阿司匹林抑制 PI3K 通路作为头颈部淋巴管畸形的一种新的医学治疗方法。
Acetylsalicylic acid suppression of the PI3K pathway as a novel medical therapy for head and neck lymphatic malformations.
机构信息
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.
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.
出版信息
Int J Pediatr Otorhinolaryngol. 2021 Dec;151:110869. doi: 10.1016/j.ijporl.2021.110869. Epub 2021 Aug 5.
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.
目的
头颈部淋巴管畸形（HNLM）是由 PIK3CA 获得性功能体细胞突变引起的。阿司匹林（ASA/aspirin）被认为通过抑制 PI3K 通路来限制 PIK3CA 突变肿瘤的生长。我们试图确定 ASA 是否对 HNLM 有益。
方法
对 2010 年至 2018 年期间接受 ASA（3-5mg/kg/天）治疗 HNLM 的患者（0-18 岁）进行回顾性病例系列研究。记录临床和治疗特征、患者报告的症状改善、药物耐受性、依从性和并发症。治疗反应通过患者/护理人员报告的症状变化或 HNLM 大小[完全（解决）、部分（减少）或稳定]来确定。
结果
53 例患者接受 ASA 治疗，23 例（43%）接受治疗（中位年龄 10 岁，IQR 6-14）。与拒绝治疗的患者相比，接受 ASA 治疗的患者更有可能存在广泛的畸形：宫外分娩处理程序、双侧畸形、口腔位置、≥2 种侵袭性治疗或气管切开术（p<0.05）。所有有组织样本的患者均存在 PIK3CA 突变（13/23）。治疗指征包括口腔疼痛/水疱（12，52%）、复发性疼痛/肿胀（6，26%）或突发/持续性肿胀（5，22%）。治疗方案通常为每天服用 1 片 81mg 片剂（19，83%），持续 3-12 个月（8，42%）。18 例患者（78%）报告了治疗依从性。18 例患者症状改善[疼痛减轻（9，39%）和肿胀减轻（8，35%）]。治疗结果为部分（14，61%）或完全缓解（4，17%）。3 例患者出现口腔水疱出血，停药后出血缓解。
结论
ASA 似乎是一种耐受性良好、风险低的 HNLM 治疗药物。这项初步研究表明，它通常可以改善症状并缩小 HNLM 大小。需要进一步进行前瞻性、随机研究，以全面评估适应证、安全性和疗效。
证据水平
4 级。
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