Evaluation of two different transarterial chemoembolization protocols using Lipiodol and degradable starch microspheres in therapy of hepatocellular carcinoma: a prospective trial

Abstract

Background: This prospective randomized trial is designed to compare the performance of conventional transarterial chemoembolization (cTACE) using Lipiodol-only with additional use of degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) in BCLC-stage-B based on metric tumor response.

Methods: Sixty-one patients (44 men; 17 women; range 44-85) with HCC were evaluated in this IRB-approved HIPPA compliant study. The treatment protocol included three TACE-sessions in 4-week intervals, in all cases with Mitomycin C as a chemotherapeutic agent. Multiparametric magnetic resonance imaging (MRI) was performed prior to the first and 4 weeks after the last TACE. Two treatment groups were determined using a randomization sheet: In 30 patients, TACE was performed using Lipiodol only (group 1). In 31 cases Lipiodol was combined with DSMs (group 2). Response according to tumor volume, diameter, mRECIST criteria, and the development of necrotic areas were analyzed and compared using the Mann-Whitney-U, Kruskal-Wallis-H-test, and Spearman-Rho. Survival data were analyzed using the Kaplan-Meier estimator.

Results: A mean overall tumor volume reduction of 21.45% (± 62.34%) was observed with an average tumor volume reduction of 19.95% in group 1 vs. 22.95% in group 2 (p = 0.653). Mean diameter reduction was measured with 6.26% (± 34.75%), for group 1 with 11.86% vs. 4.06% in group 2 (p = 0.678). Regarding mRECIST criteria, group 1 versus group 2 showed complete response in 0 versus 3 cases, partial response in 2 versus 7 cases, stable disease in 21 versus 17 cases, and progressive disease in 3 versus 1 cases (p = 0.010). Estimated overall survival was in mean 33.4 months (95% CI 25.5-41.4) for cTACE with Lipiosol plus DSM, and 32.5 months (95% CI 26.6-38.4), for cTACE with Lipiodol-only (p = 0.844), respectively.

Conclusions: The additional application of DSM during cTACE showed a significant benefit in tumor response according to mRECIST compared to cTACE with Lipiodol-only. No benefit in survival time was observed.

Keywords: DSM; Hepatocellular carcinoma; Lipiodol; Magnetic resonance imaging; Mitomycin C; Necrotic area; Response; Survival; TACE; Tumor volume.

Fig. 1

Patient inclusion, exclusion, and randomization diagram

Fig. 2

MRI in a representative 40-year-old participant with hepatitis B and cirrhosis who presented with two HCC lesions in segment 7 and segment 8. a Axial acquired contrast-enhanced T1-weighted MRI at baseline showing an HCC-typical lesion in segment 7 with central necrosis. b Baseline ADC-map demonstrating low ADC-values in the tumor mass and high signal in the necrotic area compared to normal ADC-values. c Axial contrast-enhanced T1-weighted MRI performed following the third TACE + DSM showing a RECIST partial response with an increase in size of the necrotic area. d ADC-map post-study completion showing increased ADC-values in the tumor mass as a predictor of therapy response. Values in the necrotic area remain increased. e Angiography demonstrating typical HCC hypervascularization with additional segment 8 hypervascularity of the second lesion. f Computed tomography following a 4-week-interval after the first TACE + DSM demonstrating prolonged Lipiodol uptake in the HCC lesion. g A post-contrast T1 sequence was linked to the ADC map for delineation of ROIs on the higher spatial resolution T1 images

Fig. 3

Kaplan– Patient Mayer plot of the study groups