Hydration During Breast Radiotherapy May Lower Skin Toxicity

To the Editor: Women undergoing whole breast radiation are marked by a high incidence (35–55%) of radiationrelated breast and axillary skin dermatitis (1–3). In particular, women with relatively large bra sizes have the greatest hazard for radiation-related dermatitis (1,4) due to lengthy on-beam times for breast irradiation and dose inhomogeneity, sometimes manifesting toxicity as skin peeling or bleeding induced by abrasion or ulceration. Alkaline water, an important donor of free hydroxyl ions, has emerged as a commercial water source that demonstrates therapeutic skin benefits (5–9), buffers cancer tumor-related acidity (10,11), and impacts cancer biology by altering disease progression in mice (11,12). To investigate whether alkaline water could lower rates of radiation-related breast dermatitis, we obtained approval from University Hospitals of Cleveland (Cleveland, Ohio) to conduct a blinded randomized phase II trial of alkaline (pH 9) versus distilled (pH 7) water in women with breast cancer between July 2010 through October 2012 (Fig. 1, Table 1). All patients provided written informed consent. Enrollees underwent conventional two-field, threefield, or four-field breast radiation therapy to a dose of 46 Gy (breast and regional lymph nodes) with a tumor bed boost to a total of 62 Gy in 31 daily fractions (13). For trial, they consumed a 250-mL (i.e., approximately eight ounces) glass of pH 9 alkaline water or pH 7 distilled water daily before and after each radiation treatment. A Jupiter Orion Water Ionizer with Ultra Filter (JP109; Jupiter Ionizers, Hudson, FL) with platinum-titanium electrodes made room temperature pH 9 or pH 7 water at a flow rate of 2.5 L/min and an oxidative reduction potential (ORP) of 250 mV. The first 10 women enrolled in an alkaline water safety lead-in portion of the clinical trial that monitored alkaline water treatment effect by urine pH pretherapy (day 0) and on-treatment (day 33). A paired sample t-test (a = 0.05, SPSS 18.0, SPSS Inc., Chicago, IL) assessed change in urine pH. Afterward, 35 women were randomly assigned water to drink. Physician and nurse observers unaware of water group randomization scored skin toxicity in all women both weekly and at a 1-month follow-up appointment according to the Common Terminology Criteria for Adverse Events (version 3.0) dermatitis scale. Here, a score of 0 represents no change from baseline, one faint erythema or desquamation, two brisk erythema or patchy moist desquamation restricted to skin folds and creases, three moist desquamation other than skin folds and creases associated with bleeding induced by minor trauma or abrasion, four skin necrosis or ulceration of full thickness dermis and spontaneous bleeding, and five death. The rates of skin dermatitis were tabulated and compared by logistic regression at a 5% level of significance (SPSS 18.0), adjusting for age at treatment and breast separation (i.e., the distance between the midsternum and midaxillary line) as a surrogate for bra size. Overall, the two water groups were well balanced with regard to the baseline characteristics (Table 1). A total of 31% of patients in the distilled water and 41% of patients in the alkaline water groups received chemotherapy prior to radiation therapy. Average breast separation was 22.8 cm (standard deviation [SD] = 3.2 cm) in the distilled water group and 23.6 cm (SD = 3.4 cm) in the alkaline water group (p = 0.37). Among the 10 safety lead-in patients who received pH 9 alkaline water during radiation therapy, the pretherapy day 0 mean urine pH was 5.6 (SD = 0.7). The on-treatment day 33 mean urine pH was 6.1 (SD = 1.0, p = 0.32). The incidence of grade 2 or higher skin dermatitis was 38% (95% CI: 23–56%) in the alkaline water group and 38% (95% CI: 18–61%) in the distilled water group (p = 0.90). There were no grade 3 or Address correspondence and reprint requests to: Charles Kunos, MD, PhD, Summa Cancer Institute, Department of Radiation Oncology, 161 North Forge Street, Akron, OH, USA, or e-mail: kunosc@summahealth.org