不可切除的乙肝相关肝内胆管癌行肝动脉灌注化疗的效果及安全性分析

Analysis of the efficacy and safety of hepatic arterial infusion chemotherapy for unresectable hepatitis B-related intrahepatic cholangiocarcinoma

目的:探讨不可切除的乙肝相关肝内胆管癌(ICC)行肝动脉灌注化疗(HAIC)的效果和安全性。方法:本研究为回顾性病例对照研究。回顾性收集2015年3月至2023年6月在中山大学肿瘤防治中心接受HAIC的140例不可切除ICC患者的资料,其中乙肝表面抗原(HBsAg)阴性组72例[男性43例,女性29例,年龄(59.6±9.5)岁(范围:34~81岁)],HBsAg阳性组68例[男性48例,女性20例,年龄(53.4±11.4)岁(范围:29~82岁)]。HAIC采用联合奥沙利铂、亚叶酸钙和氟尿嘧啶的FOLFOX方案。分析两组患者HAIC的效果、预后和不良反应的差异。所有变量均以分类资料形式表示,组间比较采取 χ^(2)检验或Fisher确切概率法,采用Kaplan-Meier法绘制生存曲线,通过Log-rank检验比较组间的差异。 结果:根据实体瘤疗效评估标准RECIST 1.1版,HBsAg阴性组客观缓解率(ORR)为23.2%(16/69),HBsAg阳性组的ORR为40.3%(25/62),两组患者ORR的差异有统计学意义( χ^(2)=4.459, P=0.035)。根据改良RECIST(mRECIST)标准,HBsAg阴性组的ORR为27.5%(19/69),HBsAg阳性组ORR为45.2%(28/62),两组患者ORR的差异有统计学意义( χ^(2)=4.410, P=0.036)。HBsAg阴性组和阳性组中位无进展生存(PFS)时间分别为7.1个月(95 %CI:5.8~13.2个月)和7.3个月(95 %CI:5.7~10.3个月),中位总体生存(OS)时间分别为16.3个月(95 %CI:12.5~33.9个月)和15.9个月(95 %CI:9.2~20.7个月),两组PFS、OS的差异均无统计学意义( P值均>0.05)。两组患者的主要严重不良反应包括AST升高、ALT升高、血小板减少症和中性粒细胞减少症,HAIC后不良反应的差异均无统计学意义( P值均>0.05)。 结论:HBsAg阳性的不可切除ICC患者更有可能从HAIC中获益。

Objective To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC)for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC).Methods This is a retrospective controlled study.Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected,including 72 patients in the hepatitis B surface antigen(HBsAg)negative group(43 males and 29 females,aged(59.6±9.5)years(range:34 to 81 years)),68 cases in the HBsAg-positive group(48 males,20 females,aged(53.4±11.4)years(range:29 to 82 years)).HAIC treatment used the FOLFOX regimen combined with oxaliplatin,leucovorin,and fluorouracil.The differences in effects,prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed.All variables were expressed as categorical data.The χ^(2) test or Fisher′s exact probability method was used to compare between groups.The Kaplan-Meier method was used to draw survival curves.The difference of survival curve between groups were compared through the Log-rank test.Results According to the Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1,the objective response rate(ORR)of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62).The difference in ORR between the two groups was statistically significant(χ^(2)=4.459,P=0.035).According to the modified RECIST(mRECIST)criteria,the ORR of the HBsAg-negative group was 27.5%(19/69),and the ORR of the HBsAg-positive group was 45.2%(28/62).The difference in ORR between the two groups was statistically significant(χ^(2)=4.410,P=0.036).The median progression-free survival(PFS)of the HBsAg-negative group and the positive group were 7.1 months(95%CI:5.8 to 13.2 months)and 7.3 months(95%CI:5.7 to 10.3 months),respectively,and the median overall survival(OS)were 16.3 months(95%CI:12.5 to 33.9 months)and 15.9 months(95%CI:9.2 to 20.7 months)respectively.There were no statistically significant differences in PFS and OS between the two groups(both P>0.05).The main serious adverse reactions of the two groups of patients included increased AST,increased ALT,thrombocytopenia,and neutropenia.There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment(all P>0.05).Conclusion Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.