The disease control rate was higher in the observation group compared with the control group (P<0.05). The occurrence rates of diarrhea, increased urine protein, and hypertension in the observation group were 8.33%, 5.56%, and 0.00%, respectively, which were lower than those of 27.78%, 22.22%, and 13.89% in the control group (P<0.05). After treatment, the PTA and AFP levels in the observation group were (88.71 ± 3.95)% and (210.93 ± 32.08) μg/L, respectively, which were better than those of (86.14 ± 6.09)% and (229.41 ± 34.57) μg/L in the control group (P<0.05). The PFS and OS curves in the observation group were higher than those in the control group (both P<0.05). Conclusion DEB-TACE combined with radiotherapy and either lenvatinib or apatinib demonstrates good short-term efficacy in the treatment of hepatocellular carcinoma with portal vein tumor thrombosis. Patients treated with the combination of DEB-TACE, radiotherapy, and lenvatinib experience greater survival benefits and the treatment is more suitable for patients with underlying renal insufficiency and hypertension.

Key words: Hepatocellular carcinoma, Portal vein tumor thrombosis, Drug-loaded microsphere transarterial chemoembolization, radiotherapy, Lenvatinib, Apatinib

ZHENG Xue-li, LI Hua-yu, ZHAO Si-qi, HUANG Ping. A comparison of the efficacy of DEB-TACE, radiotherapy combined with lenvatinib or apatinib in the treatment of hepatocellular carcinoma with portal vein tumor thrombus[J]. Chinese Hepatolgy, 2025, 30(11): 1483-1488.

References

[1] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2024,74(3):229-263.
[2] 吕国悦. 肝细胞癌合并门静脉癌栓肝移植治疗进展[J]. 中华消化外科杂志,2024,23(2):215-220.
[3] Mukozu T, Nagai H, Matsui D, et al. Adaptation of lenvatinib treatment in patients with hepatocellular carcinoma and portal vein tumor thrombosis[J]. Cancer Chemother Pharmacol,2022,89(1):11-20.
[4] Fu Y, Peng W, Zhang W, et al. Induction therapy with hepatic arterial infusion chemotherapy enhances the efficacy of lenvatinib and pd1 inhibitors in treating hepatocellular carcinoma patients with portal vein tumor thrombosis[J]. J Gastroenterol,2023,58(4):413-424.
[5] Park J, Lee Y B, Ko Y, et al. Comparison of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis[J]. J Liver Cancer,2024,24(1):81-91.
[6] 张灵智,王庆东,严茂军,等. DEB-TACE联合仑伐替尼治疗不可切除大肝癌合并门脉癌栓疗效[J]. 中国现代普通外科进展,2024,27(8):627-632.
[7] 李臻,李杰,李鑫,等. 非侵入性肝纤维化诊断模型对肝癌DEB-TACE术后急性肝功能恶化的预测与生存分析[J]. 临床放射学杂志,2023,42(9):1507-1512.
[8] 杨晓欣,卢伟. 常规TACE与药物洗脱微球TACE治疗CNLC Ⅱb和Ⅲa期肝细胞癌效果及患者预后影响因素[J]. 中国介入影像与治疗学,2023,20(10):582-586.
[9] 曹洪祥,黄平. 肝细胞癌合并门静脉癌栓的治疗现状[J]. 肝胆胰外科杂志,2023,35(4):252-256.
[10] Ji X, Xu Z, Sun J, et al. Lenvatinib with or without stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective study[J]. Radiat Oncol,2023,18(1):101.
[11] 彭林辉,陈涛,徐云修修,等. mFOLFOX7方案全身化疗联合卡瑞利珠单克隆抗体和阿帕替尼治疗肝细胞癌合并Vp4型门静脉癌栓的疗效[J]. 中华消化外科杂志,2024,23(2):265-271.
[12] Reig M, Forner A, Avila M A, et al. Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH[J]. Med Clin (Barc),2021,156(9):461-463.
[13] Kudo M, Kitano M, Sakurai T, et al. General rules for the clinical and pathological study of primary liver cancer, nationwide follow-up survey and clinical practice guidelines: the outstanding achievements of the Liver Cancer Study Group of Japan[J]. Dig Dis,2015,33(6):765-770.
[14] Eisenhauer E A, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)[J]. Eur J Cancer,2009,45(2):228-247.
[15] National Cancer Institute. Common terminology criteria for adverse events (CTCAE) v4.0[S]. 2009.
[16] 李一帆,李臻,余鹏,等. 不同粒径载药微球序贯TACE用于治疗巨块型原发性肝癌伴肝静脉或门静脉癌栓[J]. 中国介入影像与治疗学,2024,21(5):307-309.
[17] 蒋富强,杜鹏,张嘉诚. FOLFOX4方案肝动脉灌注化疗联合¹²⁵I粒子植入治疗原发性肝癌合并Ⅲ型门静脉癌栓患者的疗效与安全性研究[J]. 中国医师进修杂志,2022,45(5):415-421.
[18] Zou X, Xu Q, You R, et al. Evaluating the benefits of TACE combined with lenvatinib plus PD-1 inhibitor for hepatocellular carcinoma with portal vein tumor thrombus[J]. Adv Ther,2023,40(4):1686-1704.
[19] Hur M H, Cho Y, Kim D Y, et al. Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis[J]. Clin Mol Hepatol,2023,29(3):763-778.
[20] Llovet J M, Vogel A, Madoff D C, et al. Randomized phase 3 LEAP-012 study: transarterial chemoembolization with or without lenvatinib plus pembrolizumab for intermediate-stage hepatocellular carcinoma not amenable to curative treatment[J]. Cardiovasc Intervent Radiol,2022,45(4):405-412.
[21] Lin Z, Chen D, Hu X, et al. Clinical efficacy of HAIC (FOLFOX) combined with lenvatinib plus PD-1 inhibitors vs. TACE combined with lenvatinib plus PD-1 inhibitors in the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombus and arterioportal fistulas[J]. Am J Cancer Res,2023,13(11):5455-5465.
[22] 何华星,刘璐琳,刘颖茵,等. 丁酸钠与索拉非尼可能通过YAP诱导铁死亡协同抑制肝癌细胞增殖[J]. 南方医科大学学报,2024,44(7):1425-1430.
[23] 丁丁,付守忠,戴锋,等. 介入联合索拉菲尼治疗肝癌伴门脉癌栓的疗效观察[J]. 中国医学计算机成像杂志,2023,29(4):433-437.
[24] Lin L W, Yan L Y, Ke K, et al. Efficacy and safety of transarterial chemoembolization combined with lenvatinib, programmed death-1 inhibitor, and iodine-125 seed brachytherapy for hepatocellular carcinoma with portal vein tumor thrombosis[J]. Brachytherapy,2023,22(6):858-871.
[25] 林晓纯,萧聪勤,林坤鹏. 阿帕替尼联合肝动脉化疗栓塞术治疗肝癌合并门静脉癌栓的Meta分析[J]. 广州医科大学学报,2022,50(4):34-41.
[26] 张学贤,丁雨寒,李威,等. 经导管动脉化疗栓塞联合仑伐替尼及卡瑞利珠单抗治疗中晚期肝细胞癌临床效果[J]. 介入放射学杂志,2024,33(1):57-62.
[27] 张延藏,王满周,韩新巍,等. 载药栓塞微球经肝动脉化疗栓塞术联合阿帕替尼治疗不可切除肝癌后二线追加卡瑞利珠单抗的安全性和有效性分析[J]. 临床肝胆病杂志,2023,39(4):834-842.
[28] 陈博文,程家敏,张林枝,等. 肝细胞癌治疗方式对门静脉压力的影响[J]. 临床肝胆病杂志,2022,38(7):1658-1661.
[29] Kato H, Asano Y, Ito M, et al. A case of Vp4 hepatocellular carcinoma with tumor thrombosis extending into the confluence of the splenic/portal vein achieved a good prognosis with emergent hepatectomy and postoperative adjuvant therapy with lenvatinib[J]. World J Surg Oncol,2022,20(1):278.
[30] Li X, Ding X, Liu M, et al. A multicenter prospective study of TACE combined with lenvatinib and camrelizumab for hepatocellular carcinoma with portal vein tumor thrombus[J]. Cancer Med,2023,12(16):16805-16814.