Masatoshi Kudo教授分享ORR/DpR/DoR对肝癌患者的预后及治疗指导价值

Kudo教授： 在评估应答时，有三个关键因素：ORR、DpR和DoR。ORR与OS的相关性已为人熟知。DpR衡量的是肿瘤退缩的程度，并被分为五个等级。A级代表退缩60%至100%，B级退缩30%至60%，C级退缩0%至30%，D级为无变化至增长20%，E级为增长超过20%，表示疾病进展（PD）。稳定疾病（SD）包括退缩低于30%至增长20%的情况。这种缓解深度的分类使我们能够评估肿瘤退缩的程度。

另一方面，DoR适用于缓解者——即肿瘤退缩超过30%的患者，并衡量这种缓解持续的时间。DpR和DoR共同构成了至关重要的指标，为我们提供了关于肿瘤退缩程度和肿瘤应答持久性的重要见解，这两者在评估治疗疗效时至关重要。

图1. DpR分层

Oncology Frontier: In your study, how were Depth of Response (DpR) and Duration of Response (DoR) specifically defined, and what is their significance in assessing the treatment efficacy for patients with unresectable HCC?

Dr. Kudo: There are three key factors in evaluating response: objective response, Depth of Response (DpR), and Duration of Response (DoR). Objective response is well known for its correlation with OS. Depth of Response measures how much tumor shrinkage is achieved and is classified into five grades. Grade A represents shrinkage from 60% to 100%, Grade B from 30% to 60%, Grade C from 0% to 30%, Grade D ranges from no change to 20% growth, and Grade E includes growth beyond 20%, indicating progressive disease. Stable disease includes shrinkage below 30% up to 20% growth. This depth classification allows us to assess how significantly the tumor has shrunk.

Duration of Response, on the other hand, applies to responders—patients who experience over 30% tumor reduction—and measures how long this response is maintained. Together, DpR and DoR are crucial metrics, providing essential insights into both the degree of tumor shrinkage and the durability of the response, which are key in evaluating treatment efficacy.

Kudo教授： 迄今为止，还没有确定的数据将DpR或DoR与OS联系起来。在这项研究中，我们专门针对靶免联合治疗的一线治疗分析了这些指标。鉴于一线和二线治疗中有多种药物可供选择，我们想要确定初始治疗的缓解深度和持续时间是否影响OS。

我们的研究结果显示，五个DpR等级与OS之间存在强烈的相关性，每个等级都提供了清晰的生存结局分层结果。这表明，使用一线药物实现显著的深度缓解对OS具有持久影响，即使患者接受后续治疗也是如此。此外，在稳定疾病中，那些肿瘤有所退缩的患者比那些没有退缩的患者表现出更好的生存率，这凸显了实现至少部分肿瘤退缩的重要性。如果无法获得显著退缩，增加局部治疗可能会改善生存结局。

图2. 根据DpR分层的阶段性OS亚组分析

图3. 根据DpR分层的阶段性PFS亚组分析

Oncology Frontier: Your findings indicate an association between DpR and DoR with Overall Survival (OS). Could you elaborate on the specific nature and strength of this association?

Dr. Kudo: Until now, there was no definitive data linking DpR or DoR with OS. In this study, we analyzed these metrics specifically for the first-line treatment. With many drugs available across first- and second-line therapies, we wanted to determine if depth and duration of response to the initial therapy impacted OS.

Our findings show a strong correlation between the five DpR grades and OS, with each grade providing a clear stratification of survival outcomes. This suggests that achieving significant depth with the first-line agent has a lasting influence on OS, even when patients receive subsequent therapies. Additionally, within stable disease, those with some tumor shrinkage showed better survival rates than those without any reduction, highlighting the importance of achieving at least partial shrinkage. If significant shrinkage is not obtained, adding local therapies could potentially improve survival outcomes.

Kudo教授： 实现深度缓解似乎对生存率有积极影响。肿瘤显著退缩的患者通常预后更好，因此临床试验中深度缓解患者的比例可以指示治疗改善OS的潜力。对于未达到显著退缩的患者，策略可能需要包括局部区域治疗，以改变疾病的自然进程，从而可能同时提高生存率和生活质量。

这种方法也适用于肿瘤几乎无退缩或没有退缩的稳定疾病病例。在这种情况下，将局部治疗与系统治疗相结合可能有助于改善患者结局。根据肿瘤应答的质量（如深度和持续时间）来调整治疗，可能提供更个性化的方法，从而提高患者的生存率和生活质量。