MRI for Response Assessment of Extensive Lymphatic Malformations in Children Treated With Sirolimus.

Background: Extensive lymphatic malformations (LM) may cause substantial morbidity. The mTOR (mammalian target of rapamycin) inhibitor sirolimus shows promise for treating vascular anomalies, though response assessment is not standardized. Objective: To retrospectively characterize changes on MRI in extensive LM in children treated with sirolimus. Methods: Twenty-five children treated with sirolimus for extensive LM were included. Baseline MRI was defined as MRI closest to therapy initiation; follow-up MRI was defined as most recent MRI while on therapy. Two pediatric radiologists independently determined MRI lesion volume by tracing lesion contours on all slices (normalized to patient body mass index) and signal by placing an ROI on lesions' dominant portion (normalized to CSF signal), on baseline and follow-up T2-weighted sequences. Inter-reader agreement was determined, and values averaged for further analysis. Volume and signal changes were compared with patient, lesion, and therapy characteristics. Results: Mean (±SD) interval between sirolimus initiation and follow-up MRI was 22.1±13.8 months. Mean lesion volume index on baseline and follow-up MRI was 728 mL/m2 ± 970 mL/m2 and 345 mL/m2±501 mL/m2, respectively (p 10% (mean volume change -46.4%±28.2%). Volume change was inversely correlated with age (r=-0.466, p=.02). Mean volume change was -64.7%±25.4% in children under 2 years old versus -32.0%±21.6% in remaining children (p=.008). Mean volume change was -58.1%±24.0% for craniocervical lesions versus -35.5%±28.2% for body and extremity lesions (p=.03). Mean lesion signal ratio on baseline and follow-up MRI was 0.81±0.29, and 0.59±0.26, respectively (p .05). Inter-reader agreement for volume index change was excellent [intraclass correlation coefficient (ICC)=0.983] and for signal ratio change was moderate-good (ICC=0.764). Conclusion: Sirolimus treatment for extensive LM in children is associated with significant reductions in volume and signal on T2-weighted MRI. The volume decrease is greater in younger children and craniocervical lesions. Clinical Impact: The results may facilitate development of standardized MRI-based criteria for assessing pharmacotherapy response of vascular malformations.