Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 5  |  Page : 1027-1037

Transarterial chemoembolization combined with microwave ablation versus microwave ablation only for Barcelona clinic liver cancer Stage B hepatocellular carcinoma: A propensity score matching study


1 Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
2 Department of Hepatobiliary Surgery, The 908th Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Yingtan, China

Date of Submission30-May-2019
Date of Decision12-Sep-2019
Date of Acceptance09-Nov-2019
Date of Web Publication29-Sep-2020

Correspondence Address:
Jie Yu
Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853
China
Ping Liang
Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_380_19

Rights and Permissions
 > Abstract 


Purpose: We aimed to compare the outcomes of microwave ablation (MWA) alone with those of transarterial chemoembolization combined with MWA (TACE-MWA) for Barcelona clinic liver cancer (BCLC) Stage B hepatocellular carcinoma (HCC) and to identify the prognostic factors associated with the two treatments.
Materials and Methods: This retrospective study was conducted in 150 BCLC Stage B HCC patients from April 2006 to November 2017. Of these, 88 patients were treated with MWA alone while 62 with TACE-MWA. Propensity score matching (PSM) was conducted to adjust for imbalances in clinical parameters. Procedure-related complications, local tumor progression (LTP), recurrence-free survival (RFS), and overall survival (OS) were analyzed.
Results: Before PSM, the maximal tumor diameters were 6.0 ± 1.0 cm and 6.7 ± 1.3 cm in the TACE-MWA and MWA groups, respectively, with a significant difference (P = 0.002); a significant difference was also detected in α-fetoprotein level (P = 0.013). After PSM, no difference was found in the two parameters (P = 0.067, 0.470). Before and after PSM, no difference was detected in the procedure-related complications (P = 0.803 vs. 1.000, P = 1.000 vs. 1.000), RFS (P = 0.786 vs. 0.689), and OS (P = 0.684 vs. 0.929). Tumor size and α-fetoprotein level were independent influencing factors for OS before and after PSM (P = 0.009, 0.023), while tumor size (D > 7) was an independent risk factor for poor OS (P = 0.011). Tumor number was an independent risk factor for RFS before and after PSM (P = 0.007 vs. P = 0.008). A significant difference was detected in LTP between the two groups with single tumor before and after PSM (P = 0.059 vs. P = 0.006).
Conclusions: The MWA alone group had RFS and OS comparable to that of the TACE-MWA group. TACE-MWA was effective in controlling LTP in patients with a single tumor.

Keywords: Hepatocellular carcinoma, microwave ablation, propensity score matching, transarterial chemoembolization


How to cite this article:
Li X, Chen B, An C, Cheng Z, Han Z, Liu F, Yu J, Liang P. Transarterial chemoembolization combined with microwave ablation versus microwave ablation only for Barcelona clinic liver cancer Stage B hepatocellular carcinoma: A propensity score matching study. J Can Res Ther 2020;16:1027-37

How to cite this URL:
Li X, Chen B, An C, Cheng Z, Han Z, Liu F, Yu J, Liang P. Transarterial chemoembolization combined with microwave ablation versus microwave ablation only for Barcelona clinic liver cancer Stage B hepatocellular carcinoma: A propensity score matching study. J Can Res Ther [serial online] 2020 [cited 2020 Oct 30];16:1027-37. Available from: https://www.cancerjournal.net/text.asp?2020/16/5/1027/296434

Xin Li and Baohua Chen contributed equally to this work





 > Introduction Top


Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer-related mortality worldwide, and morbidity and mortality are still increasing.[1],[2],[3] Surgery is the standard treatment for early-stage HCC, but most HCC patients with intermediate and advanced stages are not surgical candidates and managed with local ablative therapies (LATs) and transarterial chemoembolization (TACE).[4] The Barcelona clinic liver cancer (BCLC) guidelines have been adopted by the American Association for the Study of Liver Disease and the European Association for the Study of the Liver as consensus recommendations for the treatments of HCC stratified by stage and performance status, which is the most widely used tool to predict prognosis and determine treatment modalities.[5],[6] Although TACE is the recommended treatment for patients with intermediate-stage and multifocal tumors, those with larger or infiltrative tumors and tumors bridging two or more liver Couinaud Bismuth segments could not be managed by monotherapies as they have lower rates of complete response.[7] Due to the location and size of the tumor, stratification of treatment according to the BCLC guidelines is difficult to achieve based on the imaging results. Therefore, an effective alternative method should be used to address this problem.

TACE could slow tumor progression and improve survival and is considered as a palliative treatment for BCLC Stage B HCC. However, it can cause tumor ischemic necrosis by arterial embolization, induce tumor death by cytotoxicity of chemotherapeutic drugs, and cause a combination of these effects.[8] Microwave ablation (MWA) as the main LAT with acceptable therapeutic efficiency for HCC has several advantages: it can produce larger ablation volume rapidly, is less affected by heat sink, and is less dependent on the electrical conductivities.[9],[10],[11] MWA and TACE have their own limitations, which affect the adequate control of large HCC.[12],[13] The effect of TACE is influenced by blood supply, tumor size, and the ultra-selectivity of the catheter, and complete tumor necrosis is impossible to achieve by TACE alone. The remaining tumor cells may cause local recurrence and distant metastasis.[14],[15] For MWA, the incidence of incomplete ablation and local recurrence significantly increased with increasing tumor size, as high as 25% and 40.9% for larger HCC.[12],[16] The combined use of TACE and MWA might be appealing with synergistic effect. TACE has the following mechanisms: (1) It can block the hepatic arterial flow and decrease the heat-sink effect and increase the thermal efficiency and intratumor temperature of MWA; (2) The chemotherapeutic drugs and iodized oil that are used in TACE might increase the thermal sensitivity of tumor cells and the thermal conductivity of MWA.[17],[18],[19] As reported recently, combination therapy can reduce HCC recurrence and improve survival compared with TACE or MWA alone.[20],[21],[22] The combination therapy can be used as an alternative treatment and for the successful eradication of tumor and maximal preservation of liver function. However, only a few studies have provided a comparison between a combination of TACE and MWA and MWA alone as the treatment for BCLC Stage B HCC. Thus, this retrospective study aimed to compare the safety and efficacy of TACE combined with MWA (TACE-MWA) with MWA alone as treatment for BCLC Stage B HCC and to analyze the risk factors for oncological outcomes, including local tumor progression (LTP), recurrence-free survival (RFS), and overall survival (OS).


 > Materials and Methods Top


Data collection and modality selection

This retrospective study protocol was approved by the Ethics Committee of the Chinese PLA General Hospital (Beijing, China) and conducted in accordance with the principles of the Declaration of Helsinki. A total of 555 consecutive treatment-naive HCC patients initially treated with TACE-MWA and MWA alone were enrolled from April 2006 to November 2017. Written informed consent was obtained from each enrolled patient before treatment. Patients (1) with Eastern Cooperative Oncology Group performance score of ≤2; (2) with Child–Pugh class A or B; (3) with 5 cm ≤ tumor maximum diameter <10 cm or/and tumor number ≥3; (4) with the absence of vascular invasion or extrahepatic metastases; (5) with normal serum total bilirubin level or serum total bilirubin level of <50 μmol/L; (6) with normal albumin level or albumin level of >25 g/L; (7) with platelet count >50 × 109/mm 3 and prothromb inactivity >50%; (8) whose final diagnosis was based on the biopsy findings performed before ablation; (9) with no history of other malignancies; and (10) who refused to undergo hepatectomy or liver transplantation were included in the study. By contrast, patients (1) with incomplete clinical data, (2) whose cause of death was not related to HCC progression, (3) who were lost to follow-up 3 months after ablation, and (4) with serious heart, lung, and renal function dysfunction and active severe infection were excluded. As presented in [Figure 1], 150 treatment-naive HCC patients with BCLC Stage B were screened and divided into two groups: MWA only group (n = 88) and TACE-MWA group (n = 62).
Figure 1: Flowchart of patients screened and classified into microwave ablation group and transarterial chemoembolization-microwave ablation group

Click here to view


Clinical records were reviewed to verify patient and tumor characteristics, treatment details, and clinical outcomes. The collected clinical data were as follows: (1) patients' features (sex, age, comorbidities [hypertension, diabetes, heart disease, renal disease, pneumonectasis, and esophageal gastric varices], pathological differentiation degree, etiology, cirrhosis, Child–Pugh grade, and Eastern Cooperative Oncology Group status); (2) tumor features (size, number, and location); (3) preoperative data (alpha-fetoprotein and albumin-bilirubin grade); (4) ablation parameters (insertion points and primary complete ablation rate); and (5) postoperative data (complications, LTP, RFS, and OS).

Transarterial chemoembolization combined with microwave ablation procedure

All BCLC Stage B HCC patients were discussed at a multidisciplinary meeting, and TACE was performed 3–7 days before MWA. After routine skin sterilization, local anesthesia with 1% lidocaine was administered. Modified Seldinger catheter was used for femoral puncture, and a Simon I 4F catheter was employed for celiac artery and superior mesenteric artery angiography. When necessary, selective hepatic artery angiography was performed.[23] According to the size, location, and arterial supply of the tumor, the catheter tip was advanced toward the tumor feeding arteries for selective embolization.[24] All TACE procedures, which involved the administration of chemotherapeutic drugs through the feeding artery, were selectively performed using a microcatheter. After inserting the microcatheter into the target branch, chemotherapeutic drugs and iodized oil (Lipiodol, Guerbet) were injected followed by injection of gelatin sponge particles. Cisplatinum (30–60 mg) and fluorouracil (500–1000 mg) were used. Liquid drugs were administered directly, and powdered drugs were mixed with lipiodol for injection. Cisplatin was suspended in 5–20 ml of iodized oil. Injection of embolic materials was performed in cases of tumor shunting until complete occlusion of the shunt. Lipiodol and gelatin sponge permit the drug to concentrate in the tumor and are retained for weeks. One day after TACE, a computed tomography (CT) examination was performed [Figure 2].
Figure 2: A 58-year-old, male patient with hepatocellular carcinoma tumor (7.8cm × 6.4cm) located in the S6 who received transarterial chemoembolization (TACE)-MWA treatment. The tumor was shown on a magnetic resonance (MR) image as a T2WI with high signal intensity (a) and verified on a digital subtraction angiography image, and then a TACE was performed (b) a computed tomography (CT) exam was performed 1 day after TACE with iodized oil deposition (c); then MWA was performed with five insertions under CT guidance (d) ablation was considered complete if there is absence of enhancement on MRI image 1 month after ablation (e) and the ablation zone gradually shrunk 6 months after ablation (f) (yellow arrow).

Click here to view


Microwave ablation procedure

Two cooled-shaft microwave systems (KY-2000, Kangyou Medical, Nanjing, China) with frequencies of 2450 MHz and 915 MHz were used with two generators, both capable of producing 1–100 W of power. The needle antenna has a diameter of 1.9 mm and one 18-cm shaft that can be easily visualized under image. A narrow radiating segment of 3 mm is embedded on the shaft, 11 or 22 mm away from the tip. The microwave machine is also equipped with a thermal monitoring system that continuously measures temperature in real time during ablation. The thermal monitoring needle has a diameter of 0.8 mm.

An automatic biopsy gun with an 18-G cutting needle was used to carry out an ultrasound (US)-guided biopsy immediately before ablation. Consequently, the antennas were percutaneously inserted into the tumor and placed at a designated location under CT or US guidance. For tumors ≤2.0 cm, one antenna was inserted; for 2.0–3.0-cm tumors, two antennae were used simultaneously with two insertions; and for 3.0–5.0-cm tumors, four insertions were needed. A power output of 50–60 W was routinely used during MWA. After all insertions, intravenous anesthesia was administered during standard hemodynamic monitoring. Completed ablation was considered as the heat-generated hyperechoic water vapor completely encompassing the entire tumor in US image or no enhancement in CT image. As many of the tumors were located at challenging locations, induction of artificial pleural effusion and ascites was also performed.[25],[26] A case is shown in [Figure 3].
Figure 3: A 65-year-old, male patient with hepatocellular carcinoma tumor (6.7cm × 5.8cm) located in the S6 who received MWA alone. The tumor was detected on a contrast-enhanced ultrasound image (a) and verified on a magnetic resonance (MR) image as hyperenhancement in the arterial phase (b); MWA was performed with four insertions with under ultrasound-guidance (c); the ablation was considered complete when there is absence of enhancement in the arterial phase on the MR image 1 month after ablation (d), and the ablation zone gradually shrunk 3 months after ablation (e) (yellow arrow)

Click here to view


Assistive technologies

The assistive technologies included in this study were hydrodissection, thermal monitoring, three-dimensional (3D) visualization planning, and multimodal image fusion guidance. If the lesions abutting gastrointestinal tract or diaphragm were found before MWA, hydrodissection is performed. A thermal monitoring needle was inserted into the tumor margin for real-time temperature monitoring during ablation. 3D visualization planning was defined as the interactive manual simulation of the tumor size, location, and the relationship between tumor and the surrounding organs in the 3D model. Multimodal image fusion guidance was defined as the puncture guidance by fused image from the registration of preoperatively acquired images (CT or magnetic resonance imaging) with intraoperative images (US) based on the specified anatomical landmark.

Follow-up and outcomes

Three days after the last course of a defined ablation protocol, contrast-enhanced imaging was performed to evaluate the treatment efficacy. Presence of an irregular peripheral enhancement in a scattered, nodular, or eccentric pattern indicates incomplete ablation, and another ablation was performed. Otherwise, complete ablation was achieved; then, routine contrast-enhanced imaging and serum tumor marker test were performed at 1 month, 3 months, and then every 6 months after treatment. For patients with suspected metastasis, chest CT, bone scan, or positron emission tomography-CT was performed. The end points of this study were death or termination. LTP was calculated from the date after treatment to the progression of the lesions. OS was calculated from the date of first session of MWA treatment to the date of death or last follow-up. RFS was calculated from the date of first session of MWA treatment to the date of tumor recurrence or the last follow-up. Complications were classified according to the Society of Interventional Radiology Classification System for Complications by Outcome.[27] If recurrence and metastasis were detected, proper treatments were administered.

Statistical analysis

All patients who met the eligibility criteria at baseline were included, and their data were analyzed. The quantitative data were expressed as mean ± standard deviation (SD), and qualitative data were expressed as frequency. Differences in clinical parameters and imaging response outcomes between groups were calculated using logistic regression with propensity score matching (PSM), which was conducted using the nearest-neighbor algorithm (1:1). Before PSM, categorical data were compared using the Chi-square test or Fisher's exact test. After PSM, the Cochran–Mantel–Haenszel test was used to evaluate the differences in the categorical covariates. Conditional logistic regression was used after matching to account for the formation of pairs in the matched cohort. LTP, RFS, and OS rates were assessed by the Kaplan–Meier method using the log-rank test. A Cox proportional hazards model was used to identify the significant effects of risk factors on RFS and OS. Univariate and multivariate analyses of independent prognostic factors were evaluated by means of the forward stepwise Cox regression model. Statistical analyses were performed using SPSS 21.0 (SPSS, Chicago, IL, USA) and R software version (http://www.r-project.org/) 3.0.2. A P < 0.05 was considered statistically significant.


 > Results Top


Baseline of patient, tumor, and ablation characteristics before and after propensity score matching

The clinical and pathological characteristics of 150 BCLC Stage B HCC patients with 288 tumors are summarized in [Table 1]. There were 24 female and 126 male patients with a mean age of 62.2 ± 11.3 years (range: 34–83). The mean ± SD of maximal tumor diameter was 6.3 ± 1.2 cm (5.1–10.0). Among the 15 clinical parameters, two showed a significant difference. The maximal tumor diameter in the TACE-MWA group (6.7 ± 1.3 cm) was significantly larger than that in the MWA only group (6.0 ± 1.0 cm) before PSM (P = 0.002). After further analysis, according to maximal tumor diameter (larger than 7 cm or <7 cm), the number of patients (19, 30.1%) in the TACE-MWA group with tumor larger than 7 cm was significantly higher than that in the MWA only group (11, 12.5%) (P = 0.006) before PSM. A significant difference was detected in preoperative α-fetoprotein levels of the TACE-MWA group (36 cases, 58.1%), which was higher than that in the MWA only group (33 cases, 37.5%) (P = 0.013). No difference was observed in the rest of the clinical parameters.
Table 1: Baseline patient characteristics before and after propensity score matching

Click here to view


To further eliminate the differences among the clinical parameters, PSM was performed. There was no difference in the maximal tumor diameter (P = 0.067, 0.093) and preoperative α-fetoprotein level (P = 0.470) after PSM between the TACE-MWA group and MWA only group. Although no difference was detected in the primary complete ablation rate, the rate in MWA only group was slightly higher than that in the TACE-MWA group before and after PSM (P = 0.525, 0.812).

Comparison of long-term oncological outcomes between the transarterial chemoembolization combined with microwave ablation group and microwave ablation only group before and after propensity score matching

The median follow-up period was 37.8 months (range: 3–136). The 1- and 3-year RFS rates in the MWA only group were 56.6% and 35.5%, respectively, which were higher than that in the TACE-MWA group (51.4% and 32.3%). The 5-year RFS in the MWA only group was 22.3%, which was lower than that in the TACE-MWA group (27.6%), and no difference was detected before PSM (P = 0.786) by Kaplan–Meier method using the log-rank test [Figure 4]a. After PSM, the 1-, 3-, and 5-year RFS rates in the MWA only group were 51.6%, 34.5%, and 22.6%, which were similar to that in the TACE-MWA group (51.4%, 32.3%, and 27.6%) (P = 0.689) [Figure 4]b.
Figure 4: Before (a) and after (b) propensity score matching, the 1-, 3-, and 5-year recurrence-free survival rates in the microwave ablation only group were compared with those in the transarterial chemoembolization combined with microwave ablation group (P = 0.786, P = 0.689)

Click here to view


The 1-year OS in the MWA only group was 82.3%, which was higher than that in the TACE-MWA group (78.2%). The 3- and 5-year OS rates were 48.6% and 21.8%, respectively, which were lower than that in the TACE-MWA group (49.2% and 28.8%), and no difference was detected before PSM (P = 0.684) [Figure 5]a. After PSM, the 1-, 3-, and 5-year OS rates in the MWA only group were 83.7%, 47.6%, and 21.2%, respectively, which were similar to that in the TACE-MWA group before PSM (78.2%, 49.2%, and 28.8%) (P = 0.929) [Figure 5]b.
Figure 5: Before (a) and after (b) propensity score matching, the 1-, 3-, and 5-year overall survival rates in the microwave ablation only group were compared with those in the transarterial chemoembolization combined with microwave ablation group (P = 0.684, P = 0.929)

Click here to view


Complications related to microwave ablation only and transarterial chemoembolization combined with microwave ablation groups before and after propensity score matching

The complications related to MWA only and TACE-MWA procedures are listed in [Table 2]. The major complications detected in the MWA only group were pleural effusion requiring drainage (n = 5), massive hemorrhage of gastrointestinal tract (n = 1), subcapsular hemorrhage (n = 2), liver abscess (n = 1), and tumor needle seeding (n = 1), while the minor complications were new ascites (n = 3), pleural effusion (n = 3), hemoglobinuria (n = 1), liver dysfunction (n = 1), and others (n = 2). The corresponding results in TACE-MWA procedures were 4, 0, 2, 1, 0, 4, 2, 1, 2, and 3 cases, respectively. There was no difference in major and minor complications between the two groups before and after PSM (P = 0.803, 1.000 and P = 1.000, 1.000). The results suggested that the two procedures with similar safety were suitable for BCLC Stage B HCC patients. Moreover, all complications were treated, and the patients recovered within 1 week.
Table 2: Complications related to microwave ablation or transarterial chemoembolization

Click here to view


Univariate and multivariate analyses of independent prognostic factors for overall survival and recurrence-free survival

Univariate and multivariate logistic regression analyses were performed to identify the factors influencing the long-term outcomes of BCLC Stage B HCC patients who underwent MWA alone or TACE-MWA. The univariate analyses showed significant differences in terms of OS, depending on tumor size (P = 0.009) and preoperative α-fetoprotein levels (P = 0.032) [Table 3]. The multivariate analyses showed that the tumor size (D > 7 cm) was an independent risk factor for poor OS (P = 0.011, hazard ratio [HR]: 1.932, 95% confidence interval [CI]: 1.165–3.206) [Table 3].
Table 3: Factors associated with overall survival

Click here to view


The univariate analysis showed significant differences in terms of RFS, depending on the tumor number only (P = 0.007). Further, the multivariate analysis showed that tumor number >1 was an independent risk factor for RFS (P = 0.008, HR: 1.804, 95% CI: 1.170–2.782) [Table 4].
Table 4: Factors associated with recurrence-free survival

Click here to view


Local tumor progression control in Barcelona clinic liver cancer Stage B hepatocellular carcinoma patients with a single tumor

LTP was an important factor influencing the long-term outcomes in HCC patients who underwent treatments.[28],[29] The results of univariate and multivariate analyses of independent risk factors for OS and RFS, tumor size, and number were important independent risk factors. Hence, 51 BCLC Stage B HCC patients with single tumor were selected, and the LTP was analyzed.

The 1-, 3-, 6-, and 12-month LTP rates in the MWA only group were 8.6%, 9.8%, 28.8%, and 35.7%, respectively, which were higher than that in the TACE-MWA group (0%, 5.2%, 17.5%, and 21.7%), and no difference was detected before PSM (P = 0.059) by Kaplan–Meier method using the log-rank test [Figure 6]a. After PSM, 1-, 3-, 6-, and 12-month LTP rates in the MWA only group were 8.6%, 14.7%, 33.0%, and 44.2%, respectively, which were obviously higher than that in the TACE-MWA groups (0%, 5.2%, 17.5%, and 21.7%), and a significant difference was detected (P = 0.006) [Figure 6]b.
Figure 6: Before (a) and after (b) propensity score matching, the 1-, 3-, 6-, and 12-month local tumor progression rates in the microwave ablation only group were compared with those in the transarterial chemoembolization combined with microwave ablation group (P = 0.054, P = 0.006)

Click here to view



 > Discussion Top


In our present study, the safety and efficiency of MWA alone were compared with those of TACE-MWA in BCLC Stage B HCC patients. After the analysis, the results showed that MWA alone and TACE-MWA had similar survival outcomes. Specifically, the MWA only group had a tendency to have longer 1- and 3-year RFS than the TACE-MWA group, but no significant difference was observed. By contrast, the 5-year RFS rate in the MWA only group was lower than that in the TACE-MWA group before PSM with no significant difference. With regard to OS, the tendency toward longer 1-year OS was observed in the MWA only group compared with the TACE-MWA group without significant difference, while the 3- and 5-year OS rates in the MWA only group were lower than that in the TACE-MWA group before PSM with no difference. The results indicate that the MWA only group showed better short-term tumor control than the TACE-MWA group, while the TACE-MWA group showed long-term tumor control and survival. This is probably because MWA causes complete coagulation necrosis, while TACE induces hypoxia within the tumor; moreover, ischemic injury after embolization induces the upregulation of angiogenic factors, which may favor tumor proliferation.[30],[31] However, this tendency disappeared, and the RFS and OS rates between the two groups were almost the same after PSM. Therefore, there was no difference detected in the procedure-related major and minor complications, RFS, and OS between the two groups. All of these results indicated that the safety and clinical efficiency of TACE-MWA and MWA alone were similar, and both procedures could be considered as alternative treatments for BCLC Stage B HCC. Moreover, the RFS and OS rates were similar to those reported in previous studies using combination therapy.[18],[32] This is probably due to the adjustment of the differences in clinical variables between the two groups. PSM is a statistical method that attempts to reduce the bias due to confounding variables that could occur when estimating the treatment effect obtained from simply comparing the outcomes of patients who received the treatment from those who did not receive the treatments, which has been used in several nonrandomized clinical studies.[33],[34],[35] In this study, patients in the TACE-MWA group tend to have larger tumor size and higher α-fetoprotein level. As reported in this study, the tumor size was related to the α-fetoprotein level in some HCC patients.[36] After PSM, the difference in α-fetoprotein level was eliminated. The use of PSM helped reduce the bias between the two groups.

To determine the risk factors affecting the long-term survival, univariate and multivariate analyses were performed. The tumor size and number were vital influencing factors. Similar to other reports, our study results suggested that tumor size larger than 7 cm and tumor number >1 were associated with poor survival.[37],[38] Although the tumor size in the TACE-MWA group was larger than that in the MWA group, no significant difference was detected in the RFS and OS rates between the two groups. This can be explained by the fact that TACE performed before MWA could reduce the tumor size and further promote thermal efficiency, expand the ablated area, and facilitate complete ablation.[19],[39]

Based on the above analysis, tumor size was vital for predicting the RFS and OS in BCLC Stage B HCC patients. LTP was also an important factor for predicting long-term outcomes. Hence, the BCLC Stage B HCC patients with single tumor were selected, and the LTP was analyzed. Furthermore, the 1-, 3-, 6-, and 12-month LTP in the MWA only group was obviously higher than that in the TACE-MWA group, but no significant difference was detected before PSM, while a significant difference was detected after PSM. The results further indicated that TACE played an important role in LTP control, especially in the single tumors larger than 7 cm. These findings were also attributed to the mechanisms of TACE.

Our study has several limitations that must be addressed. First, this was a retrospective study and the possibility of variation in operators' technical proficiency might affect the accuracy of ablation results. Second, MWA was performed under CT guidance as combination treatment, while the US guidance was applied in the MWA only group. The difference might also influence the results. Third, the sample size of this study is relatively small. Hence, a multicenter study with larger sample size should be performed to consolidate these results.


 > Conclusions Top


This study demonstrated that MWA alone could provide RFS and OS comparable to that of TACE-MWA for BCLC Stage B HCC patients. Both modalities are capable of achieving favorable imaging response and oncological outcomes. Tumor size and number were also independent risk factors for long-term prognosis. For tumor size larger than 7 cm, TACE-MWA was more effective in controlling LTP in patients with a single tumor. These results suggest other therapeutic alternatives for BCLC Stage B HCC patients, aside from TACE.

Financial support and sponsorship

This work was supported by the National Key R and D Program of China (No. 2017YFC0112000), grants (81430039, 81627803, and 81801723) from the National Scientific Foundation Committee of China, by the National Natural Science Foundation of China (No. 81771955), and by the Clinical Research Support Foundation of the Chinese PLA General Hospital (No. 2017FC-CXYY-3005).

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
de Lope CR, Tremosini S, Forner A, Reig M, Bruix J. Management of HCC. J Hepatol 2012;56 Suppl 1:S75-87.  Back to cited text no. 1
    
2.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.  Back to cited text no. 2
    
3.
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29.  Back to cited text no. 3
    
4.
Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet 2018;391:1301-14.  Back to cited text no. 4
    
5.
Yamakado K, Hirota S. Sub-classification of intermediate-stage (Barcelona Clinic Liver Cancer Stage-B) hepatocellular carcinomas. World J Gastroenterol 2015;21:10604-8.  Back to cited text no. 5
    
6.
Bruix J, Sherman M, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: An update. Hepatology 2011;53:1020-2.  Back to cited text no. 6
    
7.
Kothary N, Takehana C, Mueller K, Sullivan P, Tahvildari A, Sidhar V, et al. Watershed Hepatocellular Carcinomas: The risk of incomplete response following transhepatic arterial chemoembolization. J Vasc Interv Radiol 2015;26:1122-9.  Back to cited text no. 7
    
8.
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003;37:429-42.  Back to cited text no. 8
    
9.
Liang P, Yu J, Yu XL, Wang XH, Wei Q, Yu SY, et al. Percutaneous cooled-tip microwave ablation under ultrasound guidance for primary liver cancer: A multicentre analysis of 1363 treatment-naive lesions in 1007 patients in China. Gut 2012;61:1100-1.  Back to cited text no. 9
    
10.
Yu J, Yu XL, Han ZY, Cheng ZG, Liu FY, Zhai HY, et al. Percutaneous cooled-probe microwave versus radiofrequency ablation in early-stage hepatocellular carcinoma: A phase III randomised controlled trial. Gut 2017;66:1172-3.  Back to cited text no. 10
    
11.
Lopresto V, Pinto R, Farina L, Cavagnaro M. Microwave thermal ablation: Effects of tissue properties variations on predictive models for treatment planning. Med Eng Phys 2017;46:63-70.  Back to cited text no. 11
    
12.
Liu Y, Zheng Y, Li S, Li B, Zhang Y, Yuan Y. Percutaneous microwave ablation of larger hepatocellular carcinoma. Clin Radiol 2013;68:21-6.  Back to cited text no. 12
    
13.
Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology 2006;131:461-9.  Back to cited text no. 13
    
14.
Zhou J, Liu Y, Ren Z, Zhang Y, Zhang M. Transarterial chemoembolization with gelatin sponge microparticles for barcelona clinic liver cancer Stage C and large hepatocellular carcinoma: Initial clinical experience. J Cancer Res Ther 2017;13:767-72.  Back to cited text no. 14
    
15.
Li W, Man W, Guo H, Yang P. Clinical study of transcatheter arterial chemoembolization combined with microwave ablation in the treatment of advanced hepatocellular carcinoma. J Cancer Res Ther 2016;12:C217-20.  Back to cited text no. 15
    
16.
Mulier S, Ni Y, Jamart J, Ruers T, Marchal G, Michel L. Local recurrence after hepatic radiofrequency coagulation: Multivariate meta-analysis and review of contributing factors. Ann Surg 2005;242:158-71.  Back to cited text no. 16
    
17.
Biederman DM, Titano JJ, Bishay VL, Durrani RJ, Dayan E, Tabori N, et al. Radiation Segmentectomy versus TACE Combined with Microwave Ablation for Unresectable Solitary Hepatocellular Carcinoma Up to 3 cm: A propensity score matching study. Radiology 2017;283:895-905.  Back to cited text no. 17
    
18.
Hu H, Chen GF, Yuan W, Wang JH, Zhai B. Microwave ablation with chemoembolization for large hepatocellular carcinoma in patients with cirrhosis. Int J Hyperthermia 2018;34:1351-8.  Back to cited text no. 18
    
19.
Ako S, Nakamura S, Nouso K, Dohi C, Wada N, Morimoto Y, et al. Transcatheter Arterial Chemoembolization to Reduce Size of Hepatocellular Carcinoma before Radiofrequency Ablation. Acta Med Okayama 2018;72:47-52.  Back to cited text no. 19
    
20.
Yan JY, Zhang JL, Wang MQ, Yuan K, Bai YH, Wang Y, et al. Combined transcatheter arterial chemoembolization and radiofrequency ablation in single-session for solitary hepatocellular carcinoma larger than 7 cm. Asia Pac J Clin Oncol 2018;14:300-9.  Back to cited text no. 20
    
21.
Hou YF, Wei YG, Yang JY, Wen TF, Xu MQ, Yan LN, et al. Combined hepatectomy and radiofrequency ablation versus TACE in improving survival of patients with unresectable BCLC stage B HCC. Hepatobiliary Pancreat Dis Int 2016;15:378-85.  Back to cited text no. 21
    
22.
Katsanos K, Kitrou P, Spiliopoulos S, Maroulis I, Petsas T, Karnabatidis D. Comparative effectiveness of different transarterial embolization therapies alone or in combination with local ablative or adjuvant systemic treatments for unresectable hepatocellular carcinoma: A network meta-analysis of randomized controlled trials. PLoS One 2017;12:e0184597.  Back to cited text no. 22
    
23.
Zhu K, Huang J, Lai L, Huang W, Cai M, Zhou J, et al. Medium or large hepatocellular carcinoma: Sorafenib combined with transarterial chemoembolization and radiofrequency ablation. Radiology 2018;288:300-7.  Back to cited text no. 23
    
24.
Yin X, Zhang L, Wang YH, Zhang BH, Gan YH, Ge NL, et al. Transcatheter arterial chemoembolization combined with radiofrequency ablation delays tumor progression and prolongs overall survival in patients with intermediate (BCLC B) hepatocellular carcinoma. BMC Cancer 2014;14:849.  Back to cited text no. 24
    
25.
Minami Y, Kudo M, Kawasaki T, Chung H, Ogawa C, Inoue T, et al. Percutaneous ultrasound-guided radiofrequency ablation with artificial pleural effusion for hepatocellular carcinoma in the hepatic dome. J Gastroenterol 2003;38:1066-70.  Back to cited text no. 25
    
26.
Uehara T, Hirooka M, Ishida K, Hiraoka A, Kumagi T, Kisaka Y, et al. Percutaneous ultrasound-guided radiofrequency ablation of hepatocellular carcinoma with artificially induced pleural effusion and ascites. J Gastroenterol 2007;42:306-11.  Back to cited text no. 26
    
27.
Cardella JF, Kundu S, Miller DL, Millward SF, Sacks D, Society of Interventional Radiology. Society of interventional radiology clinical practice guidelines. J Vasc Interv Radiol 2009;20:S189-91.  Back to cited text no. 27
    
28.
Yu J, Liang P, Yu XL, Cheng ZG, Han ZY, Mu MJ, et al. Local tumour progression after ultrasound-guided microwave ablation of liver malignancies: Risk factors analysis of 2529 tumours. Eur Radiol 2015;25:1119-26.  Back to cited text no. 28
    
29.
Xu XF, Xing H, Han J, Li ZL, Lau WY, Zhou YH, et al. Risk factors, patterns, and outcomes of late recurrence after liver resection for hepatocellular carcinoma: A multicenter study from China. JAMA Surg 2019;154:209-17.  Back to cited text no. 29
    
30.
Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology 2016;150:835-53.  Back to cited text no. 30
    
31.
Hirooka M, Hiraoka A, Ochi H, Kisaka Y, Joko K, Michitaka K, et al. Transcatheter arterial chemoembolization with or without radiofrequency ablation: Outcomes in patients with barcelona clinic liver cancer stage b hepatocellular carcinoma. AJR Am J Roentgenol 2018;210:891-8.  Back to cited text no. 31
    
32.
Peng Z, Wei M, Chen S, Lin M, Jiang C, Mei J, et al. Combined transcatheter arterial chemoembolization and radiofrequency ablation versus hepatectomy for recurrent hepatocellular carcinoma after initial surgery: A propensity score matching study. Eur Radiol 2018;28:3522-31.  Back to cited text no. 32
    
33.
D'Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 1998;17:2265-81.  Back to cited text no. 33
    
34.
Song KD, Lim HK, Rhim H, Lee MW, Kim YS, Lee WJ, et al. Repeated hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma after hepatic resection: A propensity score matching study. Radiology 2015;275:599-608.  Back to cited text no. 34
    
35.
Takuma Y, Takabatake H, Morimoto Y, Toshikuni N, Kayahara T, Makino Y, et al. Comparison of combined transcatheter arterial chemoembolization and radiofrequency ablation with surgical resection by using propensity score matching in patients with hepatocellular carcinoma within Milan criteria. Radiology 2013;269:927-37.  Back to cited text no. 35
    
36.
Hu HT, Wang Z, Huang XW, Chen SL, Zheng X, Ruan SM, et al. Ultrasound-based radiomics score: A potential biomarker for the prediction of microvascular invasion in hepatocellular carcinoma. Eur Radiol 2019;29:2890-901.  Back to cited text no. 36
    
37.
Wu FX, Chen J, Bai T, Zhu SL, Yang TB, Qi LN, et al. The safety and efficacy of transarterial chemoembolization combined with sorafenib and sorafenib mono-therapy in patients with BCLC stage B/C hepatocellular carcinoma. BMC Cancer 2017;17:645.  Back to cited text no. 37
    
38.
Noh JH, Kim TS, Ahn KS, Kim YH, Kang KJ. Prognostic factors after hepatic resection for the single hepatocellular carcinoma larger than 5 cm. Ann Surg Treat Res 2016;91:104-11.  Back to cited text no. 38
    
39.
Ahmed M, Technology Assessment Committee of the Society of Interventional Radiology. Image-guided tumor ablation: Standardization of terminology and reporting criteria-a 10-year update: Supplement to the consensus document. J Vasc Interv Radiol 2014;25:1706-8.  Back to cited text no. 39
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Materials and Me...>Results>Discussion>Conclusions>Article Figures>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed195    
    Printed4    
    Emailed0    
    PDF Downloaded3    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]