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

T. Walter (1) , T Tougeron (2) , Emmanuel 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)

1 HCL - Hospices Civils de Lyon
2 CHU de Poitiers - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
3 IGR - Institut Gustave Roussy
4 Fédération Francophone de la Cancérologie Digestive, FFCD
5 CHU Trousseau [Tours]
6 Hôpital Beaujon
7 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
8 Centre hospitalier [Valenciennes, Nord]
9 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
10 Hôpital 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 universitaire Robert Debré [Reims]
21 CHU Estaing [Clermont-Ferrand]
22 Hôpital Haut-Lévêque
23 Hôpital Côte de Nacre [CHU Caen]
24 CSJL - Clinique Saint-Jean Languedoc [Toulouse]
25 CHU Amiens-Picardie
26 Hôpital Duchenne
27 Polyclinique Francheville
28 CCS - Centre Catherine-de-Sienne [Nantes]
29 PBNA - Polyclinique Bordeaux Nord Aquitaine
30 Hôpital Michallon
31 CH du Haut Anjou (Château-Gontier)
32 CH Annecy Genevois
33 CHU 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/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]

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.

Mots clés: Gastrointestinal cancer; Ki67 index; Neuroendocrine carcinoma; Prognosis; Treatment

Domaines: Cancer

T. Walter, T Tougeron, Emmanuel 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, 2017, 79, pp.158 - 165. ⟨10.1016/j.ejca.2017.04.009⟩. ⟨hal-01609152⟩