特瑞普利单抗联合仑伐替尼 TACE治疗晚期肝癌的疗效及对肿瘤标志物预后的影响

doi:10.3969/j.issn.1006-6233.2024.10.030

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摘要 目的:探究特瑞普利单抗联合仑伐替尼、肝动脉化疗栓塞术(TACE)治疗晚期肝癌的疗效,并分析其对肿瘤标志物、预后的影响。方法:选取2022年1月至2023年3月中南大学湘雅医学院附属常德医院(常德市第一人民医院)108例晚期肝癌患者,根据简单随机化法分为研究组、对照组,各54例。对照组采用仑伐替尼+TACE治疗,研究组采用特瑞普利单抗+仑伐替尼+TACE治疗,以21d为1个疗程,连续治疗3个疗程。治疗3个疗程后比较两组治疗效果、不良反应。比较两组治疗前、治疗3个疗程后肿瘤标志物[高尔基体糖蛋白73(GP73)、癌胚抗原(CEA)、肿瘤特异性生长因子(TSGF)、糖类抗原19-9(CA19-9)]、免疫功能(T淋巴细胞亚群)、血清因子[白细胞介素-1β(IL-1β)、胎球蛋白(AHSG)、核因子-κB(NF-κB)、分泌型人类表皮生长因子受体3(sErbB3)]、生存质量[癌症患者生命质量测定量表(FACT-G)评分]、功能状态[卡氏功能(KPS)评分]。统计比较两组治疗后1年内预后情况。结果:研究组客观缓解率(ORR)高于对照组,有统计学差异(59.26% vs 37.04%,χ²=5.341,P=0.021);研究组治疗后血清GP73、CEA、TSGF、CA19-9水平分别为(198.62±61.79)ng/mL、(20.45±2.48)ng/mL、(62.08±7.12)U/mL、(26.07±3.49)U/mL,低于对照组的(237.91±66.35)ng/mL、(25.63±2.79)ng/mL、(70.61±7.59)U/mL、(29.58±3.86)U/mL(P<0.05);研究组治疗后CD3⁺、CD4⁺、CD4⁺/CD8⁺水平高于对照组(P<0.05);研究组治疗后血清IL-1β、AHSG、NF-κB、sErbB3水平分别为(15.88±3.64)pg/mL、(9.39±3.13)ng/mL、(175.49±38.62)ng/L、(2791.36±256.84)ng/mL,低于对照组的(20.56±4.37)pg/mL、(11.72±3.41)ng/mL、(212.83±43.57)ng/L、(2983.49±268.07)ng/mL(P<0.05);研究组治疗后FACT-G、KPS评分高于对照组(P<0.05);两组不良反应对比无明显差异(P>0.05);研究组治疗后1年生存率为29.63%,高于对照组的18.52%(P<0.05)。结论:特瑞普利单抗+仑伐替尼+TACE治疗晚期肝癌的疗效确切,可降低肿瘤标志物水平,改善免疫功能、肿瘤微环境,提高生存质量,并可改善功能状态,提高生存率,且具有一定安全性。

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关键词 ：肝癌, 仑伐替尼, 肝动脉化疗栓塞术, 特瑞普利单抗, 肿瘤标志物

Abstract：Objective: To explore the efficacy of toripalimab combined with lenvatinib and transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) and analyze its effects on tumor markers and prognosis. Methods: A total of 108 patients with advanced HCC admitted to the Affiliated Hospital of Xiangya School of Medicine, Central South University (Changde First People's Hospital) from January 2022 to March 2023 were selected and randomly divided into two groups: the study group and the control group, with 54 patients in each group. The control group received lenvatinib + TACE treatment, while the study group received toripalimab + lenvatinib + TACE treatment. Each treatment course lasted 21 days, and three consecutive courses were administered. The treatment efficacy and adverse reactions were compared between the two groups after three courses. Tumor markers [Golgi protein 73 (GP73), carcinoembryonic antigen (CEA), tumor-specific growth factor (TSGF), carbohydrate antigen 19-9 (CA19-9)], immune function (T lymphocyte subsets), serum factors [interleukin-1β (IL-1β), alpha-2-HS-glycoprotein (AHSG), nuclear factor kappa B (NF-κB), soluble epidermal growth factor receptor 3 (sErbB3)], quality of life [FACT-G (Functional Assessment of Cancer Therapy-General) score], and functional status [Karnofsky Performance Status (KPS) score] were compared before and after treatment. Prognosis was assessed within one year after treatment in both groups. Results: The objective response rate (ORR) of the study group was significantly higher than that of the control group (59.26% vs. 37.04%, χ²=5.341, P=0.021). After treatment, serum levels of GP73, CEA, TSGF, and CA19-9 in the study group were significantly lower than those in the control group [(198.62±61.79) ng/mL, (20.45±2.48) ng/mL, (62.08±7.12) U/mL, (26.07±3.49) U/mL vs. (237.91±66.35) ng/mL, (25.63±2.79) ng/mL, (70.61±7.59) U/mL, (29.58±3.86) U/mL, P<0.05]. The levels of CD3⁺, CD4⁺, and CD4⁺/CD8⁺ in the study group were significantly higher than in the control group (P<0.05). Serum levels of IL-1β, AHSG, NF-κB, and sErbB3 in the study group were lower than those in the control group [(15.88±3.64) pg/mL, (9.39±3.13) ng/mL, (175.49±38.62) ng/L, (2791.36±256.84) ng/mL vs. (20.56±4.37) pg/mL, (11.72±3.41) ng/mL, (212.83±43.57) ng/L, (2983.49±268.07) ng/mL, P<0.05]. FACT-G and KPS scores were higher in the study group than in the control group after treatment (P<0.05). There was no significant difference in adverse reactions between the two groups (P>0.05). The 1-year survival rate in the study group was 29.63%, significantly higher than the 18.52% in the control group (P<0.05). Conclusion: Toripalimab combined with lenvatinib and TACE has a significant therapeutic effect on advanced hepatocellular carcinoma. It can reduce tumor marker levels, improve immune function and the tumor microenvironment, enhance the quality of life and functional status, and increase the survival rate, with good safety.

Key words： Hepatocellular carcinoma Lenvatinib Transarterial chemoembolization Toripalimab Tumor markers

基金资助:湖南省创新型省份建设专项,(编号:S2021JJZZLH1563)

通讯作者: 罗韬

引用本文:

吴小龙, 邓婧, 罗韬. 特瑞普利单抗联合仑伐替尼 TACE治疗晚期肝癌的疗效及对肿瘤标志物预后的影响[J]. 河北医学, 2024, 30(10): 1745-1750.
WU Xiaolong, et al. Efficacy of Toripalimab Combined with Lenvatinib and TACE in the Treatment of Advanced Hepatocellular Carcinoma and Its Impact on Tumor Markers and Prognosis. HeBei Med, 2024, 30(10): 1745-1750.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2024.10.030 或 http://www.hbyxzzs.cn/CN/Y2024/V30/I10/1745

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