Vitamin D deficiency and tumor aggressiveness in gastroenteropancreatic neuroendocrine tumors

Purpose: Data regarding vitamin D status in patients affected by gastroenteropancreatic (GEP) neuroendocrine tumor (NET) are limited and often showing contrasting results. The aim of the study was to evaluate the incidence of vitamin D deficiency (<20 ng/mL) in GEP-NET patients and compare the 25-hydroxyvitamin D (25(OH)D) levels with clinicopathological parameters and clinical outcome. Methods: A retrospective cross-sectional study including 75 low grade (G1-G2) GEP-NETs and 123 healthy controls matched for age, sex, and body mass index, was performed. Results: GEP-NET patients had significantly lower 25(OH)D levels compared to controls (17.9 ± 7.8 vs 24.2 ± 7.7 ng/mL, p< 0.0001). Ileal NETs were associated to lower 25(OH)D levels compared to other primary tumor sites (p= 0.049) and small bowel resection posed a significant increased risk of severe vitamin D deficiency (OR = 2.81, 95% CI = 1.25–3.37, p= 0.018). No correlation with somatostatin analogs treatment was found. 25(OH)D levels were significantly lower in G2 compared to G1 GEP-NETs (15.6 ± 7.8 vs 19.9 ± 7.4 ng/mL, p= 0.016) and in patients with progressive disease (12.6 ± 5.7 ng/mL) compared to those with stable disease (mean 21.5 ± 8.2 ng/mL, p= 0.001) or tumor free after surgery (19.6 ± 7.3 ng/mL, p= 0.002). Patients with vitamin D deficiency and insufficiency had shorter progression-free survival compared to those with sufficiency (p= 0.014), whereas no correlation was found with disease-specific survival. Conclusions: Vitamin D deficiency is highly prevalent among GEP-NETs and could be associated with high tumor grade and disease progression. Therefore, the monitoring of 25(OH)D levels is relevant in these patients and vitamin D supplementation should be considered in the management of GEP-NET patients with vitamin D deficiency or insufficiency.