基于 iRECIST 和 RECIST 1.1 标准评估程序性细胞死亡蛋白-1 抑制剂治疗转移性透明细胞肾细胞癌患者的影像学肿瘤反应比较。

OBJECTIVE: To evaluate the radiological tumor response patterns and compare the response assessments based on immune-based therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and RECIST 1.1 in metastatic clear-cell renal cell carcinoma (mccRCC) patients treated with programmed cell death-1 (PD-1) inhibitors. MATERIALS AND METHODS: All mccRCC patients treated with PD-1 inhibitors at Henan Cancer Hospital, China, between January 2018 and April 2019, were retrospectively studied. A total of 30 mccRCC patients (20 males and 10 females; mean age, 55.6 years; age range, 37-79 years) were analyzed. The target lesions were quantified on consecutive CT scans during therapy using iRECIST and RECIST 1.1. The tumor growth rate was calculated before and after therapy initiation. The response patterns were analyzed, and the differences in tumor response assessments of the two criteria were compared. The intra- and inter-observer variabilities of iRECIST and RECIST 1.1 were also analyzed. RESULTS: The objective response rate throughout therapy was 50% (95% confidence interval [CI]: 32.1-67.9) based on iRECIST and 30% (95% CI: 13.6-46.4) based on RECIST 1.1. The time-to-progression (TTP) based on iRECIST was longer than that based on RECIST 1.1 (median TTP: not reached vs. 170 days, = 0.04). iRECIST and RECIST 1.1 were discordant in 8 cases, which were evaluated as immune-unconfirmed PD based on iRECIST and PD based on RECIST 1.1. Six patients (20%, 6/30) had pseudoprogression based on iRECIST, of which four demonstrated early pseudoprogression and two had delayed pseudoprogression. Significant differences in the tumor response assessments based on the two criteria were observed ( < 0.001). No patients demonstrated hyperprogression during the study period. CONCLUSION: Our study confirmed that the iRECIST criteria are more capable of capturing immune-related atypical responses during immunotherapy, whereas conventional RECIST 1.1 may underestimate the benefit of PD-1 inhibitors. Pseudoprogression is not rare in mccRCC patients during PD-1 inhibitor therapy, and it may last for more than the recommended maximum of 8 weeks, indicating a limitation of the current strategy for immune response monitoring.

目的：评估基于免疫治疗的实体瘤反应评估标准（iRECIST）与 RECIST 1.1 在接受程序性细胞死亡-1（PD-1）抑制剂治疗的转移性透明细胞肾细胞癌（mccRCC）患者中的放射学肿瘤反应模式，并比较这两种标准的反应评估。

材料与方法：本研究回顾性分析了 2018 年 1 月至 2019 年 4 月在中国河南省肿瘤医院接受 PD-1 抑制剂治疗的所有 mccRCC 患者。共分析了 30 例 mccRCC 患者（20 例男性，10 例女性；平均年龄 55.6 岁；年龄范围 37-79 岁）。在治疗过程中，通过 iRECIST 和 RECIST 1.1 连续 CT 扫描对靶病灶进行定量。计算治疗前后的肿瘤生长率。分析肿瘤反应模式，并比较两种标准的肿瘤反应评估差异。还分析了 iRECIST 和 RECIST 1.1 的观察者内和观察者间变异性。

结果：根据 iRECIST，整个治疗过程中的客观缓解率为 50%（95%置信区间[CI]：32.1-67.9），根据 RECIST 1.1 则为 30%（95%CI：13.6-46.4）。根据 iRECIST 的无进展生存期（TTP）长于根据 RECIST 1.1 的 TTP（中位 TTP：未达到 vs. 170 天，= 0.04）。根据 iRECIST 和 RECIST 1.1，有 8 例结果不一致，根据 iRECIST 评估为免疫未确认的疾病进展（PD），而根据 RECIST 1.1 评估为 PD。根据 iRECIST，有 6 例（20%，6/30）出现假性进展，其中 4 例为早期假性进展，2 例为延迟性假性进展。两种标准的肿瘤反应评估差异具有统计学意义（<0.001）。研究期间无患者出现超进展。

结论：本研究证实，iRECIST 标准更能捕获免疫治疗期间与免疫相关的非典型反应，而传统的 RECIST 1.1 可能低估 PD-1 抑制剂的获益。在 PD-1 抑制剂治疗期间，mccRCC 患者的假性进展并不罕见，其持续时间可能超过 8 周的推荐最大值，表明目前的免疫反应监测策略存在局限性。