AUTHOR=Neirotti A. , Barat V. , Coppo P. , La Selva R. , Manicone R. , Cotti R. , Sensini M. , Mussa A. , Gatto M. , Farri F. , Basso M. E. , Fagioli F. 

TITLE=Therapy with sirolimus in vascular anomalies: the experience of two Italian centers on 14 pediatric patients

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 12 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2024.1434493

DOI=10.3389/fped.2024.1434493

ISSN=2296-2360

ABSTRACT=Introduction-Vascular anomalies (VAs) constitute a heterogeneous group of tumors and malformations capable of inducing significant clinical events in specific patients, such as the compression of vital organs, pain, functional impairment, or acquired coagulopathy. Molecular investigations into the underlying mechanisms of VAs have unveiled frequent involvement of the PI3K/AKT/mTOR pathway. Sirolimus, a specific mTOR inhibitor, has emerged as a potential therapeutic agent; however, its routine clinical application in complex VAs is currently restricted by a lack of extensive clinical experience. Methods-We administered Sirolimus from 2015 to 2024 to 14 pediatric patients with various types of vascular anomalies in two Italian centers, subjecting them to clinical and instrumental follow-up to investigate its efficacy and the possible occurrence of adverse events. Results-86% of patients reported an overall improvement or stability of their vascular anomalies. We also assessed toxicity, noting a low prevalence of life-threatening adverse events: only 1 case of sepsis was reported in a patient with a severe clinical condition, and 4 cases of recurrent aphthosis (28%). The most common side effect was dyslipidemia, with 43% of patients developing hypercholesterolemia (21%) or hypertriglyceridemia (21%), generally not reaching severe levels. Discussion-In line with data in the literature, according to our experience, medical therapy with Sirolimus should be considered in pediatric patients affected by vascular anomalies.