High level of circulating vitamin D during neoadjuvant therapy may lower risk of metastatic progression in high-risk rectal cancer

Abstract

Background Following curative-intent neoadjuvant therapy in locally advanced rectal cancer, metastatic progression is still dominant. We investigated if patients’ circulating 25-hydroxyvitamin D [25(OH)D] levels were associated with outcome. Methods Serum 25(OH)D concentration was assessed by liquid chromatography-mass spectrometry in samples collected from 84 patients at baseline, completion of the neoadjuvant therapy, and treatment evaluation before surgery, and analyzed with respect to season, disease presentation, and treatment effects. Results In the cohort of patients residing at latitude 58–62°N, baseline 25(OH)D differed significantly over the seasons, with highest measures (mean of 71.2 ± 5.6 nmol/L) in summer and lowest (48.7 ± 4.5 nmol/L) in spring, and changed over the three-month neoadjuvant period till response evaluation solely owing to season. The patient subgroup with slightly reduced performance status, anemia, and T4 disease that did not respond to the neoadjuvant therapy (ypT4 cases), had significantly lower baseline 25(OH)D (below 50 nmol/L) than T4 cases with response (ypT0–3) and T2–3 cases (above 60 nmol/L). Compared to the T4 patients with levels above 50 nmol/L, regarded as sufficient for a healthy bone status, those presenting levels below had significantly heightened risk of disease progression (mainly metastasis) and death, with hazard ratio of 3 and 17, respectively, on adjustment for age, sex, body mass index, and season. Conclusion Rectal cancer T4 cases had high risk of metastatic progression and death if circulating 25(OH)D levels were insufficient but obtained short-term and long-term outcome to neoadjuvant treatment no worse than patients with T2–3 disease when 25(OH)D was sufficient. Trial registration ClinicalTrials.gov NCT00278694 ; registration date: 16 January 2006, retrospective to enrollment of the first 10 patients of the current report.

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

“…The highly similar effect of calcitriol on colon tumor and rectal tumor organoids is consistent with the finding that colon and rectal cancers, excluding hypermutated cancers, have similar patterns of genetic alterations [ 65 ]. Moreover, our finding also agrees with the proposed protective effect of vitamin D on both colon and rectal cancers [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

“…The gut physiology is profoundly affected by the action of vitamin D [ 17 ], and observational studies have established a link between vitamin D deficiency and an elevated risk and poor prognosis of CRC, suggesting that colon and rectal cancer patients might preferentially benefit from an adequate vitamin D status [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Data from recent interventional clinical studies indicate that the addition of vitamin D to standard chemotherapy improves the progression-free survival of metastatic CRC patients [ 29 ]; however, another randomized trial showed no preventive effect on adenoma recurrence [ 30 ].…”

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

“…The antitumour effect of vitamin D is a popular research topic. Epidemiological studies have compared the relationship between serum vitamin D levels and prognosis in patients with breast cancer 25 and rectal cancer 26 and have found that the higher the serum level of vitamin D is, the better is patient prognosis. The regulatory relationship between vitamin D and tumours has not yet been elucidated, and its mechanism has not been clarified.…”

The relation of preoperative 25-OH Vitamin D Levels with Postoperative Complications in Patients undergoing Colorectal Cancer Surgery

“…In recent years, there has been an increasing number of studies investigating the effect of 25-OH vitamin D on progression-free survival and overall survival in patients with colorectal cancer (24)(25)(26). It has been also revealed that infective complications are increased in hospitalized patients with vitamin D de ciency because of its decreased immunomodulatory effects (27,28).…”