Background: The ART score (a point score for the assessment of retreatment with transarterial chemoembolization, TACE) has been recently developed in Austria to differentiate patients who may benefit from multiple sessions of TACE for hepatocellular carcinoma (HCC) treatment. The primary aim of the study was to test the validity of the ART score in an Italian study cohort. The secondary aims were to evaluate overall survival (OS) and clinical determinants of improved survival in patients treated with multiple TACE sessions. Methods: The ART score and the clinical outcome of 51 consecutive patients with HCC submitted to multiple TACE sessions from April 2002 to December 2009 were retrospectively analyzed. Results: Median OS was 26.0 months (95% confidence interval 18.4-33.6) with 1-, 3- and 5-year survival rates of 75, 33 and 11%, respectively). Thirty-three patients had an ART score of 0-1.5 and in 18 it was ≥2.5, but in our patient series, the ART score was not found to be a predictor of survival (p = 0.173). At univariate analysis, tumor extent (uni- vs. bilobar: 34.0 vs. 9.0 months; p < 0.001), Child-Pugh score before the second TACE (A vs. B7 vs. B8-9: 26.0 vs. 16.0 vs. 5.0 months; p = 0.005) and Child-Pugh score increase between the first and second TACE (absent vs. + 1 point vs. + ≥2 points: 27.0 vs. 4.0 vs. 5.0 months; p < 0.001) were statistically related with survival. At multivariate analysis, only Child-Pugh score increase remained a significant predictor of worse survival (p = 0.001, hazard rate = 11.6). Conclusions: The ART score was not found to work as an objective tool to guide TACE retreatment in our Italian patient series, only the Child-Pugh score increase was an independent predictor of a shorter survival.

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BR55 appears to be useful in the prediction of response to sorafenib in a xenograft model of HCC.

BackgroundDevelopment of escape pathways from antiangiogenic treatments was reported to be associated with enhanced tumor aggressiveness and rebound effect was suggested after treatment stop. Aim of the study was to evaluate tumor response simulating different conditions of administration of antiangiogenic treatment (transient or definitive treatment stop) in a mouse model of hepatocellular carcinoma.MethodsSubcutaneous tumors were created by inoculating 5×106 Huh7 cells into the right flank of 14 nude mice. When tumor size reached 5–10 mm, mice were divided in 3 groups: group 1 was treated with placebo, group 2 was treated with sorafenib (62 mg/kg via gavage) but temporarily suspended from day +5 to +9, whereas in group 3 sorafenib was definitively stopped at day +5. At day +13 all mice were sacrificed, collecting masses for Western-Blot analyses. Volume was calculated with B-mode ultrasonography at day 0, +5, +9, +11 and +13. VEGFR2-targeted contrast-enhanced ultrasound using BR55 (Bracco Imaging) was performed at day +5 and +13 and elastonosography (Esaote) at day +9 and +11 to assess tumor stiffness.ResultsMedian growth percentage delta at day +13 versus day 0 was 197% (115–329) in group 1, 81% (48–144) in group 2 and 111% (27–167) in group 3. Median growth delta at day +13 with respect to day +5 was 79% (48–127), 37% (−14128) and 81% (15–87) in groups 1, 2 and 3, respectively. Quantification of targeted-CEUS at day +13 showed higher values in group 3 (509 Arbitrary Units AI, range 293–652) than group 1 (275 AI, range 191–494) and group 2 (181 AI, range 63–318) (p = 0.033). Western-Blot analysis demonstrated higher VEGFR2 expression in group 3 with respect to group 1 and 2.ConclusionsA transient interruption of antiangiogenic treatment does not impede restoration of tumor response, while a definitive interruption tends to stimulate a rebound of angiogenesis to higher level than without treatment.