Hyaluronic acid 0.2 % cream for preventing radiation dermatitis in breast cancer patients treated with postoperative radiotherapy: A randomized, double-blind, placebo-controlled study

Abstract

Introduction: This randomized trial evaluated the efficacy and safety of the prophylactic use of a hyaluronic acid (HA) 0.2 %-containing cream to reduce acute radiodermatitis in breast cancer patients undergoing adjuvant radiotherapy (RT).

Methods: Candidates for conventionally-fractionated or hypofractionated adjuvant RT for unilateral stage I-III breast cancer were randomized 1:1 to the HA cream or neutral comparator applied twice daily from 14 days before starting until 14 days after completing local RT. The primary endpoint was the development of acute skin dermatitis of grade ≥2 according to RTOG scale at the end of RT.

Results: The study closed early after 86 of the planned 120 patients were enrolled because of an unexpectedly low frequency of acute skin toxicity. Cumulative acute grade ≥2 radiodermatitis was lower with the HA cream (21.1 %) than the comparator group (35.3 %) but did not reach statistical significance in the primary endpoint (p = 0.3). At the end of RT, acute dermatitis grade ≥1 occurred in 92 % of patients undergoing conventionally-fractionated RT and 50 % in the hypofractionation subgroup. Physician-based RTOG grading scale and quantitative assessment with skin reflectance spectrophotometry (SRS) measures were comparable in detecting skin toxicity. However, an increase in SRS values was detectable a week before the first signs of radiodermatitis were depicted using RTOG scores.

Conclusion: Compared to physician-based grading, SRS enabled earlier detection of skin toxicity and may be used as a valid and effective tool for assessing radiodermatitis. Prophylactic topical HA may help mitigate this toxicity; however adequately powered prospective trials are needed.

Keywords: Acute radiation dermatitis; Breast cancer; Hyaluronic acid; Patients reported outcomes; Radiotherapy; Skin reflectance spectrophotometry; Skin toxicity.

Fig. 1

Areas for skin reflectance spectrophotometry (SRS) measurements. 1 axilla, 2 inframammary fold, 3 inner midline breast. Points 4 to 6 are the equivalent areas on the contralateral breast.

Fig. 2

Study design and subject disposition.

Fig. 3

Evolution of RTOG visual score ≥1 and SRS scores over time in the ITT set (n = 86). Radiodermatitis was assessed at three specific points using SRS and RTOG visual scores. A, conventional fractionation, and B, hypofractionation (Axilla). C, standard fractionation, and D, hypofractionation (Inner midline). E, conventional fractionation, and F, hypofractionation (Inframammary fold). G, Mean (SD) cumulative SRS score (AUC). Conventional fractionation follow-up period: n = 19 (0.2 % HA cream) and n = 14 (Neutral comparator); Hypofractionation follow-up period: n = 23 (0.2 % HA cream) and n = 26 (Neutral comparator). Abbreviations: AUC, area under the concentration-time curve; HA, hyaluronic acid; infram, inframammary; ITT, intention-to-treat; RTOG, Radiation Therapy Oncology Group; SRS, Skin reflectance spectrophotometry.