Sirolimus for pediatric cervicofacial lymphatic malformation; a systematic review and meta-analysis.

Objective: This study is a systematic review and meta-analysis of the efficacy and safety of sirolimus in the management of pediatric cervicofacial lymphatic malformations (LMs). Data Sources: EMBASE, Medline, Scopus, and Cochrane databases were searched, along with the reference list of all included articles. Review Methods: The study protocol was registered with PROSPERO and a systematic literature search strategy was designed and conducted with the aid of a medical librarian. All studies including case reports were included, with pooled analysis of raw data. A meta-analysis was conducted of magnetic resonance imaging (MRI), clinical, and airway outcomes. Results: Thirteen case series and five individual case reports were included. Meta-analysis showed 78% (95% CI 57%–94%) of 62 patients had a reduction in LM volume, on MRI criteria, by 20% or more, and 32% (95% CI 11%–57%) had a reduction of 50% or more. Further meta-analysis showed 97% (95% CI 88%–100%) of 78 patients reported some clinical improvement on sirolimus. Sirolimus may be of particular value in management of airway LMs; out of 27 tracheostomy-dependent patients, meta-analysis showed 33% (95% CI 1%–78%) were decannulated after starting sirolimus. Individual patient meta-analysis on 24 individuals showed a statistically significant better response to sirolimus when initiated under the age of 2 years. Conclusion: This review and meta-analysis support the efficacy of sirolimus in pediatric LMs of the head, neck, and airway. A large multi-center trial is needed to further explore its role and limitations. Laryngoscope, 2023.