Callispheres-TACE术联合信迪利单抗治疗不可切除肝细胞癌的有效性

摘要/Abstract

摘要： 目的探讨Callispheres-肝动脉化疗栓塞(TACE)术联合信迪利单抗治疗不可切除肝细胞癌的有效性。方法选取2020年1月—2022年1月期间海安市人民医院收治的不可切除肝细胞癌患者110例,随机分为对照组与观察组各55例,对照组使用Callispheres-TACE术治疗,观察组使用Callispheres-TACE术联合信迪利单抗方案治疗。对比两组肿瘤标志物[甲胎蛋白(AFP)、CA242、CA724]、肿瘤生长因子[碱性成纤维细胞生长因子(bFGF)、血管内皮生长因子(VEGF)]、抗肿瘤免疫应答因子[CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺]、癌基因[增殖相关基因(C-myc)、成纤维细胞生长因子2(FGF2)]和抑癌基因[细胞周期依赖性蛋白激酶抑制剂(P16)、铁凋亡蛋白(Hepcidin)]水平并统计近期疗效、不良反应及生存状况。结果疗程结束后,观察组的AFP、CA242、CA724水平为(405.12±40.86)μg/L、(6.57±1.02)U/mL、(13.34±3.08)U/mL,低于对照组的(557.56±67.45)μg/L、(9.69±1.63)U/mL、(16.34±3.69)U/mL,差异有统计学意义(t=14.340、12.108、8.377,均P<0.05)。观察组的bFGF和VEGF水平为(3.64±0.57)、(155.71±15.72)pg/mL,低于对照组的(6.33±0.86)、(221.46±36.33)pg/mL,差异有统计学意义(t=19.340、12.320,均P<0.05)。观察组的CD3⁺、CD4⁺、CD4⁺/CD8⁺水平为(68.31±7.42)%、(44.12±5.13)%、1.58±0.26,高于对照组的(56.43±6.36)%、(36.35±4.20)%、1.25±0.14;观察组的CD8+水平为(21.24±2.01)%,低于对照组的(26.34±2.71)%,差异有统计学意义(t=9.015、8.691、11.210、8.288,均P<0.05)。观察组的C-myc、FGF2水平为(1.09±0.14)、(1.21±0.25)pg/mL,低于对照组的(6.75±1.22)、(5.78±1.33)pg/mL;观察组的P16和Hepcidin水平为(11.42±0.83)、(12.95±1.27)pg/mL,高于对照组的(7.45±0.98)、8.42±1.35 pg/mL,差异有统计学意义(t=34.180、25.040、22.930、18. 130,均P<0.05)。两组的客观缓解率(ORR)为80.00%,高于对照组的61.82%,差异有统计学意义(P<0.05)。两组的不良反应发生率比较差异无统计学意义(P>0.05)。观察组的中位无进展生存时间、中位总生存时间、12个月生存率为(8.12±1.09)个月、(10.35±1.04)个月、72.73%,高于对照组的(6.84±0.87)个月、(8.98±1.43)个月、52.73%(t=6.807、5.823、4.705,均P<0.05)。结论 Callispheres-TACE术联合信迪利单抗可能通过抑制病灶生长,改变癌基因、抑癌基因表达失衡,从而延长不可切除的肝细胞癌患者生存周期,提高近期疗效。

关键词: 肝细胞癌, Callispheres-肝动脉化疗栓塞术, 信迪利单抗, 生存周期

Abstract: Objective To evaluate the effectiveness of combining Callispheres-hepatic arterial chemoembolization (TACE) with sindillimab in the management of unresectable hepatocellular carcinoma. Methods A total of 110 patients with unresectable hepatocellular carcinoma were admitted to our hospital from January 2020 to January 2022. They were randomly divided into the control group or the observation group, with 55 patients in each group. The control group received Callispheres-TACE treatment, while the observation group received Callispheres-TACE combined with sindillimab. The levels of tumor markers [alpha-fetoprotein (AFP), CA242, CA724], tumor growth factors [basic fibroblast growth factor (bFGF) vascular endothelial growth factor (VEGF)], anti-tumor immune response factors [CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺], oncogenes [proliferation-related genes (C-myc), fibroblast growth factor 2 (FGF2)] and tumor suppressor genes [cell cycle dependent protein kinase inhibitor (P16), iron apoptotic protein (Hepcidin)] were compared between the two groups. Furthermore, a comparative analysis of the recent treatment efficacy, adverse reactions, and survival status was conducted between the two groups. Results After treatment, the observation group demonstrated significantly lower AFP, CA242 and CA724 (405.12±40.86 μg/L, 6.57±1.02 U/mL, 13.34±3.08 U/mL, respectively), compared to the control group (557.56±67.45μg/L, 9.69±1.63 U/mL and 16.34±3.69 U/mL), with statistically significant differences (t=14.340, 12.108, 8.377, P<0.05). Similarly, the levels of bFGF and VEGF in the observation group (3.64±0.57 pg/mL and 155.71±15.72 pg/mL) were significantly lower than those in the control group (6.33±0.86 pg/mL and 221.46±36.33 pg/mL), with statistically significant differences (t=19.340, 12.320, P<0.05). Furthermore, the observation group exhibited higher levels of CD3⁺, CD4⁺, and CD4⁺/CD8⁺ (68.31±7.42%, 44.12±5.13% and 1.58±0.26) and a lower level of CD8⁺ (21.24±2.01%) when compared to the control group (56.43±6.36%, 36.35±4.20%, 1.25±0.14, and 26.34±2.71%, respectively), and the difference was statistically significant (t=9.015, 8.691, 11.210, 8.288, all P<0.05). The levels of C-myc and FGF2 in the observation group (1.09±0.14 pg/mL and 1.21±0.25 pg/mL, respectively) were also lower than those in the control group (6.75±1.22 pg/mL and 5.78±1.33 pg/mL) while the levels of P16 and Hepcidin in the observation group (11.42±0.83 pg/mL and 12.95±1.27 pg/mL) were higher than those in the control group (7.45±0.98 pg/mL and 8.42±1.35 pg/mL). The difference was statistically significant (t=34.180, 25.040, 22.930, 18.130, all P<0.05). The observation group achieved a higher objective response rate (ORR) of 80.00% compared to the control group’s 61.82% (P<0.05). However, there was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Additionally, the observation group demonstrated longer median progression-free survival time, median overall survival time, and 12-month survival rate (8.12±1.09 months, 10.35±1.04 months and 72.73%, respectively), compared to the control group (6.84±0.87 months, 8.98±1.43 months, 52.73%) (t=6.807, 5.823, 4.705, all P<0.05). Conclusion The combination of Callispheres-TACE and Sindillimab shows promise in inhibiting lesion growth, restoring the expression imbalance of oncogenes and tumor suppressor genes, and improving survival outcomes in patients with unresectable hepatocellular carcinoma, thereby enhancing short-term efficacy.

Key words: Hepatocellular carcinoma, Callispheres-Hepatic arterial chemoembolization, Sinilizumab, Life cycle

张永红, 储建华, 陈国栋. Callispheres-TACE术联合信迪利单抗治疗不可切除肝细胞癌的有效性[J]. 肝脏, 2024, 29(2): 202-207.

ZHANG Yong-hong, CHU Jian-hua, CHEN Guo-dong. Efficacy of Callispheres-TACE in combination with Sindillimab for unresectable hepatocellular carcinoma[J]. Chinese Hepatolgy, 2024, 29(2): 202-207.

参考文献

[1] Zhang J, Feng GA, Li Y, et al. Drug-eluting bead transarterial chemoembolization with medium-sized ersus small-sized CalliSpheres microspheres in unresectable primary liver cancer[J]. Asia Pac J Clin Oncol. 2022,18(4):388-393.
[2] Chidambaranathan RS, Fisher PB, Sarkar D. Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification[J]. Adv Cancer Res.2021,149(1):1-61.
[3] 黄鑫龙, 王君松, 苏振清. CalliSpheres载药微球TACE术联合微波消融治疗原发性肝癌[J].中西医结合肝病杂志,2022,32(12):1102-1105.
[4] Zheng Y, Wang S, Cai J, et al. The progress of immune checkpoint therapy in primary liver cancer[J]. Biochim Biophys Acta Rev Cancer.2021,1876(2):188638.
[5] 王俊洁, 徐龙, 袁国盛, 等. 信迪利单抗联合仑伐替尼二线治疗不可切除肝细胞肝癌的临床疗效及安全性[J]. 实用医学杂志,2022,38(9):1130-1135.
[6] 中华人民共和国国家卫生健康委员会医政医管局.原发性肝癌诊疗规范(2019年版)[J]. 中华消化外科杂志,2020,19(1):1-20.
[7] 徐鹏程, 张庆桥, 徐浩, 等. CalliSpheres载药微球TACE联合微波消融治疗原发性大肝癌疗效评价[J]. 医学影像学杂志,2020,30(4):620-623.
[8] 寸江平, 姜永能, 宗璇, 等. CalliSpheres微球联合空白微球TACE治疗中晚期肝癌的近期疗效及安全性研究[J].介入放射学杂志,2019,28(3):237-241.
[9] 吕然, 刘琛志. CalliSpheres载药微球TACE序贯微波消融治疗单发直径＞5 cm原发性老年肝癌的临床研究[J]. 中华肿瘤防治杂志,2022,29(15):1136-1142.
[10] 李红, 尹芳, 罗贯虹, 等. CalliSpheres载药脂微球联合TACE与传统TACE治疗肝癌疗效对比分析[J]. 胃肠病学和肝病学杂志,2019,28(2):171-174.
[11] 宋文, 彭赵宏, 张德志, 等. CalliSpheres载药微球在肝癌介入治疗中的临床疗效评价[J]. 安徽医科大学学报,2020,55(8):1307-1311.
[12] 谢璇丞, 赵卫, 范宏杰, 等. CalliSpheres载药微球动脉化疗栓塞术治疗中晚期肝癌的安全性及有效性分析[J].实用放射学杂志,2020,36(5):792-795.
[13] 滕颖, 丁晓燕, 李文东, 等. 程序性细胞死亡受体1抑制剂联合仑伐替尼治疗晚期原发性肝癌的效果及不良反应[J]. 临床肝胆病杂志,2021,37(3):606-610.
[14] 丁晓燕, 孙巍, 申燕军, 等. 仑伐替尼联合信迪利单抗二线治疗肝内胆管癌的效果和安全性[J]. 临床肝胆病杂志,2022,38(8):1813-1818.
[15] 杨建奇, 曹文淼, 吴银霞, 等. 卡瑞利珠单抗或信迪利单抗联合仑伐替尼治疗肝癌的效果及对肿瘤标志物的影响[J]. 肝脏,2022,27(10):1080-1083.
[16] 李利珍, 孙振亚, 陈明明, 等. 经导管动脉化疗栓塞联合信迪利单抗治疗原发性中晚期肝癌的近期疗效及安全性分析[J]. 肿瘤综合治疗电子杂志,2022,8(3):136-140.
[17] Zheng X, Jin W, Wang S, et al. Progression on the Roles and Mechanisms of Tumor-Infiltrating TLymphocytes in Patients With Hepatocellular Carcinoma[J]. Front Immunol,2021,12(1):729705.
[18] 刘慧敏, 刘晓利, 王欣惠, 等. 原发性肝癌患者外周血CD4⁺T、CD8⁺T、Tc17、Th17和Treg淋巴细胞的变化及其意义[J]. 实用肝脏病杂志,2022,25(2):255-258.
[19] 杨惠元, 高君. 肝细胞肝癌患者血清中癌基因、抑癌基因表达及临床意义[J].中国老年学杂志, 2019,39(10):2367-2369.
[20] Zhou JN, Zhang B, Wang HY, et al. A Functional Screening Identifies a New Organic SeleniumCompound Targeting Cancer Stem Cells: Role of c-Myc Transcription Activity Inhibition in Liver Cancer[J]. Adv Sci (Weinh),2022,9(22):e2201166.
[21] Jia H, Yan D, Xiao Q, et al. Correlations of ultrasonic features with severity of liver cancer and p16 expression in patients with liver cancer[J]. Neoplasma,2019,66(1):149-154.
[22] Wang J, Liu W, Li JC, et al. Hepcidin Downregulation Correlates With Disease AggressivenessAnd Immune Infiltration in Liver Cancers[J]. Front Oncol, 2021,11(1):714756.