早期肝失代偿可识别接受阿替利珠单抗联合贝伐单抗或索拉非尼治疗的肝细胞癌患者中死亡风险最高的患者。
Early Hepatic Decompensation Identifies Patients with Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab or Sorafenib at Highest Risk of Death.
作者信息
Cabibbo Giuseppe, Celsa Ciro, Battaglia Salvatore, Enea Marco, Di Maria Gabriele, Grova Alessandro, Ciccia Roberta, Manfredi Giulia F, Iavarone Massimo, Vogel Arndt, Singal Amit G, Reig Maria, Pinato David J, Cammà Calogero
机构信息
Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child-Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Palermo, Italy.
Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom.
出版信息
Clin Cancer Res. 2025 Feb 3;31(3):543-550. doi: 10.1158/1078-0432.CCR-24-2582.
PURPOSE
The prognosis of patients with unresectable hepatocellular carcinoma (HCC) and compensated cirrhosis is influenced by cancer progression. Data on the incidence and the prognostic role of clinical hepatic decompensation (CHD) following immune checkpoint inhibitor therapy are lacking. We aimed to assess whether early CHD within 3 months from commencement of systemic therapy affects overall survival (OS) of patients treated with atezolizumab plus bevacizumab or sorafenib.
PATIENTS AND METHODS
Individual patient data from the IMbrave150 trial were analyzed. Cumulative incidence of CHD was assessed by competing risk analysis against HCC radiologic progression. Early CHD and HCC radiologic progression were assessed as predictors of OS by the time-dependent Cox model.
RESULTS
The 3- and 12-month rates of CHD were 7% and 12%, respectively, whereas the 3- and 12-month rates of HCC radiologic progression were 23% and 52%, respectively. Albumin-bilirubin grade 2 [subdistribution HR (sHR) = 1.79, 95% confidence interval (CI), 1.01-3.19; P = 0.049], INR (sHR = 1.97, 95% CI, 1.64-2.37; P < 0.001), and presence of neoplastic macrovascular invasion (sHR = 2.01, 95% CI, 1.14-3.54; P = 0.020) were independently associated with higher risk of CHD. Early CHD (HR = 7.56, 95% CI, 4.47-12.8) and early HCC radiologic progression (HR = 5.92, 95% CI, 4.03-8.69), as first events, were independently associated with higher mortality.
CONCLUSIONS
This study provides robust evidence that early CHD is associated with the highest risk of death in patients with unresectable HCC undergoing systemic treatment. Within well-compensated participants, albumin-bilirubin, INR, and macrovascular invasion identify a population at higher risk of decompensation. Inclusion of clinical decompensation events in future prospective clinical trials may improve characterization of OS from systemic therapy of HCC.
目的
不可切除肝细胞癌（HCC）合并代偿期肝硬化患者的预后受癌症进展影响。免疫检查点抑制剂治疗后临床肝失代偿（CHD）的发生率及预后作用的数据尚缺乏。我们旨在评估全身治疗开始后3个月内发生的早期CHD是否会影响接受阿替利珠单抗联合贝伐单抗或索拉非尼治疗患者的总生存期（OS）。
患者与方法
对IMbrave150试验的个体患者数据进行分析。通过竞争风险分析评估CHD相对于HCC影像学进展的累积发生率。采用时间依赖性Cox模型评估早期CHD和HCC影像学进展作为OS的预测因素。
结果
CHD的3个月和12个月发生率分别为7%和12%，而HCC影像学进展的3个月和12个月发生率分别为23%和52%。白蛋白-胆红素分级2级[亚分布风险比（sHR）=1.79，95%置信区间（CI），1.01 - 3.19；P = 0.049]、国际标准化比值（INR）（sHR = 1.97，95%CI，1.64 - 2.37；P < 0.001）以及肿瘤性大血管侵犯的存在（sHR = 2.01，95%CI，1.14 - 3.54；P = 0.020）与CHD的较高风险独立相关。作为首要事件，早期CHD（HR = 7.56，95%CI，4.47 - 12.8）和早期HCC影像学进展（HR = 5.92，95%CI，4.03 - 8.69）与较高的死亡率独立相关。
结论
本研究提供了有力证据，表明早期CHD与接受全身治疗且不可切除HCC患者的最高死亡风险相关。在代偿良好的参与者中，白蛋白-胆红素、INR和大血管侵犯可识别出失代偿风险较高的人群。在未来的前瞻性临床试验中纳入临床失代偿事件可能会改善对HCC全身治疗OS的特征描述。
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