Pinnix, C., Perkins, G.H., Strom, E.A., Tereffe, W., Woodward, W., Oh, J. L., . . . Yu, T.K. (2011). Topical hyaluronic acid vs. standard of care for the prevention of radiation dermatitis after adjuvant radiotherapy for breast cancer: Single-blind randomized phase III clinical trial. International Journal of Radiation Oncology, Biology, Physics, 83(4), 1089–1094.

To determine effectiveness of an hyaluronic acid-based emulsion to reduce development of greater than or equal to grade 2 radiodermatitis in women receiving adjuvant breast radiation

Women were randomly assigned to use topical hyaluronic acid on the medical or lateral half of the irradiated breast, and a control, petrolatum-based substance to the other half of the breast. Agents were to be applied three times daily beginning one day before the start of radiation therapy and continuing throughout the treatment period. Agents were not applied within four hours prior to radiation treatment. Patients were not to apply other topical products unless otherwise instructed by the physician. All other agents used were to be documented.

• The study sample (N = 65) was comprised of female patients with breast cancer.
• Mean age of the sample was 55.4 years.
• Of patients in the sample, 93% had medium or large breast size.
• Patients were treated with intensity-modulated radiation therapy (IMRT), receiving 50 Gy in 25 daily fractions with or without a boost of 10–16 Gy. 
• Fifteen percent of the study sample were African American and 15% were Hispanic.

The study took place at MD Anderson Cancer Center in Houston, TX.

Patients were undergoing active anti-tumor treatment.

The study used a single-blind controlled trial design.

The National Cancer Institute Common Toxicity Criteria (version 3) for skin toxicity grading was used.

Twelve percent dropped out of the study for a variety of reasons. In weeks 1–5 there were no differences between groups in severity of dermatitis in intent to treat and evaluable patient groups. In week 6 the side of the breast treated with hyaluronic acid was scored worse (p = 0.009). No associations were found between severity of dermatitis and body mass index, breast size, smoking history, diabetes or radiation dose. Forty-nine percent of control areas developed greater than grade 2 dermatitis compared to 61% of evaluable areas using hyaluronic acid emulsion. Overall, 1.4% developed grade 3 radiodermatitis.

Prophylactic application of a hyaluronic acid-based emulsion did not reduce the incidence of greather than or equal to grade 2 radiodermatitis in this group of women receiving adjuvant radiation therapy for breast cancer.

• The sample size was small, with less than 100 participants.
• Findings are not generalizable to other patient groups based on radiation therapy dosage and site.
• No information regarding patient adherence to the protocol is provided. 
• Procedures state that the attending physician had discretion to order additional treatments; however, no information is provided as to whether this occurred or not. 
• The study was ended early.

In the study, hyaluronic acid gel was not as effective as a petrolatum based gel for reducing the severity of radiodermatitis. Authors noted that the radiation therapy approach was forward-planned IMRT, which may also have led to significant reduction in severe dermatitis, since the percent of patients with grade 3 dermatitis in the study was lower than reported elsewhere. Other studies that showed hyaluronic acid to be effective were in patients who had higher doses of radiation. It is also not clear if there is a difference in effect of hyaluronic acid for prevention or treatment of radiodermatitis.