Study: vitamin D as melanoma treatment

Study: vitamin D as melanoma treatment

reference

Fang S, Sui D, Wang Y, et al. Association of vitamin D levels with outcome in patients with melanoma after adaptation for C-reactive protein [published online Ahead of print March 21, 2016]. J Clin oncol. doi: JCO641357.

Design

This observation study is part of an ongoing prospective examination that includes patients with all stages of invasive skin melanoma. The researchers evaluated blood samples to a connection between vitamin D mirror and results measurements in patients with melanoma, while they check the systemic inflammatory reaction (SIR) based on simultaneous measurements of the C reactive protein (CRP).

participant

plasma samples of 1,042 melana melana patients were examined prospectively. The average age of blood was taken 54.8 years. The group was 43.4 % female (452 ​​patients). The median vitamin D level was 25.0 ng/ml. 24.6 % of the participants had a vitamin D level 20 ng/ml and ≤ 30 ng/ml; And 27.7 % had values> 30 ng/ml. The middle CRP was 1.7. The participants were observed for a median of 7.1 years.

target parameter

progression -free survival (PFS), melanoma -specific survival (MSS) and overall survival (OS). In addition, Kaplan-Meier and Cox regression analyzes were carried out.

important knowledge

A lower vitamin D content in patients with melanoma was associated with poorer results. Although low vitamin D was strongly associated with higher CRP, the associations of low vitamin D with poorer OS, MSS and PFS were regardless of this association.
A lower vitamin D content was associated with blood sampling in the autumn/winter months ( p <0.001), older age ( p = 0.001), increased CRP ( p <0.001), increased tumor thick ( p <0.001), ulcerated tumor ( p = 0.0105) and in the advanced melanoma stage ( p = 0.0024).

Your data indicate that higher vitamin D levels actually bring advantages.

In the univariate analysis, a lower vitamin D content was associated with a poorer overall survival (OS; p <0.001), melanoma-specific survival (MSS; p = 0.0025) and disease-free survival (DFS; p = 0.0466). The effect of vitamin D on these end points also continued after adaptation for CRP and other covariates. Multivariable hazard ratios (HRS) per vitamin D acceptance per unit was 1.02 for OS [95% Confidence Interval (CI): 1.01 to 1.04; p = 0.0051] 1.02 for MSS (95 % KI: 1.00 to 1.04; p = 0.048) and 1.02 for DFS (95 %-KI: 1.00 to 1.04; p = 0.0427).
For values ​​below the optimal limit value of 16 ng/ml (determined by recursive partitioning), patients had a poor overall survival (HR: 2.0; 95 % KI: 1.50–2.66; p <0.001), MSS (HR: 1.76; 95 % KI: 1.22–2.53; p = 0.003) and DFS (HR: 1.62; 95 % KI: 1.04-2.53; p = 0.036) In the univariate analysis and associations, there were significant in multivariabling analysis.

practice implications

While the role that vitamin D plays in melanoma is still confusing, these results indicate that interventions could benefit patients with melanoma to increase vitamin D or reduce systemic inflammatory reactions.
Our general assumption that vitamin D protects against all types of cancer was not clear in melanoma. We try to predict the result of 2 competing actions in connection with solar radiation. Sun exposure increases the vitamin D level and could reduce the risk of melanoma, but at the same time, sunlight increases skin damage, which could increase the risk. Which of these actions will prevail?
in vitro looks good vitamin D; It has anti-proliferative effects on melanoma cells, inhibits tumor growth and invasion and promotes the DNA repair. 1-4 As far as humans are concerned, the previous studies (in vivo) were contradictory.
A prospective study by Major et al. From 2012 was the first to search for a connection between vitamin D and melanoma risk. They did not report any significant association.
in March 2013 Reddy reported that vitamin D levels of more than 30 ng/ml are associated with an increased risk of melanoma. 5 In the same month, Afzal reported that the melanomal risk in people with a vitamin D level over 20 ng/ml was 4.7 times higher than in people with a vitamin D level under 10 ng/ml. 6
Caini et al performed a meta -analysis that was published in October 2014 European magazine for cancer . They combined data from 20 separate studies and compared the highest with the lowest vitamin D levels. While the authors reported a 14 percent decrease in the relative risk (RR) between the highest and the lowest quintile of the vitamin D intake (RR = 0.86; 95 % KI: 0.63-1.13) for skin melanoma, these results did not achieve statistical significance.
Only last year, in June 2015, data were published that indicated that vitamin D had a significant benefit in patients with melanoma in history.
Newton bishop observed a group of 2,182 melana patients for almost 8 years and reported that higher vitamin D levels were associated with a lower risk of melanoma and that low vitamin D levels were associated with an increase in more than 50 %.
While it remains unclear whether the vitamin D level is associated with the risk of developing a melanoma or not, this current work by Fang et al. Another question: Does vitamin D affect the forecast for someone with melanoma? Your data suggests that higher vitamin D levels actually bring advantages, although there may not be much vitamin D. Note again that your data analysis showed that serum levels above 16 ng/ml were associated with significantly better results.
While we consider vitamin D in these scenarios more as "the good", both the Newton bishop paper and the fishing paper from vitamin D speak as a possible biomarker. Both research groups ask whether the effects of vitamin D depend on its anti -inflammatory effect. Both studies also examined the CRP mirrors in their cohorts. In the case of melanoma patients there is an reverse association between vitamin D and CRP. Even the slightly lower vitamin D levels measured during the winter months were associated with higher CRP mirrors. Fang showed that after adaptation for CRP, vitamin D an independent predictor for OS, MSS and DFS remained, which indicates that vitamin D and CRP correlate with each other, but have an independent effect on each other in order to predict the clinical result in melana patients. Although this has not yet been proven, we can and should be able to consider both markers as goals for our clinical intervention in this patient population.
Several clinical studies are underway that may provide better answers. In Australia there is the MEL-D study, a prospective placebo-controlled study in which patients with the diagnosis of skin melanoma vitamin D receive vitamin D as adjuvant therapy after the primary treatment has been completed. In this study, the patients receive a large oral saturation dose of vitamin D (500,000 IE), followed by a lower dose of 50,000 IE once a month for 2 years.
Another clinical study, the Melavid study, is in progress in Europe. The patients receive 100,000 IE vitamin D3 every 50 days. The expected conclusion of this study is in 2025. 10
In the meantime, we should continue to monitor our patients on vitamin D deficiency, which certainly seems to worsen the forecast.

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  10. European Institute of Oncology. Melavid: A study on the vitamin D supplement in resected melanoma patients in stage II (Melavid). In: Clinicaltrials.gov. Bethesda (MD): National Library for Medicine (USA). Last updated in October 2015. Access on May 26, 2016. href = "https://clinicalaltrials.gov/ct2/Show/nct01264874"> https://clinicalaltrials.gov/ct2/show/nct01264874 .

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