Radiation Therapy–Induced Cutaneous Events Treated with High-Dose Vitamin D
Radiation dermatitis is a common and often severe complication of radiation therapy that affects more than 90% of patients undergoing treatment, with half of these individuals experiencing grade 2 toxicity, according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events.31,32 Radiation damage to basal keratinocytes and hair follicle stem cells disrupts the renewal of the skin’s outer layer, while a surge of free radicals causes irreversible DNA damage.33 Symptoms of radiation dermatitis can vary from mild pink erythema to tissue ulceration and necrosis, typically within 1 to 4 weeks of radiation exposure.34 The resulting dermatitis can take 2 to 4 weeks to heal, notably impacting patient quality of life and often necessitating modifications or interruptions in cancer therapy.33
Prior studies have demonstrated the use of high-dose VD to improve the healing of UV-irradiated skin. A randomized controlled trial investigated high-dose vitamin D3 to treat experimentally induced sunburn in 20 healthy adults. Compared with those who received a placebo, participants receiving the oral dose of 200,000 IU of vitamin D3 demonstrated suppression of the pro-inflammatory mediators tumor necrosis factor α (P=.04) and inducible nitric oxide synthase (P=.02), while expression of tissue repair enhancer arginase 1 was increased (P<.005).35 The mechanism of this enhanced tissue repair was investigated using a mouse model, in which intraperitoneal 25(OH)D was administered following severe UV-induced skin injury. On immunofluorescence microscopy, mice treated with VD showed enhanced autophagy within the macrophages infiltrating UV-irradiated skin.36 The use of high-dose VD to treat UV-irradiated skin in these studies established a precedent for using VD to heal cutaneous injury caused by ionizing radiation therapy.
Some studies have focused on the role of VD for treating acute radiation dermatitis. A study of 23 patients with ductal carcinoma in situ or localized invasive ductal carcinoma breast cancer compared the effectiveness of topical calcipotriol to that of a standard hydrating ointment.37 Participants were randomized to 1 of 2 treatments before starting adjuvant radiotherapy to evaluate their potential in preventing radiation dermatitis. In 87% (20/23) of these patients, no difference in skin reaction was observed between the 2 treatments, suggesting that topical VD application may not offer any advantage over the standard hydrating ointment for the prevention of radiation dermatitis.37
Benefits of high-dose oral VD for treating radiation dermatitis also have been reported. Nguyen et al38 documented 3 cases in which patients with neuroendocrine carcinoma of the pancreas, tonsillar carcinoma, and breast cancer received 200,000 IU of oral ergocalciferol distributed over 2 doses given 7 days apart for radiation dermatitis. These patients experienced substantial improvements in pain, swelling, and redness within a week of the initial dose. Additionally, a case of radiation recall dermatitis, which occurred a week after vinorelbine chemotherapy, was treated with 2 doses totaling 100,000 IU of oral ergocalciferol. This patient also had improvement in pain and swelling but continued to have tumor-related induration and ulceration.39
Although topical VD did not show significant benefits over standard treatments for radiation dermatitis, high-dose oral VD appears promising in improving patient outcomes of pain and swelling more rapidly than current practices. Further research is needed to confirm these findings and establish standardized treatment protocols.