Sirolimus for the treatment of kaposiform hemangioendothelioma: In a trough level-dependent way.

With the accumulation of clinical practice, sirolimus is now widely viewed as an effective agent in kaposiform hemangioendothelioma (KHE) treatment using a dose based on experience. Therefore, this retrospective research aimed to provide evidence-based suggestions on the most appropriate dose and trough level of sirolimus. All unresectable KHE cases diagnosed at our center from January 2016 to December 2019 were included. Sirolimus monotherapy was initiated when there was no sign of Kasabach-Merritt phenomenon (KMP) at a dose of 0.8 mg/m2 twice a day in order to keep the trough level at 5-20 ng/mL. Patients' clinical information, tumor volume change, trough level fluctuation, and complication occurrence were all recorded. Efficacy represented by tumor shrinkage speed and safety manifested by complication grades were compared between different trough level groups (5-10 vs. 10-15 vs. >15 ng/mL). Twenty-one patients (10 girls and 11 boys) were enrolled. There were eight patients in the 5-10 ng/mL group, seven in the 10-15 ng/mL group, and six in the more than 15 ng/mL group. Trough level over 10 ng/mL manifested better efficacy in tumor shrinkage (t-test, p = 0.011) while a level over 15 ng/mL had no further benefit in efficacy (t-test, p = 0.65). In addition, tumors at a central location reacted better to sirolimus (t-test, p = 0.022). No significant differences were observed in complication occurrence among different concentrations, although boys seemed to be at higher risk of more severe complications (>grade II, χ2 -test, p = 0.009, odds ratio = 4.52, range = 1.20-17.24). It proved to be most efficacious in the management of KHE at a trough level between 10 and 15 ng/mL. Such concentration was safe and well tolerated.