Vitamin D Supplementation and Disease-Free Survival in Stage II Melanoma: A Randomized Placebo Controlled Trial.

Harriet Johansson,Bernardo Bonanni,Saverio Cinieri,Giovanni Mazzarol,Elisabetta Pennacchioli,Luigia Stefania Stucci,Sara Gandini,Giulio Tosti,Pier Francesco Ferrucci,Patrizia Gnagnarella,Costantino Jemos,Giuseppe Spadola,Alessandro Testori,Debora Macis,Federica Baldini,Valentina Aristarco,Leonardo Zichichi,Emilia Cocorocchio,Mario Mandalà,Paola Queirolo,Ines Tedeschi,Elena Albertazzi,Emanuela Omodeo Salè,Alessandro Marco Minisini

doi:10.3390/nu13061931

Abstract

Patients with newly resected stage II melanoma (n = 104) were randomized to receive adjuvant vitamin D3 (100,000 IU every 50 days) or placebo for 3 years to investigate vitamin D3 protective effects on developing a recurrent disease. Median age at diagnosis was 50 years, and 43% of the patients were female. Median serum 25-hydroxy vitamin D (25OHD) level at baseline was 18 ng/mL, interquartile range (IQ) was 13–24 ng/mL, and 80% of the patients had insufficient vitamin D levels. We observed pronounced increases in 25OHD levels after 4 months in the active arm (median 32.9 ng/mL; IQ range 25.9–38.4) against placebo (median 19.05 ng/mL; IQ range 13.0–25.9), constantly rising during treatment. Remarkably, patients with low Breslow score (<3 mm) had a double increase in 25OHD levels from baseline, whereas patients with Breslow score ≥3 mm had a significantly lower increase over time. After 12 months, subjects with low 25OHD levels and Breslow score ≥3 mm had shorter disease-free survival (p = 0.02) compared to those with Breslow score <3 mm and/or high levels of 25OHD. Adjusting for age and treatment arm, the hazard ratio for relapse was 4.81 (95% CI: 1.44–16.09, p = 0.011). Despite the evidence of a role of 25OHD in melanoma prognosis, larger trials with vitamin D supplementation involving subjects with melanoma are needed.

Highlights

IntroductionIts incidence has increased faster than that of all other cancers, this increase has not been followed by a similar rise in mortality rates, possibly reflecting the positive impact of education and prevention programs [1]
Cutaneous malignant melanoma is a major public health problem in many countries
Secondary endpoints were to investigate the association of changes in time of serum 25OHD levels and percentage of patients that reached the 25OHD cut-off level of sufficiency (>30 ng/mL from August to November and >20 ng/mL from January to July) during the 1st year, with melanoma outcome, and to assess the relationship between genetic polymorphisms (VDR and other genes involved in vitamin D metabolism), risk biomarkers, and melanoma prognosis

Summary

Introduction

Its incidence has increased faster than that of all other cancers, this increase has not been followed by a similar rise in mortality rates, possibly reflecting the positive impact of education and prevention programs [1]. In Italy, the agestandardized incidence rate reported in 2020 was 12.6 per 100,000 person per year in males and 12.0 in females, with mortality rates around 1.5 (https://gco.iarc.fr/today/data/ factsheets/populations/380-italy-fact-sheets.pdf (accessed on March 2021)). Some germline mutations, multiple benign or atypical nevi, and previous diagnosis of melanoma are major risk factors for melanoma development. Breslow thickness is the single most important prognostic factor for clinically localized primary melanoma [2] It defines the tumor depth from the surface of the epidermal granular layer to the point of maximum tumor thickness

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