Childs Alexa, Kirkwood Amy, Edeline Julien, Luong Tu Vinh, Watkins Jennifer, Lamarca Angela, Alrifai Doraid, Nsiah-Sarbeng Phyllis, Gillmore Roopinder, Mayer Astrid, Thirlwell Christina, Sarker Debashis, Valle Juan W, Meyer Tim
Department of OncologyRoyal Free London NHS Foundation Trust, London, UK.
Cancer Research UK & UCL Cancer Trials CentreLondon, UK.
Endocr Relat Cancer. 2016 Jul;23(7):563-70. doi: 10.1530/ERC-16-0099.
Chemotherapy (CT) is widely used for neuroendocrine tumours (NETs), but there are no validated biomarkers to predict response. The Ki-67 proliferation index has been proposed as a means of selecting patients for CT, but robust data are lacking. The aim of this study was to investigate the relationship between response to chemotherapy and Ki-67 in NET. We reviewed data from 222 NET patients treated with CT. Tumours were graded according to Ki-67 index: G1 ≤2%, G2 3-20% and G3 >20%. Response was assessed according to RECIST and survival calculated from start of chemotherapy to death. To explore Ki-67 as a marker of response, we calculated the likelihood ratio and performed receiver operating characteristic analysis. Overall, 193 patients had a documented Ki-67 index, of which 173 were also evaluable for radiological response: 10% were G1, 46% G2 and 43% G3; 46% were pancreatic NET (PNET). Median overall survival was 22.1 months. Overall response rate was 30% (39% in PNET vs 22% in non-PNET) and 43% of patients had stable disease. Response rate increased with grade: 6% in G1 tumours, 24% in G2 and 43% in G3. However, maximum likelihood ratio was 2.3 at Ki-67=35%, and the area under the ROC curve was 0.60. As reported previously, a high Ki-67 was an adverse prognostic factor for overall survival. In conclusion, response to CT increases with Ki-67 index, but Ki-67 alone is an unreliable means to select patients for CT. Improved methods to stratify patients for systemic therapy are required.
化疗（CT）广泛应用于神经内分泌肿瘤（NETs），但尚无经过验证的生物标志物来预测疗效。Ki-67增殖指数已被提议作为选择接受CT治疗患者的一种方法，但缺乏有力的数据支持。本研究的目的是探讨NET中化疗疗效与Ki-67之间的关系。我们回顾了222例接受CT治疗的NET患者的数据。根据Ki-67指数对肿瘤进行分级：G1≤2%，G2为3%-20%，G3>20%。根据实体瘤疗效评价标准（RECIST）评估疗效，并计算从化疗开始至死亡的生存期。为了探究Ki-67作为疗效标志物的作用，我们计算了似然比并进行了受试者工作特征分析。总体而言，193例患者有记录的Ki-67指数，其中173例也可评估放射学疗效：10%为G-1级，46%为G2级，43%为G3级；46%为胰腺NET（PNET）。中位总生存期为22.1个月。总缓解率为30%（PNET中为39%，非PNET中为22%），43%的患者疾病稳定。缓解率随分级增加：G1级肿瘤为6%，G2级为24%，G3级为43%。然而，在Ki-67=35%时，最大似然比为2.3，ROC曲线下面积为0.60。如先前报道，高Ki-67是总生存期的不良预后因素。总之，CT疗效随Ki-67指数增加，但仅Ki-67本身是选择接受CT治疗患者的不可靠方法。需要改进对患者进行全身治疗分层的方法。
