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

<b><i>Background &amp; Aims:</i></b> 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. <b><i>Methods:</i></b> 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 (<i>n</i> = 65) and a group in which MTAs were not administered (<i>n</i> = 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. <b><i>Results:</i></b> 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, <i>p</i> &lt; 0.001; median survival time [MST]: 44.6 vs. 26.6 months, <i>p</i> = 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, <i>p</i> = 0.01; MST: 53.4 vs. 33.3 months, <i>p</i> = 0.01). <b><i>Conclusion:</i></b> The administration of MTAs in patients with intermediate-stage HCC contributes to the prevention of stage progression and prolongs OS.

<b><i>背景与研究目的：</i></b> 随着各类分子靶向药物（molecular-targeted agents, MTAs）的研发与临床应用，中期肝细胞癌（hepatocellular carcinoma, HCC）的治疗方案日趋复杂。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，是否可预防疾病进展至晚期阶段。<b><i>研究方法：</i></b> 本研究回顾性纳入289例Child-Pugh A级（Child-Pugh class A）、确诊为中期肝细胞癌且接受首次经动脉化疗栓塞（trans-arterial chemoembolization, TACE）的患者。经倾向性评分匹配（propensity score matching, PSM）后，将患者分为两组：一组为经TACE治疗后病情难治的患者，予分子靶向药物治疗（n=65）；另一组为中期肝细胞癌阶段未接受分子靶向药物治疗的患者（n=65）。采用Kaplan-Meier法计算疾病分期进展时间（time to stage progression, TTSP）与总生存期（overall survival, OS），并通过log-rank检验进行组间比较分析。<b><i>研究结果：</i></b> 分子靶向药物治疗组的疾病分期进展时间与总生存期均显著长于未治疗组（疾病分期进展时间：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，符合up-to-seven标准以及在中期肝细胞癌阶段接受分子靶向药物治疗，是疾病分期进展时间与总生存期的独立预测因素。多分子靶向药物治疗时代组的疾病分期进展时间与总生存期，均显著长于单分子靶向药物治疗时代组（疾病分期进展时间：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）。<b><i>研究结论：</i></b> 中期肝细胞癌患者接受分子靶向药物治疗，可有效延缓疾病分期进展并延长总生存期。