Evidence map›Paper›PMID 34537546›Full record

ArticleInternational journal of pediatric otorhinolaryngology2021

Acetylsalicylic acid suppression of the PI3K pathway as a novel medical therapy for head and neck 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 and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of pediatric otorhinolaryngology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Treatments and Outcomes of Pediatric Head and Neck Lymphatic Malformations: A 20-Year Single Institution Experience.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2025
    Article
  3. Article
  4. Alpelisib for the treatment of PIK3CA-related head and neck lymphatic malformations and overgrowth.Genetics in medicine : official journal of the American College of Medical Genetics · 2022
    Article
  5. Somatic activatingHGG advances · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Juliana Bonilla-VelezDivision 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.
Kathryn B WhitlockDivision of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA, USA.
Sheila GantiDivision of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA, USA.
Kaitlyn ZennerDivision 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.
Chi Vicky ChengCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
Dana M JensenCenter for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA.
Minh-Hang M PhamCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
Ryan M MitchellDivision of Pediatric Otolaryngology, Seattle Children's Hospital, Seattle, WA, USA; Department of Otolaryngology-Head and Neck Surgery, Indiana University, Indianapolis, IN, USA.
William DobynsCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
Randall A BlyDivision 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.
James T BennettCenter 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.
John P DahlDivision 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.
Jonathan A PerkinsDivision 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.
Seattle Children's Hospital · US

Funding

Research Training in OtolaryngologyT32DC000018 · NIDCD · UNIVERSITY OF WASHINGTON · PI STONE, JENNIFER S. · 1989 to 2023
$7.8M
Mosaic: post-zygotic mutations in vascular malformationsR01HL130996 · NHLBI · SEATTLE CHILDREN'S HOSPITAL · PI BENNETT, JAMES T · 2016 to 2024
$7.5M
Characterization of the PIK3CA mutation spectrum in lymphatic malformationsF32HL147398 · NHLBI · SEATTLE CHILDREN'S HOSPITAL · PI ZENNER, KAITLYN · 2019 to 2019
$64k
NHLBI NIH HHS F32 HL147398NHLBI NIH HHS R01 HL130996NIDCD NIH HHS T32 DC000018
6 · The paper itself

Abstract

objectivesHead 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.

methodsRetrospective 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].

resultsFifty-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.

conclusionASA 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.

Indexed as

Lymphatic AbnormalitiesPhosphatidylinositol 3-KinasesAspirinChildHumansPilot ProjectsRetrospective StudiesAspirinPhosphatidylinositol 3-KinasesAcetylsalicylic acidLymphatic abnormalitiesLymphatic malformationPI3KTreatment

Identifiers

PMID34537546
PMCPMC9632366
OpenAlexW3192950573

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.