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, metastaticprogression is still dominant. We investigated if patients’circulating 25-hydroxyvitamin D [25(OH)D] levels wereassociated with outcome.Methods:Serum 25(OH)D concentration was assessed by liquid chromatography-mass spectrometry in samplescollected from 84 patients at baseline, completion of the neoadjuvant therapy, and treatment evaluation beforesurgery, 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 theseasons, with highest measures (mean of 71.2 ± 5.6 nmol/L) in summer and lowest (48.7 ± 4.5 nmol/L) in spring, andchanged over the three-month neoadjuvant period till response evaluation solely owing to season. The patientsubgroup with slightly reduced performance status, anemia, and T4 disease that did not respond to theneoadjuvant therapy (ypT4 cases), had significantly lower baseline 25(OH)D (below 50 nmol/L) than T4 cases withresponse (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 ofdisease progression (mainly metastasis) and death, with hazard ratio of 3 and 17, respectively, on adjustment forage, sex, body mass index, and season.Conclusion:Rectal cancer T4 cases had high risk of metastatic progression and death if circulating 25(OH)D levelswere insufficient but obtained short-term and long-term outcome to neoadjuvant treatment no worse thanpatients with T2–3 disease when 25(OH)D was sufficient.