Neoplastic macrovascular invasion represents an independent risk factor for dismal survival in sorafenib treatment for hepatocellular carcinoma

Aim: Sorafenib efficacy and safety in advanced hepatocellular carcinoma (HCC) have been demonstrated in two randomized international clinical trials and in clinical practice studies. Because of poor survival advantage, to identify clinical and biological parameters remains an unmet clinical need. Methods: Eighty-four patients treated with sorafenib were evaluated for response to therapy and prognostic factors possibly associated with survival. Results: Median overall survival was 8.5 months. Median duration of therapy was 2.5 months with a median daily dose of 800 mg (IQR 600-800). Dose was adjusted in 52% of patients. Radiological response to therapy showed a significant impact on survival. Child-Pugh score and neoplastic invasion of the portal system were negatively associated with survival. Continuation of sorafenib even at lower dose was positively correlated with survival. The multivariate analysis identified vascular invasion as the only independent variable: median survival of 5.5 months for neoplastic portal vein thrombosis compared to 12 months in the remaining subjects. Conclusion: A lower sorafenib daily dose is advantageous, even though the reason of this association cannot be explained at present. Neoplastic portal vein thrombosis is strongly associated with dismal survival. Alternative or complementary treatment approaches should be studied in order to improve outcome in this subgroup of patients.