Impact of Vitamin D on the Clinical Outcome of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: Report on a Series from a Single Institute

Abstract

Background/Aims: Vitamin D deficiency is hypothesized to represent a risk factor in several neoplasms. The aim of this study was to determine whether serum 25-hydroxyvitamin D (25-OHvitD) deficiency represents a risk factor for neuroendocrine neoplasms (NENs) and can be associated with overall survival (OS) and progression-free survival (PFS). Methods: From 2010 to 2015, 138 patients with gastro- entero-pancreatic NENs (61 females; median age, 63 years) were included in the study. Serum 25-OHvitD levels, which were measured at baseline, were defined as deficient if ≤20 ng/mL. In such cases, 25-OHvitD supplementation was administered to the patients. The possible associations between 25-OHvitD levels and disease grading, staging, overall OS, and PFS were considered. Furthermore, the possible association between 25-OHvitD supplementation and PFS or OS was evaluated by Cox proportional hazards regression. Results: Median 25-OHvitD levels were 12.9 ng/mL (range 2-32); in detail, 94 patients (68%) had ≤20 ng/mL, with 46 cases (33%) having ≤10 ng/mL. An inverse correlation was observed between 25-OHvitD levels and OS (p = 0.03, rs = -0.18) and PFS (p = 0.01, rs = -0.22). At Cox proportional hazards regression, mortality was not related to 25-OHvitD levels; however, there was an association between 25-OHvitD supplementation and OS (p < 0.002). Conclusions: Vitamin D deficiency is highly prevalent among NEN patients. 25-OHvitD supplementation potentially plays an important role in the correction of 25-OHvitD values, and has an influence on the clinical outcome. However, further studies are needed to confirm this observation.

Bone Metabolism and Vitamin D Implication in Gastroenteropancreatic Neuroendocrine Tumors

“…In a recent study, Massironi et al found vitamin D deficiency in 33% and insufficiency in 68% of cases in an Italian population of 138 GEP-NET patients [22]. No differences in vitamin D levels were observed between pNET and other tumor sites, as well as no difference when considering tumor grades and staging [22]. Similarly, a more recent study by Robbins et al evaluating 183 patients with GEP-NET showed a prevalence of vitamin D deficiency/insufficiency in 63% of cases [30].…”

“…The influence of medical treatment with SSAs on vitamin D levels is controversial. In the Italian study, it was highlighted that there were lower vitamin D levels in GEP-NET patients treated with SSAs compared to those not treated by SSAs [22]. On the contrary, the other two studies did not find any differences in vitamin D levels between NET patients with or without SSA treatment [29,30].…”

“…Lind et al found a high prevalence of low BMD (82% of cases) and of vitamin D and B12 deficiency (74% and 32% of cases, respectively) in a cohort of 50 patients with small intestinal NET [21]. In a recent study, Massironi et al found vitamin D deficiency in 33% and insufficiency in 68% of cases in an Italian population of 138 GEP-NET patients [22]. No differences in vitamin D levels were observed between pNET and other tumor sites, as well as no difference when considering tumor grades and staging [22].…”

“…As mentioned above, GEP-NET patients have an increased risk of malnutrition due to tumor hormonal secretion and treatments, which affect the absorption of nutrients, including vitamin D [19]. Vitamin D deficiency, defined as 25(OH)D levels ≤20 ng/mL (≤50 nmol/L) and insufficiency, defined as 25(OH)D levels ranging from 20 to 29.9 ng/mL (52-72 nmol/L) [105], is described in between 46% and 81% of patients with NET (Table 1) [21,22,29,30]. This large range observed in the prevalence of vitamin D deficiency or insufficiency could be due to several factors, including latitude of the country, seasons and different assays used for the measurements of vitamin D levels [106,107].…”

“…It has been demonstrated that NET patients have a greater clinical burden of disease than matched control subjects, with increased risk of cardiovascular, hepatic, and gastrointestinal diseases, as well as osteopenia and osteoporosis [18]. Moreover, the tumor itself and the systemic therapy may have an impact on patients' nutritional status [19,20], leading to a deficiency of different vitamins, including vitamin D [21,22]. It is well demonstrated that vitamin D plays a key role in the process of bone formation [23].…”