Lower vitamin D levels associated with worse outcomes in melanoma

Lower levels of vitamin D correlated with poorer outcomes in patients with melanoma, according to prospective study results.

Prior research showed elevated C-reactive protein (CRP) independently predicted poorer melanoma-specific survival.

“Because CRP levels are inversely associated with vitamin D levels in blood, and because levels of vitamin D — an acute-phase reactant — decline with inflammation, measured vitamin D levels in patients with melanoma could reflect systemic inflammatory response,” Shenying Fang, MD, assistant professor of surgical oncology research at The University of Texas MD Anderson Cancer Center, and colleagues wrote.

Fang and colleagues collected blood samples from 1,042 patients with melanoma to examine the relationship between blood vitamin D levels and outcomes. Researchers accounted for cofounders, such as demographics, tumor histopathology and disease stage.

OS, melanoma-specific survival and DFS served as the primary endpoints.

The researchers reported a median vitamin D level of 25 ng/mL, and about one-quarter (24.6%) of study participants maintained levels below 20 ng/mL.

Fang and colleagues identified several factors associated with lower vitamin D levels, including blood draws during fall or winter compared with spring or summer (median, 23.59 ng/mL vs. 26.39 ng/mL; P < .001), older age (P = .001), increased CRP (P < .001), greater tumor thickness (P < .001), ulcerated tumor (P = .011) and advanced melanoma stage (P = .002).

Median follow-up was 7.1 years.

After adjustments for age, disease stage, sex, blood draw season and CRP, results revealed statistically significant associations between lower vitamin D levels and shorter OS (HR per unit decrease = 1.02; 95% CI, 1.01-1.04), melanoma-specific survival (HR per unit decrease = 1.02; 95% CI, 1-1.04) and DFS (HR = 1.02 per unit decrease of vitamin D; 95% CI, 1-1.04).

“An investigation of the roles of each of these biomarkers is important in clinical studies of outcomes in patients with melanoma and in clinical trials of novel therapies,” Fang and colleagues wrote. “Furthermore, these data suggest that interventions to increase vitamin D or to reduce systemic inflammatory response and CRP could ultimately benet patients with melanoma.”

Researchers also compared outcomes among patients with vitamin D level of 16 ng/mL or greater with those who had vitamin D levels less than 16 ng/mL.

Univariate analysis showed patients with vitamin D levels less than 16 ng/mL were significantly more likely to die of any cause (HR = 2; 95% CI, 1.5-2.66), die of melanoma (HR = 1.76; 95% CI, 1.22-2.53) or develop disease recurrence (HR = 1.62; 95% CI, 1.04-2.53). These associations remained significant on multivariable analysis.

Fang and colleagues acknowledged several potential limitations to their investigation, including the possibility that the study population — which consisted only of patients referred to a large cancer hospital — might not be representative. Also, researchers did not collect patient-specific sun exposure data or include measures of vitamin D intake.

Fang and colleagues recommended that future investigations determine whether supplementation of vitamin D or interventions to reduce maladaptive systemic inammation could benefit patients with melanoma.

“[This] investigation is the first, to our knowledge, to report a significant, independent association between lower vitamin D levels and poorer melanoma survival after adjustment for the influence of the systemic inflammatory response through simultaneous measurement of CRP,” they wrote. “A coordinated investigation of the mechanisms responsible for the independent association of these two important inammatory biomarkers with outcomes in patients with melanoma is likely to be clinically relevant and may have implications for other cancers.” — by Kristie L. Kahl

Disclosure: Fang reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.