Validation of Photograph-Based Toxicity Score for Topical 5-Fluorouracil Cream Application

Abstract

Background: An objective tool quantifying the toxicity of 5-fluorouracil (5-FU) from photographs was recently reported, and its reliability was confirmed. Objective: The aim of this study was to validate the photograph-based toxicity score. Methods: Photograph-based toxicity scores of participants assigned to the 5-FU arm of a randomized placebo-controlled trial were tested for correlations with their patient-reported symptom scores and baseline characteristics. Results: Each pair of individual and overall scores of patient-reported symptoms and photograph-based toxicity was correlated at 2 and 4 weeks (correlation coefficient range, 0.34-0.95; P < .001 for all). Older age, more actinic keratoses, previous topical 5-FU use, and more keratinocyte carcinomas on the face and ears in the previous 5 years were correlated with increased 5-FU toxicity at 2 weeks ( P < .05). An increase in the total number of 5-FU applications during the trial was correlated with less severe toxicity at 2 weeks ( P < .001), but with increased toxicity at 4 weeks ( P < .001). Conclusion: This study provides evidence for construct validity of the photograph-based 5-FU toxicity score. The tool can be used to objectively measure 5-FU toxicity in clinical or research setting, and it can be a prototype for toxicity measurements of other topical medications.