Genetic classification helps with precise sirolimus treatment in Slow Flow Vascular Malformations
Description
Background: Targeted therapy of slow-flow vascular malformations (SFVM) needs genetic classification. The efficacy differences between genotypes are still vague. Objective: To investigate the genomic spectrum of SFVM and sirolimus efficacy differences between various genotypes and phenotypes. Methods: In a genetic cohort study based on a biobank, participants prospectively received biopsy and genetic sequencing to investigate the genomic spectrum of SFVM. In the sirolimus cohort study, participants of 3 groups based on genetic classifications prospectively received sirolimus for 6 months. Results: 263 samples from 214 participants were enrolled in the genetic cohort, yielding an overall genetic diagnosis rate of 60.98%. We classified the genetic subtypes as PIK3CA-related vascular malformation (PRVM), TEK-related vascular malformation (TRVM), special types (ST), and non-diagnosed types (ND). 41 participants received a 6-month sirolimus treatment. The total response rate (tRR) and objective response rate (ORR) were 87.80% and 48.78%. ORR of the mutated group (PRVM+TRVM, 64.29%) was significantly higher than ND (15.38%). tRR and ORR of Klippel-Trenaunay syndrome (KTS, 55.56%, 33.33%) were lower than non-KTS SFVM (96.88%, 53.13%). Limitations: Non-placebo, nonrandomization, small sample size, and single-center design. Conclusion: Genetic classification may help to indicate targeted therapy. Non-KTS PRVM and TRVM benefit more from sirolimus treatment in lesion regression.