Acetylsalicylic acid suppression of the PI3K pathway as a novel medical therapy for head and neck lymphatic malformations.

Autor: Bonilla-Velez J; Division of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: Juliana.Bonilla-Velez@seattlechildrens.org., Whitlock KB; Division of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA, USA., Ganti S; Division of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA, USA., Zenner K; Division of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA, USA., Cheng CV; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA., Jensen DM; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA., Pham MM; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA., Mitchell RM; Division of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Department of Otolaryngology-Head and Neck Surgery, Indiana University, Indianapolis, IN, USA., Dobyns W; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA., Bly RA; Division of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA, USA., Bennett JT; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA; Division of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA., Dahl JP; Division of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA, USA., Perkins JA; Division of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle, WA, USA; Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA, USA. Electronic address: jonathan.perkins@seattlechildrens.org.
Jazyk: angličtina
Zdroj: International journal of pediatric otorhinolaryngology [Int J Pediatr Otorhinolaryngol] 2021 Dec; Vol. 151, pp. 110869. Date of Electronic Publication: 2021 Aug 05.
DOI: 10.1016/j.ijporl.2021.110869
Abstrakt: Objectives: Head and neck lymphatic malformations (HNLM) are caused by gain-of-function somatic mutations in PIK3CA. Acetylsalicylic acid (ASA/aspirin) is thought to limit growth in PIK3CA-mutated neoplasms through PI3K pathway suppression. We sought to determine if ASA could be beneficial for HNLM.
Methods: Retrospective case series of patients (0-18 years) offered ASA (3-5 mg/kg/day) for HNLM treatment (2010-2018). Clinical and treatment characteristics, patient-reported symptom improvement, medication tolerance, compliance, and complications were recorded. Treatment response was determined by change in patient/caregiver-reported symptoms, or HNLM size [complete (resolved), partial (decreased), or stable].
Results: Fifty-three patients were offered ASA, 23 (43%) accepted (median age 10 years, IQR 6-14). Compared to patients who declined, patients receiving ASA were more likely to have extensive malformations: ex-utero intrapartum treatment procedure, bilateral malformations, oral cavity location, ≥2 invasive treatments, or tracheotomy (p < 0.05). All patients with tissue available had PIK3CA mutations (13/23). Treatment indications included oral pain/blebs (12, 52%), recurrent pain/swelling (6, 26%), or sudden/persistent swelling (5, 22%). Treatment plan was commonly one 81 mg tablet daily (19, 83%) for 3-12 months (8, 42%). Therapeutic adherence was reported by 18 patients (78%). Symptoms improved in 18 patients [78%; decreased pain (9, 39%) and swelling (8, 35%)]. Treatment resulted in partial (14, 61%) or complete response (4, 17%). Three patients developed oral bleb bleeding, which resolved with medication discontinuation.
Conclusion: ASA seems to be a well-tolerated, low-risk medication for HNLM treatment. This pilot study suggests that it often improves symptoms and reduces HNLM size. Further prospective, randomized studies are warranted to comprehensively assess indications, safety, and efficacy.
Level of Evidence: Level 4.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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