Effects of doxorubicin (DOX) delivery on tumor necrosis after drug-eluting bead transarterial chemoembolization (DEB-TACE)

Purpose: Genetic analysis is an encouraging approach to improve the understanding of biochemical mechanisms that underlie tumor therapeutic outcome. While gene assays have been previously applied to liver tissues to identify genetic signatures associated with cytotoxic and ischemic tissue insults, investigation of the association between HCC gene expression and TACE treatment outcomes has not been performed. This study was undertaken to explore the relationship between HCC genetics and TACE response in order to identify potential biomarkers associated with enhanced treatment efficacy. Materials and Methods: In this single-institution study, pretreatment HCC biopsy specimens for tumors treated with TACE between 2007-2013 were analyzed for a panel of 60 chemosensitivity, hypoxia response, mitosis, and inflammatory mediator genes using the QuantiGenes Plex 2.0 mRNA detection assay (Affymetrix). Medical record and imaging review was used to collect demographic, disease, and procedure data, as well as tumor response outcomes, assessed using necrosis (EASL) criteria. Quantitative mRNA levels were compared between tumors exhibiting complete (CR) versus partial (PR) radiographic response. Results: The study sample included 19 biopsied index tumors (mean size 3.0 cm) from 19 patients (14 men, 5 women; mean age 59 years) who underwent mean 2 TACE sessions using 1:1 chemotherapy to ethiodized oil particle embolization. Thirteen and 6 tumors exhibited CR and PR, respectively, at mean 116 days post-treatment. CR tumors showed a statistical increase (Po0.05) in or trend (Po0.1) toward higher pre-treatment chemosensitivity and mitosis (ATF4, BAX, CCNE1, KIF11, NFX1, PPP3CA, SNX1, TOP2A, and TOP2B) gene mRNA expression compared to PR tumors, lower CXCL10 levels, and statistically higher (Po0.05) baseline VEGF-alpha levels. Conclusion: Genetic signatures may allow pre-TACE stratification of tumor response probability, and gene analysis may thus offer an opportunity to personalize locoregional therapy by enhancing treatment modality allocation (e.g. TACE vs. yttrium-90 radioembolization vs. ablative therapy). Further confirmation of identified markers and exploration of their respective predictive capacity thresholds is necessary.