Johnson Philip J, Boswell Ellen L
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom.
Biochemistry, Cell and Systems Biology, University of Liverpool, Liverpool, United Kingdom.
JCO Precis Oncol. 2025 Jul;9:e2500015. doi: 10.1200/PO-25-00015. Epub 2025 Jul 16.
Progression-free survival (PFS) has been proposed as a surrogate end point in clinical trials for advanced hepatocellular carcinoma (aHCC). However, there have been concerns about the discrepancy between PFS and overall survival. Here, we aimed to characterize the behavior of individual lesions within the same patient/liver that play a key role in response assessment to a systemic treatment and how this changed temporally.
We obtained serial lesion measurement data from six clinical trials undertaken in the modern era (by which we mean since the first controlled trial in aHCC). In each patient, the percentage change of their lesion size was calculated at each visit compared with the baseline/screening phase. To assess lesion behavior, the patients were classified according to the degree of divergence (DOD) categories that ranged from 0 (all lesions behaved similarly) to 2 (completely discordant behavior). Finally, the results were summarized per treatment arm as the proportion of patients in each divergence category per follow-up visit.
Of the 8,260 visits where DOD was assessed in patients, there was a considerable proportion of patients with divergent lesion behavior at the treatment arm level-approximately 58% were DOD 0, 38% were DOD 1, and 4% were DOD 2. Individually, there was evidence of lesions both increasing and decreasing in size within the same liver despite the treatment remaining the same.
The evidence presented here suggests that caution should be exercised in the application of progression-based metrics such as PFS as an end point in HCC clinical trials. Ultimately, there was consistently a considerable proportion of patients who were classified as having lesions within their liver which had a divergent response to treatment.
无进展生存期（PFS）已被提议作为晚期肝细胞癌（aHCC）临床试验中的替代终点。然而，人们一直担心PFS与总生存期之间的差异。在此，我们旨在描述同一患者/肝脏内个体病变在全身治疗反应评估中所起的关键作用及其随时间的变化情况。
我们从现代进行的六项临床试验中获取了系列病变测量数据（我们指的是自aHCC的首个对照试验以来）。在每位患者中，每次就诊时计算其病变大小相对于基线/筛查阶段的百分比变化。为了评估病变行为，根据差异程度（DOD）类别对患者进行分类，范围从0（所有病变行为相似）到2（完全不一致的行为）。最后，按治疗组总结结果，即每次随访时每个差异类别中的患者比例。
在对患者进行DOD评估的8260次就诊中，在治疗组水平上有相当比例的患者病变行为存在差异——约58%为DOD 0，38%为DOD 1，4%为DOD 2。个体而言，尽管治疗保持不变，但同一肝脏内有证据表明病变大小既有增大的也有减小的。
此处提供的证据表明，在将基于进展的指标（如PFS）用作HCC临床试验的终点时应谨慎。最终，始终有相当比例的患者被分类为肝脏内有病变对治疗反应不同。
