Gertner Julian, Tsoli Marina, Hayes Aimee R, O'Mahony Luke Furtado, Laskaratos Faidon-Marios, Glover Thomas, Karia Priyesh, Butt Mohsin F, Eastwood Oliver, Mandair Dalvinder, Caplin Martyn, Toumpanakis Christos
University College London Hospital, London NW1 2BU, UK.
Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London NW3 2QG, UK.
Cancers (Basel). 2024 Jul 10;16(14):2506. doi: 10.3390/cancers16142506.
Current biomarkers do not adequately predict the behaviour of neuroendocrine neoplasms (NENs). This study assessed the NETest, a multianalyte blood biomarker, in patients with small intestinal NENs (Si-NENs). We studied two patient groups: Group 1: metastatic Si-NENs ( = 102) and Group 2: post-operatively disease-free according to 68Ga-DOTATATE PET ( = 16). NETest scores were ≤20% (normal), 21-40% (low), 41-79% (intermediate), or ≥80% (high). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. In Group 1, the median NETest score was 40% (IQR: 33.3-46.7%). The NETest value (HR: 1.032, 95% CI: 1.003-1.062, = 0.033) and high-risk NETest category (HR: 10.5, 95% CI: 1.35-81.7, = 0.025) were independent predictors of PFS, along with presence of lung metastases, CgA levels > 10 × ULN, and tumour growth rate (TGR). Independent predictors of OS were the NETest value (HR: 1.035, 95% CI: 1.005-1.066, = 0.024) and high-risk NETest category (HR: 15.2, 95% CI: 1.52-151, = 0.02), along with presence of lung metastases and CgA levels > 10 × ULN. In Group 2, ROC analysis identified an AUC of 0.909 (95% CI: 0.75-0.100) for prediction of local or metastatic recurrence. Blood NETest scores were associated with PFS and OS in patients with metastatic Si-NENs, along with TGR, CgA > 10 × ULN, and presence of lung metastases.
目前的生物标志物尚不能充分预测神经内分泌肿瘤（NENs）的行为。本研究评估了多分析物血液生物标志物NETest在小肠神经内分泌肿瘤（Si-NENs）患者中的情况。我们研究了两组患者：第1组：转移性Si-NENs（n = 102）和第2组：根据68Ga-DOTATATE PET检查术后无疾病（n = 16）。NETest评分≤20%（正常）、21 - 40%（低）、41 - 79%（中等）或≥80%（高）。采用Kaplan-Meier方法评估总生存期（OS）和无进展生存期（PFS）。使用Cox比例风险模型进行单因素和多因素分析。在第1组中，NETest评分中位数为40%（四分位间距：33.3 - 46.7%）。NETest值（风险比：1.032，95%置信区间：1.003 - 1.062，P = 0.033）和高风险NETest类别（风险比：10.5，95%置信区间：1.35 - 81.7，P = 0.025）是PFS的独立预测因素，同时还有肺转移的存在、嗜铬粒蛋白A（CgA）水平>10倍正常上限（ULN）以及肿瘤生长率（TGR）。OS的独立预测因素是NETest值（风险比：1.035，95%置信区间：1.005 - 1.066，P = 0.024）和高风险NETest类别（风险比：15.2，95%置信区间：1.52 - 151，P = 0.02），以及肺转移的存在和CgA水平>10倍ULN。在第2组中，ROC分析确定预测局部或远处复发的曲线下面积（AUC）为0.909（95%置信区间：0.75 - 1.00）。血液NETest评分与转移性Si-NENs患者的PFS和OS相关，同时还与TGR、CgA>10倍ULN以及肺转移的存在有关。
