Nakayama Goro, Fujii Tsutomu, Murotani Kenta, Uehara Keisuke, Hattori Norifumi, Hayashi Masamichi, Tanaka Chie, Kobayashi Daisuke, Kanda Mitsuro, Yamada Suguru, Sugimoto Hiroyuki, Koike Masahiko, Fujiwara Michitaka, Ando Yuichi, Kodera Yasuhiro
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Division of Biostatistics, Clinical Research Center, Aichi Medical University Hospital, Nagakute, Japan.
Cancer Sci. 2016 Oct;107(10):1492-1498. doi: 10.1111/cas.13023.
The identification of surrogate markers for long-term outcomes in patients with metastatic colorectal cancer (mCRC) may help in designing treatment regimens. The aim of this study was to assess whether two-dimensional response (2-DR) can serve as a new surrogate marker for overall survival (OS) in patients with mCRC. The study group consisted of 99 patients with mCRC from two independent cohorts who were treated with oxaliplatin-based chemotherapy plus bevacizumab. Two-dimensional response was defined as an area enclosed by coordinate points, including early tumor shrinkage at 8 weeks, depth of response at nadir, and 20% increase over nadir at progression. Each variable was weighted by its contribution rate to OS. The model was developed and internally validated in the learning cohort, and the performance of this model was externally verified in the validation cohort. Spearman correlation coefficients for 2-DR and OS in the learning and validation cohorts were 0.593 and 0.661, respectively. The C-indexes in predicting OS were 0.724 (95% confidence interval, 0.623-0.815) in the learning cohort and 0.762 (95% confidence interval, 0.651-0.873) in the validation cohort. Overall survival was significantly longer in patients with high 2-DR values than in patients with low 2-DR values in both the learning (37.0 vs. 24.1 months, P < 0.001) and validation (41.2 vs. 20.4 months, P < 0.001) cohorts. In contrast, differences in early tumor shrinkage and depth of response were not statistically significant. Multivariate analyses showed that 2-DR was an independent prognostic factor for OS.
确定转移性结直肠癌（mCRC）患者长期预后的替代标志物可能有助于设计治疗方案。本研究的目的是评估二维反应（2-DR）是否可作为mCRC患者总生存期（OS）的新替代标志物。研究组由来自两个独立队列的99例mCRC患者组成，这些患者接受了以奥沙利铂为基础的化疗加贝伐单抗治疗。二维反应定义为坐标点围成的面积，包括8周时的早期肿瘤缩小、最低点时的反应深度以及进展时相对于最低点增加20%。每个变量根据其对总生存期的贡献率进行加权。该模型在学习队列中开发并进行内部验证，其性能在验证队列中进行外部验证。学习队列和验证队列中2-DR与总生存期的Spearman相关系数分别为0.593和0.661。学习队列中预测总生存期的C指数为0.724（95%置信区间，0.623 - 0.815），验证队列中为0.762（95%置信区间，0.651 - 0.873）。在学习队列（37.0个月对24.1个月，P < 0.001）和验证队列（41.2个月对20.4个月，P < 0.001）中，2-DR值高的患者总生存期均显著长于2-DR值低的患者。相比之下，早期肿瘤缩小和反应深度的差异无统计学意义。多因素分析表明，2-DR是总生存期的独立预后因素。
