Objectives: 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. Methods: At diagnosis, 38 GEP-NET patients received octreotide 200 g 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. Results: 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). Conclusions: 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.
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