Julien Hadoux1, Christina Kanaan2, Alice Durand3, Ségolène Hescot4, Vincent Hautefeuille5, Guillaume Cadiot6, Igor Tauveron7, Sandrine Laboureau8, Christine Do Cao9, Thomas Walter3, Caroline Petorin10, Odile Blanchet11, Arnaud Jannin9, Céline Gu12, Matthieu Faron13, Emmanuelle Leteurtre14, Marie-Christine Rousselet15, Juliette J Zakeyh16, Aude Marchal17, Denis Chatelain18, Clément Beaulaton12, Valérie Hervieu19, Michel Ducreux20, Jean-Yves Scoazec21, Eric Baudin22. 1. Oncologie endocrinienne, Département d'imagerie, Gustave Roussy, Villejuif, F-94805, France. Electronic address: Julien.hadoux@gustaveroussy.fr. 2. Service de Pathologie, Département de biologie et pathologie médicale, Gustave Roussy, Villejuif, F-94805, France. 3. Service d'oncologie, ENETS Centre of Excellence, Hospices Civils de Lyon et université de Lyon, Lyon, France. 4. Département d'oncologie, Institut Curie, Paris, F-75005, France. 5. Département d'hépato-gastro-entérologie, CHU d'Amiens, Amiens, France. 6. Département d'hépato-gastro-entérologie, CHU de Reims, Reims, France. 7. Service d'endocrinologie, diabétologie et maladies métaboliques, CHU Clermont-Ferrand, F-63003, Clermont-Ferrand, France; Laboratoire GReD, Université Clermont Auvergne, Clermont-Ferrand, F-63000, France. 8. Département d'Endocrinologie-Diabétologie-Nutrition, CHU d'Angers, 4 rue Larrey, Angers cedex 9, F-49933, France. 9. Département d'Endocrinologie, CHU de Lille, Lille, F-59000, France. 10. CHU Clermont-Ferrand, Service de Chirurgie Digestive et Hépatobiliaire, 1 rue Lucie et Raymond Aubrac, F-63003, Clermont-Ferrand, France. 11. CRB, CHU d'Angers, 4 rue Larrey, Angers cedex 9, F-49933, France. 12. Service d'anatomo-pathologie, Institut Curie, Paris, F-75005, France. 13. Département de chirurgie, Gustave Roussy, Villejuif, F-94805, France. 14. CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, Université de Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277, Lille, F-59000, France. 15. Département de pathologie, CHU d'Angers, 4 rue Larrey, Angers cedex 9, 49933, France. 16. Laboratoire d'Anatomie Pathologique, CHU Clermont-Ferrand, 1 rue Lucie et Raymond Aubrac, Clermont-Ferrand, F-63003, France. 17. Service d'anatomo-pathologie, CHU Reims, Reims, France. 18. Service d'anatomo-pathologie, CHU Amiens, Amiens, France. 19. Service d'anatomo-pathologie, ENETS Centre of Excellence, Hospices Civils de Lyon et université de Lyon, Lyon, France. 20. Service d'oncologie digestive, département de médecine, Gustave Roussy, Villejuif, F-94805, France; Faculté de Médecine, Université Paris Saclay, Le Kremlin-Bicêtre, F-94270, France. 21. Service de Pathologie, Département de biologie et pathologie médicale, Gustave Roussy, Villejuif, F-94805, France; Faculté de Médecine, Université Paris Saclay, Le Kremlin-Bicêtre, F-94270, France. 22. Oncologie endocrinienne, Département d'imagerie, Gustave Roussy, Villejuif, F-94805, France.
Abstract
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.
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.