Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Neuroendocrinology. 2021;111(8):752-763. doi: 10.1159/000510159. Epub 2020 Jul 15.
The efficacy of the capecitabine/temozolomide (CAPTEM) regimen has been demonstrated in metastatic neuroendocrine neoplasms (NENs), but because of 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.
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.
The overall response rate (ORR) and disease control rate 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 in the Ki-67 range group 10-40% demonstrated a significantly higher ORR than those in 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 O6-methylguanine-DNA methyltransferase 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.
卡培他滨/替莫唑胺（CAPTEM）方案已在转移性神经内分泌肿瘤（NEN）中显示出疗效，但由于患者的反应率不同，因此非常需要预测其反应的生物标志物。在这里，我们研究了 Ki-67 指数预测 CAPTEM 方案客观反应的临床实用性，并选择可能从该方案中受益的患者。
从 4 家高容量医疗中心选择接受 CAPTEM 方案治疗的转移性 NEN 患者，并将其分组为训练和验证队列。生成分类回归树（CART），以确定 Ki-67 的最佳阈值，根据患者对 CAPTEM 方案的反应将其分为不同的 Ki-67 范围组。
整个队列（N = 151）的总缓解率（ORR）和疾病控制率分别为 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 ORR 明显高于 Ki-67>40%和<10%组（训练队列中 p<0.001，验证队列中 p=0.036）。对 CAPTEM 方案的反应不受 O6-甲基鸟嘌呤-DNA 甲基转移酶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。提出的 Ki-67 指数经外部验证可用于临床识别适合使用 CAPTEM 方案实现最佳细胞减灭的转移性 NEN 患者。
