High dose vitamin D supplementation does not improve outcome in a cutaneous melanoma population: results of a randomized double-blind, placebo-controlled study (ViDMe trial).

BACKGROUND: Observational studies in cutaneous melanoma have indicated an inverse relationship between levels of 25-hydroxy vitamin D and Breslow thickness, as well as a protective effect of high 25- hydroxy vitamin D levels on clinical outcome. OBJECTIVES: To evaluate whether high dose vitamin D supplementation in curatively resected cutaneous melanoma reduces melanoma relapse. METHODS: In a prospective, randomized, double-blind, placebo-controlled trial, 436 patients with resected cutaneous melanoma stage IA to III (8th American Joint Committee on Cancer staging) were randomized. Among them, 218 received a placebo while 218 received monthly 100,000 IU cholecalciferol for a minimum of 6 months and a maximum of 42 months (treatment arm). Following randomization, patients were followed for a median of 52 months, with a maximum follow-up of 116 months. The primary endpoint was relapse-free survival. Secondary endpoints were melanoma-related mortality, overall survival, and the evolution of 25-hydroxy vitamin D serum levels over time. RESULTS: In our population (mean age 55 years, 54% female) Vitamin D supplementation increased 25- hydroxy vitamin D serum levels after 6 months of supplementation in the treatment arm by a median 17 ng/ml (95%CI: 9; 26) compared to 0 ng/ml (95%CI: -6; 8) in the placebo arm (P < 0.001; Wilcoxon test) and remained at a steady state during the whole treatment period. The estimated event rate for relapse-free survival at 72 months after inclusion was 26.51% in the vitamin D supplemented arm (95% CI: 19.37; 35.64) versus 20.70% (95%CI: 14.26; 29.52) in the placebo arm, [hazard ratio 1.27 (95%CI 0.79; 2.03), P = 0.32]. After adjusting for confounding factors (including baseline stage, body mass index, age, gender, and baseline season), the hazard ratio was 1.20 (95% CI 0.74; 1.94, P = 0.46). Deaths from progression of cutaneous melanoma and non-melanoma related deaths were similar in both vitamin D supplemented and placebo group (n = 10 and 11 and n = 3 and 2, respectively). No major adverse events were observed during the study. CONCLUSION: In cutaneous melanoma patients, monthly high dose vitamin D supplementation was safe, resulted in a sustained increase in 25-hydroxy vitamin D levels during the treatment period, but did not improve relapse-free survival, melanoma-related death or overall survival.

Clinical and genetic determinants of vitamin D receptor expression in cutaneous melanoma patients.

Decrease of vitamin D receptor (VDR) expression is observed in melanocytic naevi and melanoma compared to normal skin. Little is known about factors influencing VDR expression in cutaneous melanoma (CM). We investigated the correlation of VDR expression in CM with 25-hydroxy vitamin D (25OHD) levels, demographic/clinical parameters, genetic variants of VDR and pathology of the primary tumor. Demographic/clinical parameters were recorded in 407 prospectively recruited CM patients of a multi-center controlled study (ViDMe trial). We determined VDR expression both in the nucleus and in the cytoplasm by semi-quantitative assessment in CM tissue using histochemistry in 279 patients, expressed in percentages and histoscore (H-score). Genomic DNA from 332 patients was extracted to genotype thirteen VDR single nucleotide polymorphisms (SNPs) using TaqMan. VDR expression in CM tissue from 279 patients was correlated with clinical/demographic parameters and 25OHD levels (univariable and multivariable analysis), VDR SNPs (univariable analysis) and pathology parameters of primary CM tissue (univariable analysis). Cytoplasmic VDR expression was increased in patients who stated to have a high sun exposure during their life compared to patients with low sun exposure (p H-score,univariable : 0.001, p H-score,multivariable : 0.004). The A allele of the genetic VDR polymorphism Fok1 was associated with a higher expression of the VDR in the cytoplasm (p cytoplasmic, univariable : 0.001 and p H-score, univariable : 0.02). In the primary tumor, presence of mitosis (p nucleus,%, univariable : 0.002) and perineural invasion (p nucleus,%,univariable : 0.03) were significantly associated with low nuclear VDR expression. ClinicalTrials.gov Identifier: NCT01748448.

Can Multispectral Dermoscopy Help In Distinguishing Blue Color?

INTRODUCTION: The interpretation of colors is essential in the dermoscopic evaluation of skin lesions. The same blue color on white dermoscopy may indicate blood or pigment deep in the dermis. Contrary to white dermoscopy, multispectral dermoscopy uses different wavelengths of light to illuminate a lesion and is able to decompose the dermoscopic image into individual maps that allow to more clearly visualize specific skin structures such as pigment distribution (pigment map) and vasculature (blood map). These maps are called skin parameter maps. OBJECTIVES: The aim of this research is to investigate whether skin parameter maps can be used to objectively identify and distinguish the presence of pigment and blood, by using blue naevi and angiomas as models for respectively pigment and blood. METHODS: We retrospectively analyzed 24 blue naevi and 79 angiomas. The skin parameter maps of each of the lesions were independently reviewed by 3 expert dermoscopists, in the absence of the regular white-light dermoscopic image. RESULTS: All the observers provided high levels of diagnostic accuracy for blue naevus and angioma based on skin parameter maps alone, and the dermoscopic diagnosis was considered substantially reliable because of the 79% of diagnostic K agreement. Percentages of blue naevi and angiomas that showed respectively deep pigment and blood were very high at 95.8% and 97.5%. There was a percentage of lesions that counterintuitively showed blood in blue naevi (37.5%) and deep pigment in angiomas (28.8%). CONCLUSIONS: Skin parameter maps based on multispectral images can help to objectify the presence of deep pigment or blood in blue naevi and angiomas. The application of these skin parameter maps could help in the differential diagnosis between pigmented and vascular lesions.

Preoperative assessment of cutaneous melanoma thickness by multispectral dermoscopy.

Preoperative assessment of Breslow thickness by means of sonography and clinical and dermoscopic criteria in white light dermoscopy has been reported, but up until now, the use of multispectral dermoscopy has not been investigated. Aim of this research is to determine whether multispectral dermoscopy and more specifically pigment maps can be used as a predictive marker for Breslow thickness in melanoma. Pigment maps are generated in real time from multispectral dermoscopic images and help to visualize the presence of pigment in a lesion. Multispectral images of 110 melanomas were collected, using a digital handheld multispectral dermatoscope, and assessed independently by five observers for the presence or absence of deep pigment compared with the surrounding skin. According to histopathological examination, the mean Breslow thickness of all 110 melanomas was 1.04 mm (ranging from 0.1 to 14 mm). The group of melanomas where deep pigment was visualized on the multispectral image (n = 78) had a significantly higher Breslow thickness (1.19 mm) than the group where no deep pigment was observed (n = 32, mean Breslow 0.68 mm) (P = 0.025). This study is unique in preoperative assessment of tumour thickness by means of multispectral dermoscopy. Our data indicate that the presence of deep pigment as visualized in digital dermoscopic skin parameter maps identifies a group of thicker melanomas. Further prospective research is needed to validate these pigment maps, generated by multispectral dermoscopy as a measure to predict invasiveness in melanoma.

Determinants of 25-hydroxyvitamin D Status in a Cutaneous Melanoma Population.

Vitamin D status is influenced by well-known determinants, but factors associated with low 25-hydroxyvitamin D levels in the cutaneous melanoma population are not well defined. The aim of this study was to confirm the well-known determinants and to assess new determinants for 25-hydroxyvitamin D levels in a cutaneous melanoma population. In a prospectively included cohort of 387 patients with cutaneous melanoma the association of 25-hydroxyvitamin D levels with sex, age, body mass index, time of blood withdrawal, Fitzpatrick phototype, vitamin D supplementation, score for intensity of lifetime sun exposure, smoking, education level, hair and skin colour, eye colour, total number of benign naevi, freckles and parameters of chronic sun damage was investigated. In addition, 25-hydroxyvitamin D levels were correlated with pathological parameters of the primary tumour and melanoma stage (8th edition of the American Joint Committee on Cancer (AJCC). Univariate and multivariate logistic regressions were performed using R software. The following factors had a significant effect on vitamin D status: body mass index, seasonal time of blood sampling, vitamin D supplementation, and a subtype of skin, and hair colour.

Enhanced visualization of blood and pigment in multispectral skin dermoscopy.

BACKGROUND AND OBJECTIVES: Dermoscopy has proven its value in the diagnosis of skin cancer and, therefore, is well established in daily dermatology practice. Up until now, analogue white light dermoscopy is the standard. Multispectral dermoscopy is based on illumination of the skin with narrowband light sources with different wavelengths. Each of these wavelengths is differently absorbed by skin chromophores, such as pigment or (de)oxygenated blood. Multispectral dermoscopy could be a way to enhance the visualization of vasculature and pigment. We illustrate possible additional information by such "skin parameter maps" in some cases of basal cell carcinoma and Bowen's disease. METHODS: Using a new digital multispectral dermatoscope, skin images at multiple wavelengths are collected from different types of skin lesions. These particular images together with the knowledge on skin absorption properties, result in so called "skin parameter maps". RESULTS: A "pigment contrast map," which shows the relative concentration of primarily pigment, and a "blood contrast map" which shows the relative concentration of primarily blood were created. Especially, the latter is of importance in diagnosing keratinocyte skin cancer hence vascular structures are a characteristic feature, as further illustrated in the study. CONCLUSIONS: Skin parameter maps based on multispectral images can give better insight in the inner structures of lesions, especially in lesions with characteristic blood vessels such as Bowen's disease and basal cell carcinoma. Skin parameter maps can be used complementary to regular dermoscopy and could potentially facilitate diagnosing skin lesions.