Abstract
BackgroundFollowing 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.MethodsSerum 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.ResultsIn 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.ConclusionRectal 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 registrationClinicalTrials.gov NCT00278694; registration date: 16 January 2006, retrospective to enrollment of the first 10 patients of the current report.
Highlights
Following curative-intent neoadjuvant therapy in locally advanced rectal cancer, metastatic progression is still dominant
It has been hypothesized that high incidence and poor prognosis may partly be attributed to an insufficient vitamin D status [2,3,4]
After season adjustment for each case by the linear-mixed model, only minor alterations in serum 25(OH) D were observed from baseline to post-Rx and evaluation, indicating that the neoadjuvant treatment as such may not have affected circulating 25(OH)D
Summary
Following curative-intent neoadjuvant therapy in locally advanced rectal cancer, metastatic progression is still dominant. Circulating vitamin D is strongly associated with exposure to solar ultraviolet radiation [5], which in the Nordic countries (mainland latitude 55-72oN) results in significant variation over the year [6, 7], especially if the diet is scarce in supplementary vitamin D in calendar months when the basic requirement cannot be met by sun exposure alone [8] In both northern and southern regions of Norway the prognosis of CRC across all disease stages seems to be better when diagnosed in summer and fall compared to winter and spring [9, 10]. Vitamin D sufficiency may be protective against development of inflammatory bowel disease [15] and deficient circulating levels are associated with heightened risk of CRC development in these patients [16], supporting an association between vitamin D, inflammation, and CRC
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