Han Xu, Zhang Chunyan, Tang Min, Xu Xuefeng, Liu Lingxiao, Ji Yuan, Pan Baishen, Lou Wenhui
Departments of aPancreatic Surgery bClinical Laboratory cRadiology dInterventional Radiology ePathology, Zhongshan Hospital, Fudan University, Shanghai, China.
Eur J Gastroenterol Hepatol. 2015 May;27(5):527-35. doi: 10.1097/MEG.0000000000000332.
To investigate the usefulness of serum chromogranin A (CgA) for the prediction of tumor burden, therapeutic response, and nomogram-based survival in well-moderate nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) with liver metastases (LMs).
This prospective study included 51 NF-PNETs of LMs patients, 134 other neuroendocrine tumors, and 125 controls. Serum CgA levels were determined by enzyme-linked immunosorbent assay at baseline and after treatment. LMs tumor burden was computed simultaneously from computed tomography/MRI scan with thin slices using a semiquantitative three-dimensional reconstruction approach. Predictive CgA for therapeutic response was assessed using the response evaluation criteria in solid tumors criteria. A nomogram to predict the prognostic value of CgA with variables selected in the multivariate Cox proportional hazards model was constructed; the accuracy of the nomogram was quantified by the (concordance index) C-index and a calibration plot.
Considering NF-PNETs, CgA correlated with the tumor grade and differentiation (P<0.05). There was a nonlinear exponential regression between LMs tumor burden and CgA levels (P<0.001). The alteration in CgA correlated with therapeutic response (P<0.001). Increased CgA presented significantly lower progression-free survival than the stable/decreased CgA subgroup (P<0.001). For overall survival, a baseline CgA increase greater than 2.5 upper limit of normal level was predictive of a poor prognosis (P<0.001). Baseline CgA level, LMs tumor burden, and Ki-67 were selected as independent factors for the nomogram to predict overall survival; the nomogram showed fitting calibration with a C-index of 0.87 (95% confidence interval, 0.82-0.92).
Serum CgA could be used to reflect tumor burden, evaluate the therapeutic response, and predict the survival outcomes for NF-PNETs with LMs. An effective nomogram including CgA was proposed for prediction.
探讨血清嗜铬粒蛋白A（CgA）在预测伴肝转移（LM）的中高分化非功能性胰腺神经内分泌肿瘤（NF-PNET）的肿瘤负荷、治疗反应及基于列线图的生存情况中的作用。
这项前瞻性研究纳入了51例伴LM的NF-PNET患者、134例其他神经内分泌肿瘤患者及125例对照。在基线期及治疗后通过酶联免疫吸附测定法测定血清CgA水平。使用半定量三维重建方法通过薄层计算机断层扫描/磁共振成像扫描同时计算LM的肿瘤负荷。采用实体瘤疗效评价标准评估CgA对治疗反应的预测价值。构建一个列线图，用于预测在多变量Cox比例风险模型中选择的变量的CgA预后价值；通过一致性指数（C指数）和校准图对列线图的准确性进行量化。
就NF-PNET而言，CgA与肿瘤分级及分化相关（P<0.05）。LM肿瘤负荷与CgA水平之间存在非线性指数回归关系（P<0.001）。CgA的变化与治疗反应相关（P<0.001）。CgA升高组的无进展生存期显著低于CgA稳定/降低亚组（P<0.001）。对于总生存期，基线CgA升高超过正常水平上限2.5倍可预测预后不良（P<0.001）。基线CgA水平、LM肿瘤负荷及Ki-67被选为列线图预测总生存期的独立因素；该列线图显示拟合校准良好，C指数为0.87（95%置信区间，0.82 - 0.92）。
血清CgA可用于反映伴LM的NF-PNET的肿瘤负荷、评估治疗反应并预测生存结局。提出了一个包含CgA的有效列线图用于预测。
