Introduction: Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial. Methods: Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (n = 68) were screened and classified according to their PD, six weeks after treatment initiation (early PD; n = 13). Of these, four patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (n = 60) and evaluated in patients treated with lenvatinib. Results: No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (< 333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs 227 days; HR: 2.41, 95% CI: 1.22–4.80, p = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without. Conclusion: Baseline low serum CXCL9 (< 333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.


中文翻译：

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低基线 CXCL9 可预测阿特珠单抗加贝伐单抗治疗的不可切除 HCC 的早期进展性疾病

简介：阿替珠单抗联合贝伐珠单抗治疗对于不可切除的肝细胞癌 (HCC) 患者非常有效。然而，接受 atezolizumab 加贝伐珠单抗治疗的 HCC 患者中约 20% 发生进展性疾病 (PD)，导致预后不良。因此，HCC的预测和早期发现至关重要。方法：在治疗开始后六周（早期 PD；n = 13），对接受 atezolizumab 加贝伐单抗治疗且基线保留血清的不可切除 HCC 患者 (n = 68) 根据其 PD 进行筛选和分类。其中，选择患有和不患有早期PD的四名患者进行细胞因子阵列和遗传分析。确定的因素在经过验证的队列（n = 60）中得到验证，并在接受仑伐替尼治疗的患者中进行了评估。结果：循环肿瘤 DNA 的遗传改变没有观察到显着差异。细胞因子阵列数据显示，患有和不患有早期 PD 的患者之间的基线 MIG (CXCL9)、ENA-78 和 RANTES 存在显着差异。验证队列的后续分析显示，早期 PD 患者的基线 CXCL9 显着低于非早期 PD 患者，血清 CXCL9 预测早期 PD 的最佳临界值为 333 pg/mL（灵敏度：0.600，特异性：0.923，AUC = 0.75）。在血清 CXCL9 较低 (< 333 pg/mL) 的患者中，35.3% (12/34) 在阿特珠单抗联合贝伐单抗治疗后经历了早期 PD，而无进展生存期 (PFS) 相对于无进展生存期 (中位 PFS、中位 PFS、 126 天与 227 天；HR：2.41，95% CI：1.22–4.80，p = 0.0084）。而对乐伐替尼有客观反应的患者的 CXCL9 水平显着低于没有客观反应的患者。结论：基线低血清 CXCL9 (< 333 pg/mL) 水平可以预测接受阿特朱单抗加贝伐单抗治疗的不可切除 HCC 患者的早期 PD。