[Efficacy of Sirolimus in treating complex lymphatic anomalies with thoracic involvement in children]

Objective: To evaluate the efficacy and safety of sirolimus for thoracic lesions in children with complex lymphatic anomalies (CLA). Methods: A retrospective cohort study was conducted on 41 children with thoracic-involved CLA in Department No.2 of Respiratory Medicine of Beijing Children's Hospital, Capital Medical University, from December 2013 to December 2024. Clinical data, including general information, clinical manifestations, imaging evaluations, and follow-up records, were analyzed. Patients were grouped by sirolimus exposure. Disease improvement was defined as improvement in at least one imaging or clinical parameter. Intergroup comparisons were conducted using t-test, Mann-Whitney U test, χ² test and Fisher's exact test. Adverse events were identified and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0. Results: The cohort included 22 males and 19 females, with onset age (6±4) years and presentation age (8±4) years. The treatment group (20 cases) and non-treatment group (21 cases) showed no significant baseline differences (all P>0.05), including gender composition, age at onset, baseline disease duration, follow-up time, surgical rate, clinical presentations (chronic cough, expectoration, dyspnea, recurrent respiratory infections), and imaging findings (mediastinal lesions, interlobular septum thickening, ground-glass opacity, thoracic duct abnormalities). Sirolimus improved disease outcomes: improvement rate, pleural effusion resolution, and reduced progression and mortality (80% (16/20) vs. 14% (2/21), 14/17 vs. 7/18, 10% (2/20) vs. 52% (11/21), all P<0.05). Clinical symptoms improved in 16 cases (80%), while imaging improvement was observed in only 2 patients (10%) after sirolimus treatment. Adverse events occurred in 75% (15/20) of treated patients, totaling 25 incidents dominated by oral mucositis (7 episodes, 28%) and gastrointestinal distress (5 episodes, 20%). According to CTCAE, Grade 1, 2, and 3 events accounted for 72%, 16%, and 12% of adverse events, respectively. Conclusions: Sirolimus shows overall efficacy and safety in children with thoracic-involved CLA. Radiologic improvements lag behind clinical symptom relief, with potential irreversible lesions.