Background and Objectives: Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors in children historically associated with significant morbidity and mortality. This study was conducted to determine first line therapy in the absence of available prospective clinical trials. Methods: Patients from 17 institutions diagnosed with KHE/TA between 2005-2020 with > 6 months follow-up were included. Response rates to sirolimus and vincristine were compared at 3 and 6 months. Durability of response and response to other treatment modalities were also evaluated. Results: Of 159 unique KHE/TA subjects, Kasabach-Merritt phenomenon (KMP) was present in 64 (40.3%) and only 2 patients were deceased (1.3%). Over 60% (n=96) demonstrated treatment response at 3 months and >70% (n=114) by 6 months (no significant difference across groups). The vincristine group had higher radiologic response at 3 months compared to sirolimus (72.7% vs 20%, p=0.03) but there was no differences between these groups at 6 months. There were no differences in rates of recurrent or progressive disease between vincristine and sirolimus. Conclusions: In this large, multicenter cohort of 159 patients with KHE/TA, rates of KMP were consistent with historical literature but the mortality rate (1.3%) was much lower. Overall treatment response rates were high (>70%) and there were no significant difference in treatment response or durability of disease comparing sirolimus to vincristine. Our results support individualized treatment decision plans depending on clinical scenario and patient/physician preferences. Response criteria and response rates reported here will be useful for guiding future treatment protocols for vascular tumors.

Background and Objectives: Initially developed as immunosuppressive agents, mTOR inhibitors are currently used widely in the management of vascular malformations and tumors. The incidence of infectious complications in the vascular anomalies (VA) population is not well defined. The goal of this systematic review was to better define the types and severity of reported infectious complications in patients with VAs treated with mTOR inhibition. Methods: This was a systematic review conducted following PRISMA guidelines evaluating all research articles focused on infectious complications in patients with VAs treated with sirolimus or everolimus. Thirty articles including 1181 total patients and 315 infections (in 290 unique patients) were ultimately included. Results: The majority of infections were viral upper respiratory (n=137, 54%), followed by pneumonia (n=52, 20%), and cutaneous infections (n=20, 8%). There were 6 total infection-related fatalities, which all occurred in patients younger than 2 years. Only 1 case of Pneumocystis jirovecii pneumonia (PJP) was reported. This was in an infant with KHE who was also treated with steroids and did not receive PJP prophylaxis. Almost 1/3 (n=95, 32%) of infectious complications were graded 3 to 4 according to CTCAE criteria. Details of patient age, subtype of VA, and timing of infection were lacking from many reports. Conclusions: Most infectious complications reported in patients with VA on mTOR inhibitors were viral respiratory infections and non-severe. Bacteremia, infectious fatalities, and PJP are exceedingly rare. Future studies are needed to clarify the spectrum of infectious risks in VA patients and to provide guidance for infection prevention.