Supplementary Material for: Decreased Blood Flow after Sorafenib Administration Is an Imaging Biomarker to Predict Overall Survival in Patients with Advanced Hepatocellular Carcinoma

Background: Sorafenib is a multikinase inhibitor targeting Raf and protein tyrosine kinases, which are involved in cell growth and tumor angiogenesis. Sorafenib administration induces temporary inhibition of tumor growth and a decrease in arterial blood flow in a considerable number of hepatocellular carcinoma (HCC) patients. We retrospectively evaluated the association between decreased blood flow and the overall survival (OS) of HCC patients after the initiation of sorafenib therapy. Patients and Methods: Therapeutic responses of 158 advanced HCC patients with hypervascular tumors who had received sorafenib for more than 1 month were analyzed. To assess their therapeutic response, patients underwent radiological evaluation before and every 4-6 weeks after the initiation of sorafenib treatment. After the classification of patients into three groups based on the change in arterial enhancement during treatment (no change, decrease and disappearance), the OS of each group was compared using the Kaplan-Meier method. Results: Statistically significant differences in OS were observed among the three groups (p < 0.001). A decrease or disappearance of arterial enhancement was significantly associated with improved OS compared to patients with no change in arterial enhancement; the median OS was 19.9 months (95% confidence interval, CI, 16.4-24.5 months) and 6.0 months (95% CI, 4.0-8.8 months), respectively (p < 0.001). However, there was no difference in OS between the decrease and disappearance groups (p = 0.88). Conclusion: We conclude that decreased arterial enhancement during sorafenib treatment was associated with the longest OS and could therefore reflect an effective response.背景：索拉非尼（Sorafenib）是一种靶向参与细胞增殖与肿瘤血管生成的Raf激酶与蛋白酪氨酸激酶的多激酶抑制剂。在相当一部分肝细胞癌（hepatocellular carcinoma, HCC）患者中，索拉非尼给药可暂时抑制肿瘤生长，并降低动脉血流量。本研究回顾性分析了索拉非尼治疗启动后，肝癌患者血流量降低与总生存期（overall survival, OS）之间的关联。 患者与方法：本研究对158例接受索拉非尼治疗超过1个月的晚期高血管化肝细胞癌患者的治疗应答情况进行了分析。为评估患者的治疗应答，所有患者均在索拉非尼治疗启动前及治疗后每4~6周接受影像学评估。根据治疗期间动脉增强程度的变化将患者分为三组（无变化、降低、消失），采用Kaplan-Meier法比较各组的总生存期。 结果：三组患者的总生存期存在统计学显著性差异（p < 0.001）。与动脉增强无变化的患者相比，动脉增强降低或消失的患者总生存期显著延长：其中位总生存期分别为19.9个月（95%置信区间（confidence interval, CI）：16.4~24.5个月）与6.0个月（95%置信区间（CI）：4.0~8.8个月）（p < 0.001）。但动脉增强降低组与消失组的总生存期无显著差异（p = 0.88）。 结论：本研究认为，索拉非尼治疗期间动脉增强降低与最长总生存期相关，因此可作为有效治疗应答的反映指标。