Pavel Marianne, Jann Henning, Prasad Vikas, Drozdov Ignat, Modlin Irvin M, Kidd Mark
Department of Hepatology and Gastroenterology, Campus-Virchow-Klinikum, Berlin, Germany.
Neuroendocrinology. 2017;104(2):170-182. doi: 10.1159/000446025. Epub 2016 Apr 15.
BACKGROUND/AIMS: A key issue in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is early identification and prediction of disease progression. Clinical evaluation and imaging are limited due to the lack of sensitivity and disease indolence. We assessed the NETest as a predictive and prognostic marker of progression in a long-term follow-up study.
GEP-NETs (n = 34) followed for a median 4 years (2.2-5.4) were evaluated. WHO tumor grade/stage grade 1: n = 17, grade 2: n = 14, grade 3: n = 1 (for 2, no grade was available); 31 (91%) were stage IV. Baseline and longitudinal imaging and blood biomarkers were available in all, and progression was defined per standard clinical protocols (RECIST 1.0). The NETest was measured by quantitative PCR of blood and multianalyte algorithmic analysis (disease activity scaled 0-100% with low <40% and high activity risk cutoffs >80%); chromogranin A (CgA) was measured by radioimmunoassay (normal <150 µg/l); progression-free survival (PFS) was analyzed by Cox proportional-hazard regression and Kaplan-Meier analysis.
At baseline, 100% were NETest positive, and CgA was elevated in 50%. The only baseline variable (Cox modeling) associated with PFS was NETest (hazard ratio = 1.022, 95% confidence interval = 1.005-1.04; p < 0.012). Using Kaplan-Meier analyses, the baseline NETest (>80%) was significantly associated (p = 0.01) with disease progression (median PFS 0.68 vs. 2.78 years with <40% levels). The NETest was more informative (96%) than CgA changes (
The NETest correlated with a well-differentiated GEP-NET clinical status. The NETest has predictive and prognostic utility for GEP-NETs identifying clinically actionable alterations ∼1 year before image-based evidence of progression.
背景/目的：胃肠胰神经内分泌肿瘤（GEP-NETs）的一个关键问题是疾病进展的早期识别和预测。由于缺乏敏感性以及疾病进展缓慢，临床评估和影像学检查存在局限性。我们在一项长期随访研究中评估了NETest作为疾病进展的预测和预后标志物。
对34例GEP-NETs患者进行了评估，随访时间中位数为4年（2.2 - 5.4年）。世界卫生组织肿瘤分级/分期：1级：n = 17，2级：n = 14，3级：n = 1（另有2例未分级）；31例（91%）为IV期。所有患者均有基线和纵向影像学检查及血液生物标志物数据，疾病进展根据标准临床方案（RECIST 1.0）定义。通过血液定量PCR和多分析物算法分析测量NETest（疾病活动度范围为0 - 100%，低活动度<40%，高活动度风险临界值>80%）；通过放射免疫测定法测量嗜铬粒蛋白A（CgA）（正常范围<150 μg/l）；采用Cox比例风险回归和Kaplan-Meier分析评估无进展生存期（PFS）。
基线时，100%的患者NETest呈阳性，50%的患者CgA升高。与PFS相关的唯一基线变量（Cox模型）是NETest（风险比 = 1.022，95%置信区间 = 1.005 - 1.04；p < 0.012）。使用Kaplan-Meier分析，基线NETest（>80%）与疾病进展显著相关（p = 0.01）（NETest <40%水平时的中位PFS为2.78年，而>80%水平时为0.68年）。在持续预测疾病变化方面，NETest比CgA变化（<25%）更具信息价值（96%对<25%，p < 2×10 - 5，χ2 = 18）。NETest比影像学检查出现变化的时间点更早（1.02 ± 0.15年）。疾病稳定时基线NETest水平>40%对疾病进展的预后判断准确率为100%，而CgA为（χ2 = 5，p < 0.03）。基线NETest值<40%准确（100%）预测了5年的疾病稳定性（p = 0.05，χ2 = 3.8，与CgA相比）。
NETest与高分化GEP-NET的临床状态相关。NETest对GEP-NETs具有预测和预后价值，可在基于影像学的疾病进展证据出现前约1年识别出临床可采取行动的改变。
