Supplementary Material for: Multimolecular-Targeted Agents for Intermediate-Stage Hepatocellular Carcinoma Influence Time to Stage Progression and Overall Survival

Background & Aims: Intermediate hepatocellular carcinoma (HCC) treatment has become complicated due to the development of various molecular-targeted agents (MTAs). We aimed to determine whether the administration of MTAs in patients with intermediate-stage HCC contributed to the prevention of progression to an advanced stage. Methods: We enrolled and retrospectively examined 289 patients with Child-Pugh class A who had been diagnosed with intermediate-stage HCC and underwent initial trans-arterial chemoembolization (TACE). Patients were classified into 2 groups: a group in which MTAs were administered to patients whose condition was refractory to TACE (n = 65) and a group in which MTAs were not administered (n = 65) at intermediate-stage HCC after propensity score matching (PSM). Time to stage progression (TTSP) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed using a log-rank test after PSM. Results: TTSP and OS of the group with MTA administration were significantly longer than those of the group without MTA administration (TTSP: 36.4 vs. 17.9 months, p < 0.001; median survival time [MST]: 44.6 vs. 26.6 months, p = 0.001). Within the up-to-seven criteria and administration of MTAs at the intermediate-stage HCC were identified as independent factors for TTSP and OS in the multivariate analysis. TTSP and OS in the era of the multi-MTA group were significantly longer than those in the era of the mono-MTA group (TTSP: 44.8 vs. 27.4 months, p = 0.01; MST: 53.4 vs. 33.3 months, p = 0.01). Conclusion: The administration of MTAs in patients with intermediate-stage HCC contributes to the prevention of stage progression and prolongs OS.

背景与目的：中期肝细胞癌（hepatocellular carcinoma，HCC）的治疗因各类分子靶向药物（molecular-targeted agents，MTAs）的问世而日趋复杂。本研究旨在明确中期肝细胞癌患者接受分子靶向药物治疗是否有助于预防病情进展至晚期阶段。
方法：本研究回顾性纳入289例Child-Pugh A级、确诊为中期肝细胞癌且初始接受经动脉化疗栓塞（trans-arterial chemoembolization，TACE）的患者。通过倾向得分匹配（propensity score matching，PSM）将患者分为两组：一组为经动脉化疗栓塞难治性患者予分子靶向药物治疗组（n=65），另一组为中期肝细胞癌阶段未予分子靶向药物治疗组（n=65）。采用Kaplan-Meier法计算病情进展至晚期的时间（time to stage progression，TTSP）与总生存期（overall survival，OS），并在倾向得分匹配后通过log-rank检验进行统计学分析。
结果：分子靶向药物治疗组的病情进展至晚期的时间与总生存期均显著长于未给药组（病情进展至晚期的时间：36.4 vs 17.9个月，p<0.001；中位生存期（median survival time，MST）：44.6 vs 26.6个月，p=0.001）。多因素分析显示，中期肝细胞癌阶段使用分子靶向药物以及符合up-to-seven标准（up-to-seven criteria）均为病情进展至晚期的时间与总生存期的独立影响因素。多种分子靶向药物应用时代组的病情进展至晚期的时间与总生存期均显著长于单一分子靶向药物应用时代组（病情进展至晚期的时间：44.8 vs 27.4个月，p=0.01；中位生存期：53.4 vs 33.3个月，p=0.01）。
结论：中期肝细胞癌患者接受分子靶向药物治疗，有助于预防病情进展至晚期，并可延长总生存期。