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

• DOI: 10.1016/j.ejca.2017.04.009
• Publication Date: 2017-05-11T22:02:12Z
• Authors: T. Walter; D. Tougeron; E. Baudin; K. Le Malicot; T. Lecomte; D. Malka; O. Hentic; S. Manfredi; I. Bonnet; R. Guimbaud; R. Coriat; C. Lepère; C. Desauw; A. Thirot-Bidault; L. Dahan; G. Roquin; T. Aparicio; J.-L. Legoux; C. Lombard-Bohas; J.-Y. Scoazec; C. Lepage; G. Cadiot; Laetitia Stephanie; Ivan Borbath; Castex; Caroline Petorin; Eric Terrebonne; Karine Bouhier-Le...; Etienne Suc; Vincent Hautefeuille; Vincent Bourgeois; Laurent Cany; François Dewaele; Patricia Niccoli; Jean-François Seitz; Cédric Lecaille; Christine Rebischung; Valérie Rossi; Mathieu Baconnier; Olivier Dubreuil; Marc Ferec; Gael Deplanque; Guillaume Geslin; Isabelle Wanicki ...; Sandrine Lavau Denes; Laurent Bedenne; Catherine Ligeza; Eric Maringe; Anne-Laure Ran-Royo; Joel Guigay; Philippe Rougier
• Keywords: Male; 0301 basic medicine; 610; [SDV.CAN]Life Sciences [q-bio]/Cancer; Carboplatin; Cohort Studies; Gastrointestinal cancer; 03 medical and health sciences; [SDV.CAN] Life Sciences [q-bio]/Cancer; 616; Antineoplastic Combined Chemotherapy Protocols; Humans; Neoplasm Metastasis; Aged; Etoposide; Gastrointestinal Neoplasms; Ki67 index; Prognosis; Carcinoma, Neuroendocrine; 3. Good health; Treatment; Pancreatic Neoplasms; Cell Transformation, Neoplastic; Neuroendocrine carcinoma; Female; Cisplatin

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.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.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).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.