Liguori, V., Guillemin, C., Pesce, G.F., Mirimanoff, R.O., & Bernier, J. (1997). Double-blind, randomized clinical study comparing hyaluronic acid cream to placebo in patients treated with radiotherapy. Radiotherapy and Oncology, 42, 155–161.

To determine if prophylactic use of hyaluronic acid cream postpones acute radiodermatitis or reduces its severity and to evaluate the efficacy of hyaluronic acid to delay the onset of necrosis or to accelerate recovery in case of ulceration

Hyaluronic or placebo cream was applied to irradiated skin area twice daily. The first application was one-to-two hours after the radiation therapy session and the second was in the evening. The topic treatment was continued over a six-week period.

• The study sample (N = 134) was comprised of male (n = 74) and female (n = 60) patients with head and neck (n = 90), breast (n = 30), or pelvic cancer (n = 14).
• Mean age was 59.9 years in the treatment group and 55.7 years in the placebo group.

The study took place at Ospedale San Giovanni and Centre Hospitlier Universitaire, both in Switzerland.

The study used a randomized placebo-controlled double-blind trial design.

• Skin was evaluated using a scale of 0–5 (0 = normal skin, 1 = light epidermal irritation, 2 = erythema with dry desquamation, 3 = exudate less than 50%, 4 = exudate more than 50%, 5 = ulcer).
• Healing was reported using a 1–4 scale (1 = minimum and maximum lesion diameters, 2 = lesion cleaning, 3 = beginning of proliferation process and proliferation of tissue granulation, 4 = re-epithelialization).
• Physician global judgment on therapeutic efficacy was evaluated using a 0–3 verbal scale (0 = poor, 1 = fair, 2 = good, 3 = excellent).

• Acute radiodermatitis scores were significantly higher in the placebo group (p < 0.01 at 3–7 weeks and p < 0.05 at 8–10 weeks).
• Global efficacy judgment by both physician and patient showed a significant difference in favor of the intervention (p < 0.01 to p < 0.05).
• A statistically significant difference in skin reactions was reported in favor of the intervention group based on global efficacy (p < 0.01).
• A significant difference was reported for the head and neck group in favor of the intervention following observation at week 3 (p = 0.0003), week 4 (p = 0.0001), and week 5 (p = 0.0035).

The prophylactic use of hyaluronic acid cream is shown to reduce the incidence of high-grade radiodermatitis.

• Very small numbers for evaluation of healing.
• Did not allow statistical evaluation to be carried out for this aspect of the study.
• No discussion of evaluation tools or the reliability or validity of tool.