Internal radiation therapy for hepatocellular carcinoma. Results of a french multicenter phase II trial of transarterial injection of iodine 131-labeled lipiodol

Abstract

Preliminary Phase I trials have shown iodine 131 (131I)‐Lipiodol (ethiodized oil; Laboratoires Guerbet, Aulnay‐sous‐Bois, France) to be well tolerated and most likely effective in the treatment of hepatocellular carcinoma (HCC). In this multicenter Phase II trial, the authors tested the feasibility and reproducibility of this treatment in other medical institutions and evaluated its efficacy in 50 patients with unresectable Stage I or II HCC, by the classification of Okuda et al. The authors studied 47 men and 3 women (63.9 ± M 7.1 years old) with Stage I (n = 18) or II (n = 32) HCC, by the classification of Okuda et al., which was verified by histologic findings (n = 25), cytologic findings (n = 11), or association of a tumor with alpha‐fetoprotein serum values greater than μg500 /tg/l (n = 14). This multicenter trial (1) confirmed that the 131I‐Lipiodol treatment is well tolerated; (2) showed that there is a high reproducibility of results with respect to other institutions and an objective tumor response in 40% of the cases; and (3) indicated the necessity of performing a randomized controlled study.

Patient dosimetry for 131I-lipiodol therapy

“…1, the mean absorbed dose for the most relevant organs was comparable between the MCNP calculations and MIRDOSE. Our result for the normal liver is comparable to the absorbed liver dose calculated by Raoul et al [14] (5.5 Gy, SD 8.7), although their absorbed dose to the lungs was lower, with a maximum of 2.9 Gy (SD 2.2). Direct effects after therapy were never observed even though some of our patients were treated with 131 I-lipiodol up to 5 times.…”

Eradication of hepatocellular carcinoma xenografts by radiolabelled, lipiodol-inducible gene therapy

“…30 These findings indicate that I-131-Lip has potential advantages for use in hepatoma therapy. [31][32][33] The selective delivery and retention of lipiodol are thought to result from the developed neovasculature, enhanced permeability and the poor reticuloendothelial systems observed in hepatoma tissues. Despite this capacity for the selective accumulation at the tumor site, clinical studies have shown the effectiveness of such I-131-Lip therapy alone to only be temporary, and early HCC recurrence was observed in many cases.…”

Therapy of Hepatocellular Carcinoma with Iodine-131-Lipidiol

“…A phase I study 24 and a multi centric phase II trial 30 could not demonstrate any specific toxic effects of 131I-Lipiodol. The main limiting factor was the long patient isolation required for the purpose of radioprotection.…”

“…Tumour response adversely correlates with tumour size. High response rates have been found in tumour nodes with diameters below 6 cm in which an absorbed dose of up to 288 Gy has been calculated 25,30,59 . However, it must be considered that a reduction in tumour mass does not necessarily correlate with improved survival 6 .…”