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. 2022 May 20;12:839816. doi: 10.3389/fonc.2022.839816

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Copyright © 2022 Reichrath, Biersack, Wagenpfeil, Schöpe, Pföhler, Saternus and Vogt

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Low 25(OH)D serum concentrations (s.c.) predict poor overall survival (OS) in melanoma patients treated for advanced disease with immunotherapy and/or BRAF/MEK inhibitors. (A) Association of OS with baseline 25(OH)D s.c. in patients treated for advanced melanoma with ICIs and/or BRAF/MEK inhibitors. Cohort divided in subgroups according to 25(OH)D s.c. measured immediately before starting therapy with ICIs and/or BRAF/MEK inhibitors [“baseline 25(OH)D”]. Kaplan–Meier analysis shows a significant difference in survival, with only 50.8% of individuals in the subgroup of severely vitamin D-deficient patients [defined as 25(OH)D s.c. <10 ng/ml] being alive after 1 year of the observation period (OP) as compared to 71.0% in the subgroup of patients with 25(OH)D s.c. ≥10 ng/ml (p = 0.008). The mean OS (100.66 weeks in all patients included in this study) was almost 2-fold increased in the subgroup of patients with baseline 25(OH)D s.c. ≥10 ng/ml (116 weeks) as compared to the subgroup of patients with baseline 25(OH)D s.c. <10 ng/ml (66 weeks) (p = 0.008). Rounding error may occur. Number of patients may differ from total sample sizes due to missing data. (B) Association of OS with average 25(OH)D s.c. in patients treated for advanced melanoma with ICIs and/or BRAF/MEK inhibitors. Cohort of melanoma patients divided in subgroups according to average values of all 25(OH)D serum concentrations that were measured for each patient during the observation period [“average 25(OH)D”]. Kaplan–Meier analysis shows a significant difference in OS, with only 26.9% of individuals in the subgroup of vitamin D-deficient patients [average 25(OH)D s.c. <10 ng/ml] being alive after 1 year of the OP as compared to 77.2% in the subgroup of patients with average 25(OH)D serum concentrations ≥10 ng/ml (p = 0.000001). After 2 years, 0% and 52.1%, and after 4 years, 0% and 14.9% of individuals were alive in the subgroups of patients with average 25(OH)D s.c. <10 ng/ml and ≥10 ng/ml, respectively (p = 0.000001). The mean OS (100 weeks in all patients included in this study) was almost 4-fold increased in the subgroup of patients with average 25(OH)D s.c. ≥10 ng/ml (112 weeks) as compared to the subgroup of patients with average 25(OH)D s.c. <10 ng/ml (29 weeks) (p = 0.000001). Rounding error may occur. Number of patients may differ from total sample sizes due to missing data. BRAF, B-rapidly accelerated fibrosarcoma; ICI, immune checkpoint inhibitor; LDH, lactate dehydrogenase; MEK, mitogen activated protein kinase; OS, overall survival.