Long-term treatment with sirolimus for pediatric vascular anomalies

Although sirolimus has emerged as a safe and effective treatment modality for unresectable vascular anomalies, comprehensive long-term follow-up data remain scarce in the current literature. This study aims to evaluate the long-term clinical experience of pediatric patients with vascular anomalies who received sirolimus treatment over five years.

We retrospectively analysed 17 pediatric patients with vascular anomalies treated with sirolimus over five years in Asan Medical Center. Lesion volumes were measured via 3D volumetric MRI and normalized to body surface area (BSA). Adverse drug effects and therapeutic responses were periodically assessed. Longitudinal response was modeled using generalized additive mixed-effects models (GAMM). Tapering protocols were initiated after 24 months of stability, and alpelisib switch was considered for sirolimus-refractory cases with documented PIK3CA mutations.

With a median follow-up of 78 months, the overall response rate was 81.3%. GAMM analysis demonstrated a significant non-linear volume reduction (p < 0.0001), characterized by a rapid initial response within 12-24 months followed by a sustained plateau. Tapering was successful in 70.6% of patients without disease progression. Three patients with suboptimal responses transitioned to alpelisib; those with sufficient follow-up achieved additional volume reduction within 12 months. Long-term sirolimus use was well-tolerated, with no Grade ≥ 3 adverse events reported.

Sirolimus provides sustained long-term efficacy and safety in pediatric vascular anomalies. The observed treatment plateau suggests that dose tapering is a viable strategy for sustained responders. Furthermore, genotype-guided transition to alpelisib offers an effective alternative for refractory PIK3CA-mutant cases.