Table 1.
(n=) | OP (weeks) | Age (mean) | Gender | 25(OH)D s.c. (ng/ml)2 | Survival3 (weeks) | Tumor load4 | Adverse events (side effects ratio)5 | Mutation status (wt/mut)6 | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline2 (mean) | Average2 | OS | PFS | LDH (U/L)(Baseline2/Average2) | S100 (µg/L) | BRAF | NRAS | c-KIT | ||||||
All patients1 | 83 | 54.32 | 63.43 | 45m 38f | 19.61 | 21.05 | 100.66/97.00 | 53.94/34.00 | 321.6/344.0 | 0.74/1.02 | 0.5438 | 24 | 22 | 3 |
25(OH)D s.c. <10 ng/ml | 13 | 25.30 | 63.15 | 7m 6f | 7.2 | 7.36 | 29.59/19.00 | 20.30/12.00 | 419.5/490.1 | 1.51/2.35 | 0.6982 | 3 | 6 | 0 |
25(OH)D s.c. ≥10 ng/ml | 70 | 59.78 | 63.49 | 38m 32f | 22.05 | 23.71 | 112.04/117.00 | 60.83/48.00 | 305.0/319.3 | 0.6/0.77 | 0.518 | 21 | 16 | 3 |
BRAF wt | 59 | 53.28 | 66.53 | 32m 27f | 15.83 | 20.48 | 109.29/97.00 | 54.07/33.00 | 299.1/330.5 | 0.7/1.02 | 0.6156 | |||
25(OH)D s.c. <10 ng/ml | 10 | 24.20 | 68.10 | 6m 4f | 7.45 | 7.59 | 29.92/19.00 | 14.09/11.00 | 413.6/491.3 | 1.60/2.62 | 0.7680 | |||
25(OH)D s.c. ≥10 ng/ml | 49 | 59.22 | 66.2 | 26m 23f | 17.58 | 23.11 | 121.23/142.00 | 61.52/48.00 | 275.2/297.7 | 0.50/0.69 | 0.5845 | |||
BRAF mut | 24 | 56.96 | 55.83 | 13m 11f | 30.02 | 22.64 | 83.98/63.00 | 57.00/60.00 | 394.3/391.0 | 0.89/1.02 | 0.308 | |||
25(OH)D s.c. <10 ng/ml | 3 | 29.00 | 46.67 | 1m 2f | 6.37 | 6.58 | 29.00/16.00 | 37.00/13.00 | N.A.7 | 1.02/1.02 | N.A.7 | |||
25(OH)D s.c. ≥10 ng/ml | 21 | 61.15 | 57.14 | 12m 9f | 33.97 | 25.32 | 93.40/68.00 | 60.85/34.00 | 389.4/385.6 | 0.87/1.02 | 0.3265 | |||
Treatment modalities1 | ||||||||||||||
BRAF-/MEK- inhibitors1 | 19 | 62.42 | 56.05 | 9m 10f | 31.5 | 22.9 | 81.77/62.00 | 54.70/34.00 | 310.57/287.9 | 0.24/0.58 | 0.4062 | 18 | 0 | 0 |
Immunotherapy1 | ||||||||||||||
CTLA-4 and PD-1 inhibitors | 16 | 46.25 | 48.13 | 7m 9f | 32.68 | 22.54 | 82.53/97.00 | 43.62/48.00 | 393.5/419.6 | 1.18/1.34 | 0.8150 | 6 | 4 | 2 |
CTLA-4-inhibitors | 13 | 103.23 | 60.77 | 4m 9f | 12.31 | 21.66 | 108.87/78.00 | 47.97/22.00 | 270.9/297.7 | 0.54/0.76 | 0.6738 | 1 | 5 | 0 |
PD-1 inhibitors | 63 | 60.56 | 67.17 | 34m 29f | 16.52 | 21.44 | 106.62/97.00 | 55.44/33.00 | 294.3/318.3 | 0.59/0.91 | 0.4844 | 12 | 19 | 1 |
Patients with Metastases before therapy (n=) | other | Total number of metastasized organs | Total number of metastasized organs/number of patients | |||||||||||
(n=) | brain | lung | liver | skin/soft tissue | ||||||||||
All patients1 | 82 | 19 | 50 | 25 | 29 | 39 | 162 | 1.95 | ||||||
25(OH)D s.c. < 10 ng/mL | 13 | 5 | 10 | 5 | 3 | 6 | 29 | 2.23 | ||||||
25(OH)D s.c. ≥ 10 ng/mL | 69 | 14 | 40 | 20 | 26 | 33 | 133 | 1.92 | ||||||
BRAF and MEK inhibitors | 19 | 5 | 8 | 4 | 3 | 13 | 33 | 1.7 | ||||||
Immunotherapy1 | ||||||||||||||
CTLA-4 and PD-1 inhibitors | 16 | 5 | 7 | 5 | 2 | 11 | 30 | 1.88 | ||||||
CTLA-4-inhibitors | 13 | 3 | 9 | 3 | 6 | 5 | 26 | 2 | ||||||
PD-1 inhibitors | 63 | 16 | 40 | 16 | 27 | 30 | 129 | 2.04 |
1For treatment modalities, please see Table 2 .
225(OH)D serum concentrations were investigated as described in the Methods. In short, 25(OH)D serum concentration was either assessed when starting therapy with ICIs or BRAFi/MEKi [“baseline 25(OH)D”] or calculated as average value of all 25(OH)D serum concentrations that were measured for each patient during the complete observation period [“average 25(OH)D”].
3Mean and Median Survival Estimates was assessed as described in the Methods.
4Tumor load was estimated by analyzing serum concentrations of LDH and S100 protein, as described in the Methods.
5Adverse events were assessed according to CTCAE criteria as described in the Methods.
6Mutation status was assessed as described in the Methods.
7Missing data due to small case number.
BRAF, B-rapidly accelerated fibrosarcoma; CTCAE, common terminology criteria for adverse events; CTLA, cytotoxic T-lymphocyte-associated protein; LDH, lactate dehydrogenase; MEK, mitogen-activated protein kinase kinase; Mut, mutated; OP, observation period; 25(OH)D s.c., 25(OH)D serum concentration; OS, overall survival; PD, programmed cell death protein; PFS, progress-free survival; TL, tumor load; wt, wild-type.
Rounding errors may occur in the data table. The number of patients may differ from the total sample size owing to missing data.