Surgery or whole-brain radiotherapy (WBRT) for the management of brain metastasis of hepatocellular carcinoma (HCC) is associated with improved survival. However, the efficacy of multi-tyrosine kinase inhibitors (TKIs) and possible bleeding complications have not been studied in these patients. Therefore, this study aimed at investigating TKI safety and efficacy in these patients. We retrospectively reviewed 39 patients who underwent surgery or WBRT for brain metastasis of HCC. Intracranial tumor bleeding rates were compared between patients who did and did not receive TKIs. Survival outcomes were analyzed using the log-rank and Cox regression tests. A total of 22 and 7 patients received sorafenib and lenvatinib, respectively. The intracranial tumor bleeding rates were 61.5% and 70% in patients who did and did not receive TKIs, respectively (p > 0.99). Survival analysis revealed craniotomy (adjusted odds ratio [AOR]: 0.45, p = 0.04), a higher Karnofsky Performance Score (AOR: 0.97, p < 0.01), and TKI use (AOR: 0.26, p < 0.01) were positive prognostic factors for overall survival. TKIs were associated with better survival outcomes in patients who underwent surgery or WBRT for brain metastasis of HCC and did not increase intracranial bleeding. Therefore, TKIs are efficacious and safe for treating brain metastasis of HCC.
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