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

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. 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]. 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