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.