■几十年来,一线临床研究的分层标准高度统一.然而,对于基于免疫检查点抑制剂(ICIs)的全身治疗进展后的限制,尚无原则或共识.这项研究的目的是评估不符合手术干预条件的晚期肝细胞癌(HCC)患者的疾病进展模式。在使用免疫检查点抑制剂之后。
■这是一项回顾性研究,涉及无法手术的中国肝脏分期(CNLC)IIIa和/或IIIb的患者。这些患者于2017年1月至2022年10月在中国的八个中心接受治疗。所有患者接受至少两个周期的含有免疫检查点抑制剂的一线治疗。使用RECIST标准1.1评估疾病进展的模式。已经基于成像进展的特性识别了不同的进展模式。研究的主要结果指标是进展后生存期(PPS)和总生存期(OS)。使用Kaplan-Meier方法绘制生存曲线以比较四组之间的差异。进行亚组分析以比较不同免疫治疗组合的疗效。在显示甲胎蛋白(AFP)水平等于或超过400ng/mL的患者组中,免疫疗法的功效也有差异。与AFP水平低于400ng/mL的患者相反。
■这项研究确定了四种不同的进展模式,即p-IIb,p-IIIa,p-IIIb,和p-IIIc.不同的进展模式表明PPS和OS两者存在显著差异。p-IIb组最长的PPS为12.7m(95%9.3-16.1)和OS19.6m(95%15.6-23.5),其余各组在PPS10.5个月(95CI:7.9-13.1)和OS19.2个月(95CI15.1-23.3)时表现为p-IIIb.同样,p-IIIc在PPS5.7个月(95CI:4.2-7.2)和OS11.0个月(95CI9.0-12.9),同时在PPS3.4个月(95CI:2.7-4.1)和OS8.2个月(95CI6.8-9.5)时也观察到p-IIIa。进行了额外的分层分析,显示单独或联合免疫疗法在OS(HR=0.92,95CI:0.59-1.43,P=0.68)和PPS(HR=0.88,95CI:0.57-1.36,P=0.54)方面没有差异;对于AFP水平0.400mL或0.39ng-0.95%CI(HR=0.86,P=0.61),OS水平没有显着差异。然而,观察到AFP水平高于400ng/mL的患者PPS的中位进展较短(8.0个月vs.5.0个月)接受免疫治疗后。
■在这项对接受免疫检查点抑制剂治疗的中国患者的晚期肝细胞癌的调查中,我们确定了四种不同的进展模式(p-IIb,p-IIIa,p-IIIb和p-IIIc)显示出PPS和OS的显着差异。这些发现证明了免疫治疗失败后疾病进展和预后的异质性。在大型队列中进一步验证对于开发整合不同进展模式以指导后续治疗决策的预后模型是必要的。此外,AFP水平≥400ng/mL患者的免疫治疗后进展表明中位PPS缩短.这些发现为未来的个性化治疗决策提供了有价值的见解。
UNASSIGNED: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this
study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors.
UNASSIGNED: This is a retrospective
study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The
study\'s main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL.
UNASSIGNED: The
study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy.
UNASSIGNED: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.