Transarterial Embolization Using a Liquid Embolic Enhances Tumor Necrosis to Enable Improved Efficacy Compared with a Particle Embolic in a Translational Rat Model of Hepatocellular Carcinoma

Gurevich, A.; Islam, A.; Wakim, J.; Yarsky, E.; Kiefer, R.; El-Ghazal, R.; McClung, G.; Cormode, D. P.; Nadolski, G. J.; Avritscher, R.; Hunt, S. J.; Gade, T. P. F.

doi:10.1101/2024.05.23.595637

bioRxiv · 10.1101/2024.05.23.595637

Transarterial Embolization Using a Liquid Embolic Enhances Tumor Necrosis to Enable Improved Efficacy Compared with a Particle Embolic in a Translational Rat Model of Hepatocellular Carcinoma

Gurevich, A.·Islam, A.·Wakim, J.·Yarsky, E.·Kiefer, R.·El-Ghazal, R.·McClung, G.·Cormode, D. P.·Nadolski, G. J.·Avritscher, R.·Hunt, S. J.·Gade, T. P. F.

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Abstract

PurposeTo compare the effectiveness of transarterial embolization (TAE) using a liquid embolic (LE) to TAE using particle embolics (PE) with respect to tumor ischemia and treatment response in a translational rat model. Materials and MethodsHCC was induced in male Wistar rats using diethylnitrosamine. Rats were randomized into three treatment groups: sham transarterial embolization (TAE), TAE with LE, and TAE with PE. Tumor response to TAE was monitored via serial T2-weighted MRI scans and assessed using RECIST. Tumor necrosis and hypoxia were assessed through hematoxylin and eosin staining and pimonidazole immunohistochemistry, respectively. Statistical analyses were performed using chi-square tests, Kaplan-Meier estimates, and one-way ANOVAs, with significance set at p<0.05. ResultsTwenty-nine rats were randomized to TAE with LE (n=13), PE (n=13), or sham (n=3). TAE with LE demonstrated a significantly higher objective response rate (83%) compared to TAE with PE (28%; {chi}2 = 11.25, P=0.0008). Complete responses were observed in 50% of the LE-treated tumors versus 10% in the PE-treated group. LE treatment prolonged local progression-free survival (hazard ratio = 0.23; p=0.0085). Histological analysis, with an additional 14 rats randomized to TAE with LE (n=5), PE (n=6), or sham (n=3), showed greater necrosis and hypoxia in LE-treated tumors compared to PE. LE induced a significant reduction in viable tumor tissue (p<0.05) and increased necrotic and hypoxic tissue areas compared to PE (p<0.01). ConclusionLE significantly enhanced the therapeutic efficacy of TAE in a rat model of HCC compared to conventional PE. The results highlight LEs potential to improve ischemia and necrosis, thereby offering a promising option improving the efficacy of embolization for HCC treatment.

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Gurevich, A., Islam, A., Wakim, J., Yarsky, E., Kiefer, R., El-Ghazal, R., McClung, G., Cormode, D. P., Nadolski, G. J., Avritscher, R., Hunt, S. J., Gade, T. P. F.. 2024-05-26. Transarterial Embolization Using a Liquid Embolic Enhances Tumor Necrosis to Enable Improved Efficacy Compared with a Particle Embolic in a Translational Rat Model of Hepatocellular Carcinoma. https://doi.org/10.1101/2024.05.23.595637

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