Background/Objectives:Immune checkpoint inhibitor (ICI)-based combinations are the standard first-line therapy for unresectable hepatocellular carcinoma (HCC). A major challenge is the early identification of patients with primary progression (1st-PD) and those who experience early progression despite initial disease control (2nd-PD). This study evaluated whether very early treatment changes in alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) could serve as predictors of treatment response during atezolizumab plus bevacizumab (Atz + Bev) therapy.Methods:A total of 147 patients treated with Atz + Bev were retrospectively analyzed. Serum tumor markers were measured approximately every 3 weeks, and radiologic responses were assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 at week 6 (first evaluation) and again at a median of 14.8 weeks (second evaluation).Results:At the first evaluation, 32 patients achieved a partial response, 81 showed stable disease, and 25 had progression. In the week 3 landmark analysis, early increases in AFP (ratio ≥ 1.4) or DCP (ratio ≥ 1.0) identified patients who would experience primary radiologic progression, with a clear separation in landmark progression-free survival (PFS) (3.4 vs. 13.1 months;p< 0.001). Among the 109 patients with disease control at week 6, 92 maintained control and 17 progressed at the second evaluation. In the week 9 landmark cohort, modest rises in AFP (ratio ≥ 1.1) or DCP (ratio ≥ 1.5) identified individuals at risk for early secondary progression, again showing marked differences in landmark PFS (3.8 vs. 14.0 months;p< 0.001).Conclusions:The dynamic monitoring of AFP and DCP provides a simple framework for biomarker-based responder selection and adaptive treatment optimization during Atz + Bev therapy. Clinically actionable thresholds at weeks 3 and 9 may support timely treatment switching and the integration of locoregional strategies, enabling personalized, biomarker-guided management to improve outcomes in unresectable HCC.
背景/目的：基于免疫检查点抑制剂（ICI）的联合疗法已成为不可切除肝细胞癌（HCC）的一线标准治疗方案。当前面临的主要挑战在于早期识别原发性进展（1st-PD）患者，以及那些初始疾病控制后仍出现早期进展（2nd-PD）的患者。本研究旨在评估甲胎蛋白（AFP）和脱-γ-羧基凝血酶原（DCP）在阿替利珠单抗联合贝伐珠单抗（Atz+Bev）治疗期间的极早期变化能否作为治疗反应的预测指标。 方法：本研究回顾性分析了147例接受Atz+Bev治疗的患者。血清肿瘤标志物约每3周检测一次，并在第6周（首次评估）和中位14.8周（二次评估）时采用实体瘤疗效评价标准1.1版进行影像学疗效评估。 结果：首次评估时，32例患者达到部分缓解，81例疾病稳定，25例出现进展。在第3周界标分析中，AFP（比值≥1.4）或DCP（比值≥1.0）的早期升高可识别出将发生原发性影像学进展的患者，其界标无进展生存期（PFS）呈现显著差异（3.4个月 vs 13.1个月；p<0.001）。在第6周获得疾病控制的109例患者中，92例维持控制，17例在二次评估时出现进展。在第9周界标队列中，AFP（比值≥1.1）或DCP（比值≥1.5）的适度升高可识别出存在早期继发性进展风险的患者，其界标PFS同样呈现显著差异（3.8个月 vs 14.0个月；p<0.001）。 结论：AFP和DCP的动态监测为Atz+Bev治疗期间基于生物标志物的应答者筛选及适应性治疗优化提供了简易框架。第3周和第9周具有临床指导意义的阈值可能支持及时转换治疗方案并整合局部区域治疗策略，从而实现个体化、生物标志物引导的临床管理，以改善不可切除HCC患者的预后。
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