International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationVitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients
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.
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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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This work was supported by Isfahan University of Medical Sciences grant 391464.
Conflict of interest: none.