Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort

T. Walter 1, * T Tougeron 2 E. Baudin 3 K. Le Malicot 4 T. Lecomte 5 D. Malka 3 O. Hentic 6 S. Manfredi 7 I. Bonnet 8 R. Guimbaud 9 R. Coriat 10 C. Lepère 11 C. Desauw 12 A. Thirot-Bidault 13 L. Dahan 14 G. Roquin 15 T. Aparicio 16 J.-L. Legoux 17 C. Lombard-Bohas 18 J.-Y. Scoazec 3 C. Lepage 4, 19 G. Cadiot 20 Laetitia Stephanie Ivan Borbath Caroline Pétorin 21 Eric Terrebonne 22 Karine Bouhier-Leporrier 23 Etienne Suc 24 Vincent Hautefeuille 25 Vincent Bourgeois 26 Laurent Cany 27 François Dewaele 28 Patricia Niccoli 14 Jean-Francois Seitz 14 Cédric Lecaille 29 Christine Rebischung 30 Valérie Rossi 31 Mathieu Baconnier 32 Olivier Dubreuil 33 Marc Ferec 34 Gael Deplanque 35 Guillaume Geslin 36 Isabelle Wanicki Caron 37 Sandrine Lavau Denes 38 Laurent Bedenne 39 Catherine Ligeza 40 Eric Maringe 41 Anne-Laure Ran-Royo 42 Joël Guigay 43 Philippe Rougier 11
* Auteur correspondant
1 HCL - Hospices Civils de Lyon
2 CHU Poitiers - Centre hospitalier universitaire de Poitiers
3 IGR - Institut Gustave Roussy
4 Fédération Francophone de la Cancérologie Digestive, FFCD
5 CHU Trousseau [Tours]
6 Hôpital Beaujon
7 CHU Pontchaillou [Rennes]
8 CHU Valenciennes
9 CHU Toulouse [Toulouse]
10 CHU Cochin [AP-HP]
11 HEGP - Hôpital Européen Georges Pompidou [APHP]
12 CHU de Lille
13 Hôpital Bicêtre
14 TIMONE - Hôpital de la Timone [CHU - APHM]
15 CHU Angers - Centre Hospitalier Universitaire d'Angers
16 Service de Gastro-entérologie [Avicenne]
17 Hôpital de la source
18 CHU Lyon
19 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
20 Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France
21 CHU Estaing [Clermont-Ferrand]
22 Hôpital Haut-Lévêque
23 Hôpital Côte de Nacre [CHU Caen]
24 Clinique Privée Saint Jean Languedoc
25 CHU Amiens-Picardie
26 Hôpital Duchenne
27 Polyclinique Francheville
28 Centre Catherine de Sienne
29 Polyclinique Bordeaux Nord Aquitaine
30 CHU Albert Michallon
31 CH du Haut Anjou (Château-Gontier)
32 CH Annecy Genevois
33 Groupe hospitalier Pitié- Salpêtrière, AP-HP
34 Centre Hospitalier du pays de Morlaix
35 Hôpital Saint-Joseph, Assistance Publique-Hôpitaux de Paris
36 Cabinet privé des Dr Geslin Provost (Vannes)
37 CHU Rouen
38 CHU Dupuytren
39 CHU Dijon
40 Clinique Mutualiste de l'Estuaire (Saint Nazaire)
41 Hospices Civils de Beaune [Centre hospitalier de Beaune]
42 Centre de radiothérapie et d'oncologie médicale privée (Béziers)
43 UNICANCER - Centre Antoine Lacassagne [Nice]
Abstract : Background Diagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC. Patients and methods All patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded. Results 253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0–1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20–100). Median overall survival was 15.6 (13.6–17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE > 2 upper limit of normal [ULN]; HR = 3.2), CgA > 2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72). Conclusions We report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.
Keywords : Gastrointestinal cancer Ki67 index Neuroendocrine carcinoma Prognosis Treatment
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01609152
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : mardi 3 octobre 2017 - 11:51:28
Dernière modification le : lundi 4 mars 2019 - 11:36:08

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UNIV-BOURGOGNE | LNC-EPICAD | FNCLCC | IGR | UNIV-PARIS7 | HCL | UNAM | UNIV-PARIS13 | USPC | UNIV-PARIS-SACLAY | LNC-UMR866

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T. Walter, T Tougeron, E. Baudin, K. Le Malicot, T. Lecomte, et al.. Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort. European Journal of Cancer, Elsevier, 2017, 79, pp.158 - 165. 〈http://www.sciencedirect.com/science/article/pii/S0959804917308869?via%3Dihub〉. 〈10.1016/j.ejca.2017.04.009〉. 〈hal-01609152〉

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