Acetylsalicylic acid suppression of the PI3K pathway as a novel medical therapy for head and neck lymphatic malformations: Aspirin Treatment for Lymphatic Malformations

Juliana Bonilla-Velez, Kathryn B. Whitlock, Sheila Ganti, Kaitlyn Zenner, Chi Vicky Cheng, Dana M. Jensen, Minh Hang M. Pham, Ryan M. Mitchell, William Dobyns, Randall A. Bly, James T. Bennett, John P. Dahl, Jonathan A. Perkins

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number110869
JournalInternational Journal of Pediatric Otorhinolaryngology
Volume151
Early online dateAug 5 2021
DOIs
StatePublished - Dec 2021
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank Eden Palmer for her assistance with preparation of the figures. Kaitlyn Zenner was supported by The National Heart, Lung, and Blood Institute (PI: Kaitlyn Zenner; F32 HL147398) and The National Institute on Deafness and Other Communication Disorders via the University of Washington Otolaryngology Research Training Program (PI: Dr. Jennifer Stone, PhD; T32 DC000018 ). Lymphatic malformation genotyping was supported by 1RO1 HL103996 from the National Heart, Lung, and Blood Institute (PI: William B. Dobyns).

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

  • Acetylsalicylic acid
  • Lymphatic abnormalities
  • Lymphatic malformation
  • PI3K
  • Treatment

PubMed: MeSH publication types

  • Journal Article

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