Introduction: In the era of biomarker-driven cancer therapy, robust biomarkers for hepatocellular carcinoma (HCC) have not been well-defined. In this hypothesis-generating study, we investigated biomarkers that can be incorporated to predict treatment outcomes in patients with locally advanced HCC who are administered liver-directed combined radiotherapy (LDCRT). Methods: Ninety-nine patients with HCC who were treated with conventional fractionation LDCRT between July 2016 and October 2018 were enrolled in this prospective single-arm study. Clinical outcomes and possible serum biomarkers, including sPD-L1, IL-10, IL-6, cfDNA, ITIH4, and IFN-γ, were analyzed. The primary endpoint was disease progression, and additional endpoints were local failure-free rate, intrahepatic failure-free rate, and lung metastasis-free rate. Results: The median follow-up period was 18.7 months. The one-year progression-free rate was 38.2%. Increasing baseline sPD-L1 per pg/mL, previous treatment history, PIVKA-II > 1629 mAU/mL, and multiple tumors were the adverse factors for progression based on multivariate analysis. Survival tree analysis revealed three prognostic groups for progression, in which patients with multiple lesions and baseline sPD-L1 ≥ 41.07 pg/mL showed the worst outcomes. For dynamic changes in biomarker levels, sPD-L1 fold change and cfDNA fold change values were unfavorable factors for progression. Conclusion: Baseline sPD-L1, sPD-L1 fold change, and cfDNA fold change values showed the highest potential as biomarkers for predicting post-treatment progression after LDCRT in HCC patients. By incorporating clinical factors, these biomarkers may be useful for devising a biomarker-driven treatment paradigm in locally advanced HCC.


中文翻译：

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肝定向联合放疗治疗局部晚期肝细胞癌患者的生物标志物

简介：在生物标志物驱动的癌症治疗时代，肝细胞癌 (HCC) 的可靠生物标志物尚未明确定义。在这项产生假设的研究中，我们研究了可用于预测接受肝定向联合放疗 (LDCRT) 的局部晚期 HCC 患者治疗结果的生物标志物。方法：2016 年 7 月至 2018 年 10 月期间接受常规分割 LDCRT 治疗的 99 名 HCC 患者参加了这项前瞻性单臂研究。分析了临床结果和可能的血清生物标志物，包括 sPD-L1、IL-10、IL-6、cfDNA、ITIH4 和 IFN-γ。主要终点是疾病进展，其他终点是局部无失败率、肝内无失败率和无肺转移率。结果：中位随访时间为 18.7 个月。一年无进展率为38.2%。根据多变量分析，基线 sPD-L1 每 pg/mL 增加、既往治疗史、PIVKA-II > 1629 mAU/mL 和多个肿瘤是进展的不利因素。生存树分析揭示了三个预后组的进展，其中有多个病变且基线 sPD-L1 ≥ 41.07 pg/mL 的患者表现出最差的结果。对于生物标志物水平的动态变化，sPD-L1 倍数变化和 cfDNA 倍数变化值是进展的不利因素。结论：基线 sPD-L1、sPD-L1 倍数变化和 cfDNA 倍数变化值显示出作为预测 HCC 患者 LDCRT 治疗后进展的生物标志物的最高潜力。通过结合临床因素，