title: Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms.
abstract: Data on gastroenteropancreatic neuroendocrine neoplasms (NEN) G3 (well-differentiated neuroendocrine tumors (NET G3) and neuroendocrine carcinoma (NEC)) are limited. We retrospectively study patients with NET G3 and NEC from eight European centers. Data examined included clinical and pathological characteristics at diagnosis, therapies and outcomes. Two hundred and four patients were analyzed (37 NET G3 and 167 NEC). Median age was 64 (21-89) years. Tumor origin included pancreas (32%) and colon-rectum (27%). The primary tumor was resected in 82 (40%) patients. Metastatic disease was evident at diagnosis in 88% (liver metastases: 67%). Median Ki-67 index was 70% (30% in NET G3 and 80% in NEC; P<0.001). Median overall survival (OS) for all patients was 23 (95% CI: 18-28) months and significantly higher in NET G3 (99 vs 17 months in NEC; HR=8.3; P<0.001). Platinum-etoposide first line chemotherapy was administered in 113 (68%) NEC and 12 (32%) NET G3 patients. Disease control rate and progression free survival (PFS) were significantly higher in NEC compared to NET G3 (P<0.05), whereas OS was significantly longer in NET G3 (P=0.003). Second- and third-line therapies (mainly FOLFIRI and FOLFOX) were given in 79 and 39 of NEC patients; median PFS and OS were 3.0 and 7.6 months respectively after second-line and 2.5 and 6.2 months after third-line chemotherapy. In conclusion, NET G3 and NEC are characterized by significant differences in Ki-67 index and outcomes. While platinum-based chemotherapy is effective in NEC, it seems to have limited value in NET G3.
authors.affiliation: Department of Hepatology and GastroenterologyCharité University Hospital Berlin, Berlin, GermanyDepartment of Nuclear MedicineHopital Saint Louis, Paris, FranceDepartment of Surgical GastroenterologyEuropean NET Center of Excellence, Rigshospitalet, DenmarkDepartment of Internal MedicineDivision of Gastroenterology and Endocrinology, Philipps University, Marburg, GermanyDepartment of GastroenterologyCliniques Universitaires Saint-Luc, Bruxelles, BelgiumDepartment of Medical OncologyHospital Universitario de Burgos, Burgos, SpainDepartment of Medical OncologyHospital Univeristario La Paz, Madrid, SpainDepartment of Clinical Medicine and GastroenterologySt James's and St Vincent's Hospitals and TCD, Dublin, IrelandDepartment of Hepatology and GastroenterologyEdouard Herriot Hospital, University of Lyon, 69437 Lyon Cedex 03, France.
authors.forename: M
authors.initials: M
authors.lastname: Heetfeld
authors.affiliation: Department of Hepatology and GastroenterologyCharité University Hospital Berlin, Berlin, GermanyDepartment of Nuclear MedicineHopital Saint Louis, Paris, FranceDepartment of Surgical GastroenterologyEuropean NET Center of Excellence, Rigshospitalet, DenmarkDepartment of Internal MedicineDivision of Gastroenterology and Endocrinology, Philipps University, Marburg, GermanyDepartment of GastroenterologyCliniques Universitaires Saint-Luc, Bruxelles, BelgiumDepartment of Medical OncologyHospital Universitario de Burgos, Burgos, SpainDepartment of Medical OncologyHospital Univeristario La Paz, Madrid, SpainDepartment of Clinical Medicine and GastroenterologySt James's and St Vincent's Hospitals and TCD, Dublin, IrelandDepartment of Hepatology and GastroenterologyEdouard Herriot Hospital, University of Lyon, 69437 Lyon Cedex 03, France.
authors.forename: C N
authors.initials: CN
authors.lastname: Chougnet
authors.affiliation: Department of Hepatology and GastroenterologyCharité University Hospital Berlin, Berlin, GermanyDepartment of Nuclear MedicineHopital Saint Louis, Paris, FranceDepartment of Surgical GastroenterologyEuropean NET Center of Excellence, Rigshospitalet, DenmarkDepartment of Internal MedicineDivision of Gastroenterology and Endocrinology, Philipps University, Marburg, GermanyDepartment of GastroenterologyCliniques Universitaires Saint-Luc, Bruxelles, BelgiumDepartment of Medical OncologyHospital Universitario de Burgos, Burgos, SpainDepartment of Medical OncologyHospital Univeristario La Paz, Madrid, SpainDepartment of Clinical Medicine and GastroenterologySt James's and St Vincent's Hospitals and TCD, Dublin, IrelandDepartment of Hepatology and GastroenterologyEdouard Herriot Hospital, University of Lyon, 69437 Lyon Cedex 03, France.
authors.forename: I H
authors.initials: IH
authors.lastname: Olsen
authors.affiliation: Department of Hepatology and GastroenterologyCharité University Hospital Berlin, Berlin, GermanyDepartment of Nuclear MedicineHopital Saint Louis, Paris, FranceDepartment of Surgical GastroenterologyEuropean NET Center of Excellence, Rigshospitalet, DenmarkDepartment of Internal MedicineDivision of Gastroenterology and Endocrinology, Philipps University, Marburg, GermanyDepartment of GastroenterologyCliniques Universitaires Saint-Luc, Bruxelles, BelgiumDepartment of Medical OncologyHospital Universitario de Burgos, Burgos, SpainDepartment of Medical OncologyHospital Univeristario La Paz, Madrid, SpainDepartment of Clinical Medicine and GastroenterologySt James's and St Vincent's Hospitals and TCD, Dublin, IrelandDepartment of Hepatology and GastroenterologyEdouard Herriot Hospital, University of Lyon, 69437 Lyon Cedex 03, France.
authors.forename: A
authors.initials: A
authors.lastname: Rinke
authors.affiliation: Department of Hepatology and GastroenterologyCharité University Hospital Berlin, Berlin, GermanyDepartment of Nuclear MedicineHopital Saint Louis, Paris, FranceDepartment of Surgical GastroenterologyEuropean NET Center of Excellence, Rigshospitalet, DenmarkDepartment of Internal MedicineDivision of Gastroenterology and Endocrinology, Philipps University, Marburg, GermanyDepartment of GastroenterologyCliniques Universitaires Saint-Luc, Bruxelles, BelgiumDepartment of Medical OncologyHospital Universitario de Burgos, Burgos, SpainDepartment of Medical OncologyHospital Univeristario La Paz, Madrid, SpainDepartment of Clinical Medicine and GastroenterologySt James's and St Vincent's Hospitals and TCD, Dublin, IrelandDepartment of Hepatology and GastroenterologyEdouard Herriot Hospital, University of Lyon, 69437 Lyon Cedex 03, France.
authors.forename: I
authors.initials: I
authors.lastname: Borbath
authors.affiliation: Department of Hepatology and GastroenterologyCharité University Hospital Berlin, Berlin, GermanyDepartment of Nuclear MedicineHopital Saint Louis, Paris, FranceDepartment of Surgical GastroenterologyEuropean NET Center of Excellence, Rigshospitalet, DenmarkDepartment of Internal MedicineDivision of Gastroenterology and Endocrinology, Philipps University, Marburg, GermanyDepartment of GastroenterologyCliniques Universitaires Saint-Luc, Bruxelles, BelgiumDepartment of Medical OncologyHospital Universitario de Burgos, Burgos, SpainDepartment of Medical OncologyHospital Univeristario La Paz, Madrid, SpainDepartment of Clinical Medicine and GastroenterologySt James's and St Vincent's Hospitals and TCD, Dublin, IrelandDepartment of Hepatology and GastroenterologyEdouard Herriot Hospital, University of Lyon, 69437 Lyon Cedex 03, France.
authors.forename: G
authors.initials: G
authors.lastname: Crespo
authors.affiliation: Department of Hepatology and GastroenterologyCharité University Hospital Berlin, Berlin, GermanyDepartment of Nuclear MedicineHopital Saint Louis, Paris, FranceDepartment of Surgical GastroenterologyEuropean NET Center of Excellence, Rigshospitalet, DenmarkDepartment of Internal MedicineDivision of Gastroenterology and Endocrinology, Philipps University, Marburg, GermanyDepartment of GastroenterologyCliniques Universitaires Saint-Luc, Bruxelles, BelgiumDepartment of Medical OncologyHospital Universitario de Burgos, Burgos, SpainDepartment of Medical OncologyHospital Univeristario La Paz, Madrid, SpainDepartment of Clinical Medicine and GastroenterologySt James's and St Vincent's Hospitals and TCD, Dublin, IrelandDepartment of Hepatology and GastroenterologyEdouard Herriot Hospital, University of Lyon, 69437 Lyon Cedex 03, France.
authors.forename: J
authors.initials: J
authors.lastname: Barriuso
authors.affiliation: Department of Hepatology and GastroenterologyCharité University Hospital Berlin, Berlin, GermanyDepartment of Nuclear MedicineHopital Saint Louis, Paris, FranceDepartment of Surgical GastroenterologyEuropean NET Center of Excellence, Rigshospitalet, DenmarkDepartment of Internal MedicineDivision of Gastroenterology and Endocrinology, Philipps University, Marburg, GermanyDepartment of GastroenterologyCliniques Universitaires Saint-Luc, Bruxelles, BelgiumDepartment of Medical OncologyHospital Universitario de Burgos, Burgos, SpainDepartment of Medical OncologyHospital Univeristario La Paz, Madrid, SpainDepartment of Clinical Medicine and GastroenterologySt James's and St Vincent's Hospitals and TCD, Dublin, IrelandDepartment of Hepatology and GastroenterologyEdouard Herriot Hospital, University of Lyon, 69437 Lyon Cedex 03, France.
authors.forename: M
authors.initials: M
authors.lastname: Pavel
authors.affiliation: Department of Hepatology and GastroenterologyCharité University Hospital Berlin, Berlin, GermanyDepartment of Nuclear MedicineHopital Saint Louis, Paris, FranceDepartment of Surgical GastroenterologyEuropean NET Center of Excellence, Rigshospitalet, DenmarkDepartment of Internal MedicineDivision of Gastroenterology and Endocrinology, Philipps University, Marburg, GermanyDepartment of GastroenterologyCliniques Universitaires Saint-Luc, Bruxelles, BelgiumDepartment of Medical OncologyHospital Universitario de Burgos, Burgos, SpainDepartment of Medical OncologyHospital Univeristario La Paz, Madrid, SpainDepartment of Clinical Medicine and GastroenterologySt James's and St Vincent's Hospitals and TCD, Dublin, IrelandDepartment of Hepatology and GastroenterologyEdouard Herriot Hospital, University of Lyon, 69437 Lyon Cedex 03, France.
authors.forename: D
authors.initials: D
authors.lastname: O'Toole
authors.affiliation: Department of Hepatology and GastroenterologyCharité University Hospital Berlin, Berlin, GermanyDepartment of Nuclear MedicineHopital Saint Louis, Paris, FranceDepartment of Surgical GastroenterologyEuropean NET Center of Excellence, Rigshospitalet, DenmarkDepartment of Internal MedicineDivision of Gastroenterology and Endocrinology, Philipps University, Marburg, GermanyDepartment of GastroenterologyCliniques Universitaires Saint-Luc, Bruxelles, BelgiumDepartment of Medical OncologyHospital Universitario de Burgos, Burgos, SpainDepartment of Medical OncologyHospital Univeristario La Paz, Madrid, SpainDepartment of Clinical Medicine and GastroenterologySt James's and St Vincent's Hospitals and TCD, Dublin, IrelandDepartment of Hepatology and GastroenterologyEdouard Herriot Hospital, University of Lyon, 69437 Lyon Cedex 03, France thomas.walter@chu-lyon.fr.
authors.forename: T
authors.initials: T
authors.lastname: Walter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019394:Ki-67 Antigen; D009944:Organoplatinum Compounds; D005047:Etoposide; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Ki-67 index; chemotherapy; gastrointestinal cancer; grade 3 NET; neuroendocrine carcinoma