Jason B. Liu, MD, MS
Fellow
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Pancreatic neuroendocrine tumors (PanNET) are a cause of mortality in MEN1 patients yet much of their natural history and metastatic potential are unknown. We aimed to characterize the long-term outcomes of patients with MEN1-related PanNET treated at a high-volume center in the US.
Methods:
Longitudinal, retrospective cohort study of patients with MEN1 and imageable functional and nonfunctional (NF) PanNET (1990-2021). Liver metastasis-free survival (LMFS) and overall survival were analyzed with the Kaplan-Meier method.
Results:
Of 138 MEN1 patients, 81 (58.7%) were diagnosed with PanNET (28 functional, 53 non-functional) and followed for median 11 years (IQR 6-17). Multifocality was present at diagnosis in 17 (21%). Surgery was performed in 24 (85.7%) patients with functional PanNET (mean dominant tumor size 1.9±1.2 cm) and 18 (34%) with NF-PanNET (mean tumor size 3.3±1.7 cm). Overall, liver metastasis occurred in 20 (24.7%) and 18 (22.2%) died. Compared to patients with NF-PanNET, those with functional PanNET developed liver metastasis more often (53.6% vs. 9.4%, p< 0.001), although estimated 10-year LMFS (81.4% vs. 91.6%, p=0.11) and overall survival (87.3% vs. 93.9%, p=0.66) were no different.
Of 53 patients with NF-PanNET, 35 (66%) underwent imaging surveillance (mean tumor size 1.2±0.6 cm). The mean growth rate over median 9 years (4-14) was estimated using linear mixed modeling to be 0.04±0.02 cm/year, a statistically significant growth over time (p=0.01). Surgery was eventually required in 7 (20%) patients at a median of 6 years (3.5-7); 5 due to tumor growth and 2 to new regional nodal disease. The likelihood of liver metastasis in patients with NF-PanNET who had initial surgery was equivalent to those who underwent surveillance (11.1% vs. 8.6%, p=1.0), occurring at median 8 years (5-11).
Conclusions:
Liver metastasis occurred in 25% of patients with MEN1-related PanNET and was 6-times more likely in those with functional tumors. The growth rate of nonfunctional PanNET was slow but liver or nodal metastasis developed in 5 patients. The variable metastatic potential of MEN1-related PanNET underscores the need for multidisciplinary management and lifelong follow up.