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PURPOSE To investigate whether perfusion-CT (p-CT) imaging could depict the inhibition of tumor neoangiogenesis induced by Sorafenib in advanced hepatocellular carcinoma (HCC), and whether it could be useful in predicting survival during treatment. MATERIALS AND METHODS Ninety-eight p-CT examinations were performed among 29 cirrhotic patients, with advanced HCC, before and every 2 months after Sorafenib administration, on a 256-slice MDCT scanner. Perfusion parameters were considered and statistically compared, at baseline and follow-up, between non-progressor (complete response, stable disease or partial response) and progressor (progressive disease) group. Kaplan-Meier analyses estimated the time-to-survival in overall population, after stratifying patients according to mRECIST. RESULTS The group that responded to Sorafenib showed a significant reduction of values in HCC target lesions after anti-angiogenic therapy (p < 0.01), in comparison with progressor group that demonstrated an increase or no significant variation. When patients were stratified into mRECIST, higher survival rate was observed in the non-progressor group compared to the progressor (48.6% vs 28.6%), and statistically significant correlation (p=0.01) was found between percentage variation of perfusion parameters, from baseline to follow-up, and overall survival rate. CONCLUSION Quantitative analysis of perfusion parameters, represents prognostic indicators useful in assessment of response to anti-angiogenic therapy, allowing for optimization of individualized treatment.