Chung Seung Yeun, Kim Kyoung-Jin, Seong Jinsil
Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Radiation Oncology, Ajou University School of Medicine, Suwon-si, Republic of Korea.
Liver Cancer. 2022 Jan 24;11(3):247-255. doi: 10.1159/000522000. eCollection 2022 Jun.
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).
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 soluble programmed cell death ligand-1 (sPD-L1), interleukin (IL)-10, IL-6, cell-free DNA (cfDNA), inter-alpha inhibitor H4, and interferon-gamma, 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.
The median follow-up period was 18.7 months. The 1-year progression-free rate was 38.2%. Increasing baseline sPD-L1 per pg/mL, previous treatment history, protein induced by vitamin K absence-II >1,629 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.
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.
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得到明确界定。在这项提出假设的研究中，我们调查了可用于预测接受肝脏定向联合放疗（LDCRT）的局部晚期HCC患者治疗结果的生物标志物。
99例在2016年7月至2018年10月期间接受常规分割LDCRT治疗的HCC患者纳入了这项前瞻性单臂研究。分析了临床结果以及可能的血清生物标志物，包括可溶性程序性细胞死亡配体-1（sPD-L1）、白细胞介素（IL）-10、IL-6、游离DNA（cfDNA）、α-抑制因子H4和干扰素-γ。主要终点是疾病进展，其他终点是无局部失败率、无肝内失败率和无肺转移率。
中位随访期为18.7个月。1年无进展率为38.2%。多因素分析显示，每pg/mL基线sPD-L1升高、既往治疗史、维生素K缺乏诱导蛋白-II>1629 mAU/mL以及多发肿瘤是进展的不利因素。生存树分析揭示了三个进展预后组，其中多发灶且基线sPD-L1≥41.07 pg/mL的患者预后最差。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。
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后治疗后进展生物标志物的最大潜力。通过纳入临床因素，这些生物标志物可能有助于设计局部晚期HCC的生物标志物驱动治疗模式。
