High Responsiveness of Head and Neck Kaposiform Hemangioendothelioma Without Kasabach–Merritt Phenomenon to Sirolimus Monotherapy

OBJECTIVE: Sirolimus is the cornerstone therapy for Kaposiform hemangioendothelioma (KHE). The purpose of this study was to evaluate whether anatomical location independently predicts radiologic response to sirolimus monotherapy in KHE without Kasabach-Merritt phenomenon (KMP). PATIENTS AND METHODS: We included 21 patients with head and neck KHE without KMP and 50 matched patients with non-head and neck KHE without KMP, all treated with sirolimus monotherapy in five tertiary referral centers in China. The primary outcome was the 12-month radiologic response rate (defined as ≥ 20% tumor volume reduction on MRI). The Cochran-Mantel-Haenszel test was used to adjust for matching factors, and multivariate logistic regression was performed to identify independent predictors of treatment response. RESULTS: The head and neck group achieved a 100% 12-month radiologic response rate versus 76% in the non-head and neck group (adjusted p = 0.012). A near-complete involution rate was 81% versus 44% (adjusted p = 0.003). Multivariate analysis confirmed that head and neck location was the only independent predictor of both radiologic response (OR = 12.34, 95% CI: 1.45-105.21, p = 0.021) and near-complete involution (OR = 5.87, 95% CI: 1.89-18.23, p = 0.002). No disease progression occurred in head and neck cases, while 4% of non-head and neck lesions progressed. Safety and quality-of-life outcomes were comparable between groups. CONCLUSION: Anatomical location is a significant independent predictor of sirolimus monotherapy efficacy in KHE without KMP. The exceptional radiologic response rate and favorable safety profile support sirolimus monotherapy as a sufficient first-line therapy for head and neck KHE, providing evidence for location-based precision treatment strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04775173. SUMMARY: What is known about this subject: Kaposiform hemangioendothelioma (KHE) without Kasabach-Merritt phenomenon (KMP) can cause functional impairments, but sirolimus is used as therapy. Efficacy of sirolimus monotherapy may vary by anatomical location, though evidence is limited. This study aimed to evaluate location-specific responses to address this gap. WHAT THIS STUDY ADDS: Head and neck KHE lesions exhibit a prominent response to sirolimus monotherapy, with 100% radiologic response at 12 months, which is an independent predictor of treatment efficacy. Near-complete involution was higher in head and neck cases (81% vs. 44%), with no disease progression. Sirolimus monotherapy is recommended for head and neck KHE without KMP, while non-head and neck lesions may need aggressive approaches.