Amgen, 1 Amgen Center Drive, Thousand Oaks, CA 91320, USA.
J Clin Oncol. 2012 Jul 20;30(21):2684-90. doi: 10.1200/JCO.2011.36.4752. Epub 2012 Jun 11.
RECIST is used to quantify tumor changes during exposure to anticancer agents. Responses are categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Clinical trials dictate a patient's management options based on the category into which his or her response falls. However, the association between response and survival is not well studied in the early trial setting.
To study the correlation between response as quantified by RECIST and overall survival (OS, the gold-standard survival outcome), we analyzed 570 participants of 24 phase I trials conducted between October 2004 and May 2009, of whom 468 had quantifiable changes in tumor size. Analyses of Kaplan-Meier estimates of OS by response and null Martingale residuals of Cox models were the primary outcome measures. All analyses are landmark analyses.
Kaplan-Meier analyses revealed strong associations between change in tumor size by RECIST and survival (P = 4.5 × 10(-6) to < 1 × 10(-8)). The relationship was found to be near-linear (R(2) = 0.75 to 0.92) and confirmed by the residual analyses. No clear inflection points were found to exist in the relationship between tumor size changes and survival.
RECIST quantification of response correlates with survival, validating RECIST's use in phase I trials. However, the lack of apparent boundary values in the relationship between change in tumor size and OS demonstrates the arbitrary nature of the CR/PR/SD/PD categories and questions emphasis placed on this categorization scheme. Describing tumor responses as a continuous variable may be more informative than reporting categoric responses when evaluating novel anticancer therapies.
RECIST 用于量化抗癌药物暴露期间肿瘤的变化。反应分为完全缓解（CR）、部分缓解（PR）、疾病稳定（SD）或疾病进展（PD）。临床试验根据患者的反应类别决定其管理选择。然而，在早期试验环境中，反应与生存之间的关联尚未得到很好的研究。
为了研究 RECIST 定量评估的反应与总生存期（OS，金标准生存结果）之间的相关性，我们分析了 2004 年 10 月至 2009 年 5 月期间进行的 24 项 I 期试验中的 570 名参与者，其中 468 名患者的肿瘤大小有可量化的变化。OS 的 Kaplan-Meier 估计和 Cox 模型的零假设 Martingale 残差分析是主要的结果测量指标。所有分析均为 landmark 分析。
Kaplan-Meier 分析显示，RECIST 评估的肿瘤大小变化与生存之间存在强烈关联（P=4.5×10(-6) 至 <1×10(-8)）。这种关系接近线性（R(2)=0.75 至 0.92），残差分析也证实了这一点。在肿瘤大小变化与生存之间的关系中，未发现明显的拐点。
RECIST 对反应的定量评估与生存相关，验证了 RECIST 在 I 期试验中的应用。然而，在肿瘤大小变化与 OS 之间的关系中，没有明显的边界值，这表明 CR/PR/SD/PD 类别的任意性，并对强调这种分类方案提出了质疑。在评估新型抗癌疗法时，描述肿瘤反应为连续变量可能比报告分类反应更具信息量。
