Increasing Incidence of Brain Metastasis in Patients with Advanced Hepatocellular Carcinoma in the Era of Antiangiogenic Targeted Therapy

Abstract

Aim. Brain metastasis was regarded, until recently, as a rare and late-stage event in patients with hepatocellular carcinoma (HCC). With the prolongation of survival in patients with advanced HCC by molecular targeted agents, this may have changed. We aimed to examine whether or not the incidence of brain metastasis in these patients has increased. Methods. Between June 2005 and May 2009, 158 advanced HCC patients in total with either metastatic or locally advanced disease untreatable by locoregional therapies were enrolled in clinical trials of first-line antiangiogenic therapies. The clinicopathologic features and survival times of those who developed brain metastasis were analyzed. Results. Eleven (7%) of 158 advanced HCC patients, with a median follow-up of 26.6 months, were diagnosed with brain metastasis as a result of compatible symptoms, confirmed by brain imaging. All 11 patients had extrahepatic metastasis upon enrollment, and 10 of them had lung metastasis. The median time to brain metastasis was 9.6 months (range, 0.6–19.6 months). The median overall survival (OS) time after diagnosis of brain metastasis was 4.6 months (range, 0.7–12.6 months). Four patients received brain tumor excision, and their survival duration after brain metastasis tended to be longer than that of those who did not (median OS time, 6.1 months versus 3.1 months). Conclusions. In the era of antiangiogenic targeted therapy, the importance of brain metastasis for advanced HCC patients may have increased.