Abstract
BackgroundStudies evaluating a relationship of vitamin D in patients with primary melanoma have consistently identified an inverse correlation with Breslow thickness, but an inconsistent impact on survival. Vitamin D in later stages of melanoma has been less studied.MethodsVitamin D was measured in serum from 341 patients with resected stage IIB–IIIC melanoma recruited to the AVAST-M adjuvant melanoma randomised trial, collected prior to randomisation, then at 3 and 12 months. Vitamin D levels were compared with patient demographics, known melanoma prognostic factors, disease-free interval (DFI) and overall survival (OS).ResultsA total of 73% patients had stage III melanoma, 32% were enroled (and therefore tested) >1 year after primary melanoma diagnosis. Median pre-randomisation vitamin D level was 56.5 (range 12.6–189.0 nmol/L). Vitamin D levels did not significantly vary over 12 months (p = 0.24). Individual pre-randomisation vitamin D levels did not differ significantly for Breslow thickness, tumour ulceration, or disease stage. Neither did pre-randomisation vitamin D predict for DFI (HR = 0.98 per 10 nmol/L increase; 95% confidence interval (CI) 0.93–1.04, p = 0.59) or OS (HR = 0.96 per 10 nmol/L increase, 95% CI 0.90–1.03, p = 0.31). For stage II patients, DFI improved with higher pre-randomisation vitamin D levels for those on bevacizumab (HR = 0.74 per 10 nmol nmol/L increase; 95% CI 0.56–0.97), but not for the observation arm (HR = 1.07 per 10 nmol/L increase; 95% CI 0.85–1.34).ConclusionsIn this stage II/III melanoma cohort, vitamin D did not correlate with known prognostic markers, nor predict for DFI or OS, but there was some evidence of benefit for patients with stage II disease treated with bevacizumab.
Highlights
Vitamin D is a pro-hormone primarily responsible for maintaining calcium and phosphate homoeostasis in the body.[1,2] Its physiological functions include regulation of growth and differentiation in a wide variety of normal and malignant cells.[3]
Prerandomisation vitamin D was measured in blood collected at trial enrolment, but the primary melanoma Breslow thickness and presence of ulceration were determined at initial diagnosis, which may have been several years prior to AVAST-M trial entry and randomisation in those patients who entered the trial after resection of stage III melanoma: median time from diagnosis to randomisation was 0.47 years, range 0–22.6 years (Table 1)
We performed an exploratory study to measure vitamin D in a cohort of melanoma patients who took part in the AVAST-M trial, an adjuvant trial investigating the use of bevacizumab in patients with melanoma at a high risk of recurrence
Summary
Vitamin D is a pro-hormone primarily responsible for maintaining calcium and phosphate homoeostasis in the body.[1,2] Its physiological functions include regulation of growth and differentiation in a wide variety of normal and malignant cells.[3]. Studies evaluating a relationship of vitamin D in patients with primary melanoma have consistently identified an inverse correlation with Breslow thickness, but an inconsistent impact on survival. Vitamin D levels were compared with patient demographics, known melanoma prognostic factors, disease-free interval (DFI) and overall survival (OS). Individual pre-randomisation vitamin D levels did not differ significantly for Breslow thickness, tumour ulceration, or disease stage. For stage II patients, DFI improved with higher pre-randomisation vitamin D levels for those on bevacizumab (HR = 0.74 per 10 nmol nmol/L increase; 95% CI 0.56–0.97), but not for the observation arm (HR = 1.07 per 10 nmol/L increase; 95% CI 0.85–1.34). CONCLUSIONS: In this stage II/III melanoma cohort, vitamin D did not correlate with known prognostic markers, nor predict for DFI or OS, but there was some evidence of benefit for patients with stage II disease treated with bevacizumab
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