Prognostic factors of metastatic neuroendocrine carcinoma under first-line treatment with platinum etoposide with a focus on NEC score and Rb expression: Results from the multicentre RBNEC study of the Groupe d'Etude des Tumeurs Endocrines (GTE) and the ENDOCAN-RENATEN network

Julien Hadoux (1) , Christina Kanaan (1) , Alice Durand , Segolene Hescot (2) , Vincent Hautefeuille (3) , Guillaume Cadiot (4) , Igor Tauveron (5) , Sandrine Laboureau (6) , Christine Do Cao (7) , Thomas Walter (8, 9, 10, 11) , Caroline Petorin (12) , Odile Blanchet (13) , Arnaud Jannin (14, 15) , Celine Gu (2) , Matthieu Faron (16, 17) , Emmanuelle Leteurtre (15, 18) , Marie-Christine Rousselet (6) , Juliette J. Zakeyh , Aude Marchal (19) , Denis Chatelain (3, 20) , Clément Beaulaton , Valerie Hervieu , Michel Ducreux , Jean-Yves Scoazec , Eric Baudin

1 IGR - Institut Gustave Roussy
2 Institut Curie [Paris]
3 CHU Amiens-Picardie
4 Hôpital Robert Debré
5 GReD - Génétique, Reproduction et Développement
6 CHU Angers - Centre Hospitalier Universitaire d'Angers
7 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
8 HCL - Hospices Civils de Lyon
9 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
10 UCBL - Université Claude Bernard Lyon 1
11 Hôpital Edouard Herriot [CHU - HCL]
12 Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand]
13 VIRO - Virologie UMR1161
14 LILLE - Endocrino - Service Endocrinologie, diabétologie, maladies métaboliques et nutrition
15 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
16 U1018 (Équipe 2) - Oncostat
17 CESP - Centre de recherche en épidémiologie et santé des populations
18 Institut de Pathologie [CHU Lille]
19 Hôpital universitaire Robert Debré [Reims]
20 CHIMERE - CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516

Introduction and aim: : Neuroendocrine carcinomas (NECs) are aggressive malignant diseases. Platinum-etoposide (PE) combination is the standard first-line treatment, whatever the primary location. The NEC score and also retinoblastoma protein (Rb) status have been suggested to be predictive/prognostic factors in NEC. The primary objective of our multicentric retrospective study was to evaluate the prognostic relevance of the NEC score and Rb status, assessed by immunohistochemistry in PE-treated patients with metastatic NEC. Methods: Seven centres participated. The inclusion criteria were NEC, whatever the primary site, metastatic stage, first-line treatment with PE and tissue samples available. Rb status was determined centrally. Results: We report multicentric data from 185 metastatic patients (37% women, median age 63). There were 108 small-cell NECs (SCNECs, 58.4%), 50 large-cell NECs (LCNECs, 27%) and 27 not otherwise specified NECs (nosNECs, 14.6%). The primary sites were the thorax (37%), gastroenteropancreatic sites (38%), unknown (15%) and other (9%). The mean Ki-67 index was 76% (range 20-100). Rb status was interpretable in 122 cases. Rb expression was lost in 74% of the cases: 84% of SCNEC vs. 60% and 63% of LCNEC and nosNEC, respectively (p = 0.016). Objective response was seen in 70% of SCNEC, 45% of LCNEC and 48% of nosNEC (p < 0.001) and in 62% of Rb-negative tumours vs. 46% of Rb-positive tumours (p = 0.3). There was no difference in median progression-free survival or overall survival (OS) as per Rb status. Age, NEC score and response to chemotherapy were the main factors associated with OS in our cohort. Conclusion: In our series, Rb status had no prognostic impact in PE-treated metastatic patients with NEC, whereas age, NEC score and response to chemotherapy were the main factors associated with OS 2021 Elsevier Ltd. All rights reserved.

Domaines: Sciences du Vivant [q-bio]

Julien Hadoux, Christina Kanaan, Alice Durand, Segolene Hescot, Vincent Hautefeuille, et al.. Prognostic factors of metastatic neuroendocrine carcinoma under first-line treatment with platinum etoposide with a focus on NEC score and Rb expression: Results from the multicentre RBNEC study of the Groupe d'Etude des Tumeurs Endocrines (GTE) and the ENDOCAN-RENATEN network. European journal of cancer, 2021, 152, pp.100-115. ⟨10.1016/j.ejca.2021.04.030⟩. ⟨hal-03600262⟩