Survival of Patients With Gastroenteropancreatic Neuroendocrine Tumors and Diabetes Mellitus.

OBJECTIVES: Diabetes mellitus (DM) is associated with an increased risk of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but the association between DM and GEP-NET survival is unknown. We evaluated disease characteristics and survival in individuals with DM and GEP-NETs. METHODS: Using the Surveillance, Epidemiology, and End Results registry linked to Medicare (SEER-Medicare) claims database, we examined sociodemographics, GEP-NET characteristics, and treatment in patients with and without DM before GEP-NET diagnosis. We compared survival using univariate and multivariate analyses. RESULTS: We identified 1858 individuals with GEP-NETs: 478 (25.7%) with DM and 1380 (74.3%) without. Significant differences in race (P = 0.002) were found between the DM and non-DM groups. Compared with individuals without DM, those with DM had more gastric (9.7% vs 14.9%), duodenal (6.5% vs 10.0%), and pancreatic (17.0% vs 21.8%), and less jejunal/ileal (18.1% vs 12.8%) NETs (P < 0.0001). Patients with DM had earlier stages (stage I, 37.0%; stage IV, 30.8%) than those without (stage I, 30.6%; stage IV, 36.4%; P = 0.0012). We found no difference in survival (multivariate hazard ratio, 0.97; 95% confidence interval, 0.76-1.23) between groups. CONCLUSIONS: Among patients with and without DM before GEP-NET diagnosis, we found differences in tumor location and stage, but not survival.

Association between somatostatin analogues and diabetes mellitus in gastroenteropancreatic neuroendocrine tumor patients: A Surveillance, Epidemiology, and End Results-Medicare analysis of 5235 patients.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasingly common malignancies and tend to have favorable long-term prognoses. Somatostatin analogues (SSA) are a first-line treatment for many NETs. Short-term experiments suggest an association between SSAs and hyperglycemia. However, it is unknown whether there is a relationship between SSAs and clinically significant hyperglycemia causing development of diabetes mellitus (DM), a chronic condition with significant morbidity and mortality. AIM: In this study, we aimed to compare risk of developing DM in patients treated with SSA vs no SSA treatment. METHODS AND RESULTS: Using the Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare claims (1991-2016), we identified patients age 65+ with no prior DM diagnosis and a GEP-NET in the stomach, small intestine, appendix, colon, rectum, or pancreas. We used χ2 tests to compare SSA-treated and SSA-untreated patients and multivariable Cox regression to assess risk factors for developing DM. Among 8464 GEP-NET patients, 5235 patients had no prior DM and were included for analysis. Of these, 784 (15%) patients received SSAs. In multivariable analysis, the hazard ratio of developing DM with SSA treatment was 1.19, which was not statistically significant (95% CI 0.95-1.49). Significant risk factors for DM included black race, Hispanic ethnicity, prior pancreatic surgery, prior chemotherapy, tumor size >2 cm, pancreas tumors, and higher Charlson scores. CONCLUSION: DM was very common in GEP-NET patients, affecting 53% of our cohort. Despite prior studies suggesting an association between SSAs and hyperglycemia, our analysis found similar risk of DM in SSA-treated and SSA-untreated GEP-NET patients. Further studies are needed to better understand this relationship. As NET patients have increasingly prolonged survival, it is crucial to identify chronic conditions such as DM that these patients may be at elevated risk for.

Effect of treatment center volume on outcomes in gastroenteropancreatic neuroendocrine tumor patients.

BACKGROUND: Medical centers with varying levels of expertise treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which are relatively rare tumors. This study assesses the impact of center volume on GEP-NET treatment outcomes. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare claims data. The data includes patients diagnosed between 1995 and 2010 who had no health maintenance organization (HMO) coverage, participated in Medicare parts A and B, were older than 65 at diagnosis, had tumor differentiation information, and had no secondary cancer. We identified medical centers at which patients received GEP-NET treatment (surgery, chemotherapy, somatostatin analogues, or radiation therapy) using Medicare claims data. Center volume was divided into 3 tiers - low, medium, and high - based on the number of unique GEP-NET patients treated by a medical center over 2 years. We used Kaplan-Meier curves and Cox regression to assess the association between volume and disease-specific survival. RESULTS: We identified 899 GEP-NET patients, of whom 37, 45, and 18% received treatment at low, medium volume, and high-volume centers, respectively. Median disease-specific survival for patients at low and medium tiers were 1.4 years and 5.3 years, respectively, but was not reached for patients at high volume centers. Results showed that patients treated at high volume centers had better survival than those treated in low volume centers (HR: 0.63, 95% CI: 0.4-0.9), but showed no difference in outcomes between medium and high-volume centers. CONCLUSIONS: Our results suggest that for these increasingly common tumors, referral to a tertiary care center may be indicated. Physicians caring for GEP-NET patients should consider early referral to high volume centers.

Predictors of Recurrence and Survival in Patients With Surgically Resected Pancreatic Neuroendocrine Tumors.

OBJECTIVE: Given the lack of consensus on surveillance guidelines after pancreatic neuroendocrine tumor (PanNET) resection, we assessed outcomes in a large cohort of patients with nonmetastatic, surgically resected PanNETs. METHODS: Data of patients with PanNETs resected between 1990 and 2017 were retrospectively collected using databases at 3 academic institutions. The National Death Index was queried to determine vital status. Kaplan-Meier analysis was used to estimate recurrence-free survival (RFS) and disease-specific survival (DSS) rates. Variables associated with recurrence and disease-related death were identified through Cox multivariate analyses. RESULTS: Of 307 patients with PanNET who underwent resection, recurrence occurred in 79 (26%) of patients. For stage I and II disease, 5-year RFS rates were 90% and 43%, whereas 5-year DSS rates were 98% and 86% (P < 0.0001 and P = 0.0038, respectively). For grades 1, 2, and 3 disease, 5-year RFS rates were 87%, 49%, and 18%, and 5-year DSS rates were 98%, 89%, and 51% (P < 0.0001 for both). Stage II, grade 2, and grade 3 disease were each associated with increased recurrence and disease-specific death. CONCLUSIONS: Stage and grade are important prognostic factors that should be utilized to tailor postsurgical surveillance after curative resection of PanNET.

Incidence Trends of Gastroenteropancreatic Neuroendocrine Tumors in the United States.

BACKGROUND & AIMS: Although multiple studies have reported an increasing incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) over the past decades, there are limited national data on recent trends. Using a population-based registry, we evaluated GEP-NET incidence trends in the United States population from 1975 through 2012, based on age, calendar year at diagnosis, and year of birth. METHODS: GEP-NET cases from 1975 through 2012 were identified from the most recent version of the Surveillance, Epidemiology, and End Results registry using histologic and site codes. We calculated overall annual incidence, age-adjusted incidence (number of cases per 100,000), annual percent change (APC), and average APC by 5-year age intervals. We also evaluated the incidence rates by age, period, and birth year cohorts. RESULTS: We identified 22,744 patients with GEP-NETs. In adults 25-39 years old, GEP-NET incidence rates decreased from the mid-1970s to the early 1980s, then increased until 2012. In adults ages 40 years and older or young adults ages 15-24 years, incidence rates generally increased continuously from 1975 through 2012. Adults ages 40-69 years had the most rapid increases in average APC (approximately 4%-6% per year). Overall incidence rates were highest in adults 70-84 years old. Since the inception of the Surveillance, Epidemiology, and End Results registry, GEP-NET incidence has increased in consecutive birth cohorts. CONCLUSION: The incidence of GEP-NET continues to increase-particularly in older adults. More recent generations have had higher GEP-NET incidence rates than more distant generations.