Metastatic Potential and Survival of Duodenal and Pancreatic Tumors in Multiple Endocrine Neoplasia Type 1

Sandrine Vinault (1, 2, 3) , Anne-Sophie Mariet (4, 1) , Maëlle Le Bras (5) , Eric Mirallié (6) , Catherine Cardot-Bauters (7) , Francois Pattou (8, 9) , Philippe Ruszniewski (10, 11) , Alain Sauvanet (12) , Philippe Chanson (13, 14) , Eric Baudin (15) , Dominique Elias (16) , Fabrice Menegaux (17) , Sebastien Gaujoux (17, 18) , François Borson-Chazot (19, 20) , Jean-Christophe Lifante (19, 21) , Philippe Caron (22) , Nicolas Carrere (23) , Antoine Tabarin (24) , Christophe Laurent (25) , Marc Klein (26) , Laurent Brunaud (27) , Patricia Niccoli (28) , Frédéric Sebag (29) , Guillaume Cadiot (30) , Reza Kianmanesh (30) , Maxime Luu (31) , Christine Binquet (1, 2, 3) , Pierre Goudet (32, 2, 3)

1 CIC-EC - Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques
2 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
3 UBFC - Université Bourgogne Franche-Comté [COMUE]
4 DIM - Service Biostatistiques et Informatique Médicale (CHU de Dijon)
5 Service d'Endocrinologie [Nantes]
6 Service de Chirurgie Digestive et Endocrinienne [Nantes]
7 LILLE - Endocrino - Service Endocrinologie, diabétologie, maladies métaboliques et nutrition
8 RTD - Recherche translationnelle sur le diabète - U 1190
9 Département de chirurgie endocrinienne [Lille]
10 Service de Gastroentérologie [Hôpital Beaujon]
11 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
12 Service de chirurgie hepato-pancreato-biliaire
13 Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique
14 Service d'Endocrinologie et des Maladies de la Reproduction [AP-HP Hôpital de Bicêtre]
15 Médecine nucléaire
16 IGR - Institut Gustave Roussy
17 CHU Pitié-Salpêtrière [AP-HP]
18 Chirurgie digestive, hépato-biliaire et endocrinienne [CHU Cochin]
19 HESPER - Health Service and Performance Research
20 Département Endocrinologie-Diabétologie-Maladies Nutritionnelles [Lyon-Sud]
21 Service de chirurgie digestive et endocrinienne (centre hospitalier Lyon Sud)
22 Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse]
23 Pôle Maladies de l'appareil digestif [CHU Toulouse]
24 Service d'endocrinologie, diabétologie et nutrition (CHU de Bordeaux)
25 Service de chirurgie hépatobiliaire et transplantation hépatique (CHU de Bordeaux)
26 Service d'Endocrinologie [CHRU Nancy]
27 Service de Chirurgie Digestive Hépatobiliaire et Endocrine [CHRU Nancy]
28 IPC - Institut Paoli-Calmettes
29 Service de chirurgie générale et endocrinienne
30 Hôpital universitaire Robert Debré [Reims]
31 PIT - Plateforme d’Investigation Technologique [Centre d’Investigation Clinique 1432 module Plurithématique - Dijon]
32 Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon)

Objective: To assess the distant metastatic potential of duodeno-pancreatic neuroendocrine tumors (DP-NETs) in patients with MEN1, according to functional status and size. Summary Background Data: DP-NETs, with their numerous lesions and endocrine secretion-related symptoms, continue to be a medical challenge; unfortunately they can become aggressive tumors associated with distant metastasis, shortening survival. The survival of patients with large nonfunctional DP-NETs is known to be poor, but the overall contribution of DP-NETs to metastatic spread is poorly known. Methods: The study population included patients with DP-NETs diagnosed after 1990 and followed in the MEN1 cohort of the Groupe d’étude des Tumeurs Endocrines (GTE). A multistate Markov piecewise constant intensities model was applied to separate the effects of prognostic factors on 1) metastasis, and 2) metastasis-free death or 3) death after appearance of metastases. Results: Among the 603 patients included, 39 had metastasis at diagnosis of DP-NET, 50 developed metastases during follow-up, and 69 died. The Markov model showed that Zollinger-Ellison-related tumors (regardless of tumor size and thymic tumor pejorative impact), large tumors over 2 cm, and age over 40 years were independently associated with an increased risk of metastases. Men, patients over 40 years old and patients with tumors larger than 2 cm, also had an increased risk of death once metastasis appeared. Conclusions: DP-NETs of 2 cm in size or more, regardless of the associated secretion, should be removed to prevent metastasis and increase survival. Surgery for gastrinoma remains debatable.

Mots clés: MEN1; metastases; neuroendocrine tumors; pancreas; survival

Domaines: Cancer; Hépatologie et Gastroentérologie

Sandrine Vinault, Anne-Sophie Mariet, Maëlle Le Bras, Eric Mirallié, Catherine Cardot-Bauters, et al.. Metastatic Potential and Survival of Duodenal and Pancreatic Tumors in Multiple Endocrine Neoplasia Type 1. Annals of Surgery, 2020, 272 (6), pp.1094-1101. ⟨10.1097/SLA.0000000000003162⟩. ⟨hal-01996226⟩