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

Efficacy of Callispheres-TACE in combination with Sindillimab for unresectable hepatocellular carcinoma

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。

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±40.86μg/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.