Medard F M van den Broek1, Sonja Levy2, Wieneke A Buikhuisen3, Kim Dijke2, Koen J Hartemink4, Rachel S van Leeuwaarde1, Menno R Vriens5, Margot E T Tesselaar2, Gerlof D Valk6. 1. Department of Endocrine Oncology, University Medical Center Utrecht, 3508 GA Utrecht, the Netherlands. 2. Department of Medical Oncology, Netherlands Cancer Institute, 1006 BE Amsterdam, the Netherlands. 3. Department of Thoracic Oncology, Netherlands Cancer Institute, 1006 BE Amsterdam, the Netherlands. 4. Department of Surgical Oncology, Netherlands Cancer Institute, 1006 BE Amsterdam, the Netherlands. 5. Department of Endocrine Surgical Oncology, University Medical Center Utrecht, 3508 GA Utrecht, the Netherlands. 6. Department of Endocrine Oncology, University Medical Center Utrecht, 3508 GA Utrecht, the Netherlands. Electronic address: g.d.valk@umcutrecht.nl.
Abstract
BACKGROUND: Until now, well-differentiated bronchopulmonary neuroendocrine tumors (bpNET) occurring either sporadically (sp-bpNET) or in the context of Multiple Endocrine Neoplasia Type 1 (MEN1) and Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) are regarded as similar entities. However, in contrast to sp-bpNET: MEN1-related and DIPNECH-related bpNET rarely metastasize or lead to bpNET-related death. AIMS: To describe and compare the course of the disease of sp-bpNET, DIPNECH- and MEN1-related bpNET. METHODS: All patients with histologically confirmed MEN1-related bpNET from the DutchMEN Study Group database (1990-2017), patients with resected sp-bpNET and DIPNECH patients referred to a Dutch ENETS center between 2000-2018 were included. Fisher's exact test was used for comparison between groups. The primary endpoint was disease-specific mortality (DSM). Kaplan-Meier and logrank test were used to compare survival. Cox regression was used to identify risk factors for DSM in the sp-bpNET subgroup. RESULTS: We included 112 sp-bpNET, 29 MEN1 and 27 DIPNECH patients. Tumor classification was similar across subgroups. Twenty (18%) patients with sp-bpNET died because of bpNET, compared to none in the MEN1 group and DIPNECH group. Median disease-specific survival was 12.3 (CI 6.3-18.3) years for patients with sp-bpNET, and not estimable for the other subgroups (p<0.001). Differences in baseline characteristics did not explain worse survival in sp-bpNET. Tumor classification and age at diagnosis were independent risk factors for DSM in sp-bpNET. CONCLUSION: Patients with sp-bpNET have a significantly higher DSM compared to MEN1 or DIPNECH-related bpNET, unexplained by differences in baseline characteristics. This implies that not all bpNET are similar entities.
BACKGROUND: Until now, well-differentiated bronchopulmonary neuroendocrine tumors (bpNET) occurring either sporadically (sp-bpNET) or in the context of Multiple Endocrine Neoplasia Type 1 (MEN1) and Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) are regarded as similar entities. However, in contrast to sp-bpNET: MEN1-related and DIPNECH-related bpNET rarely metastasize or lead to bpNET-related death. AIMS: To describe and compare the course of the disease of sp-bpNET, DIPNECH- and MEN1-related bpNET. METHODS: All patients with histologically confirmed MEN1-related bpNET from the DutchMEN Study Group database (1990-2017), patients with resected sp-bpNET and DIPNECHpatients referred to a Dutch ENETS center between 2000-2018 were included. Fisher's exact test was used for comparison between groups. The primary endpoint was disease-specific mortality (DSM). Kaplan-Meier and logrank test were used to compare survival. Cox regression was used to identify risk factors for DSM in the sp-bpNET subgroup. RESULTS: We included 112 sp-bpNET, 29 MEN1 and 27 DIPNECHpatients. Tumor classification was similar across subgroups. Twenty (18%) patients with sp-bpNET died because of bpNET, compared to none in the MEN1 group and DIPNECH group. Median disease-specific survival was 12.3 (CI 6.3-18.3) years for patients with sp-bpNET, and not estimable for the other subgroups (p<0.001). Differences in baseline characteristics did not explain worse survival in sp-bpNET. Tumor classification and age at diagnosis were independent risk factors for DSM in sp-bpNET. CONCLUSION:Patients with sp-bpNET have a significantly higher DSM compared to MEN1 or DIPNECH-related bpNET, unexplained by differences in baseline characteristics. This implies that not all bpNET are similar entities.