Supplementary Material for: AFP and DCP-Based Tumor Marker Score for First-line Immunotherapy Selection in Hepatocellular Carcinoma

Background
Atezolizumab plus bevacizumab (Atez/Bev) and durvalumab plus tremelimumab (Dur/Tre) are standard first-line therapies for unresectable hepatocellular carcinoma (HCC). However, predictive biomarkers to guide treatment selection remain undefined. In this study, we aimed to evaluate the prognostic utility of a modified tumor marker (mTM) score, incorporating alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), for selecting between Atez/Bev and Dur/Tre and in stratifying treatment outcomes of unresectable HCC.
Methods
We conducted a multicenter retrospective study of 1313 patients with unresectable HCC treated with either Atez/Bev (n = 1157) or Dur/Tre (n = 156). The mTM score was defined based on baseline AFP (≥ 100 ng/mL) and DCP (≥ 100 mAU/mL), assigning one point for each elevated marker. Patients were categorized as mTM low (score 0) or mTM high (score 1–2). Survival outcomes were analyzed using Kaplan-Meier curves and Cox proportional hazards models, with inverse probability of treatment weighting (IPTW) applied for confounder adjustment.
Results
Among the mTM low patients, Atez/Bev was associated with significantly longer progression-free survival (PFS) (11.5 vs. 4.4 months, p < 0.001) and overall survival (30.6 vs. 17.0 months, p = 0.023) than Dur/Tre. In contrast, in mTM high patients, PFS was comparable between Atez/Bev and Dur/Tre (6.6 vs. 6.5 months, p = 0.873). However, in patients with DCP > 400 mAU/mL, Dur/Tre was associated with improved PFS.
Conclusion
The mTM score is a clinically relevant biomarker for treatment stratification in unresectable HCC. Atez/Bev may be preferable in mTM low patients, whereas Dur/Tre may provide greater benefit in those with elevated DCP levels. Prospective validation is warranted to refine the optimal cutoff values for clinical implementation.

背景
阿替利珠单抗联合贝伐珠单抗（Atez/Bev）与度伐利尤单抗联合替西利姆单抗（Dur/Tre）均为不可切除肝细胞癌（HCC）的标准一线治疗方案，但目前仍缺乏可指导治疗选择的预测生物标志物。本研究旨在评估一种整合了甲胎蛋白（AFP）与脱-γ-羧基凝血酶原（DCP）的改良肿瘤标志物（mTM）评分，在不可切除HCC患者的治疗选择及治疗结局分层中的预后价值。
方法
本研究为多中心回顾性队列研究，纳入1313例接受Atez/Bev（n = 1157）或Dur/Tre（n = 156）治疗的不可切除HCC患者。mTM评分基于基线AFP（≥ 100 ng/mL）与DCP（≥ 100 mAU/mL）设定，每项指标升高计1分，据此将患者分为mTM低分组（评分0分）与mTM高分组（评分1~2分）。采用Kaplan-Meier曲线与Cox比例风险模型分析生存结局，并通过治疗逆概率加权（IPTW）校正混杂因素。
结果
在mTM低分组患者中，Atez/Bev组的无进展生存期（PFS，11.5 vs. 4.4个月，p < 0.001）与总生存期（30.6 vs. 17.0个月，p = 0.023）均显著长于Dur/Tre组。与之相反，在mTM高分组患者中，Atez/Bev组与Dur/Tre组的PFS无显著差异（6.6 vs. 6.5个月，p = 0.873）；但在DCP > 400 mAU/mL的患者中，Dur/Tre组的PFS更优。
结论
mTM评分是一种可用于不可切除HCC患者治疗分层的临床相关生物标志物。mTM低分组患者更适合接受Atez/Bev治疗，而DCP水平升高的患者或可从Dur/Tre治疗中获得更大获益。未来需开展前瞻性研究以优化最佳截断值，推动其临床应用。