Acetylsalicylic acid suppression of the PI3K pathway as a novel medical therapy for head and neck lymphatic malformations.
Acetylsalicylic acid suppression of the PI3K pathway as a novel medical therapy for head and neck lymphatic malformations.
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DOI：
10.1016/j.ijporl.2021.110869
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发表时间：
2021-12
影响因子：
1.5
通讯作者：
Perkins JA
中科院分区：
文献类型：
--
作者：
Bonilla-Velez J;Whitlock KB;Ganti S;Zenner K;Cheng CV;Jensen DM;Pham MM;Mitchell RM;Dobyns W;Bly RA;Bennett JT;Dahl JP;Perkins JA
头颈部淋巴畸形(HNLM)是由PIK3CA的功能获得体细胞突变引起的。乙酰水杨酸(ASA/阿司匹林)被认为通过抑制PI3K途径来限制PIK3CA突变的肿瘤的生长。我们试图确定ASA是否对HNLM有益。回顾病例系列患者(0-18岁)服用阿司匹林(3-5 mg/kg/d)治疗HNLM(2010-2018)。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。根据患者/护理者报告的症状或HNLM大小[完全(缓解)、部分(减少)或稳定]的变化来确定治疗反应。53名患者接受ASA，23名(43%)接受(中位年龄10岁，IQR6-14)。与下降的患者相比，接受ASA的患者更有可能出现广泛的畸形：宫外分娩治疗程序、双侧畸形、口腔位置、≥2侵入性治疗或气管切开术(p<；0.05)。所有有组织可用的患者都有PIK3CA突变(13/23)。治疗指征包括口腔疼痛/水泡(12，52%)，反复疼痛/肿胀(6，26%)，或突然/持续性肿胀(5，22%)。治疗方案一般为每日1片81 mg(19.83%)，疗程3~12个月(8.42%)。18名患者(78%)报告了治疗依从性。18名患者症状改善[78%；疼痛(9，39%)和肿胀(8，35%)减轻]。治疗后部分缓解(14，61%)或完全缓解(4，17%)。3名患者出现口腔水泡出血，停药后症状缓解。阿司匹林似乎是一种耐受性良好、低风险的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的大小。有必要进行进一步的前瞻性随机研究，以全面评估适应症、安全性和有效性。4级。
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 < 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. 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 4.
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影响因子：
168.9
作者：
Burn, John;Gerdes, Anne-Marie;Macrae, Finlay;Mecklin, Jukka-Pekka;Moeslein, Gabriela;Olschwang, Sylviane;Eccles, Diane;Evans, D. Gareth;Maher, Eamonn R.;Bertario, Lucio;Bisgaard, Marie-Luise;Dunlop, Malcolm G.;Ho, Judy W. C.;Hodgson, Shirley V.;Lindblom, Annika;Lubinski, Jan;Morrison, Patrick J.;Murday, Victoria;Ramesar, Raj;Side, Lucy;Scott, Rodney J.;Thomas, Huw J. W.;Vasen, Hans F.;Barker, Gail;Crawford, Gillian;Elliott, Faye;Movahedi, Mohammad;Pylvanainen, Kirsi;Wijnen, Juul T.;Fodde, Riccardo;Lynch, Henry T.;Mathers, John C.;Bishop, D. Timothy
通讯作者：
Bishop, D. Timothy
人类癌症中PIK3CA癌基因的突变。
影响因子：
8.8
作者：
Karakas, B;Bachman, KE;Park, BH
通讯作者：
Park, BH
影响因子：
3.4
作者：
Balakrishnan, Karthik;Bauman, Nancy;Elluru, Ravindhra G.
通讯作者：
Elluru, Ravindhra G.
影响因子：
39.2
作者：
Dube, Catherine;Rostom, Alaa;Moher, David
通讯作者：
Moher, David
影响因子：
8
作者：
Adams, Denise M.;Trenor, Cameron C., III;Azizkhan, Richard G.
通讯作者：
Azizkhan, Richard G.