For patients with huge HCC, hepatectomy is the preferred treatment when their liver function is well-preserved. Only a small number of patients with huge HCC have the chance of hepatectomy.A large number of patients presented with invading the liver parenchyma in patients with huge HCC. Compared with patients with small tumors, intrahepatic metastasis is more frequent and the survival is worse in patients with huge tumors [6]. TACE is one of the important methods for the treatment of huge HCC. It can block the tumor blood supply and increase the drug concentration in the target vessel [7]. However, the traditional TACE with lipiodol as the embolization agent don’t achieve the ideal curative efficacy. It often requires repeated embolization to achieve a better treatment response, and multiple cycles of TACE will cause hepatic blood vessel and liver dysfunction, which has a bad effect on the next embolization treatment [8]. The CalliSpheres drug-elutted beads can not only load and release chemotherapeutics slowly in local area but can also embolize the tumor feeding vessels permanently [9]. Multiple clinical trials have shown that DOX loaded DEB-TACE can increase the intra-tumoral drug concentrations and reduce systemic toxicity [10-11]. Many studies showed that while TACE treatment causes hypoxia in tumor cells and surrounding liver tissues, it also up-regulates vascular endothelial growth factor and promotes the proliferation and metastasis of remaining tumor cells [12]. Obviously, the restoration of the blood supply of tumor tissue is an important cause of tumor cell survival [13]. Tsai et al. [14] have compared the short-term effect of HAIC and TACE in the treatment of large liver cancer, and the result showed that HAIC provide better survival compared with c-TACE. However, the effect of survival in between c-TACE and DEB-TACE doesn’t be compared. Therefore, we conducted this study to further explore its potential in HCC patients with the lagrest tumor size greater than 7cm.
In our study, patients in DEB-TACE group achieved higher ORR, PFS and OS compared with c-TACE group, and the difference was significant. The possible reasons are as follows: (1) DEB-TACE reduced tumor size by increasing local drug concentration and drug retention time in HCC tumors. According to previous studies, DEB-TACE shrunk tumor size resulted from increasing the localized drug concentration and drug retention time inside the tumors [15,16]. (2) Moreover, apart from the tumor-selective drug delivery, DEB-TACE has extra embolization effect, which result in the synergies of local cytotoxic activity and ischemia in the all feeding arteries of the tumor, so as to make the treatment more effective in unresectable huge HCC patients.(3) At the same time, compared with the lipiodol used in c-TACE, the dose of chemotherapeutic drugs adsorbed by CalliSpheres drug-loaded microspheres is significantly increased, and the adsorbed chemotherapeutic drugs can be released under control. And the DEB-TACE group underwent less cycles of TACE compared with DBE-TACE. This may be due to the fact that patients in the DEB-TACE group had longer PFS, which would reduce the cycles of TACE during the whole follow-up period.
In this study, the two groups had more adverse reactions due to the larger target lesions. These adverse reactions are mainly manifested as pain, nausea, vomiting and fever, which considered as post-embolization syndrome [17]. The results showed that incidence of AEs does not have the remarkable difference between the two groups, and these adverse reactions can be improved after symptomatic treatment. There were no serious complications such as liver failure, gastrointestinal hemorrhage or ectopic embolism in the two groups. However, there were 5 cases of liver abscesses in the study group and the control group, respectively. Liver abscess is considered to be caused by excessive DEBs embolization or tumor vascular reflux. The abscess was punctured and drained under ultrasound guidance. In order to prevent this complication, surgeons must strictly abide by aseptic operation in TACE treatment, and the embolization can be enforced in different times. Postoperative anti infection treatment is feasible after surgery.
There are some limitations in this study, it is a retrospective study and there may be bias in case selection; most of the cases received multiple TACE or systemic treatments after the first TACE treatment. As the limited of less cases number, subgroup analysis was not carried out about the follow up therapy, which is also key directions for our future research.
In general, DEB-TACE is a clinically effective and safe treatment choice for patients with huge HCC either alone or combined with other systemic therapies. Our findings provide the theoretical basis for further studies of TACE treatment strategy for huge HCC. The therapeutic effect of DEB-TACE combined with other therapies should be further explored and compared for patients with huge HCC in future studies.