The Management of Neuroendocrine Tumors of the Lung in MEN1: Results From the Dutch MEN1 Study Group

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 survival of patients with MEN1-related lung NETs at long-term follow-up. METHODS: The population based Dutch MEN1 Study Group (DMSG) 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 suspect of lung NETs were identified and followed for a median of 6.6 years. Tumor diameter increased 6.0% per year. The overall 15-yr survival was 78.0% (95% confidence interval (CI): 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 six 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