Objective. The efficacy of the CAPTEM regimen has been demonstrated in metastatic neuroendocrine neoplasms (NENs), but due to varying response rates among the patients, biomarkers to predict its response are greatly needed. Here, we investigated the clinical utility of a Ki-67 index to predict the CAPTEM regimen objective responses and select patients who could benefit from this regimen. Methods. Metastatic NENs patients treated with the CAPTEM regimen from 4 high-volume medical centers were selected and grouped in a training and validation cohort. The classification and regression tree (CART) was generated to identify the optimal threshold of Ki-67 for stratifying the patients into different Ki-67 range groups based on their response to the CAPTEM regimen. Results and Conclusions The overall response rate (ORR) and disease control rate (DCR) of the entire cohort (N = 151) were 26.5% and 76.2%, respectively, with a median progression-free survival (PFS) of 12.0 months. CART analysis showed that patients with the Ki-67 range group 10-40% demonstrated a significantly higher ORR than those with Ki-67 > 40% and < 10% groups (P < 0.001 in the training cohort and P = 0.036 in the validation cohort). Response to the CAPTEM regimen was not influenced by the expression of MGMT or primary tumor location. Multivariate analysis identified the Ki-67 index as the only independent prognostic factor for overall survival (P = 0.031) and PFS (P = 0.006). The proposed Ki-67 index was externally validated and could be used to clinically identify suitable metastatic NENs patients who could achieve an optimal cytoreduction using the CAPTEM regimen.


中文翻译：

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用于预测神经内分泌肿瘤中卡培他滨替莫唑胺 (CAPTEM) 方案治疗反应的 Ki-67 指数：一项回顾性多中心研究。

客观的。CAPTEM 方案的疗效已在转移性神经内分泌肿瘤 (NEN) 中得到证实，但由于患者之间的反应率不同，因此非常需要预测其反应的生物标志物。在这里，我们调查了 Ki-67 指数在预测 CAPTEM 方案客观反应和选择可以从该方案中受益的患者的临床效用。方法。从 4 个高容量医疗中心选择接受 CAPTEM 方案治疗的转移性 NEN 患者，并将其分组到培训和验证队列中。生成分类和回归树 (CART) 以确定 Ki-67 的最佳阈值，用于根据患者对 CAPTEM 方案的反应将患者分为不同的 Ki-67 范围组。结果和结论 整个队列（N = 151）的总缓解率（ORR）和疾病控制率（DCR）分别为 26.5% 和 76.2%，中位无进展生存期（PFS）为 12.0 个月。CART 分析显示，Ki-67 范围组 10-40% 的患者的 ORR 显着高于 Ki-67 > 40% 和 < 10% 组的患者（训练队列中 P < 0.001，验证中 P = 0.036队列）。对 CAPTEM 方案的反应不受 MGMT 表达或原发肿瘤位置的影响。多变量分析确定 Ki-67 指数是总生存期 (P = 0.031) 和 PFS (P = 0.006) 的唯一独立预后因素。