Introduction
Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors that primarily present in young children and are considered locally aggressive or borderline malignant tumors.1,2 TA and KHE may be a continuum of one disease as they both share histologic features and key to their pathophysiology is disrupted vasculogenesis and abnormal endothelial cell proliferation.3,4 KHE/TA are uniquely associated with Kasabach Merritt Phenomenon (KMP), which manifests as thrombocytopenia and a consumptive coagulopathy (hypofibrinogenemia and elevated d-Dimer), with variable bleeding5–7. KMP is considered a risk factor for severe KHE/TA and has a historical mortality rate of 20-30%5–8. Apart from the known risks with KMP, a validated risk stratification in KHE/TA has not been established3,9.
KHE and TA tumors rarely completely resolve, and full surgical resection is typically not possible given the infiltrative nature of this tumor. More than half of patients experience recurrence of symptoms or KMP after cessation of therapy.10–14 Front-line medical therapy for KHE/TA is not standardized, but steroids, vincristine, and sirolimus are the most commonly used systemic medications.4,15 The optimal therapy (ies), schedule, dosing, and duration of treatment are unknown10,11,16–27. Experts have proposed either vincristine and steroids or sirolimus as standard treatment4,28. A multi-center, prospective, randomized trial (NCT02110069) was recently undertaken to determine optimal front-line therapy (sirolimus vs vincristine) for high risk KHE/TA but closed early due to poor enrollment. Future prospective studies will likely be limited by disease rarity as well as the availability of sirolimus as a highly efficacious oral agent. It is unlikely that prospective data will be generated to establish a standard optimal treatment and to determine durability of response to treatment.
This study was designed and conducted to address these existing gaps in knowledge about treatment for KHE/TA. The primary objective of this multicenter retrospective cohort study was to compare 3-month and 6-month response rates to sirolimus versus vincristine. Secondary objectives included comparison of other treatment regimens and assessment of durability of treatment response.