Analysis of the curative effect of TACE combined with 125I seed implantation
Previous studies have shown that the prognosis of patients with advanced HCC with PVTT is generally poor, and PVTT is a risk factor that affects the survival of patients with HCC (23-25). In this study, TACE combined with 125I seed implantation was used to treat HCC patients with type II PVTT, and the mOS reached 12.5 months, which is similar to previous reports (15-18).
It has been reported that surgical resection may be a treatment for HCC with PVTT (26-28). However, most patients already lose the opportunity to undergo surgical resection by the time the tumor is discovered. Although TACE alone has a certain effect on patients with HCC and PVTT, its effect is often unsatisfactory, with a median survival time of only 7.1 months (29). Owing to obstruction of the portal vein caused by PVTT, reperforming TACE greatly reduces the blood supply to the liver, leading to liver tissue necrosis and liver function failure. Therefore, it is particularly important to control PVTT progression and reduce the occurrence of complete portal vein obstruction. In our study, 125I seed implantation largely controlled the progress of PVTT, with an ORR of 65%. When PVTT is well controlled, the patient's liver function can be restored to a certain extent. At the same time, a prospective study reported that TACE combined with 125I seed implantation has a certain effect on maintaining liver function (18). Therefore, for HCC patients with PVTT, it is particularly important to actively control PVTT.
Radiotherapy is also an important local treatment for PVTT (8). 125I seed implantation is as effective as Stereotactic Body Radiation Therapy (SBRT) and Three Dimensional Conformal Radiation Therapy (3DCR) as IR therapy. A randomized, open-label clinical trial to compare the efficacy and safety of TACE combined with radiotherapy and sorafenib in the treatment of liver cancer and large vessel invasion (30) showed that, compared with sorafenib, the former can prolong progression-free survival and overall survival of patients, with an mOS of 13.1 months.
The PVTT classification is closely related to the prognosis and therapeutic effects of HCC. In our study, we conducted a subgroup analysis of type IIa and type IIb PVTT and compared the difference in survival. The results showed that the mOS of patients with type IIa PVTT was significantly higher than those with type IIb PVTT. This may be because when only one branch of the portal vein is blocked by a tumor thrombus, the liver function is better, and the portal vein pressure is maintained relatively low compared to when both branches of the portal vein are blocked. Patients with type IIa PVTT have better liver function and lower portal pressure than patients with type IIb PVTT; therefore, they can withstand more treatment. Previous studies have shown that type III PVTT is an independent predictor of poor prognosis in such patients. The higher the degree of PVTT (31-33), the worse the treatment effect, which is similar to the results of the present study.
Analysis and clinical significance of predictive models
In this study, the results showed that Child-Pugh score, tumor burden, PVTT and PLT level were significant risk factors for OS. The prognostic factors of HCC have been shown to include maximum tumor diameter, tumor type, tumor stage, cirrhosis, Child-Pugh score, AFP level, and serological indicators of liver function (34-36), which are similar to the results of our study.
The “Six and Twelve” model proposed in the previous study is an excellent model for HCC treatment with TACE (37). This model indicates that patients with cumulative tumor size > 12 cm have a poor prognosis, and the mOS is only 15.8 months. This study also used the sum of tumor size (cm) and tumor number to evaluate the tumor burden. According to the characteristics of the enrolled patients, the standard deviation of the patient’s tumor burden was 7.71, indicating that the tumor burden was relatively large. However, it is worth noting that the "Six and Twelve" model does not evaluate vascular metastasis, and the appearance of PVTT undoubtedly increases the tumor burden and patient survival also deteriorate. The models established by the variables screened by different methods are not the same; however, the best model can be selected only on the basis of rigorous statistics based on previous research and practical clinical significance. This shows that even in patients with portal vein metastasis, the use of the sum of maximum tumor diameter and number to evaluate intrahepatic lesions, combined with the treatment of PVTT, can be used for HCC patients with type II PVTT who undergo TACE combined with 125I seed implantation therapy. According to the prediction model of this study, it is feasible to predict the prognosis of such patients.
A unique feature of this study was the development of a personalized predictive model to predict the prognosis of each patient. From the perspective of tumor burden, we constructed a nomogram to predict the mOS and combined the Child-Pugh score and PLT level to predict the prognosis of type II PVTT from more perspectives. Previous studies and discussions have also illustrated the impact of the Child-Pugh score on HCC patients with type II PVTT.
Simultaneously, we evaluated the model from different angles, conducted external verifications, and obtained good results. In statistical analysis, the general model usually directly brings the validation set input into the training set model to obtain the c-index. This study uses the K-fold CV procedure, and uses cross-validation to achieve multiple c-index calculations. The verification results are more robust than traditional methods (39).
Research based on TNM staging only focuses on the change in the size of the patient’s tumor and whether it has metastasized (38) while ignoring the impact of clinical indicators and the overall patient survival. It is undoubtedly one-sided to consider the survival of patients solely based on tumor status, and the development of the nomogram provides a more comprehensive basis for judgment. At present, the nomogram has been shown to have a certain role in evaluating the prognosis of many cancer patients, including those with HCC and PVTT (40-42). It reflects the characteristics of the tumor and the patient's state, including additional clinical parameters. Therefore, the nomogram is considered more advantageous than the traditional staging method. Some researchers have proposed it as an alternative method or a new standard for guiding cancer treatment (43).
Security and limitations
In terms of safety, TACE combined with 125I seed implantation for PVTT is well tolerated, consistent with the results of other studies (15-18).
This study has certain limitations. First, it is a retrospective study with a small sample size, which may have led to selection bias. The results need to be further confirmed in prospective, multicenter, randomized controlled trials. Although the Child-Pugh score, tumor burden, and PVTT type were included in the nomogram as predictors, they showed a good predictive ability. Owing to the small number of indicators included in this study, more effective indicators may not be included. Therefore, the prediction efficiency of the model must be further improved.
In conclusion, there are still controversies about the treatment of PVTT, but most of the current research and clinical practice showed that for HCC patients with PVTT, combined treatment should be used to obtain better treatment results. This study showed that TACE combined with 125I seed implantation is an effective method for the treatment of HCC with PVTT. Based on the "Six and Twelve" model, combined with the Child-Pugh score and PVTT type, it is a predictive model that can be used to predict mOS in patients with HCC and PVTT receiving treatment.