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256 Usefulness of contrast enhanced perfusional sonography in the outcome of patients with hepatocellular carcinoma submitted to non-surgical treatments
POSTERS
S 102
three techniques could not avoid that in more than 20% of HCC-preLT, findings in explants were exceeding Milan criteria.
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WHAT IS THE PLACE FOR INTRA-ARTERIAL INJECTION OF 1311-LABELED-IODIZED OIL (LIPIOCIS | IN PALLIATIVE TREATMENT OF HEPATO-CELLULAR CARCINOMA?
E. Germain 1, M.N. Hilleret 1, C. Sengel 2, J.R Vuillez 3, J.R Zarski 1'4, V. Leroy 1.4.1Departemen t d'Hepatogastroenterologie, 2Service Central de
R adiologie et d 'Imagerie Mddicale, 3Service de Biophysique et Mddecine Nucldaire, 4INSERM U 548, CHU Grenoble, Grenoble, France Intra-arterial injection of 131I-labeled-Iodized Oil (Lipiocis| is a validated treatment for hepatocellular carcinoma (HCC), which has shown an impact on survival. The aim of this study was to evaluate the tolerance and the efficacy of Lipiocis | on survival and tumour response. Methods: Fifty-two HCC patients (male: 92%; age: 67• years) seen in our centre for a first session of Lipiocis | were prospectively included in the study. The main endpoint was survival at 12 months. Secondary endpoints were objective tumour response, evolution of serum a-foetoprotein level and Chil&Pugh score, and occurrence of complications. Results: Ninety-two per cent of patients were cirrhotic (alcoholic 50%, hepatitis B 15%, hepatitis C 15%). Mean Pugh score was 5.6• (Child A: 80%). Twenty-one per cent of patients had been previously treated by surgical resection, radiofrequency ablation or percutaneous ethanol injection. HCC was uninodular in 25%, multinodular but reaching less than 50% of the liver in 52%, and infiltrating more than 50% of the liver in 23% of cases. The biggest tumour size was 53• Portal vein thrombosis was present in 29% of cases. Patients were stage I according to Okuda classification in 58% and stage 0 1 according to CLIP in 54% of cases. Tumour reduction and stabilization were observed in 7.9% and 31.6% of cases respectively. Serum a-foetoprotein level did not significantly decrease (238 vs 138 gg/L). No early severe complication occurred. Pugh score significantly increased at 3 months (6.8• p < 0.05), and 38.6% of patients presented with ascitis. Predictive factors of ascitis occurrence were Pugh score greater than 5 and portal vein thrombosis. Median survival was 7.8 months, and the one-year survival was 17%. In Cox model, age, serum a-foetoprotein level, tumour size and Pugh score were significantly associated to survival. Both CLIP and Okuda scores were predictive of survival and were more accurate than BCLC. Conclusion: Our study shows that Lipiocis | decreases or stabilizes tumour burden in 39.5% of cases. Only patients with no hepatocellular deficiency (Chil&Pugh A5) and stage ~
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USEFULNESS OF CONTRAST-ENHANCED PERFUSIONAL SONOGRAPHY IN THE OUTCOME OF PATIENTS WITH HEPATOCELLULAR CARCINOMA SUBMITTED TO NON-SURGICAL TREATMENTS
F. Giangregorio, M. Di Stasi, G. Sbolli, M. Marinone, G. Aragona, P. Tansini, E Fornari. Gastroenterology Dept. Hospital "Guglielmo da
Saliceto ", Piacenza, Italy Aims: CEUS is a new technique with a good diagnostic agreement with spiral CT in the evaluation of efficacy of non-surgical treatments of HCC. The early evaluation of these treatments with CEUS may allow to obtain a more complete necrosis of the tumoural nodules. Therefore we evaluated if CEUS is able to affect the outcome of these patients Methods: 181 cirrhotic patients with HCC (M/F:112/69; mean age 71 yrs; Child A/B: 151/30), treated from 1/1999 to 12/2004 with non-surgical treatments for unresectable lesions: 116 with RFTA; 44 with combined treatment of RFTA and TACE and 21 with PEI; solitary nodule: 132 pts; 2 3 HCC: 32; multinodular HCC: 17 cases. All patients underwent spiral CT one month after the procedure; the first 66 patients (treated
before January 2002), did not perform CEUS (group A); 115 patients were submitted to CEUS (after January 2002) 24 hours after the treatments (group B). We correlated the following variables with the survival (S) and the disease-free-survival (DFS): number and diameter of HCCs; AFP values; type of treatment; aetiology and class of Child; the early evaluation of the treatment with CEUS. Statistics was performed with chi-square and Kapla~Meier curves (SPSS release 13). Results: Mean follow-up of 181 pts: 22 months (group A: 31.4; group B: 19.2). During the follow-up 52/66 (78.8%) pts in group A and 49/115 (42.6%) pts in group B died. Recurrence was found: group A: 45/56 (80.3%) pts, group B: 73/115 (63.47%) pts. The patterns of recurrence were: new lesions away from the treated nodules: group A: 23 cases; group B: 47 cases; local tumour regrowth: group A: 22 pts; group B: 26 pts. At multivariate analysis the number and diameter of the nodules, sex, and type of the treatment were not statistically correlated with S and DFS. Value of AFP and Child class were correlated with S (S: p 0.001), the early evaluation of the efficacy of the treatment with CEUS and the association CEUS AFP were statistically correlated (CEUS: DFS: p 0.042);(CEUS and AFP: DFS: p 0.036). Conclusions: The early evaluation of the efficacy of the non-surgical treatments of HCC with CEUS allows to obtain a more complete necrosis of the tumour and to reduce the recurrence for local regrowth of the HCC achieving a higher percentage of disease-free survival.
I - ~ A N INHIBITOR OF VEGF(ZD6474) AS A POTENTIAL NEW DRUG FOR HCC: A PRECLINICAL STUDY G. Giannelli 1, C. Sgarra 1, A. Azzariti 2, L. Porcelli 2, A. Paradiso 2, S. Antonaci 1. 1Department of Internal Medicine, Immunology, and
Infectious' Diseases, Section of Internal Medicine," University of Bari Medical School, Bari, Italy," 2Clinical Experimental Oncology Laboratory, National Cancer Institute Bari, Italy Background and Aims: Hepatocellular carcinoma (HCC) is the fifth most frequent cancer and the third tumour-cause related death. It is a highly aggressive cancer, characterized by hypervascularization, neoangiogenesis formation and blood vessel invasion. Prognosis and survival are still unsatisfactory, and no therapies are currently available to inhibit cancer growth and spread. Recently, it has been demonstrated that an inhibitor of the vascular endothelial growth factor (VEGF) receptor, ZD6474, may inhibit cell growth. We investigated drug effectiveness toward a number of HCC cell lines in the presence or absence of different extra-cellular matrix (ECM) proteins including Laminin-5 (Ln-5), Ln-1, Collagen I, Collagen IV, Fibronectin, Fibrinogen and Vitronectin. Methods: ZD6474 effectiveness was investigated on cell growth, apoptosis, adhesion, migration and invasion and related to the drug-dependent modulation of main molecular targets on HCC cells. Results: ZD6474 inhibited HCC cell proliferation (IC50 in gM range); however, such effect was reverted for 90% by Ln-5 but not by other ECM proteins. ZD6474 also inhibited HCC cell adhesion, migration and invasion, whereas the simultaneous treatment with the drug and Ln-5 strongly recovered those effects. Under the same experimental conditions, ZD6474 inhibited the expression of phosphorylated EGFR in all cell lines while the effect on p-Erkl/2 was cellular invasive characteristics dependent, still Ln-5 completely recovered this effect. Conclusions: In conclusion, for the first time, we demonstrated in vitro that ZD6474 is effective in inhibiting growth and invasion of HCC cells. Our results lead to the hypothesis that ZD6474 could represent an interesting therapeutic opportunity for patients with HCC scarcely expressing the ECM protein, Ln-5.
S 102
three techniques could not avoid that in more than 20% of HCC-preLT, findings in explants were exceeding Milan criteria.
I-~
WHAT IS THE PLACE FOR INTRA-ARTERIAL INJECTION OF 1311-LABELED-IODIZED OIL (LIPIOCIS | IN PALLIATIVE TREATMENT OF HEPATO-CELLULAR CARCINOMA?
E. Germain 1, M.N. Hilleret 1, C. Sengel 2, J.R Vuillez 3, J.R Zarski 1'4, V. Leroy 1.4.1Departemen t d'Hepatogastroenterologie, 2Service Central de
R adiologie et d 'Imagerie Mddicale, 3Service de Biophysique et Mddecine Nucldaire, 4INSERM U 548, CHU Grenoble, Grenoble, France Intra-arterial injection of 131I-labeled-Iodized Oil (Lipiocis| is a validated treatment for hepatocellular carcinoma (HCC), which has shown an impact on survival. The aim of this study was to evaluate the tolerance and the efficacy of Lipiocis | on survival and tumour response. Methods: Fifty-two HCC patients (male: 92%; age: 67• years) seen in our centre for a first session of Lipiocis | were prospectively included in the study. The main endpoint was survival at 12 months. Secondary endpoints were objective tumour response, evolution of serum a-foetoprotein level and Chil&Pugh score, and occurrence of complications. Results: Ninety-two per cent of patients were cirrhotic (alcoholic 50%, hepatitis B 15%, hepatitis C 15%). Mean Pugh score was 5.6• (Child A: 80%). Twenty-one per cent of patients had been previously treated by surgical resection, radiofrequency ablation or percutaneous ethanol injection. HCC was uninodular in 25%, multinodular but reaching less than 50% of the liver in 52%, and infiltrating more than 50% of the liver in 23% of cases. The biggest tumour size was 53• Portal vein thrombosis was present in 29% of cases. Patients were stage I according to Okuda classification in 58% and stage 0 1 according to CLIP in 54% of cases. Tumour reduction and stabilization were observed in 7.9% and 31.6% of cases respectively. Serum a-foetoprotein level did not significantly decrease (238 vs 138 gg/L). No early severe complication occurred. Pugh score significantly increased at 3 months (6.8• p < 0.05), and 38.6% of patients presented with ascitis. Predictive factors of ascitis occurrence were Pugh score greater than 5 and portal vein thrombosis. Median survival was 7.8 months, and the one-year survival was 17%. In Cox model, age, serum a-foetoprotein level, tumour size and Pugh score were significantly associated to survival. Both CLIP and Okuda scores were predictive of survival and were more accurate than BCLC. Conclusion: Our study shows that Lipiocis | decreases or stabilizes tumour burden in 39.5% of cases. Only patients with no hepatocellular deficiency (Chil&Pugh A5) and stage ~
I•
USEFULNESS OF CONTRAST-ENHANCED PERFUSIONAL SONOGRAPHY IN THE OUTCOME OF PATIENTS WITH HEPATOCELLULAR CARCINOMA SUBMITTED TO NON-SURGICAL TREATMENTS
F. Giangregorio, M. Di Stasi, G. Sbolli, M. Marinone, G. Aragona, P. Tansini, E Fornari. Gastroenterology Dept. Hospital "Guglielmo da
Saliceto ", Piacenza, Italy Aims: CEUS is a new technique with a good diagnostic agreement with spiral CT in the evaluation of efficacy of non-surgical treatments of HCC. The early evaluation of these treatments with CEUS may allow to obtain a more complete necrosis of the tumoural nodules. Therefore we evaluated if CEUS is able to affect the outcome of these patients Methods: 181 cirrhotic patients with HCC (M/F:112/69; mean age 71 yrs; Child A/B: 151/30), treated from 1/1999 to 12/2004 with non-surgical treatments for unresectable lesions: 116 with RFTA; 44 with combined treatment of RFTA and TACE and 21 with PEI; solitary nodule: 132 pts; 2 3 HCC: 32; multinodular HCC: 17 cases. All patients underwent spiral CT one month after the procedure; the first 66 patients (treated
before January 2002), did not perform CEUS (group A); 115 patients were submitted to CEUS (after January 2002) 24 hours after the treatments (group B). We correlated the following variables with the survival (S) and the disease-free-survival (DFS): number and diameter of HCCs; AFP values; type of treatment; aetiology and class of Child; the early evaluation of the treatment with CEUS. Statistics was performed with chi-square and Kapla~Meier curves (SPSS release 13). Results: Mean follow-up of 181 pts: 22 months (group A: 31.4; group B: 19.2). During the follow-up 52/66 (78.8%) pts in group A and 49/115 (42.6%) pts in group B died. Recurrence was found: group A: 45/56 (80.3%) pts, group B: 73/115 (63.47%) pts. The patterns of recurrence were: new lesions away from the treated nodules: group A: 23 cases; group B: 47 cases; local tumour regrowth: group A: 22 pts; group B: 26 pts. At multivariate analysis the number and diameter of the nodules, sex, and type of the treatment were not statistically correlated with S and DFS. Value of AFP and Child class were correlated with S (S: p 0.001), the early evaluation of the efficacy of the treatment with CEUS and the association CEUS AFP were statistically correlated (CEUS: DFS: p 0.042);(CEUS and AFP: DFS: p 0.036). Conclusions: The early evaluation of the efficacy of the non-surgical treatments of HCC with CEUS allows to obtain a more complete necrosis of the tumour and to reduce the recurrence for local regrowth of the HCC achieving a higher percentage of disease-free survival.
I - ~ A N INHIBITOR OF VEGF(ZD6474) AS A POTENTIAL NEW DRUG FOR HCC: A PRECLINICAL STUDY G. Giannelli 1, C. Sgarra 1, A. Azzariti 2, L. Porcelli 2, A. Paradiso 2, S. Antonaci 1. 1Department of Internal Medicine, Immunology, and
Infectious' Diseases, Section of Internal Medicine," University of Bari Medical School, Bari, Italy," 2Clinical Experimental Oncology Laboratory, National Cancer Institute Bari, Italy Background and Aims: Hepatocellular carcinoma (HCC) is the fifth most frequent cancer and the third tumour-cause related death. It is a highly aggressive cancer, characterized by hypervascularization, neoangiogenesis formation and blood vessel invasion. Prognosis and survival are still unsatisfactory, and no therapies are currently available to inhibit cancer growth and spread. Recently, it has been demonstrated that an inhibitor of the vascular endothelial growth factor (VEGF) receptor, ZD6474, may inhibit cell growth. We investigated drug effectiveness toward a number of HCC cell lines in the presence or absence of different extra-cellular matrix (ECM) proteins including Laminin-5 (Ln-5), Ln-1, Collagen I, Collagen IV, Fibronectin, Fibrinogen and Vitronectin. Methods: ZD6474 effectiveness was investigated on cell growth, apoptosis, adhesion, migration and invasion and related to the drug-dependent modulation of main molecular targets on HCC cells. Results: ZD6474 inhibited HCC cell proliferation (IC50 in gM range); however, such effect was reverted for 90% by Ln-5 but not by other ECM proteins. ZD6474 also inhibited HCC cell adhesion, migration and invasion, whereas the simultaneous treatment with the drug and Ln-5 strongly recovered those effects. Under the same experimental conditions, ZD6474 inhibited the expression of phosphorylated EGFR in all cell lines while the effect on p-Erkl/2 was cellular invasive characteristics dependent, still Ln-5 completely recovered this effect. Conclusions: In conclusion, for the first time, we demonstrated in vitro that ZD6474 is effective in inhibiting growth and invasion of HCC cells. Our results lead to the hypothesis that ZD6474 could represent an interesting therapeutic opportunity for patients with HCC scarcely expressing the ECM protein, Ln-5.