Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network

Annegret Holm,Veronika Dvorakova,Päivi Salminen,Friedrich G Kapp,Sophie Duignan,Maroeska Te Loo,Leo Schultze Kool,Laurence M Boon,Eulalia Baselga,Nader Ghaffarpour,Miikka Vikkula,Charlotte M Niemeyer,Veronica Celis,Alan D Irvine,Jochen Rössler

doi:10.3389/fped.2021.697960

Abstract

Extensive lymphatic malformations (LMs) of the head and neck region may require tracheostomy to secure the airway. Treatment of these life-threatening LMs is usually multimodal and includes sclerotherapy and surgery, among others. Recently, systemic therapy with sirolimus has been introduced as an effective treatment for venous and lymphatic malformations; its efficacy and safety profile in patients with extensive LM requiring tracheostomy are, however, as yet not fully known. We performed a retrospective, multicenter review and identified 13 patients with an extensive LM of the head and neck region, who previously underwent placement of tracheostomy and subsequently received sirolimus treatment with the aim to improve the local respiratory situation and remove the tracheostomy. Under sirolimus therapy, tracheostomy could be reversed in 8/13 (62%) patients, a further 2/13 (15%) patients improved markedly, and removal of the tracheostomy was planned at the time of writing, while 3/13 (23%) patients showed insufficient or absent response to sirolimus, rendering tracheostomy reversal not feasible. The median duration of sirolimus treatment until removal of tracheostomy was 18 months (range, 8 months to 5.6 years). Adverse events of sirolimus therapy were common [10/13 (77%) patients], yet the majority of these were mild [9/10 (90%) patients] and only one severe adverse event was recorded, with ulceration and necrosis at a catheter insertion site. In conclusion, sirolimus can be considered an effective and safe salvage treatment in patients with extensive LM even after placement of a tracheostomy, as closure of the latter was possible in the majority of patients (62%) of our retrospective cohort. A better understanding of when to start sirolimus therapy, of the duration of treatment, and of factors allowing the prediction of treatment response will require further investigation.

Highlights

Extensive lymphatic malformations (LMs) of the head and neck region can be life-threatening due to infiltration of vital structures of the airway and may require early intubation, e.g., by ex utero intrapartum treatment (EXIT) procedure, mechanical ventilation, and even long-term placement of tracheostomy to secure the airway and/or feeding tubes to realize nutrition
Sirolimus has recently been introduced as an alternative systemic treatment option in complex vascular anomalies [3, 4] and it has been further demonstrated that neonates with extensive LM benefit from lowdose systemic treatment with sirolimus immediately after birth, while experiencing only mild side effects [5]
Tracheostomy had been performed in 13 patients with lifethreatening LM of the head and neck region prior to treatment with sirolimus

Summary

Introduction

Extensive lymphatic malformations (LMs) of the head and neck region can be life-threatening due to infiltration of vital structures of the airway and may require early intubation, e.g., by ex utero intrapartum treatment (EXIT) procedure, mechanical ventilation, and even long-term placement of tracheostomy to secure the airway and/or feeding tubes to realize nutrition. The majority of extensive cervical LMs are diagnosed pre- or post-natally and generally require treatment early during the neonatal period. The complexity and the variable presentation of extensive head and neck LM complicate the understanding of the natural history and the response to different treatment modalities of this rare disease. Sirolimus has recently been introduced as an alternative systemic treatment option in complex vascular anomalies [3, 4] and it has been further demonstrated that neonates with extensive LM benefit from lowdose systemic treatment with sirolimus immediately after birth, while experiencing only mild side effects [5]

Results

Discussion

Conclusion