The OS of HCC patients has been improved because of a variety of effective implemented in recent decades, but the prognosis of HCC patients with PVTT, especially those with type III-IV PVTT, is still very poor[25]. The treatment of HCC complicated with type III-IV PVTT has become a hot topic in clinical research.
TACE is an effective treatment for HCC with PVTT[26], and sorafenib is the first-line systemic therapy treatment for advanced HCC[27, 28]. However, the MSTs of HCC patients with type III PVTT after treatment with TACE, sorafenib, and TACE combined with sorafenib were only 4.1 months[13], 3.9 months[29], and 3.0-7.0 months[3, 10, 30], respectively. Moreover, surgical resection did not achieve superior outcomes compared TACE[31, 32]. Wang[31] reported that the efficacy of radiotherapy combined with TACE was better than that of TACE or TACE combined with sorafenib for HCC patients with type III PVTT. However, it was found that the MST of EVBT combined with TACE (11.7 months) was longer than that of radiotherapy combined with TACE (9.5 months) for the treatment of HCC with type III PVTT[20].
The advantages of EVBT combined with TACE are considered to be the following: (1) Compared with other treatments, it is possible to restore portal vein perfusion of the liver more quickly and to improve the liver function of patients after treatment with EVBT combined with TACE. (2) Continuous radiotherapy with 125I seeds in EVBT elicits an anti-intimal hyperplasia effect[33] and can also improve stent patency[34, 35]. (3) EVBT can effectively inhibit the progression of PVTT, reduce the intrahepatic spread of HCC caused by PVTT, and ensure a normal functional liver volume[19]. (4) TACE treatment can effectively control tumor lesions[36].
The results of this study showed that the MST of of HCC with type III-IV PVTT treated with EVBT combined with TACE was 7.0 months in the treatment, which was longer than those of patients treated with TACE, sorafenib, and TACE combined with sorafenib. However, compared with other studies focusing on EVBT combined with TACE for the treatment of HCC patients with PVTT, the OS of our study was shorter (7.0 months vs. 9.3-11.7 months)[19, 20]. This was mainly because the enrolled patients in our study differed from the patients in other studies. In this study, there were 10 patients (18.5%) with HCC complicated with type IV PVTT and 34 patients (63%) with invaded main portal veins and bilateral primary branches. In addition, the tumors of 27 patients (50%) were >10 cm, with only 5 patients (13%) having tumors <5 cm. However, in other studies[19, 20], patients with HCC complicated with type IV PVTT were excluded, and 32%-36% of patients had tumors <5 cm. Therefore, the patients enrolled in our study had a larger tumor burden and more severe PVTT, leading to a shorter MST for patients receiving of EVBT combined with TACE than that reported in other similar studies.
There was no significant difference in OS between patients with type III and type IV PVTT in our study. Among the 10 patients with type IV PVTT, there were 7 patients with Child-Pugh grade A and 3 patients with Child-Pugh grade B. Only one patient had an HCC >10 cm, 9 patients had hemihepatic HCC, and 10 patients had good portal collateral vessels supplying the liver. The low tumor burden and hemihepatic HCC observed in patients with type IV PVTT may be why there was a lack of a significant difference in OS between patients with type III and type IV PVTT.
The efficacy of EVBT combined with TACE for the treatment of HCC with type III-IV PVTT in this study was encouraging. However, this study was a single-center retrospective study, and the postoperative treatments were also different. Therefore, potential selection bias was unavoidable. The efficacy and advantages of EVBT combined with TACE for the treatment of HCC with type III-IV PVTT still require further prospective randomized controlled trials for confirmation.
The embolization method of TACE was also improved upon in this study. Although the c-TACE method of lipiodol combined with gelatin sponge was applied for the treatment of TACE in other studies. in this study, many patients with HCC with PVTT had arterioportal fistulas, and 34 patients had arterioportal fistulas of varying levels. To achieve a good embolization effect and to ensure that embolization agents such as lipiodol do not enter the portal vein system of the healthy liver through the arterioportal fistula, we used a small amount of lipiodol mixed with 500- to 710-µm PVA particles for embolization. The disease control rate was 96.3% one month after TACE with this improved embolization method. Therefore, we believe that this approach can be useful for EVBT combined with TACE therapy, but further research is needed to confirm these findings.
When the PVTT remained at the puncture point of the portal vein, the length of the 125I seed strand was determined according to the distance from the puncture point on the healthy side or the relatively healthy side (i.e., the side with lower tumor burden) to the distal end of the PVTT, which can minimize HCC progression and the further deterioration of liver function caused by the progression of PVTT in the healthy or relatively healthy liver tissue.
In addition, most of the 125I seeds were released on one side of the vessel. The results of this study indicated that there was no progression of PVTT in any patients treated with 125I seeds and that there were no adverse events related to 125I seed treatments, indicating that eccentric 125I seeds can effectively control PVTT.