Efficacy of transarterial targeted treatments on survival of patients with hepatocellular carcinoma. An Italian Experience

Abstract

Background. Most patients with hepatocellular carcinoma (HCC) are not suitable for surgical therapy. Systemic chemotherapy, immunotherapy, and hormonotherapy have not had convincingly acceptable results. Therefore, transarterial catheter‐targeted therapies such as intraarterial chemotherapy (IAC), possibly followed by transcatheter arterial chemoembolization (TACE), have been proposed. Methods. A survival analysis curve was drawn using the Kaplan‐Meier method for 164 patients, 100 with HCC who underwent TACE (69) or IAC (31), and a matched historic group of 64 who did not receive specific antineoplastic treatment. Results. A significantly more favorable survival was observed for TACE‐treated patients compared with IAC‐treated patients (P < 0.001); TACE‐ and IAC‐treated patients had a statistically superior survival than that of untreated patients (P < 0.001 and P < 0.025, respectively). This difference was still significant (P < 0.001) when the patients were subdivided into Classes A and B and Stages I and II following Child's and Okuda's criteria. The TACE‐ and IAC‐treated groups had a good relationship between technical efficacy of therapy and survival. Stratifying the patients according to the degree of iodized oil (Lipiodol Ultrafluid, Guerbet, Aulnay‐Sous‐Bois, France) uptake in the three groups with Group 1 having an uptake greater than 75% of tumor mass, Group 2 having an uptake of 50%‐75%, and Group 3 having an uptake less than 50%, survival at 6, 12, 24, 36, and 48 months was calculated as 94%, 88%, 67%, 53%, and 30%, respectively, for Group 1; 86%, 68%, 13%, 13%, and 0% for Group 2, and 43%, 23%, 6%, 6%, and 0% for Group 3 (Group 1 vs. Group 2: P < 0.001; Group 1 vs. Group 3: P < 0.001; Group 2 vs. Group 3: P < 0.001, respectively). The most important side effects after the intraarterial procedure were fever (46.2%), abdominal pain (36.6%), chemical cholecystitis (8%), and pancreatitis (1.7%). Death strictly related to treatment occurred in two patients; one had massive bleeding due to ruptured esophageal varices, and the other had a subphrenic abscess of a superficial HCC of the VIII segment. Conclusions. Transcatheter arterial chemoembolization and IAC were effective and relatively safe, and the authors believe that they have a primary role in treating patients with unresectable HCC larger than 5 cm; iodized oil uptake can be considered a suitable prognostic marker.

Predisposing factors for hepatocellular carcinoma recurrence following initial remission after transcatheter arterial chemoembolization

“…Early recurrence following a CR achieved by TACE may be mainly attributed to residual tumors that were undetectable on angiography. The distribution of lipiodol uptake determined by tumor differentiation and the blood vessel network have been shown to affect the local recurrence rate and long-term outcome in patients with HCC (37,38). Furthermore, consistent with the present study, a previous study showed that local recurrence developed more frequently in patients with early recurrence (≤1 year) compared with those with late recurrence (>1 year) (27).…”

Comparison of 7 staging systems for patients with hepatocellular carcinoma undergoing transarterial chemoembolization

“…In the current study, the factors that were significant in multivariate analysis were similar to the factors that constitute the CLIP score, and they also were similar to the factors determined in previous studies of TACE. 28,29 The most powerful prognostic factor of poor survival was vascular invasion in this study, and similar results were reported in patients who underwent liver resection or transplantation. 1,[30][31][32] Although the BCLC system was validated as the most suitable prognostic system for patients with HCC in Italy and the United States, it was not considered a suitable prognostic system in the Eastern countries until now.…”

Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial

“…We chose TAE and 5-FU as standard treatment before introducing pravastatin administration. TAE prevents tumour progression (Charnsagavej et al, 1983;Yamada et al, 1983;Stefanini et al, 1995) and is one of the standard treatments for unresectable HCC in Japan. 5-FU also has activity against HCC (Cavalli et al, 1981;Coi et al, 1984;Falkson et al, 1984).…”

“…We administered pravastatin (40 mg day -1 ), for which the liver has a high affinity, to HCC patients in a randomized controlled trial after transcatheter arterial embolization (TAE) (Charnsagavej et al, 1983;Yamada et al, 1983;Stefanini et al, 1995) and oral 5-fluorouracil (5-FU) as standard treatment.…”