Supplementary Material for: Redefining Tumor Burden in Patients with Intermediate-Stage Hepatocellular Carcinoma: The Seven-Eleven Criteria

Background and Aims: For patients with intermediate-stage hepatocellular carcinoma (HCC), the definition of high tumor burden remains controversial. This study aimed to compare the prognostic value of different criteria of tumor burden in patients with intermediate-stage HCC undergoing transarterial chemoembolization (TACE). Methods: From 2007 to 2019, 632 treatment-naive patients with intermediate-stage HCC undergoing TACE were retrospectively enrolled. We compared different criteria of tumor burden in discriminating radiologic response and survival, including up-to-7, up-to-11, 5–7, 7 lesions criteria, and newly proposed 7–11 criteria. Results: The proportions of patients classified as high tumor burden were varied by different criteria. Among the 5 criteria, 7–11 criteria have the best performance to discriminate complete response (CR) and overall survival (OS) after TACE. In patients with low, intermediate, and high tumor burden classified by 7–11 criteria, the CR rate was 21, 12, and 2.5%, respectively (p < 0.001), and the median OS was 33.1, 22.3, and 11.9 months, respectively (p < 0.001). By multivariate analysis, 7–11 criteria were significantly associated with CR (intermediate vs. high burden, odds ratio = 4.617, p = 0.002; low vs. high burden, odds ratio = 8.675, p < 0.001) and OS (intermediate vs. high burden, hazard ratio = 0.650, p < 0.001; low vs. high burden, hazard ratio = 0.520, p < 0.001). Seven to 11 criteria also had the lowest corrected Akaike information criteria, highest homogeneity value, and highest area under the receiver operating characteristic curve in predicting 1-, 2-, and 3-year mortality among all criteria. Conclusion: Conventional definitions of tumor burden were not optimal for patients with intermediate HCC. The new 7–11 criteria had the best discriminative power in predicting radiologic response and survival in patients with intermediate-stage HCC undergoing TACE.

背景与目的：对于中期肝细胞癌（hepatocellular carcinoma, HCC）患者，高肿瘤负荷的定义仍存在争议。本研究旨在比较不同肿瘤负荷判定标准在接受经动脉化疗栓塞（transarterial chemoembolization, TACE）治疗的中期HCC患者中的预后价值。

方法：2007年至2019年间，632例初治且接受TACE治疗的中期HCC患者被回顾性纳入本研究。我们对比了多种肿瘤负荷判定标准在区分影像学应答与生存结局方面的效能，包括"up-to-7"、"up-to-11"、5~7个病灶标准以及新提出的7~11个病灶标准。

结果：不同判定标准下，被归类为高肿瘤负荷的患者比例存在显著差异。在5种判定标准中，7~11个病灶标准在区分TACE术后完全缓解（complete response, CR）率与总生存期（overall survival, OS）方面表现最优。根据7~11个病灶标准划分的低、中、高肿瘤负荷患者群体中，其CR率分别为21%、12%与2.5%（p < 0.001），中位OS分别为33.1个月、22.3个月与11.9个月（p < 0.001）。多因素分析显示，7~11个病灶标准与CR（中负荷vs.高负荷：比值比=4.617，p=0.002；低负荷vs.高负荷：比值比=8.675，p < 0.001）及OS（中负荷vs.高负荷：风险比=0.650，p < 0.001；低负荷vs.高负荷：风险比=0.520，p < 0.001）显著相关。相较于其余标准，7~11个病灶标准在预测1年、2年及3年死亡率时，校正后赤池信息准则最低、同质性最高，且受试者工作特征曲线下面积最大。

结论：传统肿瘤负荷定义并不适用于中期HCC患者。新提出的7~11个病灶标准在预测接受TACE治疗的中期HCC患者的影像学应答与生存预后方面，具备最优的区分效能。