Affiliations of authors: Department of Medical Oncology, The Christie NHS Foundation Trust (ENETS Centre of Excellence), Manchester, UK (AL, MGM, RAH, JWV, JB); Department of Medical Oncology, Hospices Civils de Lyon Edouard Herriot Hospital, University of Lyon, Lyon, France (TW, PF); Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany (MP); Department of Gastroenterology, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium (IB); Department of Medical Oncology, Doce de Octubre University Hospital, Madrid, Spain (BN, RGC); Department of Medical Oncology, Royal Free London NHS Foundation Trust (ENETS Centre of Excellence), London, UK (AC, TM); Institute of Cancer Sciences (MGM, JWV) and Faculty of Biology, Medicine and Health (JB), University of Manchester, Manchester, UK.
J Natl Cancer Inst. 2017 Jan 27;109(5). doi: 10.1093/jnci/djw277. Print 2017 Jan.
Prognostic markers for risk stratification of patients with gastrointestinal high-grade neuroendocrine carcinomas (GI-NECs) are lacking; we designed and validated a prognostic score for overall survival (OS).
Consecutive patients diagnosed in five neuroendocrine specialist European centers were included. Patients were divided into three cohorts: a training cohort (TC), an external validation cohort (EVC), and a prospective validation cohort (PVC). Prognostic factors were identified by log-rank test, Cox-regression, and logistic regression analyses. The derived score was internally and externally validated. All statistical tests were two-sided.
Of 395 patients screened, 313 were eligible (TC = 109 patients, EVC = 184 patients, and PVC = 20 patients). The derived prognostic score included five variables: presence of liver metastases, alkaline phosphatase (ALK), lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group performance status (ECOG PS), and Ki67. In multivariable analysis, the score was prognostic for OS (hazard ratio [HR] = 1.86, 95% confidence interval [CI] = 1.47 to 2.35, P < .001) and had good discrimination (C-index = 0.76) and calibration (mean error = 0.021, 90th percentile = 0.037) in the TC. These results were validated in the EVC and PVC, in which our score was able to prognosticate for OS when adjusted for other prognostic variables in the multivariable analysis (HR = 1.85, 95% CI = 1.27 to 2.71, P = .001; and HR = 4.51, 95% CI = 1.87 to 10.87, P = .001, respectively). The score classified patients into two groups with incremental risk of death: group A (0-2 points, 181 patients [63.9%], median OS = 19.4 months, 95% CI = 16.1 to 25.1) and group B (3-6 points, 102 patients [36.1%], median OS = 5.2 months, 95% CI = 3.6 to 6.9).
The GI-NEC score identifies two distinct patient cohorts; it provides a tool for clinicians when making treatment decisions and may be used as a stratification factor in future clinical trials.
目前缺乏用于胃肠道高级别神经内分泌癌（GI-NEC）患者风险分层的预后标志物；本研究旨在设计和验证一种用于总生存（OS）的预后评分。
连续纳入在 5 个欧洲神经内分泌专家中心诊断的患者。患者被分为 3 个队列：训练队列（TC）、外部验证队列（EVC）和前瞻性验证队列（PVC）。通过对数秩检验、Cox 回归和逻辑回归分析确定预后因素。该评分在内部和外部均得到验证。所有统计检验均为双侧检验。
在筛选的 395 名患者中，有 313 名符合入选标准（TC=109 例，EVC=184 例，PVC=20 例）。该预后评分包含 5 个变量：肝转移、碱性磷酸酶（ALP）、乳酸脱氢酶（LDH）、东部肿瘤协作组体能状态（ECOG PS）和 Ki67。多变量分析显示，该评分与 OS 相关（风险比[HR]=1.86，95%置信区间[CI]：1.47 至 2.35，P<0.001），且在 TC 中具有良好的区分度（C 指数=0.76）和校准度（平均误差=0.021，第 90 百分位数=0.037）。这些结果在 EVC 和 PVC 中得到了验证，在多变量分析中调整其他预后变量后，该评分能够预测 OS（HR=1.85，95%CI=1.27 至 2.71，P=0.001；HR=4.51，95%CI=1.87 至 10.87，P=0.001）。该评分将患者分为两组，死亡风险逐渐增加：A 组（0-2 分，181 例[63.9%]，中位 OS=19.4 个月，95%CI=16.1 至 25.1）和 B 组（3-6 分，102 例[36.1%]，中位 OS=5.2 个月，95%CI=3.6 至 6.9）。
GI-NEC 评分可识别出两组不同的患者人群；可为临床医生制定治疗决策提供工具，并可作为未来临床试验中的分层因素。
