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

Alpelisib Infiltrating lipomatosis Lymphatic malformation PIK3CA-related overgrowth spectrum (PROS) Precision medicine

Journal

Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831

Informations de publication

Date de publication:
11 2022
Historique:
received: 12 05 2022
revised: 26 07 2022
accepted: 27 07 2022
pubmed: 7 9 2022
medline: 9 11 2022
entrez: 6 9 2022
Statut: ppublish

Résumé

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

Identifiants

pubmed: 36066547
pii: S1098-3600(22)00891-7
doi: 10.1016/j.gim.2022.07.026
pii:
doi:

Substances chimiques

Alpelisib 08W5N2C97Q
Phosphatidylinositol 3-Kinases EC 2.7.1.-
Class I Phosphatidylinositol 3-Kinases EC 2.7.1.137
Thiazoles 0
PIK3CA protein, human EC 2.7.1.137

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2318-2328

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL130996
Pays : United States
Organisme : NHLBI NIH HHS
ID : F32 HL147398
Pays : United States

Informations de copyright

Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of Interest R.A.B. is a cofounder and holds a financial interest of ownership equity with Wavely Diagnostics, Inc. and Eigen Health, Inc. He is a consultant and stockholder at SPIWay, LLC. These are not related to this study. All other authors declare no conflict of interest.

Auteurs

Tara L Wenger (TL)

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. Electronic address: Tara.Wenger@seattlechildrens.org.

Sheila Ganti (S)

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.

Catherine Bull (C)

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.

Erika Lutsky (E)

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

James T Bennett (JT)

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.

Kaitlyn Zenner (K)

Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA.

Dana M Jensen (DM)

Center for Developmental Biology and Regenerative Medicine, Seattle Children's Hospital, Seattle, WA.

Victoria Dmyterko (V)

Center for Developmental Biology and Regenerative Medicine, Seattle Children's Hospital, Seattle, WA.

Ezgi Mercan (E)

Craniofacial Center, Seattle Children's Hospital, Seattle, WA.

Giri M Shivaram (GM)

Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA; Interventional Radiology, Department of Radiology, Seattle Children's Hospital, Seattle, WA.

Seth D Friedman (SD)

Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA.

Michael Bindschadler (M)

Division of Neurology, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA.

Madeleine Drusin (M)

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.

Jonathan N Perkins (JN)

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.

Ada Kong (A)

Investigational Drug Services, Seattle Children's Hospital, Seattle, WA.

Randall A Bly (RA)

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.

John P Dahl (JP)

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.

Juliana Bonilla-Velez (J)

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.

Jonathan A Perkins (JA)

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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