OBJECTIVE: Sirolimus has shown promise in treating lymphatic malformations (LMs)
however, previous studies were all single-arm clinical trials. Prior studies have reported that some LMs lesions can spontaneously reduce, which poses a potential confounding factor in evaluating therapeutic outcomes. Our study aimed to objectively assess the effectiveness and safety of oral sirolimus for LMs in the head and neck by comparing the outcomes in a control group. METHODS: This real-world study involved 57 children with LMs from 2020 to 2023 at Beijing Children's Hospital. The patients were divided into non-intervention and oral sirolimus groups. The primary outcome was lesion volume change on MRI, and the secondary outcome was improvement in clinical symptoms. Safety was assessed based on adverse reactions (regular laboratory tests and patient follow-ups) and sirolimus blood concentrations in the oral sirolimus group. RESULTS: Twenty-one children were enrolled in the non-intervention group (M/F = 14/7), with a median age of 33 months (interquartile range [IQR], 9-53.5)
36 children were enrolled in the oral sirolimus group (M/F = 15/21), with a median age of 24 months (IQR, 7.5-51.25). The median volume reduction ratio in the non-intervention group was 0.08 (IQR, 0.30-0.40), and eight cases (38.1%) were effective. The median volume reduction ratio in the oral sirolimus group was 0.67 (IQR, 0.40-0.92), and 33 cases (91.7%) were effective. Clinical symptoms improved in 9 (42.9%) children in the non-intervention group and 35 (97.2%) in the oral sirolimus group. The effective rate and volume changes differed statistically significantly (P <
0.001). The most common adverse reaction in the oral sirolimus group was an increase in myocardial enzyme levels (n = 23, 63.9%), followed by oral ulcers (n = 16, 44.4%). The overall blood concentration of sirolimus was low during the drug administration in the oral sirolimus group, among which 10 (27.8%) children had a mean blood concentration <
5 ng/ml. CONCLUSION: Sirolimus significantly reduced lesion volume and improved clinical symptoms in most patients with LMs, especially those with macrocystic components. Conservative observations were only helpful in some patients, with relatively modest volume changes.