P Lecomte1, C Binquet2,3,4, M Le Bras5, A Tabarin6, C Cardot-Bauters7, F Borson-Chazot8,9, C Lombard-Bohas10, E Baudin11, B Delemer12, M Klein13, B Vergès14, T Aparicio15, E Cosson16, A Beckers17, Ph Caron18, O Chabre19, Ph Chanson20, H Du Boullay21, I Guilhem22, P Niccoli23, V Rohmer24, J Guigay25, C Vulpoi26, J Y Scoazec27, P Goudet28. 1. Service d'Endocrinologie, Nutrition, Diabétologie END, Centre Hospitalier Regional Universitaire de Tours, Tours, France. pierre.lecomte47@orange.fr. 2. CIC, module épidémiologie clinique/essais cliniques, Centre Hospitalier Universitaire de Dijon, Dijon, France. 3. INSERM U866, Universite de Bourgogne, Dijon, France. 4. UMR866, équipe EPICAD, Université de Bourgogne-Franche Comté, Dijon, France. 5. Clinique d'Endocrinologie, Centre Hospitalier Universitaire de Nantes, Nantes, France. 6. Service d'Endocrinologie, Hôpital de Haut Lévêque, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. 7. Service de Médecine Interne et Endocrinologie, Centre Hospitalier Régional et Universitaire de Lille, Lille, France. 8. Groupement Hospitalier Est, Fédération d'Endocrinologie, Centre Hospitalier Universitaire de Lyon, Lyon, France. 9. Fédération Hospitalo Universitaire d'Endocrinologie, Université Lyon 1, Lyon, France. 10. Service d'Oncologie Médicale, Hôpital Edouard Herriot, Lyon, France. 11. Département de Médecine Nucléaire et d'Oncologie Endocrinienne, Gustave Roussy, Villejuif, France. 12. Département d'Endocrinologie, Centre Hospitalier Universitaire de Reims, Reims, France. 13. Service d'Endocrinologie, Centre Hospitalier Universitaire de Nancy, Vandœuvre-lès-Nancy, France. 14. Service d'Endocrinologie, Centre Hospitalier Universitaire de Dijon, Dijon, France. 15. Service de Gastro-Entérologie et Cancérologie Digestive, Hopital Avicenne, Bobigny, France. 16. Polyclinique d'Endocrinologie, Diabétologie, Métabolisme et Nutrition, Hopital Jean Verdier, Bondy, France. 17. Service d'Endocrinologie, Centre hospitalier universitaire de Liege, Liège, Belgium. 18. Service d'Endocrinologie et Maladies Métaboliques, Centre Hospitalier Universitaire de Toulouse, Toulouse, France. 19. Service d'Endocrinologie, Centre Hospitalier Universitaire de Grenoble, Grenoble, France. 20. Service d'Endocrinologie et des maladies de la reproduction, Centre Hospitalier Universitaire du Kremlin-Bicêtre, Le Kremlin-Bicêtre, France. 21. Service d'Endocrinologie, Centre Hospitalier Metropole Savoie, Chambéry, France. 22. Service d'Endocrinologie, Diabétologie, Nutrition, Centre Hospitalier Universitaire de Rennes, Rennes, France. 23. Département d'Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France. 24. Département d'Endocrinolgie, Centre Hospitalier Universitaire d'Angers, Angers, France. 25. Center anti Cancer A. Lacassagne of Nice, Nice, France. 26. Service d'Endocrinologie, Université de Médecine et Pharmacie "Grigore T.Popa", Iaşi, Romania. 27. Service de Pathologie Morphologique et Moléculaire, Gustave Roussy, Villejuif, France. 28. Service de Chirurgie Digestive, Cancérologique et Endocrinienne, Centre Hospitalier Universitaire de Dijon, Dijon, France.
Abstract
OBJECTIVE: To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death. br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis. METHODS: The 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5-59.6] years by the Groupe d'étude des Tumeurs Endocrines was analyzed using time-to-event techniques. RESULTS: br-NETs were found in 51 patients (4.8%, [95% CI 3.6-6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28-66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02-5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10-4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths. CONCLUSIONS: Around 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.
OBJECTIVE: To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death. br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis. METHODS: The 1023-patient series of symptomatic MEN1patients followed up in a median of 48.7 [35.5-59.6] years by the Groupe d'étude des Tumeurs Endocrines was analyzed using time-to-event techniques. RESULTS: br-NETs were found in 51 patients (4.8%, [95% CI 3.6-6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28-66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02-5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10-4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths. CONCLUSIONS: Around 5% of MEN1patients develop br-NETs. br-NETs do not decrease overall survival in MEN1patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.
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