title: Ki67 proliferation index, hepatic tumor load, and pretreatment tumor growth predict the antitumoral efficacy of lanreotide in patients with malignant digestive neuroendocrine tumors.
abstract: BACKGROUND
  An antiproliferative effect of somatostatin analogs was recently demonstrated.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology-Pancreatology, Beaujon Hospital, Clichy, Cedex, Paris, France. maxime.palazzo@bjn.aphp.fr
authors.forename: Maxime
authors.initials: M
authors.lastname: Palazzo
authors.forename: Catherine
authors.initials: C
authors.lastname: Lombard-Bohas
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cadiot
authors.forename: Tamara
authors.initials: T
authors.lastname: Matysiak-Budnik
authors.forename: Vinciane
authors.initials: V
authors.lastname: Rebours
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Vullierme
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
authors.forename: Olivia
authors.initials: O
authors.lastname: Hentic
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D004067:Digestive System Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use*; D011379:Prognosis; D012189:Retrospective Studies; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin