Sirolimus for Extracranial Arteriovenous Malformations: A Scoping Review of the Evidence in Syndromic and...

Arteriovenous malformations (AVMs) are rare, high-flow, vascular anomalies that can occur either sporadically or as part of a genetic syndrome. AVMs can progress with serious morbidity and even mortality if left unchecked. Sirolimus is an mTOR inhibitor that is effective in low-flow vascular malformations; however, its role in AVMs is unclear. This scoping review investigates the current evidence base around the use of sirolimus for AVMs. Twenty-one reports encompassing a total of 60 patients with AVMs treated with systemic sirolimus were included. Sirolimus was predominantly used as an adjunct or salvage therapy. Response was variable overall; however, there was a more consistent benefit in patients with PTEN hamartoma syndrome (PHTS)-associated AVMs, where PI3K/AKT/mTOR pathway dysregulation provides a molecular basis for sirolimus efficacy. Standardised outcome reporting, routine molecular profiling, and larger multicentre collaboration are needed to better define the role of sirolimus for AVMs, particularly as part of multimodal care.