原发性肝癌TACE治疗栓塞剂对疗效和预后影响

Effect and prognosis of different embolic particles in TACE treatment of primary hepatocellular carcinoma

目的栓塞剂是肝动脉化疗栓塞术(transcatheter arterial chemoembolization,TACE)中阻塞肿瘤血供的主要物质,对于缩小肿瘤体积、降低复发和转移有重要作用。本研究旨在探讨原发性肝癌TACE治疗中应用碘化油、碘化油联合明胶海绵以及海藻酸钠载药微球的疗效和预后差异。方法选择2014-01-03-2016-06-05新疆医科大学附属肿瘤医院收治的90例原发性肝细胞癌患者,根据所用TACE栓塞剂类型分为碘化油组(30例)、明胶海绵组(30例)和载药微球组(30例),分别在TACE治疗中应用碘化油、碘化油联合明胶海绵以及海藻酸钠载药微球进行栓塞,比较3组患者术后1个月的疗效、治疗前后血清甲胎蛋白(alpha-fetoprotein,AFP)水平,以及治疗相关不良反应和远期预后。结果载药微球组、碘化油组和明胶海绵组的总有效率(overall response rate,ORR)分别为66.7%(20/30)、33.3%(10/30)和46.7%(14/30),3组疗效间差异有统计学意义,H=8.592,P=0.018。其中,载药微球组ORR明显高于碘化油组,χ~2=6.667,P=0.010;载药微球组和明胶海绵组ORR差异无统计学意义,χ~2=2.443,P=0.118。术后3组患者的AFP水平均降低(P<0.05),其中治疗后各时间点载药微球组的AFP水平均低于碘化油组和明胶海绵组,P<0.05。碘化油组、明胶海绵组和载药微球组的中位疾病进展时间分别为10.5(6～15)、15.5(8～20)和17.5(8.5～23)个月,载药微球组的疾病进展风险低于碘化油组(HR=0.423,95%CI:0.239～0.748,P=0.001),而载药微球组与明胶海绵组的差异无统计学意义(HR=0.717,95%CI:0.408～1.259,P=0.225)。碘化油组、明胶海绵组和载药微球组的中位总生存分别为14.5(8～21)、19(10～24)和22.5(15.5～24)个月,载药微球组的死亡进展风险明显低于碘化油组(HR=0.423,95%CI:0.239～0.748,P=0.001),但与明胶海绵组差异无统计学意义(HR=0.646,95%CI:0.332～1.255,P=0.188)。多因素Cox回归分析显示,栓塞剂类型是影响原发性肝癌患者TACE治疗预后的危险因素,其中,与载药微球相比,应用碘化油的死亡风险显著增高(HR=2.547,95%CI:1.333～4.868,P=0.005),载药微球和明胶海绵的死亡风险差异间无统计学意义(HR=1.607,95%CI:0.805～3.207,P=0.179)。碘化油组、明胶海绵组和载药微球组3级以上不良反应发生率分别为30.00%(9/30)、33.33%(10/30)和23.33%(7/30),差异无统计学意义,χ~2=0.757,P=0.685。结论在TACE治疗中应用海藻酸钠载药微球具有较高的临床疗效,能够显著降低AFP水平,有效改善患者的远期预后。

OBJECTIVE Embolization agent is the main substance blocking blood supply of tumor in transcatheter arterial chemoembolization(TACE),which plays an important role in reducing tumor volume and reducing recurrence and metastasis.This study aimed to explore the application of TACE in the treatment of primary liver cancer,the efficacy and prognosis of iodized oil,iodized oil combined with gelatin sponge and sodium alginate drug-loaded microspheres.METHODS Ninty patients with primary hepatocellular carcinoma admitted to the Cancer Hospital of Xinjiang Medical University from January 3,2014 to June 5,2016 were divided into iodized oil group(30 cases),gelatin sponge group(30 cases)and microsphere group(30 cases),the iodized oil,iodized oil combined with gelatin sponge and sodium alginate loaded microspheres were used for embolization in each group respectively.The therapeutic efficacy,serum alpha-fetoprotein(AFP)level,and treatment-related levels,adverse reactions and long-term prognosis were compared among the three groups.RESULTS There was a statistically significant difference in the therapeutic effects among the three groups(H=8.592,P=0.018).Among them,the ORR of the microsphere group was significantly higher than that of the iodized oil group(66.67%vs 33.33%,χ^2=6.667,P=0.010),but not with the gelatin sponge group(66.67%vs 46.67%,χ^2=2.443,P=0.118).After surgery,the AFP levels in the three groups decreased significantly(P<0.05),and the AFP levels in the microsphere were significantly lower than those in the other two groups at all time(P<0.05).The median TTP of iodized oil group,gelatin sponge group and microsphere group was 10.5(6-15)months,15.5(8-20)months and 17.5(8.5-23)months,and the risk of disease progression in microsphere group was significantly lower than the iodized oil group(HR=0.423,95%CI:0.239-0.748,P=0.001),but not with the gelatin sponge group(HR=0.717,95%CI:0.408-1.259,P=0.225).The median OS of iodized oil group,gelatin sponge group and microsphere group was 14.5(8-21)months,19(10-24)months and 22.5(15.5-24)months,and the risk of disease progression in microsphere was significantly lower than iodized oil group(HR=0.423,95%CI:0.239-0.748,P=0.001),but no with gelatin sponge group(HR=0.646,95%CI:0.332-1.255,P=0.188).Multivariate Cox regression analysis showed that embolic agents were the risk factors for the prognosis of patients with primary liver cancer.The risk of death from iodized oil was significantly higher than that of drug-loaded microspheres(HR=2.547,95%CI:1.333-4.868,P=0.005),there was no statistically significant difference in the risk of death between drug-loaded microspheres and gelatin sponge(HR=1.607,95%CI:0.805-3.207,P=0.179).There was no statistically significant in the incidence of adverse reactions in the three groups,respectively(30.00%,33.33% and 23.33%,χ^2=0.757,P=0.685).CONCLUSION The sodium alginate drug-loaded microspheres have high clinical efficacy in TACE therapy,can significantly reduce the AFP level,and effectively improve the long-term prognosis of patients.