Author(s)
Kelsey A. Loy, MD
Jonathan A. Perkins, DO
J. Nathaniel Perkins, DO
Randall A. Bly, MD
Ezgi Mercan Keremoglu, PhD
Seth D. Friedman, PhD
Michael Bindschadler, PhD
Affiliation(s)
University of Washington; Seattle Children’s Hospital;
Abstract:
Introduction: Mosaic mutations in PIK3CA cause head and neck lymphatic malformations (HNLM). The PI3K inhibitor, Alpelisib, has been FDA-approved for the targeted therapy in patients with PIK3CA-related conditions. Accurately assessing targeted therapy efficacy requires quantification of malformation change. We used three-dimensional photos (3DP) and magnetic resonance imaging (MRI) to quantify facial and malformation volume and composition. Our objectives were: 1) compare facial volumes in HNLM patients to controls and 2) examine serial 3DP and MRI in HNLM patients to quantify change in facial/malformation volume while on Alpelisib. We hypothesize that HNLM patients have larger baseline facial volumes than controls, and that targeted therapy consistently reduces facial/malformation volume.
Methods: Pediatric HNLM patients on Alpelisib were enrolled in a prospective IRB-approved cohort study. Subjects underwent serial 3DP and MRI at =6-month intervals. 3D Slicer was used to generate segmentation masks, from which facial volumes were determined. MATLAB was used to standardize regions of interest and quantitate malformation volume and composition from MRI. Normalized volume measures were determined using age-sex-matched controls or patient nasion-basion distance for 3DP and MRI respectively. Percent change in volume was analyzed.
Results: Four patients were enrolled. Median age at treatment initiation was 3.5 years (range 2-12 years). Median drug therapy duration was 13.5 months (range 12-25 months). All patients had larger baseline facial volumes compared to controls (median 34%, range 16%-63%). All patients had reduction in facial volume on 3DP (median -19%, range -5% to -26%) and malformation volume on MRI (median -17%, range -1% to -40%). Treatment resulted in reduction in malformation fat and fluid.
Conclusions: HNLM patients have larger baseline facial volumes than controls, consistent with facial overgrowth. Alpelisib reduced 3DP measured facial volume and MRI measured malformation volume in all patients over 1 year.