Effects of Doxorubicin Delivery on Tumor Necrosis after Drug-Eluting Bead Transarterial Chemoembolization

The benefit of chemotherapy as a constituent of transarterial chemoembolization (TACE) therapy has been questioned in studies showing no tumor response differences between bland embolization and TACE. Additionally, an established relationship between drug delivery and cellular necrosis following TACE is presently unproven. This study aimed to correlate the incremental tumor necrosis and drug distribution afforded by doxorubicin (DOX) during drug­eluting bead (DEB) TACE. In this IRB­approved study, VX2 liver tumors in New Zealand white rabbits were treated with DOX­loaded 70­150 micron DEBs (LC Bead M1; BTG). Rabbits were divided into 5 treatment groups with varying DOX doses: sham (saline without beads), 0 mg (bland beads), 12.5 mg, 25 mg, and 37.5 mg. 130,000 beads (10% vial) were administered per procedure. DEB­TACE was followed by sacrifice at 3 and 7 days. Histologic analysis of harvested tumors was used to quantify percent tumor necrosis using the NanoZoomer Digital Pathology System (Hamamatsu), and DOX extent and intensity using fluorescence imaging quantification and ImageJ software (NIH). Statistical comparison was performed using one­way ANOVA, the Student’s t­test and least squares linear regression modeling. The results of the current study found that incremental increases in DOX dose result in higher percent necrosis of rabbit VX2 liver tumors after DEB­TACE. The DOX extent and intensity within in the tumor increases linearly with delivered DOX dose and percent necrosis. This result indicates an essential role for chemotherapy­induced cytotoxicity in TACE efficacy, and supports the use of chemotherapeutic drugs as a component of transarterial therapy.