However, insights from the biomarkers in patients with pancreatic cancer (BIOPAC) study (NCT03311776) showed that higher levels of the inflammatory biomarkers interleukin (IL)-6, YKL-40, and C-reactive protein (CRP) were present in patients with vitamin D deficiency.5 The BIOPAC investigators specifically evaluated the association between pretreatment vitamin D levels, inflammatory biomarkers, and OS in patients with pancreatic ductal adenocarcinoma (PDAC).

Patients were stratified into 3 groups based on pretreatment vitamin D levels: sufficient (>50 nmol/L), insufficient (25-50 nmol/L), and deficient (<25 nmol/L). Forty-nine percent of all patients had either insufficient or deficient vitamin D levels, and those with vitamin D deficiency had the highest levels of IL-6, YKL-40 and CRP, regardless of cancer stage.

The median OS for patients with vitamin D deficiency and pancreatic cancer (stage I-II) who underwent resection was shorter vs that for patients who were found to have sufficient vitamin D levels (18.3 months vs 29.7 months; HR, 1.55; 95% CI, 1.04-2.31; P =.03). No significant differences in OS were seen in patients with advanced PDAC regardless of vitamin D level, Rasmussen et al said. Similarly, no statistical differences were seen in the median OS in patients with varying levels of vitamin D who received gemcitabine.

Optimal vitamin D levels were determined to be between 54 nmol/L and 80 nmol/L. The study authors postulated that patients with minimal disease after resection might be reasonable candidates for vitamin D supplementation to prevent cancer cell progression.


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The underlying pathophysiology of vitamin D in pancreatic cancer is not completely understood. The pancreatic cancer tumor microenvironment (TME) is characterized by hypoxia and immunosuppression leading to fibrosis.5 Increasing inflammation in the TME may promote angiogenesis and metastases.5 Vitamin D is likely involved in many of these steps vs just one specific pathway. Specifically, the vitamin D receptor (VDR) might play a role in stimulating an immune response with the VDR-1, 25-hydroxyvitamin-D2 complex, inhibiting angiogenesis and promoting cell differentiation and apoptosis.1,3 Vitamin D may also influence pancreatic endocrine function through the regulation of insulin.3 Data from some studies have suggested that vitamin D could be synergistic with chemotherapy by increasing cellular remodeling after treatment.3

The study insights summarized here demonstrate why vitamin D is a biomarker of interest in the pancreatic cancer setting. Measuring vitamin D levels is feasible via a routine laboratory test that is easily accessible to physicians and patients alike; this only adds to vitamin D’s appeal as a potential marker. However, future studies are needed for continued data capture on vitamin D in pancreatic cancer, especially with respect to the possible synergy between vitamin D and chemotherapy.3 The location of future studies is also important, as approximately 90% of a person’s vitamin D requirements come from sunlight.6

References

  1. Von Hoff DD, Cridebring D, Tian OY, et al. Analysis of the role of 25-hydroxyvitamin D levels in survival outcomes in patients from the phase III MPACT Trial of metastatic pancreatic cancer. Oncologist. Published online December 20, 2020. doi:10.1002/onco.13645
  2. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691-1703. doi:10.1056/NEJMoa1304369
  3. Zhang X, Huang X-Z, Cheng W-J, et al. Plasma 25-hydroxyvitamin D levels, vitamin D intake and pancreatic cancer risk or mortality: a meta-analysis. Oncotarget. 2017;8(38):64395-64406. doi:10.18632/oncotarget.18888
  4. Waterhouse M, Risch HA, Bosetti C, et al; Pancreatic Cancer Case–Control Consortium (PanC4). Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium. Ann Oncol. 2016;27(1):208. doi:10.1093/annonc/mdv236
  5. Rasmussen LS, Yilmaz MK, Falkmer UG, et al. Pre-treatment serum Vitamin D deficiency is associated with increased inflammatory biomarkers and short overall survival in patients with pancreatic cancers. Eur J Cancer. 2021;144:72-80. doi:10.1016/j.ejca.2020.10.038
  6. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004;80(Suppl 6):1678S-88S. doi:10.1093/ajcn/ 80.6.1678S