Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia

Abstract

The association of well-differentiated gastro-entero-pancreatic neuroendocrine neoplasia (WD GEP-NEN) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. However, whether obesity and metabolic syndrome risk factors are associated with GEP-NEN adverse outcomes and the poorer prognosis was unknown. The present study aimed to evaluate whether the presence of MetS or any of its individual components at WD GEP-NEN diagnosis influenced disease outcomes. A cohort of patients with non-localized WD GEP-NETs (n = 81), was classified according to the primary tumor site (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (3% ≤ Ki67 ≤ 20%) (WHO 2010)), disease extension (loco-regional or metastatic disease), presence of hormonal secretion syndrome (functioning or non-functioning), and evaluated for the presence of MetS criteria at diagnosis. MetS was present in 48 (59.3%) patients. During a median follow-up of 95.0 months (16.8–262.5), 18 patients died of the disease (10 with MetS vs. 8 without MetS). Overall survival (OS) at 5 years was 87.1% (95% CI: 73.6–94.0) for MetS and 90.9% (95% CI: 74.4–97.0) for non-Mets group, while OS at 10 years was 72.5% (95% CI: 55.3–84.0) for MetS, and 76.4% (95% CI: 53.6–89.0) for non-MetS group. Progression-Free Survival (PFS) at 5 years was 45.9% (95% CI: 30.8–59.8) for MetS and 40.0% (95% CI: 21.3–58.1) for non-MetS group, and PFS at 10 years was 18.1% (95% CI: 7.0–33.5) for MetS and 24.4% (95% CI: 9.0–43.7) for non-MetS group. Waist circumference (WC), a surrogate measure for visceral obesity, was associated with significantly shorter PFS (HR = 1.03; 95% CI: 1.01–1.06), although did not influence OS (HR = 1.01; 95% CI: 0.97–1.06). The findings of this study reinforce a potential link between visceral obesity and GEP-NEN and further suggest that obesity could influence disease prognosis.