PMID- 35669434
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231105
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - Low Vitamin D Status Predicts Poor Clinical Outcome in Advanced Melanoma Treated 
      With Immune Checkpoint or BRAF/MEK Inhibitors: A Prospective Non-Interventional 
      Side-by-Side Analysis.
PG  - 839816
LID - 10.3389/fonc.2022.839816 [doi]
LID - 839816
AB  - In melanoma and other malignancies, low vitamin D status is associated with 
      increased risk and poor prognosis. However, there are limited data of the impact 
      of 25(OH)D serum concentration (s.c.) on clinical outcome in advanced melanoma. 
      We tested the hypothesis that vitamin D status is predictive of efficacy and 
      safety in patients treated for metastasized melanoma with B-rapidly accelerated 
      fibrosarcoma (BRAF), mitogen-activated protein kinase kinase (MEK), cytotoxic T 
      lymphocyte-associated protein-4 (CTLA-4), and/or programmed cell death protein-1 
      (PD-1) inhibitors. Severe vitamin D deficiency [defined as 25(OH)D s.c. <10 
      ng/ml] was associated with markedly reduced overall (OS) and progress-free (PFS) 
      survival, with increased tumor load [TL; measured as s.c. of S100 protein or 
      lactate dehydrogenase (LDH)], and with a trend for higher frequency of adverse 
      events (AEs). An increase in average 25(OH)D s.c. of 1 ng/ml was associated with 
      a 3.9% reduced risk for progressive disease [hazard ratio (HR) = 0.961, p = 
      0.044], with a reduction of LDH s.c. of 3.86 U/l (p = 0.034, indicating a 
      reduction of TL), and with a trend for reduced frequency of AEs (AE ratio -0.005; 
      p = 0.295). Patients with average 25(OH)D s.c. >/=10 ng/ml and BRAF-mutant melanoma 
      showed a trend for a higher frequency of AEs as compared to individuals with BRAF 
      wild-type melanomas. Our data indicate that vitamin D deficiency is associated 
      with poor clinical outcome in patients treated for metastasized melanoma with 
      BRAF/MEK inhibitors or immunotherapy. Although it needs to be proven in future 
      interventional trials whether optimizing serum 25(OH)D improves clinical outcome 
      in these patients, we recommend that 25(OH)D s.c. should be analyzed and vitamin 
      D deficiency treated in all patients with advanced melanoma.
CI  - Copyright (c) 2022 Reichrath, Biersack, Wagenpfeil, Schope, Pfohler, Saternus and 
      Vogt.
FAU - Reichrath, Jorg
AU  - Reichrath J
AD  - Department of Dermatology, Saarland University Medical Center, Homburg, Germany.
FAU - Biersack, Florian
AU  - Biersack F
AD  - Department of Dermatology, Saarland University Medical Center, Homburg, Germany.
FAU - Wagenpfeil, Stefan
AU  - Wagenpfeil S
AD  - Institute of Medical Biometry, Epidemiology and Medical Informatics, Saarland 
      University Medical Center, Homburg, Germany.
FAU - Schope, Jakob
AU  - Schope J
AD  - Institute of Medical Biometry, Epidemiology and Medical Informatics, Saarland 
      University Medical Center, Homburg, Germany.
FAU - Pfohler, Claudia
AU  - Pfohler C
AD  - Department of Dermatology, Saarland University Medical Center, Homburg, Germany.
FAU - Saternus, Roman
AU  - Saternus R
AD  - Department of Dermatology, Saarland University Medical Center, Homburg, Germany.
FAU - Vogt, Thomas
AU  - Vogt T
AD  - Department of Dermatology, Saarland University Medical Center, Homburg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20220520
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9166268
OTO - NOTNLM
OT  - BRAF/MEK inhibitor
OT  - advanced melanoma
OT  - immune checkpoint inhibitor
OT  - low vitamin D status
OT  - melanoma
OT  - vitamin D
OT  - vitamin D status
COIS- Saarland University, with JR and TV as principal investigators, received funding 
      from the Jorg Wolff Foundation (Stuttgart, Germany). JR received speaker's 
      honoraria from Leo Pharma (Neu-Isenburg, Germany) and Cogitando (Neunkirchen, 
      Germany). The remaining authors declare that the research was conducted in the 
      absence of any commercial or financial relationships that could be construed as a 
      potential conflict of interest.
EDAT- 2022/06/08 06:00
MHDA- 2022/06/08 06:01
PMCR- 2022/01/01
CRDT- 2022/06/07 02:35
PHST- 2021/12/20 00:00 [received]
PHST- 2022/01/31 00:00 [accepted]
PHST- 2022/06/07 02:35 [entrez]
PHST- 2022/06/08 06:00 [pubmed]
PHST- 2022/06/08 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2022.839816 [doi]
PST - epublish
SO  - Front Oncol. 2022 May 20;12:839816. doi: 10.3389/fonc.2022.839816. eCollection 
      2022.