Xia Y X, Zhang H, Zhang F, Li X C, Rong D W, Tang W W, Cao H S, Zhao J, Wang P, Pu L Y, Qian X F, Cheng F, Wang K, Kong L B, Zhang C Y, Li D H, Song J H, Yao A H, Wu X F, Wu C, Wang X H
Hepatobiliary Center,the First Affiliated Hospital of Nanjing Medical University,Key Laboratory of Liver Transplantation,Chinese Academy of Medical Sciences,National Health Commission Key Laboratory of Living Donor Liver Transplantation, Nanjing 210000, China.
Zhonghua Wai Ke Za Zhi. 2022 Jul 1;60(7):688-694. doi: 10.3760/cma.j.cn112139-20220408-00150.
To study the surgical safety and efficacy of preoperative neoadjuvant therapy with immune checkpoint inhibitors combined with anti-angiogenic drugs in patients with China liver cancer staging(CNLC)-Ⅱb and Ⅲa resectable hepatocellular carcinoma. The data of 129 patients with Ⅱb and Ⅲa hepatocellular carcinoma who underwent surgery at the First Affiliated Hospital of Nanjing Medical University from January 2018 to December 2020 were analyzed. All patients were divided into two groups: the neoadjuvant therapy group(=14,13 males and 1 female,aged (55.4±12.6)years(range:34 to 75 years)) received immune combined targeted therapy before surgery,immune checkpoint inhibitor camrelizumab was administered intravenously at a dose of 200 mg each time,every 2 weeks for 3 cycles,anti-angiogenesis drug apatinib was taken orally and continuously with a dose of 250 mg for 3 weeks and the conventional surgery group(=115,103 males and 12 females,aged (55.8±12.0)years(range:21 to 83 years)) did not receive antitumor systemic therapy before surgery. There were 3 patients with CNLC-Ⅱb,11 with CNLC-Ⅲa in the neoadjuvant group;28 patients with CNLC-Ⅱb,87 with CNLC-Ⅲa in the conventional group. Student's test or rank-sum test was used to compare the differences between two groups for quantitative data, Fisher's exact probability method was used to compare the differences of proportions between two groups, and Log-rank test was used to compare survival differences between two groups. The 1-year recurrence rate in the neoadjuvant group was 42.9%,and the 1-year recurrence rate in the conventional group was 64.0%,with a statistically significant difference between the two groups(χ²=3.850,=0.050);The 1-year survival rate in the neoadjuvant group was 100% and that in the conventional group was 74.2%,with a statistically significant difference between the two groups(χ²=5.170,=0.023). According to the stratified analysis of the number of tumors,for single tumor,the 1-year recurrence rate in the neoadjuvant group was 25.0%,and that in the conventional surgery group was 71.0%,and the difference between the two groups was statistically significant(χ²=5.280, =0.022). For multiple tumors, the 1-year recurrence rate in the neoadjuvant group was 66.7%,and the 1-year recurrence rate in the conventional surgery group was 58.9%,with no significant difference between the two groups(χ²=0.110,=0.736). The operative time,intraoperative blood loss,and postoperative hospital stay in the neoadjuvant group were similar to those in the conventional group,and their differences were not statistically significant. Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs as a neoadjuvant therapy for resectable hepatocellular carcinoma can reduce the 1-year recurrence rate and improve the 1-year survival rate,especially for those with solitary tumor. Limited by the sample size of the neoadjuvant group,the safety of immune combined targeted therapy before surgery cannot be observed more comprehensively,and further studies will be explored.
研究免疫检查点抑制剂联合抗血管生成药物术前新辅助治疗在中国肝癌分期(CNLC)-Ⅱb和Ⅲa期可切除肝细胞癌患者中的手术安全性和疗效。分析了2018年1月至2020年12月在南京医科大学第一附属医院接受手术的129例Ⅱb和Ⅲa期肝细胞癌患者的数据。所有患者分为两组:新辅助治疗组(n = 14,男13例,女1例,年龄(55.4±12.6)岁(范围:34至75岁))术前接受免疫联合靶向治疗,免疫检查点抑制剂卡瑞利珠单抗静脉注射,每次剂量200 mg,每2周1次,共3个周期,抗血管生成药物阿帕替尼口服持续给药,剂量250 mg,共3周;传统手术组(n = 115,男103例,女12例,年龄(55.8±12.0)岁(范围:21至83岁))术前未接受抗肿瘤全身治疗。新辅助组中CNLC-Ⅱb期3例,CNLC-Ⅲa期11例;传统组中CNLC-Ⅱb期28例,CNLC-Ⅲa期87例。定量资料两组间比较采用Student's检验或秩和检验,两组间率的比较采用Fisher确切概率法,两组生存差异比较采用Log-rank检验。新辅助组1年复发率为42.9%,传统组1年复发率为64.0%,两组差异有统计学意义(χ² = 3.850,P = 0.050);新辅助组1年生存率为100%,传统组为74.2%,两组差异有统计学意义(χ² = 5.170,P = 0.023)。根据肿瘤数量进行分层分析,对于单发病灶,新辅助组1年复发率为25.0%,传统手术组为71.0%,两组差异有统计学意义(χ² = 5.280,P = 0.022)。对于多发病灶,新辅助组1年复发率为66.7%,传统手术组为58.9%,两组差异无统计学意义(χ² = 0.110,P = 0.736)。新辅助组手术时间、术中出血量和术后住院时间与传统组相似,但差异无统计学意义。免疫检查点抑制剂联合抗血管生成靶向药物作为可切除肝细胞癌的新辅助治疗可降低1年复发率并提高1年生存率,尤其是对于单发病灶患者。受新辅助组样本量限制,术前免疫联合靶向治疗的安全性无法更全面观察,将进一步开展研究探索。