Gastroenterology Unit II, Fondazione IRCCS Policlinico, Mangiagalli e Regina Elena, Milan, Italy.
Am J Gastroenterol. 2010 Sep;105(9):2072-8. doi: 10.1038/ajg.2010.154. Epub 2010 Apr 6.
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) expressing somatostatin receptors may be treated with somatostatin analogs (SSAs). Selection criteria are a positive Octreoscan or a >50% hormone level decrease after octreotide subcutaneous (s.c.) injection (octreotide test) (OT). Plasma chromogranin A (CgA) is the best general GEP-NET marker, but data on CgA response to OT are scanty. Thus, we evaluated whether plasma CgA response to OT could predict the clinical response to SSAs.
At diagnosis, 38 GEP-NET patients received octreotide 200 microg s.c., with plasma CgA determination at 0, 3, and 6 h. Long-term SSA treatment was then given by monitoring symptomatic, biochemical, and objective responses, and survival.
Basal plasma CgA levels were significantly higher in patients with functioning than non-functioning tumors (median (range): 220 (18-2,230) vs. 46 (25-8,610) U/l, P=0.03) and in those with than without metastases (171 (18-8,610) vs. 43 (28-220) U/l, P=0.04). CgA levels significantly correlated with WHO classification, clinical TNM staging, and Ki-67 proliferative index. After OT, CgA levels decreased from 146 (18-8,610) to 61 (10-8,535) U/l (basal and nadir values), P<0.001. In patients responsive to OT, a successful objective response occurred in 21/31 patients (68%). Successful symptomatic response occurred in 13/18 patients (72%), biochemical response in 25/31 (81%), and objective response in 21/31 (68%). In the remaining seven unresponsive cases, with CgA decrement <30%, disease progressed to death in six (86%). Median survival from enrollment was 48 months (6-138) in responsive and 6 (6-30) in unresponsive patients (P=0.0005).
In GEP-NETs, plasma CgA is a reliable marker, and a >30% decrease after OT has a relevant prognostic meaning allowing the identification of the subgroup of patients most likely to be responsive to chronic SSAs.
表达生长抑素受体的胃肠胰神经内分泌肿瘤（GEP-NETs）可用生长抑素类似物（SSAs）治疗。选择标准是Octreoscan 阳性或奥曲肽皮下（s.c.）注射（奥曲肽试验）后激素水平下降>50%（OT）。血浆嗜铬粒蛋白 A（CgA）是最好的一般 GEP-NET 标志物，但关于 CgA 对 OT 的反应的数据很少。因此，我们评估了 OT 对 CgA 的反应是否可以预测 SSA 的临床反应。
38 名 GEP-NET 患者在诊断时接受奥曲肽 200μg s.c.，并在 0、3 和 6 小时测定血浆 CgA。然后通过监测症状、生化和客观反应以及生存情况给予长期 SSA 治疗。
功能性肿瘤患者的基础血浆 CgA 水平明显高于非功能性肿瘤患者（中位数（范围）：220（18-2230）比 46（25-8610）U/l，P=0.03）和有转移患者比无转移患者（171（18-8610）比 43（28-220）U/l，P=0.04）。CgA 水平与 WHO 分类、临床 TNM 分期和 Ki-67 增殖指数显著相关。OT 后，CgA 水平从 146（18-8610）降至 61（10-8535）U/l（基础值和最低值），P<0.001。在对 OT 有反应的患者中，21/31 例（68%）出现成功的客观反应。13/18 例（72%）出现成功的症状反应，25/31 例（81%）出现生化反应，21/31 例（68%）出现客观反应。在其余 7 例无反应的病例中，CgA 减少<30%，6 例（86%）疾病进展至死亡。有反应患者的中位生存期为 48 个月（6-138），无反应患者为 6（6-30）个月（P=0.0005）。
在 GEP-NETs 中，血浆 CgA 是一种可靠的标志物，OT 后下降>30%具有相关的预后意义，可识别最有可能对慢性 SSA 有反应的患者亚组。
