Medard F M van den Broek1, Joanne M de Laat1,2, Rachel S van Leeuwaarde1, Annenienke C van de Ven3, Wouter W de Herder4, Olaf M Dekkers5,6, Madeleine L Drent7, Michiel N Kerstens8, Peter H Bisschop9, Bas Havekes10, Wenzel M Hackeng11, Lodewijk A A Brosens11, Menno R Vriens12, Wieneke A Buikhuisen13, Gerlof D Valk1. 1. Department of Endocrine Oncology, University Medical Center Utrecht, GA Utrecht, The Netherlands. 2. Department of Internal Medicine, University Medical Center Utrecht, GA Utrecht, The Netherlands. 3. Department of Endocrinology, Radboud University Medical Center, HB Nijmegen, The Netherlands. 4. Department of Internal Medicine, Erasmus Medical Center, CA Rotterdam, The Netherlands. 5. Department of Endocrinology and Metabolism, Leiden University Medical Center, RC Leiden, The Netherlands. 6. Department of Clinical Epidemiology, Leiden University Medical Center, RC Leiden, The Netherlands. 7. Department of Internal Medicine, Section of Endocrinology, Amsterdam UMC, location VU University Medical Center, MB Amsterdam, The Netherlands. 8. Department of Endocrinology, University Medical Center Groningen, University of Groningen, RB Groningen, The Netherlands. 9. Department of Endocrinology and Metabolism, Amsterdam UMC, location Academic Medical Center, DD Amsterdam, The Netherlands. 10. Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, AZ Maastricht, The Netherlands. 11. Department of Pathology, University Medical Center Utrecht, GA Utrecht, The Netherlands. 12. Department of Endocrine Surgical Oncology, University Medical Center Utrecht, GA Utrecht, The Netherlands. 13. Department of Thoracic Oncology, The Netherlands Cancer Institute, BE Amsterdam, The Netherlands.
Abstract
INTRODUCTION: Multiple endocrine neoplasia type 1 (MEN1)-related neuroendocrine tumors (NETs) of the lung are mostly indolent, with a good prognosis. Nevertheless, cases of aggressive lung NET do occur, and therefore the management of individual patients is challenging. AIM: To assess tumor growth and the survival of patients with MEN1-related lung NETs at long-term follow-up. METHODS: The population-based Dutch MEN1 Study Group database (n = 446) was used to identify lung NETs by histopathological and radiological examinations. Tumor diameter was assessed. Linear mixed models and the Kaplan-Meier method were used for analyzing tumor growth and survival. Molecular analyses were performed on a lung NET showing particularly aggressive behavior. RESULTS: In 102 patients (22.9% of the total MEN1 cohort), 164 lesions suspected of lung NETs were identified and followed for a median of 6.6 years. Tumor diameter increased 6.0% per year. The overall 15-year survival rate was 78.0% (95% confidence interval: 64.6-94.2%) without lung NET-related death. No prognostic factors for tumor growth or survival could be identified. A somatic c.3127A > G (p.Met1043Val) PIK3CA driver mutation was found in a case of rapid growing lung NET after 6 years of indolent disease, presumably explaining the sudden change in course. CONCLUSION: MEN1-related lung NETs are slow growing and have a good prognosis. No accurate risk factors for tumor growth could be identified. Lung NET screening should therefore be based on well-informed, shared decision-making, balancing between the low absolute risk of an aggressive tumor in individuals and the potential harms of frequent thoracic imaging.
INTRODUCTION:Multiple endocrine neoplasia type 1 (MEN1)-related neuroendocrine tumors (NETs) of the lung are mostly indolent, with a good prognosis. Nevertheless, cases of aggressive lung NET do occur, and therefore the management of individual patients is challenging. AIM: To assess tumor growth and the survival of patients with MEN1-related lung NETs at long-term follow-up. METHODS: The population-based Dutch MEN1 Study Group database (n = 446) was used to identify lung NETs by histopathological and radiological examinations. Tumor diameter was assessed. Linear mixed models and the Kaplan-Meier method were used for analyzing tumor growth and survival. Molecular analyses were performed on a lung NET showing particularly aggressive behavior. RESULTS: In 102 patients (22.9% of the total MEN1 cohort), 164 lesions suspected of lung NETs were identified and followed for a median of 6.6 years. Tumor diameter increased 6.0% per year. The overall 15-year survival rate was 78.0% (95% confidence interval: 64.6-94.2%) without lung NET-related death. No prognostic factors for tumor growth or survival could be identified. A somatic c.3127A > G (p.Met1043Val) PIK3CA driver mutation was found in a case of rapid growing lung NET after 6 years of indolent disease, presumably explaining the sudden change in course. CONCLUSION:MEN1-related lung NETs are slow growing and have a good prognosis. No accurate risk factors for tumor growth could be identified. Lung NET screening should therefore be based on well-informed, shared decision-making, balancing between the low absolute risk of an aggressive tumor in individuals and the potential harms of frequent thoracic imaging.
Authors: R M Ruggeri; E Benevento; F De Cicco; B Fazzalari; E Guadagno; I Hasballa; M G Tarsitano; A M Isidori; A Colao; A Faggiano Journal: J Endocrinol Invest Date: 2022-08-30 Impact factor: 5.467