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Ki67 proliferation index, hepatic tumor load, and pretreatment tumor growth predict the antitumoral efficacy of lanreotide in patients with malignant digestive neuroendocrine tumors

Palazzo, Maximea,b; Lombard-Bohas, Catherinee; Cadiot, Guillaumef; Matysiak-Budnik, Tamarag; Rebours, Vincianea,b; Vullierme, Marie-Pierrea,b,c; Couvelard, Anneb,d; Hentic, Oliviaa,b; Ruszniewski, Philippea,b

European Journal of Gastroenterology & Hepatology: February 2013 - Volume 25 - Issue 2 - p 232–238
doi: 10.1097/MEG.0b013e328359d1a6
Original Articles: Gastrointestinal Malignancy

Background An antiproliferative effect of somatostatin analogs was recently demonstrated.

Aim To identify factors associated with tumor control in a group of patients with well-differentiated malignant digestive neuroendocrine tumors treated with lanreotide.

Methods A retrospective study was conducted in 68 patients treated with lanreotide alone, with progression-free survival as the primary endpoint. The role of the following factors was searched for by univariate and multivariate analyses: age, sex, mode of discovery, site of the primary tumor, metastatic spread, Ki67 proliferation index, uptake on somatostatin receptor scintigraphy, pretreatment tumor growth, extent of liver involvement, resection of primary tumor, previous treatments, and tumor markers.

Results Tumor progression was observed in 39/68 patients (57.4%). Median progression-free survival was 29 months. On multivariate analysis, a Ki67 proliferation index of up to 5% [hazard ratio (HR)=0.262, P=0.009], pretreatment stability (HR=0.241, P=0.008), and hepatic tumor load of up to 25% (HR=0.237, P=0.004) were significantly associated with disease stability under lanreotide therapy.

Conclusion In patients with well-differentiated malignant digestive neuroendocrine tumors, Ki67 proliferation index of up to 5%, stable disease before treatment, and low-to-moderate hepatic tumor involvement (≤25%) are associated with tumor control during lanreotide treatment. These data if confirmed in prospective trials will help in rationalizing the use of somatostatin analogs with antiproliferative intent.

aDepartment of Gastroenterology-Pancreatology, Beaujon Hospital, Clichy

bParis 7-Denis Diderot University

cDepartment of Radiology, Beaujon Hospital, Clichy

dDepartment of Pathology, Bichat Hospital, Paris

eDepartment of Medical Oncology, Edouard Herriot Hospital, Lyon

fDepartment of Hepato-gastroenterology, Robert Debre Hospital and Reims University, Reims

gDepartment of Gastroenterology, Hôtel-Dieu Hospital and Nantes University, Nantes, France

Correspondence to Maxime Palazzo, Department of Gastroenterology-Pancreatology, Beaujon Hospital, 100, boulevard du Général Leclerc, F-92118 Clichy, Cedex, Paris, France Tel: +33 140 875 255; fax: +33 142 703 784; e-mail:

Received June 17, 2012

Accepted August 24, 2012

© 2013 Lippincott Williams & Wilkins, Inc.