Efficacy and Safety of Endovascular Brachytherapy Combined with Transarterial Chemoembolization for the Treatment of Hepatocellular Carcinoma Patients with Type III-IV Portal Vein Tumor Thrombosis

DOI: https://doi.org/10.21203/rs.3.rs-952408/v1

Abstract

Background: The purpose of this study was to evaluate the safety and efficacy of endovascular brachytherapy (EVBT) combined with transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC) complicated with type III-IV portal vein tumor thrombosis (PVTT) and to further analyze the major independent risk predictor factors of prognosis.

Methods: We retrospectively analyzed the medical records of 54 patients who were diagnosed with HCC complicated with type III or IV PVTT and who received EVBT combined with improved TACE treatment from January 2017 to June 2019. Adverse events, treatment response, overall survival (OS), progression-free survival (PFS), and stent patency were analyzed to evaluate the efficacy and safety of this treatment. Major independent risk predictors of OS were also analyzed by the regression model.

Results: No severe adverse events associated with EVBT combined with TACE were observed. The objective response and disease control rates four weeks after the treatment were 42.6% and 96.3%, respectively. The median OS and PFS were 209±46.5 days and 138±29.4 days, respectively. The cumulative stent patency rate was 70.4% at the last follow-up. AFP≥400 ng/ml, ECOG PS>1, Child-Pugh grade B, and nonhemihepatic HCC were independent risk predictors of OS.

Conclusions: EVBT combined with TACE was effective and safe for the treatment of HCC with type III-IV PVTT.

Background

Liver cancer is the fourth leading cause of cancer-related mortality globally[1], and it ranks second among the causes of cancer-related death in China[2]. Hepatocellular carcinoma (HCC) represents the major histological subtype, accounting for 70-90% of cases of liver cancer. Portal vein tumor thrombosis (PVTT) is a common complication of HCC. The incidence of HCC accompanied by PVTT was 44-62.2%[3], with a median survival time (MST) of 2.7-4.0 months[4, 5]. Cheng’s classification of PVTT has been proven to be a useful classification system for disease evaluation, treatment selection, and prognostic judgment of HCC with PVTT. According to Cheng’s classification, types III and IV PVTT refer to tumor thrombi involving the main portal vein trunk and superior mesenteric vein, respectively[6, 7], indicating advanced condition, difficult treatment, and poor prognosis. Recently, transarterial chemoembolization (TACE), targeted therapy (e.g., sorafenib), or yttrium-90 resin microspheres for locoregional selective internal radiation therapy were applied to treat the patients who cannot receive surgical treatment. Ammon these therapeutic approaches, TACE exerts its anti-tumor roles by injecting chemotherapeutic agents to hepatic artery causing the selective obstruction of the tumor-feeding arteries; whereas, sorafenib could suppress HCC growth, metastasis and angiogenesis by inhibiting the activity of tyrosine kinase. However, all these approaches only showed limited clinical efficacy in the treatment of HCC complicated with type III PVTT[813].

Iodine 125 (125I) seeds can continuously release low-energy γ-rays, which can increase the destruction of tumor cells to suffer the most destructive damage without damaging normal tissues and thus achieve tumor control. Therefore, 125I seed implantation for endovascular brachytherapy (EVBT) has been proven to be a safe and reliable local adjuvant radiotherapy treatment that can be used for the treatment of HCC, pancreatic cancer, non-small cell lung cancer, cervical cancer, and other malignant tumors[1416]. Studies have shown improved efficacy of EVBT combined with TACE versus TACE alone, TACE combined with portal vein stent implantation, and TACE combined with external radiotherapy[1720] for the treatment of HCC complicated with type III PVTT. However, type IV PVTT and type III PVTT with invasion of all second intrahepatic portal vein branches were all excluded from these studies. .Thus, there is still no effective treatment for these excluded patients, and EVBT combined with TACE may be a promising treatment strategy.

Therefore, the purpose of this study were to evaluate the safety and efficacy of EVBT combined with TACE for the treatment of HCC complicated with type III-IV PVTT, which included patients with invasion of all second intrahepatic portal vein branches, and to further analyze major independent risk predictor factors of prognosis with respect to this treatment.

Methods

Patients

This study was approved by the institutional ethics committee. Before undergoing treatment, the benefits of the treatment and possible adverse events were explained to the patients and their relatives in detail, and all patients provided written informed consent to receive treatment.

The medical records of patients who were diagnosed with HCC complicated with type III or IV PVTT and who received EVBT combined with TACE treatment from January 2017 to June 2019 were retrospectively analyzed. The inclusion criteria for this study were as follows: (1) age of patients was ≥18 years; (2) definite diagnosis of HCC according to the "standardization for the Diagnosis and Treatment of Hepatocellular Carcinoma"; (3) diagnosis of type III or IV PVTT was confirmed by contrast-enhanced abdominal computed tomography (CT) or magnetic resonance imaging (MRI); (4) Child-Pugh classification grade was A or B; (5) Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2; (6) no history of other malignant tumors. The exclusion criteria were as follows: (1) Child-Pugh grade C patients; (2) ECOG PS of 3-4 points; (3) patients had suffered from malignant tumors other than HCC; (4) patients had severe heart, lung, or kidney function insufficiency; and (5) prior TACE, surgery, ablation treatment, intrahepatic tumor 125I seed implantation, or other treatments received within 1 month before EVBT combined with TACE treatment in Fig. 1.

EVBT treatment

Stent and 125I seeds

The nitinol self-expanding stent (Luminxx III, Bard, USA) used in this study was 10-12 mm in diameter and 60-120 mm in length. The 125I seeds used were a brachytherapy source (HTA, China) with a silver wire in the core, containing 125I seeds 3.00 mm in length. The seeds were encapsulated by high-purity titanium 0.8 mm in diameter and 4.5 mm in length. The radioactivity of each 125I seed was 0.6-0.7 mCi, with a half-life of 59.43 days, and the principal photon emissions were 31.4 keV X-rays and 35.5 keV γ-rays. Meanwhile, the activated silver wire could also emit fluorescent X-rays at 22.1-22.5 keV. The half-value thickness of tissue for 125I seeds was 17 mm, and the initial dose rate was 0.0013 Gy/min. These seeds were arranged linearly and sealed into a 4F catheter continuously to construct a 125I seed strand. Studies have shown that the continuous linearly arranged 125I seed strand radiation distribution isometric curve was a cylinder, which was suitable for intracavitary treatment[2123].

Implantation of the portal vein stent and 125I seeds

Implantation of the portal vein stent and 125I seeds was performed before TACE. The first or second branches of the intrahepatic portal vein were punctured with a 22-G Chiba needle (COOK, Bloomington, USA) under ultrasound guidance, and then a 0.018-inch wire (COOK) was inserted into the portal vein after removal of the puncture needle core. A 6F NEFF set (COOK) was introduced into the portal vein, and a wire 0.035 inches in diameter and 150 cm long was manipulated across the obstructed portal vein into the superior mesenteric vein or splenic vein. The outer cannula of the NEFF set was replaced by a 6F, 55-cm-long sheath (COOK) via the wire. Venography of the splenic vein and superior mesenteric vein was conducted by a gold-labeled catheter (COOK) to determine whether there were significant esophageal gastric varices and to measure the diameter and length of the PVTT. The vein that supplies the esophageal and gastric varices was embolized with a coil (COOK) and/or GLUNRAN 2 (GEM, Viareggio, Italy). If the PVTT was still present at the puncture point of the portal vein, the measured length was the distance from the puncture point to the distal end of the PVTT. The number of 125I seeds to be implanted was determined (N = length (mm)/4.5 +4)[17]. Two 0.035-inch, 260-cm-long stiff wires (Terumo, Tokyo, Japan) were inserted into the splenic vein or superior mesenteric vein through the 6F vascular sheath. After the sheath was removed, a self-expandable stent of appropriate size and a 6F vascular sheath (55cm) were introduced into appropriate location via stiff wires. The 125I seed strand was delivered through the 6F 55cm vascular sheath, the stent was deployed, and the 125I seeds were released at the target position. Finally, the intrahepatic portal vein puncture route was blocked with GLUBRAN 2 (GEM, Viareggio, Italy). The process of implantation is shown in Fig. 2.

TACE treatment

To determine all the feeding arteries of the tumor, angiography of the abdominal trunk and superior mesenteric artery was performed with a 5F RH catheter (Terumo, Tokyo, Japan). Angiography of the left gastric artery, bilateral phrenic artery, right renal artery, and bilateral internal thoracic artery were also performed if necessary. Then, 5-8 mL of lipiodol, 1 mL of Polyvinyl Alcohol foam embolization particles(PVA) embolization particles (COOK), 30 mg of epirubicin (Pfizer, New York, USA), and 22-25 mL of ioversol were mixed and emulsified. The target artery was catheterized with a 2.7F microcatheter (Terumo). Under the guidance of Digital subtraction angiography (DSA), the target artery was embolized by the mixture. This process is shown in Fig. 2.

Postoperative treatment and follow-up

All patients were followed up at 4- to 6-week intervals after the previous therapy until death or their last follow-up (before June 30, 2020). Tumor progression and patency of the portal vein stent were evaluated by abdominal CT or MR enhancement, and laboratory tests were performed to evaluate liver and renal function, blood cell count, and the coagulation parameters of the patients. After the operation, some patients also received further treatments according to their disease conditions, such as TACE, tumor targeted ablation therapy, 125I seed implantation, or surgical resection.

Evaluation of efficacy and safety

The efficacy of EVBT combined with TACE in the treatment of HCC complicated with type III-IV PVTT was evaluated by overall survival (OS), progression-free survival (PFS), and the modified response evaluation criteria in solid tumors (mRECIST) in this study[24]. OS was the period from patients receiving EVBT combined with TACE treatment to the date of death or the last follow-up. In this study, PFS was defined as the length of time from patient receiving the combined treatment of EVBT and TACE to the progression of HCC including intrahepatic HCC spread, variceal bleeding, or liver function decompensation. According to mRECIST, the treatment efficacy was classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). The Common Terminology Criteria for Adverse Events (Version 5.0) were used to evaluate the adverse events related to EVBT combined with TACE treatment.

Statistical analysis

Data were analyzed with SPSS version 20.0 (SPSS, Chicago, Illinois). Continuous variables are presented as the mean values ± standard deviation. OS and PFS were analyzed with Kaplan–Meier curves and log-rank tests. p value <0.05 was regarded as significant. Cox regression analysis was performed to determine the independent risk factors of overall survival. The variables with p<0.05 in the univariate analysis were pick up for the multivariate analysis.

Results

Patient data

A total of 54 patients were enrolled in this study. Male patients accounted for the majority (n=52, 96.3%), with an average age of 51±8.2 years (27-68 years). There were 52 patients (96.3%) with cirrhosis caused by hepatitis B, 42 patients (77.8%) with Child-Pugh grade A and 12 patients (22.2%) with Child-Pugh grade B. Only 5 patients (9.3%)of these patients had a single tumor, and the largest tumor diameter was >10 cm in 50% of patients. The tumors of 30 patients (55.6%) were confined to the hemihepatic region. There were 44 patients (81.5%) with type III PVTT and 10 patients (18.5%) with type IV PVTT, and the diameter and length of the PVTT were 1.9±0.6 cm (0.5-3.6 cm) and 3.8±2.5 cm (0.5-12 cm), respectively. Fourteen (25.9%) patients had distant metastases, and 14 patients (25.9%) had received previous therapies (surgery, TACE, ablation, or radiotherapy) for HCC more than 1 month before treatment. Postoperative local therapy for HCC was performed in 36 patients (66.7%), among whom 32 patients received TACE, 14 patients received 125I seed implantation, 4 patients received intrahepatic tumor ablation, 2 patients received radiotherapy, and 2 patients (3.7%) underwent tumor resection. The baseline characteristics of these 54 patients are summarized in Table 1 and Table 2.

Table 1

Baseline characteristics of the patients

Characteristics

Number(proportion,%)

Characteristics

Number(proportion,%)

Sex

 

Hemihepatic HCCc

 

Male

52(96.3)

Yes

30(55.6)

Female

2(3.7)

No

24(44.4)

Age (years)

 

Distant metastasis

 

≥55

18(33.3)

Yes

14(25.9)

<55

36(66.7)

No

40(74.1)

Hepatitis B

 

PVTTd

 

Yes

52(96.3)

Type III

44(81.5)

No

2(3.7)

Type IV

10(18.5)

AFPa ( ng/ml)

 

Tumor diameter

 

≥400

29(53.7)

>10cm

27(50.0)

<400

25(46.3)

≤10cm

27(50.0)

Child-Pugh grade

 

Number of tumors

 

A

42(77.8)

Single

5(9.3)

B

12(22.2)

Multiple

49(90.7)

ECOG PSb

 

Previous treatment

 

0/1

42(77.8)

Yes

14(25.9)

2

12(22.2)

No

40(70.5)

Hepatic arterioportal fistulas

 

Postoperative treatment

 

Yes

34(73.0)

Yes

36(66.7)

No

20(37.0)

No

18(33.3)

aAFP, alpha fetoprotein;

bECOG PS, Cooperative Oncology Group performance status.

cHCC, hepatocellular carcinoma;

dPVTT, portal vein tumor thrombosis.           

Table 2

Characteristics of PVTT

Characteristic

Number (Proportion%)

Unilateral first branch invasion

20(37.0)

Left portal vein invasion

6(11.1)

Right portal vein invasion

14(25.9)

Unilateral secondary branches invasion

20(37.0)

All unilateral secondary branches invasion

16(29.6)

Bilateral first branch invasion

34(63.0)

Unilateral secondary branches invasion

11(20.4)

Bilateral secondary branches invasion

23(42.6)

All bilateral secondary branches invasion

7(13.0)

Safety analysis

No complications related to the implantation of EVBT with 125I seeds, such as abdominal bleeding, stent displacement, white blood cell decline caused by 125I seeds, or radiation damage to surrounding organs, were observed during treatment. The most common adverse events were post-chemoembolization syndrome, including fever, vomiting, liver pain, liver function damage, pleural effusion, and primary peritonitis. Grade 3 adverse events, such as primary peritonitis (3.7%) and postoperative increases in TBIL (29.6%) or ALT (9.3%), were observed, as presented in Table 3. The TBIL and ALT almost returned to the preoperative level 1 month after the treatment. There were no grade 4 adverse events in the treatment.

Table 3

Adverse treatments events

Adverse events

Number (proportion%)

Grade 1–2, n (proportion%)

Grade 3, n (proportion%)

Grade 4, n (proportion%)

Abdominal pain

26(48.1)

26(48.1)

0(0)

0(0)

Fever

23(42.6)

23(42.6)

0(0)

0(0)

Vomiting

7(13.0)

7(13.0)

0(0)

0(0)

Ascites

6(11.1)

6(11.1)

0(0)

0(0)

Pleural effusion

5(9.3)

5(9.3)

0(0)

0(0)

TBILa increase

28(81.5)

28(51.9)

16(29.6)

0(0)

ALTb increase

15(27.8)

10(18.5)

5(9.3)

0(0)

Hypoalbuminemia

43(79.6)

43(79.6)

0(0)

0(0)

Inguinal hematoma

0(0)

0(0)

0(0)

0(0)

Gastrointestinal bleeding

0(0)

0(0)

0(0)

0(0)

Pulmonary embolism

0(0)

0(0)

0(0)

0(0)

Primary peritonitis

2(3.7)

0(0)

2(3.7)

0(0)

aTBIL, total bilirubin;

bALT, alanine aminotransferase.

Efficacy analysis

Responses of HCC

The responses of HCC were evaluated according to mRECIST four weeks after the treatment. During the four-week treatment, no cases with CR or PVTT progression were observed within the coverage of 125I seeds. The PR rate and SD rate of the enrolled patients were 42.6% and 53.7% respectively.

Overall survival (OS)

During this study executing, a total of forty-four patients (81.5%) lost their life. Among them, most of the patients (42 of 44) died of liver failure caused by HCC progression. The other two patients subjected to lung infection, esophageal and gastric variceal bleeding respectively causing their death ultimately. The mean survival time of the enrolled patients was 349.7±48.1 days (95% CI, 255.5-444.0), and the median survival time is 209±46.5 days (95% CI, 117.8-300.2). The cumulative survival rates at 180, 360, 720, and 1080 days were 56%, 28%, 16%, and 12%, respectively. The cumulative survival rates at 180, 360, 720, and 1080 days in patients with type IV PVTT were 70%, 30%, 20%, and 20%, respectively.

AFP, ECOG PS, Child-Pugh grade, ascites and whether HCC was hemihepatic were significantly associated with the OS of patients in the univariate analysis. In addition, the multivariate Cox regression analysis indicated that AFP≥400 ng/ml, ECOG PS>1, Child-Pugh grade B, and nonhemihepatic HCC (HCC located in both the left and right hemiliver) were independent risk predictors of OS for the treatment of EVBT combined with TACE in our study (Table 4). It is worth noting that the type of PVTT was not an independent predictor of OS. Afterwards, Kaplan-Meier curves was applied to evaluate the prognosis of enrolled patients. All patients (n=54) were further divided into two subgroups depending on different prognostic indicators, namely, AFP (≥400 ng/ml versus <400 ng/ml), ECOG PS (>1 versus ≤1), Child Pugh grade (grade A versus grade B) or non-hemihepatic HCC (Yes versus No). The results showed that patients with high serum AFP (≥400 ng/ml, n=29) usually have short survival time comparing to those patient with low serum AFP (p=0.045, Fig. 3A). The mean OS times of the patients with high and low serum AFP were 148 and 301 respectively. Similarly, Child Pugh grade B (p=0.033), ECOP PS>1 (p=0.008) and non-hemihepatic HCC (p=0.011) were also significantly associated with poor prognosis (Fig. 3B, C, D).

Table 4

Risk predictors of OS in the univariate and multivariate analyses

Variable

Overall survival

Univariate analysis

Multivariate analysis

HR (95% CI)

P-value

HR (95% CI)

P-value

Age (≥55 years old vs <55 years old)

1.247(0.673-2.310)

0.483

   

AFPa (≥400ng/ml vs <400ng/ml)

1.858(1.014-3.404)

0.045*

1.940(1.008-3.735)

0.047*

Ascites (Have vs None)

2.15(1.171-3.948)

0.014*

   

ECOG PSb (0-1 vs 2)

2.414(1.230-4.740)

0.008*

2.574(1.278-5.185)

0.008*

Child-Pugh grade (A vs B)

2.114(1.061-4.214)

0.033*

2.913(1.385-6.123)

0.005*

Arterioportal fistula (Have vs None)

1.036(0.555-1.931)

0.912

   

Hemihepatic HCCc (Yes vs No)

0.454(0.247-0.835)

0.011*

0.517(0.269-0.992)

0.047*

HCCc diameter (>10cm vs ≤10cm)

1.454(0.802-2.636)

0.218

   

Number of tumors (Single vs Multiple)

0.327(0.100-1.260)

0.065

   

Distant metastasis (Yes vs No)

1.829(0.955-3.502)

0.069

   

Hepatic vein tumor thrombosis

(Yes vs No)

1.844(0.850-4.003)

0.122

   

Cavernous transformation collateral (Yes vs No)

0.703(0.387-1.275)

0.246

   

PVTTd type (III vs IV)

0.801(0.371-1.731)

0.573

   

Previous treatment (Yes vs No)

1.380(0.720-2.647)

0.332

   

* P<0.05

aAFP, alpha fetoprotein;

bECOG PS, Cooperative Oncology Group performance status;

cHCC, hepatocellular carcinoma;

dPVTT, portal vein tumor thrombosis.

 

Progression-free survival (PFS)

The mean PFS time of enrolled patients was 204.7days (95% CI, 154.7-254.7), and the median PFS time was 138 days (95% CI, 80.4-195.6). The cumulative PFS ratio were respectively 56%, 35%, 15%, and 2% at 90, 180, 360, and 720 days after treatment.

Stent patency

DSA angiography showed the patency of stents stent patency in 40 patients (74.0%) just immediately after 125I and stent implantation, and 42 patients (77.7%) had stent patency in the follow-up one month after the treatment. The cumulative stent patency rate was 70.4% (N=38) at the last follow-up.

Discussion

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.

Conclusions

In the present study, a combination therapeutic strategy with EVBT and TACE has been developed and applied in clinical practice. This combination therapy might be an effective and safe approach to improve the prognosis of HCC patients with type III-IV PVTT according to our results. To further evaluate the efficacy and safety of this treatment strategy, a multi-center clinical research with larger cohorts should be performed in future. Additionally, AFP≥400 ng/ml, ECOG PS>1, Child-Pugh grade B, and nonhemihepatic HCC were proved to be independent risk predictors of OS.

Abbreviations

CT

contrast-enhanced abdominal computed tomography

CR

complete response

DSA

Digital subtraction angiography

EVBT

endovascular brachytherapy

ECOG PS

Eastern Cooperative Oncology Group performance status

HCC

Hepatocellular carcinoma

Iodine 125 (125I)
MST

median survival time

MRI

magnetic resonance imaging

mRECIST

modified response evaluation criteria in solid tumors

OS

overall survival

PVTT

Portal vein tumor thrombosis

PFS

progression-free survival

PR

partial response

PD

progressive disease

PVA

Polyvinyl Alcohol foam embolization particles

SD

stable disease

TACE

Transarterial chemoembolization.

Declarations

Ethics approval and consent to participate

This study was approved by the ethics committee of Mengchao Hepatobiliary Hospital of Fujian Medical University (no.2019_13_01).

Consent for publication

Patients signed informed consent regarding publishing their data and photographs.

Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This work was supported by Social Development Medical Project of Fuzhou (2018-S-103-5); Joint Funds for the Innovation of Science and Technology of Fujian province (2017Y9117); Startup Fund for scientific research, Fujian Medical University (2019QH1298).

Authors' contributions

Wuhua Guo conceived this study. This paper was written by Ling Li. The figures and tables were designed and organized by Xinhui Huang and Niangmei Cheng. Data collection and analysis were performed by Ling Li, Xinhui Huang, Xiadi Weng and Yubin Jiao. Jingfeng Liu and Wuhua Guo revised critically the manuscript. All authors read and approved the manuscript.

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