Supplementary Material for: Number of Tumors Stratifies the Therapeutic Response to Atezolizumab Plus Bevacizumab Therapy in Barcelona Clinic Liver Cancer Stage B Unresectable Hepatocellular Carcinoma: A Multicenter Analysis

Introduction: Atezolizumab plus bevacizumab (ATZ+BV) is used for the treatment of Barcelona Clinic Liver Cancer (BCLC) stage B unresectable hepatocellular carcinoma (u-HCC) patients. However, the efficacy of ATZ+BV in various BCLC stage B conditions, especially the up-to-seven criteria in/out, has not been fully investigated.
Methods: We enrolled 83 BCLC stage B u-HCC patients with Child-Pugh class A who were treated with ATZ+BV as the first-line systemic chemotherapy in the study. All patients were evaluated for initial responses by dynamic computed tomography or magnetic resonance imaging after the initiation of ATZ+BV, and therapeutic efficacy was assessed.
Results: When stratified by up-to-seven criteria, progression-free survival (PFS) was significantly prolonged in patients with up-to-seven in (in vs. out: median 21.0 vs. 8.2 months, P = 0.006), and the Cox proportional hazard model showed that up-to-seven out/in was the significant factor contributing to PFS (out vs. in: HR 2.58, P = 0.007). We next evaluated PFS stratified by the maximum intrahepatic tumor diameter and number of intrahepatic tumors, which constitute the up-to-seven criteria. The number of tumors was a significant factor contributing to PFS (> 7 vs. ≤ 7: HR 1.75, P = 0.040), but maximum tumor size was not (> 5 cm vs. ≤ 5 cm: HR 1.19, P = 0.588).
Conclusions: In BCLC stage B u-HCC patients treated with ATZ+BV, a high number of intrahepatic tumors was associated with poor PFS. Therefore, it may be better to consider additional treatment strategies in these patients.

引言：阿替利珠单抗联合贝伐珠单抗（ATZ+BV）用于治疗巴塞罗那临床肝癌（Barcelona Clinic Liver Cancer, BCLC）分期B期不可切除肝细胞癌（u-HCC）患者。然而，ATZ+BV在不同BCLC B期亚群中的疗效，尤其是符合up-to-seven标准（up-to-seven criteria）与否的亚组，尚未得到充分研究。
方法：本研究共入组83例Child-Pugh A级（Child-Pugh class A）的BCLC B期不可切除肝细胞癌患者，均以ATZ+BV作为一线全身化疗方案接受治疗。所有患者在启动ATZ+BV治疗后，均通过动态计算机断层扫描（dynamic computed tomography）或磁共振成像（magnetic resonance imaging）评估初始治疗应答，并对治疗疗效进行评价。
结果：按up-to-seven标准分层分析时，符合该标准的患者无进展生存期（progression-free survival, PFS）显著延长（符合组vs.不符合组：中位PFS 21.0个月 vs. 8.2个月，P=0.006）；Cox比例风险模型（Cox proportional hazard model）分析显示，是否符合up-to-seven标准是影响PFS的独立危险因素（不符合组vs.符合组：风险比HR 2.58，P=0.007）。随后我们针对构成up-to-seven标准的两个核心指标——肝内最大肿瘤直径及肝内肿瘤数目——分别开展PFS分层分析。结果显示，肝内肿瘤数目是影响PFS的显著危险因素（>7个vs. ≤7个：HR 1.75，P=0.040），而最大肿瘤直径则无显著关联（>5cm vs. ≤5cm：HR 1.19，P=0.588）。
结论：在接受ATZ+BV治疗的BCLC B期不可切除肝细胞癌患者中，肝内肿瘤数目较多与较差的无进展生存期显著相关。因此，对此类患者可考虑辅以额外的治疗策略。