490 Variation in Epidermal Mutation Burden after Field Treatment with Topical 5-Fluorouracil

Cutaneous field cancerization resulting from chronic ultraviolet radiation has a high burden of clinical and subclinical actinic damage. Field treatment with topical 5-fluorouracil (5-FU) is effective in treating field cancerization. Based on the concept of field cancerization, resulting from the accumulation of genetic alterations, we hypothesised that field therapies are effective at reducing future keratinocyte cancer formation through decreasing the epidermal mutation load. In our study, adult patients aged 45 years or older with evidence of photodamaged forearms were recruited. A 2mm (diameter) punch biopsy was collected from an area devoid of skin cancers and hyperkeratinisation on the dorsal forearm, to calculate the epidermal mutation burden before and after field treatment with topical 5-FU. A saliva sample was collected for reference genomic DNA. The number of keratotic lesions on the target forearm was assessed clinically before and after field treatment. A patient-reported symptom score was used to assess pain, erythema, itching, crusting, burning, scaling and swelling. Of the 12 patients recruited, the average percentage decrease in the number of keratotic lesions following 5-FU field treatment was 68% (-5 – 100%). Patients completed an average of 40 (21 – 56) applications of 5-FU. The average symptom score was 7.9 out of 21 (4 – 18). The change in epidermal mutation burden following field treatment was variable (P = 0.81). It was reduced in half of the patients, but this did not correlate with the clinical response nor symptoms. In conclusion, topical 5-FU as a field treatment was not associated with a decrease in epidermal mutation burden despite a clinical reduction in keratotic lesions on the photodamaged forearm and symptom severity. Instead of reducing field cancerization through decreasing the mutation load, an alternative mechanism of action of topical 5-FU is possible, such as through stimulation of local immune response.