Clinical Investigation
Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

https://doi.org/10.1016/j.ijrobp.2015.02.011Get rights and content

Purpose

Radiation-induced injury to normal tissues is a common complication of radiation therapy in cancer patients. Considering the role of vitamin D in mucosal barrier hemostasis and inflammatory responses, we investigated whether vitamin D deficiency is associated with the severity of radiation-induced acute proctitis in cancer patients.

Methods and Materials

This prospective observational study was conducted in cancer patients referred for pelvic radiation therapy. Serum concentration of 25-hydroxyvitamin D was measured before radiation therapy. Vitamin D deficiency was defined as 25-hydroxyvitamin D concentrations of <35 nmol/L and <40 nmol/L in male and female patients, respectively, based on available normative data. Acute proctitis was assessed after 5 weeks of radiation therapy (total received radiation dose of 50 Gy) and graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria.

Results

Ninety-eight patients (57.1% male) with a mean age of 62.8 ± 9.1 years were studied. Vitamin D deficiency was found in 57 patients (58.1%). Symptoms of acute proctitis occurred in 72 patients (73.4%) after radiation therapy. RTOG grade was significantly higher in patients with vitamin D deficiency than in normal cases (median [interquartile range] of 2 [0.5-3] vs 1 [0-2], P=.037). Vitamin D deficiency was associated with RTOG grade of ≥2, independent of possible confounding factors; odds ratio (95% confidence interval) = 3.07 (1.27-7.50), P=.013.

Conclusions

Vitamin D deficiency is associated with increased severity of radiation-induced acute proctitis. Investigating the underlying mechanisms of this association and evaluating the effectiveness of vitamin D therapy in preventing radiation-induced acute proctitis is warranted.

Introduction

Radiation-induced injury to normal tissues is a common side effect of radiation therapy in cancer patients. Acute radiation proctitis occurs during or shortly after radiation to the pelvic region. Characteristic symptoms include diarrhea, urgency, rectal pain, and, uncommonly, rectal bleeding. The incidence of proctitis is closely associated with the applied radiation therapy technique. Despite use of techniques with lower fraction size, which reduces normal tissues injury, acute proctitis still occurs in a high proportion of patients following pelvic radiation therapy (1). Even though acute radiation proctitis is usually self-limited, it impairs the quality of life of patients. Moreover, patients may not tolerate the radiation therapy and may discontinue treatment, which can affect the outcomes (2).

The pathophysiology of radiation enteropathy involves DNA damage and intestinal epithelial cell death, leading to mucosal barrier disruption and subsequent inflammatory responses (3). Except for therapy-related factors, predictors of radiation intestinal injury are not well understood. A number of medical comorbidities increase the risk and severity of radiation intestinal injury, such as hypertension, diabetes mellitus, vascular diseases, and inflammatory bowel disease (IBD) (4). Notably, patients with IBD have a lower gastrointestinal tolerance to radiation and an increased risk of acute and chronic radiation enteropathy 5, 6. Pre-existing inflammation, impaired mucosal barrier functions, and vasculitis may explain the intolerance to radiation in IBD patients (6). Therefore, medical conditions associated with mucosal immune dysregulation and barrier dysfunction may increase the risk of radiation intestinal injury.

Cumulative evidence links vitamin D with regulation of immune responses. Vitamin D, specifically the active metabolite 1,25-dihydroxyvitamin D (1,25[OH]2D), displays anti-inflammatory properties 7, 8, 9. Recent studies introduced vitamin D deficiency as a possible risk factor for various autoimmune diseases including IBD 10, 11 and cancers (12). A couple of studies also showed that lower vitamin D level is associated with increased susceptibility to chemical-induced mucosal damage through impaired mucosal barrier functions and exaggerated inflammatory responses 13, 14. Accordingly, vitamin D may affect susceptibility to intestinal radiation injury, although direct evidence does not exist in this regard. Given the association of vitamin D deficiency with cancer risk, it is common for cancer patients undergoing radiation therapy to have a low vitamin D level. Therefore, we aimed to investigate the association between serum vitamin D level and acute radiation proctitis in cancer patients undergoing pelvic radiation therapy. We hypothesized that lower vitamin D level is associated with increased severity of radiation proctitis in these patients.

Section snippets

Study population

This prospective observational study was conducted from July to September 2013 at the Radiotherapy Oncology department of the Omid University Hospital in the Isfahan city (Iran). Men with prostate or bladder cancers and women with bladder or gynecologic cancers referred for pelvic radiation therapy were consecutively enrolled. Therapeutic plan consisted of 6 to 7 weeks of radiation therapy with a total dose of 60 to 70 Gy (18-MV photons) and applied 4-field box technique using the Saturn 20

Results

The total study period, from obtaining blood samples to measuring RTOG grades of all patients, took place during the autumn of 2013. A total of 102 eligible patients were evaluated during the study period. Blood samples of 4 patients were lost. Finally, data of 98 patients (age = 62.8 ± 9.1 years, 57.1% male) were included in the analyses. According to the post hoc analysis, the computed achieved study power was 0.71 with this sample size. Cancer types included 41 prostate cases (41.8%), 33

Discussion

Mucosal barrier disruption and subsequent inflammatory responses are major mechanisms of intestinal injury following exposure to ionizing radiation (3). A pre-existing dysfunctional mucosal barrier and dysregulated immune response, as in IBD patients, can exacerbate radiation enteropathy 5, 6. We found an association between vitamin D deficiency and increased severity of radiation proctitis in cancer patients. To our knowledge, the role of vitamin D in radiation-induced intestinal injury has

Conclusions

In conclusion, vitamin D deficiency is associated with increased severity of radiation-induced proctitis in cancer patients undergoing pelvic radiation therapy. These results should be interpreted cautiously according to the study limitations. Considering no other similar report, further studies with larger sample of patients and use of objective measures of radiation intestinal injury are required in this regard. Also, studies are required to investigate whether vitamin D deficiency is

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  • Cited by (0)

    This work was supported by Isfahan University of Medical Sciences grant 391464.

    Conflict of interest: none.

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