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Alpelisib for the treatment of PIK3CA-related head and neck lymphatic malformations and overgrowth

  • Tara L. Wenger
    Correspondence
    Correspondence and requests for materials should be addressed to Tara L. Wenger, Seattle Children's Hospital, 4800 Sand Point Way NE, Mail Stop OA.9.220, Seattle, WA 98105
    Affiliations
    Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA

    Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA
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  • Sheila Ganti
    Affiliations
    Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA

    Division of Pediatric Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA
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  • Catherine Bull
    Affiliations
    Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA

    Division of Pediatric Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA
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  • Erika Lutsky
    Affiliations
    Division of Pediatric Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA
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  • James T. Bennett
    Affiliations
    Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA

    Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Hospital, Seattle, WA
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  • Kaitlyn Zenner
    Affiliations
    Department of Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA
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  • Dana M. Jensen
    Affiliations
    Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Hospital, Seattle, WA
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  • Victoria Dmyterko
    Affiliations
    Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Hospital, Seattle, WA
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  • Ezgi Mercan
    Affiliations
    Craniofacial Center, Seattle Children's Hospital, Seattle, WA
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  • Giri M. Shivaram
    Affiliations
    Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA

    Interventional Radiology, Department of Radiology, Seattle Children’s Hospital, Seattle, WA
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  • Seth D. Friedman
    Affiliations
    Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA
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  • Michael Bindschadler
    Affiliations
    Division of Neurology, Department of Pediatrics, Seattle Children’s Hospital, Seattle, WA
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  • Madeleine Drusin
    Affiliations
    Division of Pediatric Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA

    Department of Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA
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  • Jonathan N. Perkins
    Affiliations
    Division of Pediatric Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA

    Department of Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA
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  • Ada Kong
    Affiliations
    Investigational Drug Services, Seattle Children’s Hospital, Seattle, WA
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  • Randall A. Bly
    Affiliations
    Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA

    Division of Pediatric Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA

    Department of Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA
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  • John P. Dahl
    Affiliations
    Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA

    Division of Pediatric Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA

    Department of Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA
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  • Juliana Bonilla-Velez
    Affiliations
    Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA

    Division of Pediatric Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA

    Department of Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA
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  • Jonathan A. Perkins
    Affiliations
    Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA

    Division of Pediatric Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA

    Department of Otolaryngology–Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA
    Search for articles by this author
Published:September 06, 2022DOI:https://doi.org/10.1016/j.gim.2022.07.026

      Abstract

      Purpose

      PIK3CA-related overgrowth spectrum (PROS) conditions of the head and neck are treatment challenges. Traditionally, these conditions require multiple invasive interventions, with incomplete malformation removal, disfigurement, and possible dysfunction. Use of the PI3K inhibitor alpelisib, previously shown to be effective in PROS, has not been reported in PIK3CA-associated head and neck lymphatic malformations (HNLMs) or facial infiltrating lipomatosis (FIL). We describe prospective treatment of 5 children with PIK3CA-associated HNLMs or head and neck FIL with alpelisib monotherapy.

      Methods

      A total of 5 children with PIK3CA-associated HNLMs (n = 4) or FIL (n = 1) received alpelisib monotherapy (aged 2-12 years). Treatment response was determined by parental report, clinical evaluation, diary/questionnaire, and standardized clinical photography, measuring facial volume through 3-dimensional photos and magnetic resonance imaging.

      Results

      All participants had reduction in the size of lesion, and all had improvement or resolution of malformation inflammation/pain/bleeding. Common invasive therapy was avoided (ie, tracheotomy). After 6 or more months of alpelisib therapy, facial volume was reduced (range 1%-20%) and magnetic resonance imaging anomaly volume (range 0%-23%) were reduced, and there was improvement in swallowing, upper airway patency, and speech clarity.

      Conclusion

      Individuals with head and neck PROS treated with alpelisib had decreased malformation size and locoregional overgrowth, improved function and symptoms, and fewer invasive procedures.

      Keywords

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