Transparent liver tumor imaging for transarterial chemoembolization (TACE): cancer treatment mechanism in TACE

Abstract Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-related deaths worldwide. Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage HCC. While TACE has been widely used for the treatment of HCC, there are unsolved questions on the use of chemotherapeutics agents in TACE. TACE has been thought to induce necrosis in HCC due to the complex effects of embolism and intra-arterial delivery of anticancer drugs; however, it is unclear how far a drug is delivered from the arteries before the tumor undergoes necrosis induced by embolization-induced ischemia.Methods: In this study, the drug delivery effect, time-dependent embolic effect, and immunogenic response were compared following conventional TACE (cTACE), drug-eluting embolic TACE (DEE-TACE), and transarterial embolization (TAE) in a rat model of HCC. Following each treatment, three-dimensional drug delivery was evaluated via the transparent liver tumor imaging. Time-dependent tumor necrosis was analyzed by serial tumor harvesting and histological staining. Early (24-h) and residual (7-day) immune responses were evaluated by flow cytometric analyses and immunohistochemistry. Results: The intratumoral blood vessel structure became damaged after treatment due to embolization-induced ischemia. The more severe the vascular damage caused over time or by treatment type, the greater the distance traveled by drugs. In the first 24-h, most chemotherapeutic agents were located within 80 and 110 µm of the nearest vessels after cTACE and DEE-TACE, respectively, while 85.3–97.2% of tumor cells underwent necrosis. The percentages of CD4 and IL-17+ CD4 T cells were significantly increased following treatment, but drug loading did not affect the early and residual immune responses. Conclusion: Transarterially delivered chemotherapeutic agents appeared to exert a limited role, owing to the rapid and overwhelming effect of embolization.