Refractory Head and Neck Lymphatic Malformation in Infants Treated With Sirolimus: A Case Series

Abstract

BackgroundExtensive and complex head and neck lymphatic malformations (LMs) are challenging to manage through traditional therapy. The purpose of this retrospective study was to assess the efficacy and safety of sirolimus in infants with refractory head and neck LMs.MethodsSirolimus was administered orally on a continuous dosing schedule. Patients were seen every month for the first three months and then subsequently every three months. The primary endpoints were safety and efficacy based on clinical and radiological evaluations.ResultsEight patients, refractory to standard care, were enrolled and received sirolimus continuously. After 12 months of follow-up, the response and safety to medication was evaluated: all patients experienced reductions in LMs bulk, ranging from modest to significant. Some minor adverse effects were reported: mouth sores, eczema, gastrointestinal reaction, dyslipidemia, and neutropenia.ConclusionSirolimus was efficient in children with refractory head and neck LMs and was well tolerated.

Efficacy of sirolimus in children with lymphatic malformations of the head and neck

“…In all, 28 case series and case reports and two prospective trials [ 31 , 36 ] including 105 children treated with sirolimus for LM of the head and neck, were included in this review (Table 1 ) [ 12 – 39 ]. Due to the inclusion criteria, the age of the patients ranged from newborn to 17 years.…”

“…In most studies, sirolimus was administered orally at an initial dosage of 0.8 mg/m 2 per dose, twice daily at 12-h intervals [ 13 , 17 , 19 , 21 , 23 – 26 , 28 , 34 , 36 , 39 ]. In other studies, this was modified to 0.8 mg/m 2 per day [ 29 ], 0.8 mg per day in three doses [ 32 ], or 0.08 mg/kg per day [ 30 ].…”

“…The target blood level of sirolimus was ≤ 20 ng/mL in all studies but slightly differed. The target blood level was 10–15 ng/mL in seven studies [ 14 , 17 , 20 , 23 , 24 , 26 , 39 ], 5–15 ng/mL in four studies [ 16 , 28 , 31 , 34 ] and 4–12 ng/mL in two studies [ 25 , 30 ]. In one study each, 3.5–6 ng/mL [ 30 ], 4–8 ng/mL [ 21 ], 4–10 ng/mL [ 38 ], 4–13 ng/mL [ 36 ], 5–12 ng/mL [ 33 ], 10–12 ng/mL [ 27 ], 10–13 ng/mL [ 19 ] and 12–20 ng/mL [ 35 ] were the target concentrations.…”

“…Twenty-three studies commented on possible adverse events associated with and probably being a result of sirolimus therapy [ 15 – 17 , 19 – 31 , 33 – 39 ]. In five studies no patients experienced side effects [ 15 , 22 , 29 , 30 , 37 ].…”

“…In five studies no patients experienced side effects [ 15 , 22 , 29 , 30 , 37 ]. In the other 18 studies, different adverse effects were reported [ 16 , 17 , 19 – 21 , 23 – 28 , 31 , 33 – 36 , 38 , 39 ], the most common were hyperlipidemia, neutropenia and infections such as cellulitis. There was no reporting of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE).…”