Intermediate and advanced hepatocellular carcinoma treated with the antiangiogenic agent sorafenib. Evaluation with unenhanced and contrast-enhanced ultrasonography

To evaluate the sonographic changes observed in hepatocellular carcinoma (HCC) post antiangiogenic treatment with sorafenib.Twenty one intermediate or advanced HCC patients (19 men, 2 women; mean age: 66.8 years; 32 target tumors-TTs) received sorafenib as monotherapy and were studied with unenhanced ultrasonography (US) and contrast-enhanced ultrasonography (CEUS) with a second generation echo-enhancer (SonoVue) at bimonthly intervals. Changes in lesional size, echotexture and enhancement were evaluated. Response was classified according to RECIST (Response Evaluation Criteria In Solid Tumors) and modified (m) RECIST.Cystic changes were detected on US in 4 patients (7 lesions); CEUS showed a significant (51-100%) decrease of viable, enhancing TTs in the aforementioned patients. Four additional patients (5 lesions) showed a 73-87% decrease of their viable TTs on CEUS, but no changes on US. 13/21 patients showed less than 30% decrease, no change, or increase of their viable TTs. Based on the last sonographic evaluation, response was as follows: RECIST- Complete Response, CR (n=0), Partial Response, PR (n=1), Stable Disease, SD (n=16), Progressive Disease, PD (n=4); mRECIST- CR (n=2), PR (n=6), SD (n=11), PD (n=2). The 8 responders (CR+PR) according to mRECIST had significantly longer mean overall survival (OS) compared to the 13 non-responders (21.5 vs 12.2 months, p=0.018, Kaplan-Meier method). However, statistical significance was reduced (p=0.065) after adjustment for BCLC and Child's class.US may occasionally detect changes indicative of the effect of sorafenib on HCC, but CEUS is required to evaluate and grade post-therapeutic reduction of tumoral enhancement. The latter is likely to correlate with OS.