Nakamura Kenichi, Kuwata Takeshi, Shimoda Tadakazu, Mizusawa Junki, Katayama Hiroshi, Kushima Ryoji, Taniguchi Hirokazu, Sano Takeshi, Sasako Mitsuru, Fukuda Haruhiko
JCOG Data Center/Operations Office, Multi-institutional Clinical Trial Support Center, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan,
Gastric Cancer. 2015 Jul;18(3):597-604. doi: 10.1007/s10120-014-0401-z. Epub 2014 Jun 27.
Pathological response rate (pathRR) is a common endpoint used to assess the efficacy of preoperative therapy for gastric cancer. PathRR is estimated based on the percentage of the residual tumor area in the primary tumorous bed. Various cutoff definitions used in previous trials (e.g., 10, 33, 40, 50, 67 %) often impair the comparability of pathRRs between trials.
Individual patient data were used from four JCOG trials evaluating preoperative chemotherapy (JCOG0001, JCOG0002, JCOG0210, JCOG0405). Pathological specimens were evaluated from 173 out of 188 patients (92 %) who underwent surgery. Residual tumor area and primary tumorous beds were traced on a virtual microscopic slide by one pathologist and another confirmed these areas. The hazard ratio (HR) in overall survival was calculated for each cutoff percentage by stratified Cox regression analysis, including the study as a stratification factor, and concordance probability estimates (CPE) were calculated.
The numbers of patients with 0%, 1-10 %, 11-33 %, 34-50 %, 51-66 %, and 67-100 % residual tumors were 8, 35, 33, 27, 23, and 47, respectively. HRs in 10, 33, 50, and 67 % cutoffs were 1.91, 1.70, 1.55, and 1.71 for the overall population, and CPEs were 0.56, 0.56, 0.55, and 0.55, respectively. In patients with R0 resection, HRs in 10, 33, 50, and 67 % cutoffs were 1.87, 1.54, 1.24, and 1.38, and CPEs were 0.56, 0.55, 0.52, and 0.52. In subgroup analyses, the 10 % cutoff did not predict survival well for type 4 (linitis plastica) tumors.
The 10 % cutoff should be the global standard cutoff of %residual tumor to determine pathRR. PathRR might not be recommended for clinical trials where the main subjects are type 4 tumors.
病理缓解率（pathRR）是评估胃癌术前治疗疗效常用的终点指标。PathRR是根据原发肿瘤床残留肿瘤面积的百分比来估算的。以往试验中使用的各种截断定义（如10%、33%、40%、50%、67%）常常影响各试验间pathRR的可比性。
使用来自四项日本临床肿瘤学会（JCOG）评估术前化疗的试验（JCOG0001、JCOG0002、JCOG0210、JCOG0405）的个体患者数据。对188例接受手术患者中的173例（92%）的病理标本进行了评估。由一名病理学家在虚拟显微镜载玻片上追踪残留肿瘤面积和原发肿瘤床，另一名病理学家对这些区域进行确认。通过分层Cox回归分析计算每个截断百分比的总生存风险比（HR），将研究作为分层因素，并计算一致性概率估计值（CPE）。
残留肿瘤为0%、1%-10%、11%-33%、34%-50%、51%-66%和67%-100%的患者人数分别为8例、35例、33例、27例、23例和47例。总体人群中，10%、33%、50%和67%截断值的HR分别为1.91、1.70、1.55和1.71，CPE分别为0.56、0.56、0.55和0.55。在R0切除的患者中，10%、33%、50%和67%截断值的HR分别为1.87、1.54、1.24和1.38，CPE分别为0.56、0.55、0.52和0.52。在亚组分析中，10%的截断值对4型（皮革胃）肿瘤的生存预测效果不佳。
10%的截断值应作为确定pathRR的全球标准残留肿瘤百分比截断值。对于以4型肿瘤为主要研究对象的临床试验，可能不推荐使用PathRR。
