Genomics of Basal Cell Carcinoma of skin reveals distinct mutational landscape and the role of HIPPO-YAP pathway in disease progression

Background: Locally advanced basal cell carcinoma (laBCC) is a rare cancer for which Sonic Hedgehog Inhibitors (SHHIs) are the gold standard treatment for patients who have declined surgery or radiotherapy.We present the factors associated with achieving a complete response (CR) with SHHIs in the CARADERM real-life database.Methods: Patients treated with SHHIs (Gorlin syndrome excluded) from the database were evaluated.Initial laBCC size, photo-induced nature (corresponding to the cephalic end), age, histological subtype, radiation-induced nature, previous local or systemic treatment and tumour ulceration were assessed.A multivariate Cox proportional hazards model was run to look for an association between these factors and the achievement of CR.Missing data were managed by multiple imputation methods.Results: Among the 453 patients analysed, the median tumour size was 34mm (interquartile range 20-64).At 1 year, the CR rate was 52%, and 76% at 2 years.The factors found to be independently associated with CR were: