Hospital Universitario Morales Meseguer, Universidad de Murcia, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain.
Hospital Universitario Central de Asturias, Oviedo, Spain.
J Clin Oncol. 2019 Oct 1;37(28):2571-2580. doi: 10.1200/JCO.19.00980. Epub 2019 Aug 7.
Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients.
We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom).
We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively.
The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.
生长抑素类似物（SSAs）被推荐用于大多数分化良好的胃肠胰神经内分泌肿瘤（GEP-NETs）患者的一线治疗；然而，治疗获益存在异质性。本研究旨在开发和验证 SSA 治疗患者的无进展生存期（PFS）预测模型。
我们从西班牙神经内分泌和内分泌肿瘤登记组（R-GETNE）中提取数据。患者入选标准包括 GEP 原发肿瘤、Ki-67 指数<20%，以及一线 SSA 单药治疗晚期疾病。采用加速失效时间模型来预测 PFS，结果以列线图和在线计算器的形式呈现。该列线图在一个独立的连续合格患者系列（英国曼彻斯特克里斯蒂 NHS 基金会信托医院）中进行了外部验证。
我们共招募了 535 名患者（R-GETNE 组，n=438；曼彻斯特组，n=97）。在推导队列中，中位 PFS 和总生存期分别为 28.7（95%CI，23.8 至 31.1）和 85.9 个月（95%CI，71.5 至 96.7 个月）。9 个与 PFS 显著相关的协变量包括原发肿瘤位置、Ki-67 百分比、中性粒细胞与淋巴细胞比值、碱性磷酸酶、肝脏受累程度、骨和腹膜转移的存在、记录的进展状态以及开始使用 SSA 时的症状存在。GETNE-TRASGU（在胃肠胰和未知原发 NETs 中用生长抑素类似物治疗）模型显示出良好的校准度，在推导和验证系列中，其区分能力的 C 指数值分别为 0.714（95%CI，0.680 至 0.747）和 0.732（95%CI，0.658 至 0.806）。
GETNE-TRASGU 基于证据的预后工具根据患者的估计 PFS 对接受 SSA 治疗的 GEP-NETs 患者进行分层。该列线图可能有助于在未来的试验中对神经内分泌肿瘤患者进行分层。此外，它可能是日常临床实践中制定治疗决策的有用工具。
