Immune checkpoint inhibitors (ICIs) have emerged as first-line therapy for advanced-stage HCC with modest response rates (<33%). Combination treatments offer the potential to improve response rates while improving outcomes. This study evaluates the safety and outcomes of first-line Yttrium-90 plus ICI (90Y-ICI). A retrospective, multi-center study was conducted in HCC patients receiving first-line90Y-ICI with atezolizumab plus bevacizumab (Atezo/Bev) or tremelimumab plus durvalumab (Treme/Durva). Treatment response was evaluated at follow-up for planned90Y treatment cycle. Time-to-event measures of time to progression (TTP), progression-free survival (PFS), and overall survival (OS) served as primary endpoints, with first cycle response rates and AEs as secondary outcomes. This study included 37 patients receiving90Y-ICI from 2021 to 2024 (16-month median follow-up). The cohort was predominantly Child-Pugh A (92%) with HCV-related cirrhosis (67%), advanced stage (54%), and a median index HCC size of 8.0 cm (IQR: 6—12 cm). Grade 3–4 AEs occurred in six patients (16%). The target objective response (OR) rate was 83%, with a 50% target complete response (CR) rate. Overall OR was 61% with an overall CR of 39%. Median PFS was 11 months with 1-year rates of 50%. Patients with a target CR had improved TTP (p= 0.004), PFS (p= 0.003), and OS (p= 0.003). The cohort’s 2-year OS was 41% with a median OS of 19 months (CI: 12–37 months). First-line90Y-ICI therapy in HCC is safe and effective, with no deviation in anticipated results. Patients achieving target CR showed significantly improved TTP, PFS, and OS, supporting target CR as an optimal treatment target.
免疫检查点抑制剂（ICIs）已成为晚期肝细胞癌的一线治疗方案，但缓解率有限（<33%）。联合治疗有望在改善疗效的同时提高缓解率。本研究评估一线钇-90联合免疫检查点抑制剂（90Y-ICI）方案的安全性与疗效。这项回顾性多中心研究纳入接受一线90Y-ICI联合治疗（阿替利珠单抗/贝伐珠单抗或替西木单抗/度伐利尤单抗）的肝细胞癌患者，在计划90Y治疗周期随访时评估治疗反应。以疾病进展时间、无进展生存期和总生存期作为主要终点，首周期缓解率及不良事件作为次要终点。研究纳入2021至2024年间接受90Y-ICI治疗的37例患者（中位随访16个月），队列特征主要为Child-Pugh A级（92%）、HCV相关肝硬化（67%）、晚期（54%），中位肿瘤直径8.0厘米（四分位距：6-12厘米）。3-4级不良事件发生率为16%（6例）。靶病灶客观缓解率达83%，其中完全缓解率为50%；整体客观缓解率为61%，整体完全缓解率为39%。中位无进展生存期为11个月，1年无进展生存率为50%。达到靶病灶完全缓解的患者在疾病进展时间（p=0.004）、无进展生存期（p=0.003）和总生存期（p=0.003）方面均有显著改善。队列2年总生存率为41%，中位总生存期19个月（置信区间：12-37个月）。一线90Y-ICI治疗肝细胞癌安全有效，未出现预期结果偏差。实现靶病灶完全缓解的患者生存指标显著改善，支持将靶病灶完全缓解作为优化治疗目标。
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