Transarterial chemoembolization plus radiofrequency ablation and iodine-125 seed implantation for hepatocellular carcinoma in high-risk locations: a propensity score-matched analysis

Transarterial chemoembolization plus radiofrequency ablation and iodine-125 seed implantation for hepatocellular carcinoma in high-risk locations: a propensity score-matched analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Transarterial chemoembolization plus radiofrequency ablation and iodine-125 seed implantation for hepatocellular carcinoma in high-risk locations: a propensity score-matched analysis Guilin Zhang, Yanqiao Ren, Jiayun Liu, Yanyan Cao, Fu Xiong, Bin Liang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4258024/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background & aims: The effect of transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) (TACE-RFA) for hepatocellular carcinoma (HCC) in high-risk locations is not satisfactory. The aim of this study was to compare the clinical outcomes of TACE-RFA plus iodine-125 ( 125 I) seed implantation (TACE-RFA- 125 I) therapy with those of TACE-RFA for unresectable HCC (≤5 cm) in high-risk locations. Methods: From January 2010 to June 2023, the clinical data of 126 patients with unresectable HCC (≤5 cm) in high-risk locations who received TACE-RFA- 125 I or TACE-RFA treatment were retrospectively analyzed. The clinical outcomes between the two groups were compared after propensity score matching (PSM) analysis. Results: Forty-six pairs of patients were matched. The local progression-free survival rates at 1-, 2-, 3-, 4-, and 5-years were 100%, 82.4%, 74.8%, 63.5%, and 54% in the TACE-RFA- 125 I group, which were significantly higher than 91.3%, 69.4%, 50.7%, 29.4%, and 26.7% in the TACE-RFA group, respectively ( p = 0.004). The median progression-free survival in the TACE-RFA- 125 I group was significantly longer than that in the TACE-RFA group ( p = 0.002). The overall survival rates at 1-, 2-, 3-, 4-, and 5-years were 100%, 93.4%, 80.7%, 74.9%, and 64.7% in the TACE-RFA- 125 I group, which were significantly higher than 97.8%, 78%, 68.6%, 51.1%, and 45.3% in the TACE-RFA group, respectively ( p = 0.011). There was no occurrence of major complications or procedure-related deaths in the two groups. Conclusions: Compared with the TACE-RFA treatment, TACE-RFA- 125 I should be a more effective treatment strategy for patients with unresectable HCC (≤5 cm) in high-risk locations. radiofrequency ablation transarterial chemoembolization iodine-125 seed hepatocellular carcinoma high-risk locations Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide (Sung et al. 2021 ). Radiofrequency ablation (RFA) has been accepted as an effective alternative to surgery in the management of small- to intermediate-sized (≤ 5 cm) HCCs (Wang et al. 2021 ; Bai et al. 2021 ; Lee et al. 2021 ). However, for RFA of HCCs in high-risk locations (tumors close to the diaphragm, large vessels, liver capsule, gallbladder, gastrointestinal tract, or kidney), it is difficult to achieve an effective and safe ablation periphery with a 1 cm surgical margin beyond the tumor confinement for protecting these adjacent critical structures from heat damage, which thus often leads to a local tumor recurrence. Attempts have been made to address this issue, such as RFA combined with transarterial chemoembolization (TACE) or iodine-125 ( 125 I) seed implantation (Lin et al. 2012 ; Chen et al. 2022 ). However, the local tumor recurrence rates and patients’ long-term survival are still not satisfactory (Chen et al. 2014 ; Cao et al. 2022 ). Thus, there is a pressing clinical need to develop a more effective treatment strategy to improve the effect of RFA on HCCs in high-risk locations. Due to its minimal invasiveness, safety, and effectiveness, 125 I seed implantation is a favourable therapy for some solid malignant tumors, including HCC (Strnad et al. 2023 ; Monk et al. 2023 ; Choudhury et al. 2023 ). Several previous studies (Lin et al. 2012 ; Chen et al. 2014 ; Li et al. 2019 ) reported that 125 I seed implantation could further improve the effects of TACE or RFA on HCCs. To the best of our knowledge, there was no report of the triple-combination treatment (TACE + RFA + 125 I seed implantation) for HCC in high-risk locations. Percutaneous RFA and 125 I seed implantation procedures were usually performed under ultrasound or computed tomography (CT) guidance (Chen et al. 2020 ; Hong et al. 2021 ). However, for HCCs in high-risk locations, ultrasound-guided percutaneous RFA or 125 I seed implantation is challenging for poor tumor visualization or suboptimal electrode path due to the overlapped ribs, lung, gallbladder, or gastrointestinal tract, which may result in incomplete RFA, thermal injury to the surrounding organs, or uneven distribution of 125 I seed in tumors. Although CT imaging usually provides a clearer visualization for such HCCs compared with ultrasound imaging, a CT-guided puncture may result in injury to the diaphragm, blood vessels, gastrointestinal tract, or gallbladder for lack of real-time dynamic imaging. So a real-time and accurate imaging guidance strategy is needed for RFA and 125 I seed implantation in the treatment of HCCs in high-risk locations. In the present study, patients with HCC in high-risk locations were first treated with TACE, followed by RFA and 125 I seed implantation treatments (TACE-RFA- 125 I), which were performed under ultrasound plus CT guidance, and the clinical data of these patients were retrospectively analyzed. The purpose of this study was to evaluate whether this therapy could lead to better tumor control and patients’ survival compared with TACE plus RFA (TACE-RFA) for HCC in high-risk locations, and provide a more effective and safe treatment strategy in the management of this type of HCC. Patients and methods Study design and patient selection From January 2010 to June 2023, the clinical data of 126 HCC patients who received the treatment of TACE-RFA- 125 I or TACE-RFA in our center was retrospectively analyzed. The clinical outcomes between the two treatment groups were compared after propensity score matching (PSM) analysis. Meanwhile, a subgroup analysis according to tumor size (≤ 3 cm and 3–5 cm) was performed to compare the effects of these two different treatments in the two subgroups. This retrospective study was conducted in accordance with the Declaration of Helsinki, and was approved by the Ethics Committee of our institution (approval number: UHCT-IEC-SOP-012-01-01), which waived the need for written informed consent. The report of this study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies ( Supplementary Table 1 ). The inclusion criteria of this study were as follows: (1) patients were diagnosed with HCC according to the European Association for the Study of the Liver or American Association for the Study of Liver Disease guidelines (Heimbach et al. 2018 ; Galle et al. 2018 ); (2) patients with HCC in high-risk locations, which were defined as these located < 5 mm of vital structures, such as the diaphragm, large vessels, liver capsule, gallbladder, gastrointestinal tract, and kidneys (Hsieh et al. 2019 ); (3) a solitary HCC (≤ 5.0 cm) or multiple (up to three) HCC lesions (each ≤ 3.0 cm); (4) patients were not eligible for surgical resection or liver transplantation; (5) the procedures of RFA and 125 I seed implantation were performed under combined ultrasound/CT guidance; (6) no vascular invasion or no extrahepatic metastasis; (7) Eastern Cooperative OncologyGroup (ECOG) performance status 0; (8) Child-Pugh class A or B; (9) blood platelet count > 40×10 9 /L. The exclusion criteria of this study were as follows: (1) before TACE-RFA- 125 I or TACE-RFA treatment, patients received other treatments for HCC, such as stereotactic body radiotherapy, chemotherapy, and liver transplantation, et al.; (2) patients were accompanied by other malignancies; (3) patients were accompanied by severe cardiac and renal dysfunction; (4) the clinical data of patients were incomplete or lost to follow-up. TACE procedure and ultrasound plus CT-guided RFA and 125 I seed implantation All the patients received TACE treatment before RFA and 125 I seed implantation procedures, and the TACE procedures were performed as described in our previous study (Kan et al. 2019 ). RFA was performed 5–10 days after TACE. Before RFA treatment, laboratory examinations, such as complete blood count, liver and renal function, and prothrombin time, were performed to assess whether the patients fulfilled the RFA treatment criteria. The RFA procedures were performed with a RITA 1500 generator (RITA Medical Systems Inc., Mountain View, USA) and a 14-gauge multiple electrode (Rita Medical Systems, Mountain View, California, USA) under combined ultrasound/CT guidance, as described in our previous study (Kan et al. 2019 ). The analgesia was conducted by local injection of 5 mL of 2% lidocaine and intravenous administration of 50–100 mg of a flurbiprofen axetil injection (Tide Pharmaceutical Co., Ltd., Beijing, China). The procedures of 125 I seed implantation were performed within 7 days after RFA treatment. The 125 I seeds were implanted in the insufficient ablation tumor magin or the highly suspected zone of residual viable tumors. The number and distribution of 125 I seed were determined by the Treatment Planning System (TPS) (HGGR300, Hokai Medical Instruments Co., Ltd., Zhuhai, China). An interstitial needle (17-gauge, hollow needles, 15 cm long) was inserted into the site close to the tumor under ultrasound guidance, and then CT images were used to precisely guide the placement of the interstitial needle. A Mick applicator (Mick Radionuclear Instruments, Bronx, NY) was then sequentially attached to the distal end of each needle to place the 125 I seed (0.7 millicuries per seed) into the tumor, spaced approximately 1 cm apart along the needle track. After 125 I seed implantation, a CT scan was performed again to assess the 125 I seed position and the presence of major complications, and the images were transmitted to TPS for dose verification. Follow-up Contrast-enhanced CT or contrast-enhanced magnetic resonance imaging (MRI) of the chest and liver, blood tests such as liver and kidney function, blood routine, and tumor markers were performed at each follow-up. The first follow-up was conducted 4–6 weeks after the initial treatment, and then the patients were reviewed every 3 months during the first year and every 6 months thereafter. Repeated TACE, RFA, or 125 I seed implantation was used to treat the recurrent or residual tumors. The follow-up of this study ended on November 30, 2023. In the present study, local tumor progression was defined as the appearance of any viable tumor within 1 cm from the ablated margin of tumors on CT/MRI images during follow-up, and intrahepatic tumor progression was defined as the occurrence of a new tumor within the liver, except for local tumor progression. Local progression-free survival (LPFS) was defined as the time from the initial TACE to local tumor progression or death from any cause. Progression-free survival (PFS) was defined as the time from the initial TACE to local, intrahepatic, distant tumor progression, or death from any cause. Overall survival (OS) was defined as the time from the initial TACE to any cause of the patients’ death. Tumor assessments were conducted by two radiologists with more than 10 years of experience (X.L. and B.L.), and reviewed by an independent radiologist (X.K.). Propensity score matching analysis A PSM analysis was conducted to reduce the potential biases that may have originated from differences in the baseline characteristics of patients in the present study. The baseline characteristics, including age, gender, Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, tumor size, tumor number, ascites, hepatitis B virus infection, and serum α-fetoprotein level, were matched in our model. A one-to-one matching without replacement was applied, and the value of the caliper was 0.05. Statistical analyses The x 2 test and Mann-Whitney U test were used for comparison of the baseline characteristics between the two groups. The LPFS, PFS, and OS between the two groups were estimated by the Kaplan-Meier method and compared by the log-rank test. The uni- and multi-variate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with the LPFS, PFS, and OS. The variables with a p value≤0.1 in the uni-variate analysis were entered into a multi-variate analysis. All the statistical analyses were performed using SPSS (Version 26, Chicago, Illinois, USA) or R Foundation for Statistical Computing software (Version 4.3.1, Vienna, Austria). The statistical significance was two-tailed, and a p value less than 0.05 was considered statistically significant. Results Study population, technical success rate, and safety As described in Fig. 1 , 126 patients with HCC in high-risk locations were enrolled in this study, including 70 patients in the TACE-RFA group and 56 patients in the TACE-RFA- 125 I group, and 46 pairs of patients were matched after the PSM analysis. The baseline characteristics of patients between the two groups were balanced after the PSM analysis, which were shown in Table 1 . All of the TACE, RFA, or 125 I seed implantation procedures of the 46 pairs of patients were successfully performed, and there was no occurrence of major complications or procedure-related deaths. The median follow-up period was 43.5 months (range, 31–68 months). One representative case of TACE-RFA-125I therapy for HCC in high-risk locations is shown in Fig. 2 . Table 1 The patients’ baseline characteristics between the TACE-RFA and TACE-RFA- 125 I groups before and after PSM analysis Variable Before PSM (Median, IQR; No., %) p value After PSM (Median, IQR; No., %) p value TACE-RFA (n = 70) TACE-RFA- 125 I (n = 56) TACE-RFA (n = 46) TACE-RFA- 125 I (n = 46) Age (years) 61 (54–69) 59 (56–65) 0.443 61 (54–72) 59 (53–68) 0.356 Gender 0.200 0.765 Male 63 (90.0%) 46 (82.1%) 39 (84.8%) 40 (87.0%) Female 7 (10.0%) 10 (17.9%) 7 (15.2%) 6 (13.0%) Child-Pugh class 0.026* 0.216 A 45 (64.3%) 46 (82.1%) 42 (91.3%) 38 (82.6%) B 25 (35.7%) 10 (17.9%) 4 (8.7%) 8 (17.4%) BCLC stage 0.936 0.676 A 32 (45.7%) 26 (46.4%) 23 (50.0%) 21 (45.7%) B 38 (54.3%) 30 (53.6%) 23 (50.0%) 25 (54.3%) Tumor size (cm) 0.498 0.677 ≤ 3 38 (54.3%) 27 (48.2%) 24 (52.2%) 22 (47.8%) 3–5 32 (45.7%) 29 (51.8%) 22 (47.8%) 24 (52.2%) Tumor number 0.846 0.901 1 50 (71.4%) 38 (67.9%) 35 (76.1%) 35 (76.1%) 2 11 (15.7%) 11 (19.6%) 8 (17.4%) 7 (15.2%) 3 9 (12.9%) 7 (12.5%) 3 (6.5%) 4 (8.7%) Ascites 0.014* 0.503 Absent 50 (71.4%) 50 (89.3%) 40 (87.0%) 42 (91.3%) Mild 20 (28.6%) 6 (10.7%) 6 (13.0%) 4 (8.7%) HBV infection 0.302 > 0.999 No 4 (5.7%) 6 (10.7%) 4 (8.7%) 4 (8.7%) Yes 66 (94.3%) 50 (89.3%) 42 (91.3%) 42 (91.3%) AFP (µg/L) 0.151 0.832 ≦ 400 31 (44.3%) 32 (57.1%) 27 (58.7%) 28 (60.9%) > 400 39 (55.7%) 24 (42.9%) 19 (41.3%) 18 (39.1%) Abbreviations: TACE, transarterial chemoembolization; RFA, radiofrequency ablation; PSM, propensity score matching; IQR, interquartile range; No., Number; BCLC, Barcelona Clinic Liver Cancer; HBV, hepatitis B virus; AFP, α-fetoprotein * p value < 0.05 was considered to indicate statistical significance The tumor recurrence rates between the two groups after PSM The 1-, 2-, 3-, 4-, and 5-years of local recurrence rates in the TACE-RFA- 125 I group and TACE-RFA group were 0%, 11.1%, 16.9%, 16.9%, 20.1%, and 6.5%, 15.8%, 33.2%, 46.1%, 46.1%, respectively. The overall recurrence rates (including local, intrahepatic distant, and extrahepatic recurrences) at 1-, 2-, 3-, 4-, and 5-years were 2.1%, 24.4%, 38.5%, 53.8%, and 61.5% in the TACE-RFA- 125 I group and 17.5%, 40%, 66.1%, 81.1%, and 90.9% in the TACE-RFA group, respectively. Both the local and overall recurrence rates in the TACE-RFA- 125 I group were significantly lower than those in the TACE-RFA group ( p = 0.037, p = 0.004). The local progression-free survival between the two groups after PSM analysis The 1-, 2-, 3-, 4-, and 5-years LPFS rates in the TACE-RFA- 125 I group were 100%, 82.4%, 74.8%, 63.5%, and 54%, respectively, which were significantly higher than those of 91.3%, 69.4%, 50.7%, 29.4%, and 26.7% in the TACE-RFA group, respectively ( p = 0.004; Fig. 3 A). The uni- and multi-variate analyses demonstrated that the TACE-RFA- 125 I treatment, tumor size≤ 3 cm, a solitary HCC, and BCLC stage A were the protective factors for patients’ LPFS (Table 2 ). Table 2 The uni- and multi-variate analyses of LPFS between the TACE-RFA and TACE-RFA- 125 I groups after PSM analysis Variables Univariate analysis Multivariate analysis HR (95% CI) p value HR (95% CI) p value Age (years) 0.99 (0.97–1.02) 0.710 Treatment method TACE-RFA- 125 I Ref Ref TACE-RFA 2.32 (1.30–4.16) 0.005* 3.35 (1.79–6.26) < .001** Gender Female Ref Male 2.17 (0.78–6.03) 0.138 HBV infection No Ref Yes 0.87 (0.37–2.05) 0.752 Tumor size (cm) ≤ 3 Ref Ref 3–5 6.27 (3.24–12.14) < .001* 2.56 (1.14–5.73) 0.022** Tumor number 1 Ref Ref 2–3 2.66 (1.48–4.80) 0.001* 2.84 (1.49–5.43) 0.002** BCLC stage A Ref Ref B 6.84 (3.50–13.36) 400 0.80 (0.45–1.43) 0.445 Ascites Absent Ref Mild 1.50 (0.64–3.54) 0.349 Child-Pugh class A Ref Ref B 3.83 (1.77–8.33) < .001* 2.85 (1.15–7.07) 0.024** Abbreviations: LPFS, local progression-free survival; TACE, transarterial chemoembolization; RFA, radiofrequency ablation; PSM, propensity score matching; HR, hazard ratio; CI, confidence interval; Ref, reference; HBV, hepatitis B virus; BCLC, Barcelona Clinic Liver Cancer; AFP, α-fetoprotein * p value≤0.1 in uni-variate analysis were included in multi-variate analysis, ** p value < 0.05 was considered to indicate statistical significance in multi-variate analysis The progression-free survival between the two groups after PSM analysis The 1-, 2-, 3-, 4-, and 5-years PFS rates in the TACE-RFA- 125 I group were 97.8%, 69.3%, 53.7%, 38.2%, and 31.8%, respectively, which were significantly higher than those of 84.8%, 54.3%, 29.3%, 16.3%, and 7.2% in the TACE-RFA group, respectively, and the median PFS in the TACE-RFA- 125 I group was also significantly longer than that of the TACE-RFA group (42.0 months vs. 29.0 months, p = 0.002; Fig. 3 B). The uni- and multi-variate analyses indicated that the TACE-RFA- 125 I treatment, tumor size≤ 3 cm, a solitary HCC, BCLC stage A, and absence of ascites were the protective factors for patients’ PFS (Table 3 ). Table 3 The uni- and multi-variate analyses of PFS between the TACE-RFA and TACE-RFA- 125 I groups after PSM analysis Variables Univariate analysis Multivariate analysis HR (95% CI) p value HR (95% CI) p value Age (years) 1.01 (0.98–1.03) 0.656 Treatment method TACE-RFA- 125 I Ref Ref TACE-RFA 2.07 (1.28–3.34) 0.003* 2.96 (1.75–5.01) < .001** Gender Female Ref Ref Male 2.07 (0.98–4.36) 0.057* 1.25 (0.56–2.77) 0.583 HBV infection No Ref Yes 1.70 (0.72–4.03) 0.230 Tumor size (cm) ≤ 3 Ref Ref 3–5 5.34 (2.89–9.89) < .001* 2.67 (1.25–5.68) 0.011** Tumor number 1 Ref Ref 2–3 2.39 (1.38–4.16) 0.002* 3.98 (2.06–7.71) < .001** BCLC stage A Ref Ref B 7.44 (3.83–14.43) < .001* 5.90 (2.57–13.55) 400 0.74 (0.46–1.20) 0.228 Ascites Absent Ref Ref Mild 3.72 (1.79–7.74) < .001* 2.93 (1.34–6.42) 0.007** Child-Pugh class A Ref Ref B 1.96 (0.95–4.02) 0.067* 1.08 (0.46–2.53) 0.862 Abbreviations: PFS, progression-free survival; TACE, transarterial chemoembolization; RFA, radiofrequency ablation; PSM, propensity score matching; HR, hazard ratio; CI, confidence interval; Ref, reference; HBV, hepatitis B virus; BCLC, Barcelona Clinic Liver Cancer; AFP, α-fetoprotein * p value≤0.1 in uni-variate analysis were included in multi-variate analysis, ** p value < 0.05 was considered to indicate statistical significance in multi-variate analysis The overall survival between the two groups after PSM analysis At the end of follow-up, 28.3% (13/46) patients in the TACE-RFA- 125 I group and 56.5% (26/46) patients in the TACE-RFA group died. The 1-, 2-, 3-, 4-, and 5-years OS rates were 100%, 93.4%, 80.7%, 74.9%, and 64.7% in the TACE-RFA- 125 I group, respectively, which were significantly higher than those of 97.8%, 78%, 68.6%, 51.1%, and 45.3% in the TACE-RFA group, respectively ( p = 0.011; Fig. 3 C). The uni- and multi-variate analyses showed that the TACE-RFA- 125 I treatment, tumor size≤ 3 cm, a solitary HCC, BCLC stage A, and Child-Pugh class A were the protective factors for patients’ OS (Table 4 ). Table 4 The uni- and multi-variate analyses of OS between the TACE-RFA and TACE-RFA- 125 I groups after PSM analysis Variables Univariate analysis Multivariate analysis HR (95% CI) p value HR (95% CI) p value Age (years) 0.98 (0.95–1.02) 0.315 Treatment method TACE-RFA- 125 I Ref Ref TACE-RFA 2.34 (1.20–4.56) 0.013* 4.60 (2.11–10.00) < .001** Gender Female Ref Male 2.47 (0.76–8.06) 0.133 HBV infection No Ref Yes 1.21 (0.43–3.43) 0.713 Tumor size (cm) ≤ 3 Ref Ref 3–5 11.76 (5.07–27.26) < .001* 7.46 (2.68–20.74) < .001** Tumor number 1 Ref Ref 2–3 2.66 (1.38–5.14) 0.004* 3.44 (1.66–7.11) < .001** BCLC stage A Ref Ref B 8.38 (3.71–18.90) 400 1.23 (0.65–2.33) 0.532 Ascites Absent Ref Mild 1.13 (0.40–3.20) 0.819 Child-Pugh class A Ref Ref B 6.79 (2.83–16.30) < .001* 5.84 (2.00–17.00) 0.001** Abbreviations: OS, overall survival; TACE, transarterial chemoembolization; RFA, radiofrequency ablation; PSM, propensity score matching; HR, hazard ratio; CI, confidence interval; Ref, reference; HBV, hepatitis B virus; BCLC, Barcelona Clinic Liver Cancer; AFP, α-fetoprotein * p value≤0.1 in uni-variate analysis were included in multi-variate analysis, ** p value < 0.05 was considered to indicate statistical significance in multi-variate analysis The subgroup analyses by tumor size after PSM In the subgroup analysis of patients with tumor size≤ 3 cm, the 1-, 2-, 3-, 4-, and 5-years LPFS, PFS, and OS rates in the TACE-RFA- 125 I group (LPFS rates: 100%, 92.9%, 89.1%, 85.3%, and 72.5%; PFS rates: 100%, 85.7%, 74.7%, 53.1%, and 44.2%; OS rates: 100%, 100%, 96.3%, 92.4%, and 79.8%, respectively) were all significantly better than those in the TACE-RFA group (LPFS rates: 100%, 80%, 69.4%, 44.9%, and 44.9%; PFS rates: 93.3%, 70%, 45.2%, 25.1%, and 11.2%; OS rates: 96.7%, 93.3%, 89.9%, 75%, and 66.5%, respectively) ( p = 0.005, p = 0.005, p = 0.040, Fig. 4 A-C). Meanwhile, the median PFS in the TACE-RFA- 125 I group was significantly longer than that in the TACE-RFA group (50.0 months vs. 34.0 months, p = 0.005, Fig. 4 B). As described in Fig. 4 D-F, in the subgroup analysis of patients with tumor size > 3 cm and ≤ 5 cm, the 1-, 2-, and 3-years LPFS and OS rates in the TACE-RFA- 125 I group (LPFS rates: 100%, 82.6%, and 49.1%; OS rates: 100%, 82.6%, and 48.7%, respectively) were significantly higher than those in the TACE-RFA group (LPFS rates: 75%, 48.6%, and 13.9%; OS rates: 93.8%, 48.1%, and 24.8%, respectively) ( p = 0.034, p = 0.011, respectively). The 1-, 2-years PFS rates in the TACE-RFA- 125 I group (PFS rates: 94.4%, 42.4%, respectively) were also significantly higher than those in the TACE-RFA group (PFS rates: 56.3%, 25%, respectively) ( p = 0.011). In addition, the median LPFS, PFS, and OS in the TACE-RFA- 125 I group were significantly longer than that of in the TACE-RFA group (median LPFS: 36.0 months vs. 23.0 months, p = 0.034; median PFS: 23.0 months vs. 17.0 months, p = 0.011; median OS: 36.0 months vs. 23.0 months, p = 0.011). Discussion In recent years, the application of 125 I seed implantation in the treatment of some malignant solid tumors extended the indication of brachytherapy, and the therapeutic effectiveness was proven to be preferable, such as in HCC (Chen et al. 2014 , 2023 ). The results of our study showed that, for patients with HCC ≤ 5 cm in high-risk locations, the tumor control and patients’ survival in the TACE-RFA- 125 I group were significantly better than those in the TACE-RFA group. Meanwhile, the results of our study showed that the treatment method of TACE-RFA- 125 I was an independent protective factor for tumor control and patients’ survival outcomes. These outcomes supported the hypothesis that adding 125 I seed implantation therapy on the basis of TACE-RFA can further improve the effect of TACE-RFA on unresectable HCC (≤ 5 cm) in high-risk locations. For unresectable HCC ≤ 5 cm, TACE-RFA or TACE in combination with microwave ablation (TACE-MWA) was a favourable treatment. A previous study (Shibata et al. 2009 ) reported the OS rates at 1-, 2-, 3-, and 4-years after TACE-RFA for patients with HCCs < 3 cm were 100%, 100%, 84.8%, and 72.7%, respectively, and the recurrence-free survival rates at 1-, 2-, 3-, and 4-years were 71.3%, 59.9%, 48.8%, and 36.6%, respectively. Meanwhile, a randomized controlled trial (Zaitoun et al. 2021 ) reported that 93 patients with HCC ranging from 3 to 5cm received TACE-MWA treatment, the recurrence rate at 1 year was 22.47%, and the median OS was 24 months. Compared with these studies, our study focused on HCCs in high-risk locations, the treatment effects of which are usually inferior to those of HCCs in non-high-risk locations under the same treatment. However, in the present study, the results of our study were comparable or superior to those of studies, which indicated TACE-RFA- 125 I was an excellent treatment strategy for patients with unresectable HCC (≤ 5 cm) in high-risk locations. The possible potential mechanisms of TACE-RFA- 125 I for HCC are as follows: (1) the tumor-killing effect of hyperthermia and radiotherapy complement each other. The tumor cells in the S phase of the cell cycle are less sensitive to radiotherapy, but respond relatively better to hyperthermia. Meanwhile, the sensitivity of anoxic tumor cells to radiotherapy is lower, but that to hyperthermia is relatively stable (Hall et al. 2015 ; Nishimura et al. 2015 ); (2) radiofrequency hyperthermia could increase the vasodilation and vascular permeability in the treated peritumoral area, which could increase the oxygen supply of this area, and subsequently improve the treatment effect of radiotherapy on HCC (Wang et al. 2015 ; Dabbagh et al. 2015 ); (3) the RFA treatment could trigger the systemic anti-tumor immune response, and subsequently enhance the anti-tumor effect of radiotherapy (Hong et al. 2014 ); (4) TACE treatment could embolize the tumor blood vessels and reduce the influence of heat-sink effect (Kim et al. 2012 ; Choe et al. 2014 ); (5) the deposition of lipiodol in the tumor after TACE treatment can be used as a marker, which helps to achieve a precise RFA and iodine-125 seed implantation treatment. Based on these potential mechanisms, the triple combination treatment (TACE-RFA- 125 I) strategy was used for unresectable HCC in high-risk locations in the present study. MWA of HCC is becoming increasingly popular as MWA allows for a larger ablation zone in a relatively short time. However, for MWA of HCC in high-risk locations, this feature may cause thermal injury to the adjacent important structures of HCC, such as the biliary and gastrointestinal tracts. Compared to MWA, RFA has the characteristic of a slower heating rate, and thus it may reduce the risk of thermal damage to the surrounding tissues of ablated tumors. Therefore, in the present study, we used RFA instead of MWA for HCC. In addition, in this study, RFA and 125 I seed implantation were performed under ultrasound plus CT guidance, which could provide a real-time and accurate imaging guidance. It not only avoided blood vessels and other important tissues from injuries during puncture, but also facilitated the precise placement of the radiofrequency electrode and 125 I seeds. We believed these were the main reasons for the absence of major complications and procedure-related deaths in our study. Our study had limitations. This is a single center and retrospective study. Although a PSM analysis was performed to reduce the potential selection bias, it could not be completely avoided. So a prospective multi-center randomized controlled trial is necessary to confirmed the results of this study. Conclusions Compared with TACE-RFA treatment, TACE-RFA- 125 I should be a more effective therapy for patients with unresectable HCC (≤ 5 cm) in high-risk locations. TACE-RFA- 125 I under ultrasound plus CT guidance is an excellent and safe treatment strategy for this type of unresectable HCC, and is worth of clinical promotion and application. Declarations Ackonwledgements: None. Competing interests: The study was conducted according to the Declaration of Helsinki. Informed consent was waived for the retrospective type of this study. The information of all participants is maintained with confidentiality. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding: This study was supported by the grants of National Natural Science Foundation of China (Nos. 82372069 and 82072041) and the Outstanding Youth Foundation of Hubei Province, China (2023AFA107). Author contributions: G.Z. and Y.R.: Data analysis, preparation of original draft, visualization, writing and editing. J.L., Y.C., and F.X.: Visualization, writing and editing. C.Z. and B.L.: Conceptualization, reviewing and editing. X. K.: Conceptualization, reviewing, editing, and funding acquisition.X.K. and C.Z.: Guarantor. Data availability: The data that support the study findings are available upon reasonable request from the corresponding authors Ethics approval: The study received approval from the Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Approval no.: UHCT-IEC-SOP-012-01-01). Consent to participate: The requirement for obtaining written consent was waived because of the retrospective design of the study. Consent to publish: The authors affirm that the human research participant provided informed consent for publication of the images in Fig. 2 A-E. References Bai X-M, Cui M, Yang W, et al (2021) The 10-year Survival Analysis of Radiofrequency Ablation for Solitary Hepatocellular Carcinoma 5 cm or Smaller: Primary versus Recurrent HCC. 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World J Gastroenterol 20:12588–12594. https://doi.org/10.3748/wjg.v20.i35.12588 Choudhury M, Thomas SS, Cain A, et al (2023) Timing of High-Dose Rate Brachytherapy with External Beam Radiotherapy in intermediate and high-risk localised Prostate Cancer (THEPCA): a randomised trial. Int J Radiat Oncol Biol Phys S0360-3016(23)08137–3. https://doi.org/10.1016/j.ijrobp.2023.11.011 Dabbagh A, Abdullah BJJ, Abu Kasim NH, et al (2015) A new mechanism of thermal sensitivity for rapid drug release and low systemic toxicity in hyperthermia and thermal ablation temperature ranges. Int J Hyperthermia 31:375–385. https://doi.org/10.3109/02656736.2015.1006268 Galle PR, Forner A, Llovet JM, et al (2018) EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 69:182–236. https://doi.org/10.1016/j.jhep.2018.03.019 Hall SK, Ooi EH, Payne SJ (2015) Cell death, perfusion and electrical parameters are critical in models of hepatic radiofrequency ablation. 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Abdom Radiol 44:1141–1151. https://doi.org/10.1007/s00261-018-1831-6 Kan X, Wang Y, Han P, et al (2019) Combined ultrasound/computed tomography guidance in percutaneous radiofrequency ablation after transarterial chemoembolization for hepatocellular carcinoma in the hepatic dome. Cancer Manag Res 11:7751–7757. https://doi.org/10.2147/CMAR.S212127 Kim JW, Kim JH, Won HJ, et al (2012) Hepatocellular carcinomas 2-3 cm in diameter: transarterial chemoembolization plus radiofrequency ablation vs. radiofrequency ablation alone. Eur J Radiol 81:e189-193. https://doi.org/10.1016/j.ejrad.2011.01.122 Lee DH, Lee MW, Kim PN, et al (2021) Outcome of No-Touch Radiofrequency Ablation for Small Hepatocellular Carcinoma: A Multicenter Clinical Trial. Radiology 301:229–236. https://doi.org/10.1148/radiol.2021210309 Li J, Zhang L, Xie Q, et al (2019) 125I seeds implantation for treating residual hepatocellular carcinoma located beneath the diaphragm after transcatheter arterial chemoembolization. Brachytherapy 18:420–425. https://doi.org/10.1016/j.brachy.2018.12.008 Lin Z-Y, Chen J, Deng X-F (2012) Treatment of hepatocellular carcinoma adjacent to large blood vessels using 1.5T MRI-guided percutaneous radiofrequency ablation combined with iodine-125 radioactive seed implantation. Eur J Radiol 81:3079–3083. https://doi.org/10.1016/j.ejrad.2012.05.007 Monk BJ, Toita T, Wu X, et al (2023) Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. Lancet Oncol 24:1334–1348. https://doi.org/10.1016/S1470-2045(23)00479-5 Nishimura S, Saeki H, Nakanoko T, et al (2015) Hyperthermia combined with chemotherapy for patients with residual or recurrent oesophageal cancer after definitive chemoradiotherapy. Anticancer Res 35:2299–2303 Shibata T, Isoda H, Hirokawa Y, et al (2009) Small hepatocellular carcinoma: is radiofrequency ablation combined with transcatheter arterial chemoembolization more effective than radiofrequency ablation alone for treatment? Radiology 252:905–913. https://doi.org/10.1148/radiol.2523081676 Strnad V, Polgár C, Ott OJ, et al (2023) Accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy compared with whole-breast irradiation with boost for early breast cancer: 10-year results of a GEC-ESTRO randomised, phase 3, non-inferiority trial. Lancet Oncol 24:262–272. https://doi.org/10.1016/S1470-2045(23)00018-9 Sung H, Ferlay J, Siegel RL, et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660 Wang K, Tavakkoli F, Wang S, Vafai K (2015) Analysis and analytical characterization of bioheat transfer during radiofrequency ablation. J Biomech 48:930–940. https://doi.org/10.1016/j.jbiomech.2015.02.023 Wang Q, Tang M, Zhang S (2021) Comparison of radiofrequency ablation and surgical resection for hepatocellular carcinoma conforming to the Milan criteria: a meta-analysis. ANZ J Surg 91:E432–E438. https://doi.org/10.1111/ans.16560 Zaitoun MMA, Elsayed SB, Zaitoun NA, et al (2021) Combined therapy with conventional trans-arterial chemoembolization (cTACE) and microwave ablation (MWA) for hepatocellular carcinoma >3-<5 cm. Int J Hyperthermia 38:248–256. https://doi.org/10.1080/02656736.2021.1887941 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4258024","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":290825889,"identity":"28973047-151e-4909-8e09-583542c660cf","order_by":0,"name":"Guilin Zhang","email":"","orcid":"","institution":"Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Guilin","middleName":"","lastName":"Zhang","suffix":""},{"id":290825891,"identity":"9d1b73bf-aa20-4199-803a-fee8a4b5c0f8","order_by":1,"name":"Yanqiao Ren","email":"","orcid":"","institution":"Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Yanqiao","middleName":"","lastName":"Ren","suffix":""},{"id":290825892,"identity":"af7090c9-406d-445a-b2c6-0779f45cbb49","order_by":2,"name":"Jiayun Liu","email":"","orcid":"","institution":"Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Jiayun","middleName":"","lastName":"Liu","suffix":""},{"id":290825894,"identity":"6a38a8c4-d547-4db5-ae60-3d19a3707e3b","order_by":3,"name":"Yanyan Cao","email":"","orcid":"","institution":"Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Yanyan","middleName":"","lastName":"Cao","suffix":""},{"id":290825895,"identity":"d87c5d21-53c8-4354-8fd2-944b6d099375","order_by":4,"name":"Fu Xiong","email":"","orcid":"","institution":"Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Fu","middleName":"","lastName":"Xiong","suffix":""},{"id":290825896,"identity":"852a8bbf-94df-4b26-a001-688c755fe97f","order_by":5,"name":"Bin Liang","email":"","orcid":"","institution":"Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Bin","middleName":"","lastName":"Liang","suffix":""},{"id":290825897,"identity":"800141ea-07a4-4411-9e5f-2ee96fd40d24","order_by":6,"name":"Chuansheng Zheng","email":"","orcid":"","institution":"Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Chuansheng","middleName":"","lastName":"Zheng","suffix":""},{"id":290825898,"identity":"f7ee4d19-4abd-4a21-b1fa-479a33d5cdd7","order_by":7,"name":"Xuefeng Kan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+UlEQVRIie3PsUrDQBzH8f9xkCwnWf9BaF7hwi2duvgiObqWInSJKPovASeLs1DsK7RL5384sEseQMfq6tAXEExaxC3JKHjf6Tf8P3AH4PP9xZQkhst6yJAZcxwk3UTURNcjVJaH1dCk1IPAkURg+Oo+t8AdQlfl3Ck9miYXkPHbM2aC5P79tYXEiznVZDxLneDyaYvTEAJjJi0kikRDpN0UkLl4izNBKjhvI8GJ3DVEu68lWuIOEp0dH+bsSoLmmHqQ+KGkcql3di1VxviCJi06/qKrsTt85td29bhzB7y5HSRhsf9oI7+Wf5bsc96UUN9Ln8/n+3d9A7NZT0takbvFAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Xuefeng","middleName":"","lastName":"Kan","suffix":""}],"badges":[],"createdAt":"2024-04-12 13:20:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4258024/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4258024/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55008788,"identity":"f4caa153-45c5-42b7-aa36-cf2715c56f79","added_by":"auto","created_at":"2024-04-19 19:09:00","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":902770,"visible":true,"origin":"","legend":"\u003cp\u003eThe flow diagram of patient selection. Abbreviations: Abbreviations: HCC, hepatocellular carcinoma; TACE-RFA-125I, transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) and iodine-125 seed implantation; SBRT, stereotactic body radiation therapy; PEI, percutaneous ethanol injection; MWA, microwave ablation\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4258024/v1/f6c0345263ac9c902b821e06.jpg"},{"id":55010084,"identity":"55885341-e695-48b3-b9cd-ff085b54d6fc","added_by":"auto","created_at":"2024-04-19 19:17:00","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1203645,"visible":true,"origin":"","legend":"\u003cp\u003eA 58-year-old male patient with an unresectable HCC in high-risk locations received the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI treatment. \u003cstrong\u003eA:\u003c/strong\u003e A contrast-enhanced CT scan showed a 3cm HCC near the right branch of the portal vein and the right kidney. \u003cstrong\u003eB: \u003c/strong\u003eThe\u003cstrong\u003e \u003c/strong\u003eRFA treatment was performed after the TACE treatment. \u003cstrong\u003eC:\u003c/strong\u003e The \u003csup\u003e125\u003c/sup\u003eI seed implantation procedure was performed after the RFA treatment. \u003cstrong\u003eD-E: \u003c/strong\u003eThe follow-up at seven years after TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI treatment with contrast-enhanced CT and MRI showed a significant shrinkage of tumor size, and there was no enhancement of the tumor. Meanwhile, the AFP value decreased from the initial 2800 μg/L to 2.7 μg/L in the last follow-up. The treatment effect of HCC in this patient was a complete response according to the modified Response Evaluation Criteria in Solid Tumors. Abbreviations: HCC, hepatocellular carcinoma; TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI, transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) and iodine-125 seed implantation; CT, computed tomography; MRI, magnetic resonance imaging\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4258024/v1/87a1f460753ed7f09c8e9023.jpg"},{"id":55008789,"identity":"956624bd-cd2a-4cf6-bb33-cb3b365e2f91","added_by":"auto","created_at":"2024-04-19 19:09:00","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1364138,"visible":true,"origin":"","legend":"\u003cp\u003eThe\u003cstrong\u003e \u003c/strong\u003eKaplan-Meier curves of LPFS, PFS, and OS for patients with HCC in high-risk locations who received TACE-RFA or TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI treatment after PSM. \u003cstrong\u003eA: \u003c/strong\u003eThe LPFS rates at 1-, 2-, 3-, 4-, and 5-years in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group were significantly higher than those in the TACE-RFA group (\u003cem\u003ep\u003c/em\u003e = 0.004). \u003cstrong\u003eB: \u003c/strong\u003eThe PFS rates at 1-, 2-, 3-, 4-, and 5-years in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group were significantly higher than those in the TACE-RFA group, and the median PFS in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group was also significantly longer than that of the TACE-RFA group (42.0 months vs. 29.0 months, \u003cem\u003ep\u003c/em\u003e = 0.002). \u003cstrong\u003eC: \u003c/strong\u003eThe OS rates at 1-, 2-, 3-, 4-, and 5-years were significantly higher than those in the TACE-RFA group (\u003cem\u003ep\u003c/em\u003e = 0.011). Abbreviations: LPFS, local progression-free survival; PFS, progression-free survival; OS, overall survival; HCC, hepatocellular carcinoma; TACE-RFA, transarterial chemoembolization combined with radiofrequency ablation; TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI, transarterial chemoembolization plus radiofrequency ablation and iodine-125 seed implantation; PSM, propensity score matching\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4258024/v1/08a183c27726e6572e0033fc.jpg"},{"id":55008791,"identity":"0a1ab070-881d-4d75-a1ac-79b5e5e0c80f","added_by":"auto","created_at":"2024-04-19 19:09:00","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":971791,"visible":true,"origin":"","legend":"\u003cp\u003eThe Kaplan-Meier curves of subgroup analyses for patients with tumor size ≤3 cm and 3-5 cm after PSM. For HCCs sized ≤3 cm, the 1-, 2-, 3-, 4-, and 5-years LPFS, PFS, and OS rates in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group were significantly higher than those in the TACE-RFA group (\u003cem\u003ep\u003c/em\u003e = 0.005, \u003cem\u003ep\u003c/em\u003e = 0.005, \u003cem\u003ep\u003c/em\u003e = 0.040, respectively) (\u003cstrong\u003eA-C\u003c/strong\u003e), and the median PFS in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group was also significantly longer than that of the TACE-RFA group (\u003cstrong\u003eB\u003c/strong\u003e). For HCCs sized \u0026gt;3 and ≤5 cm, the 1-, 2-, and 3-years LPFS and OS rates in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group were significantly higher than those of in the TACE-RFA group (\u003cem\u003ep\u003c/em\u003e = 0.034, \u003cem\u003ep\u003c/em\u003e = 0.011, respectively) (\u003cstrong\u003eD, F\u003c/strong\u003e), the 1-, 2-years PFS rates in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group were significantly higher than those of in the TACE-RFA group (\u003cem\u003ep\u003c/em\u003e = 0.011) (\u003cstrong\u003eE\u003c/strong\u003e), and the median LPFS, PFS, and OS in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group were also significantly longer than those of in the TACE-RFA group (\u003cstrong\u003eD-F\u003c/strong\u003e). Abbreviations: PSM, propensity score matching; HCC, hepatocellular carcinoma; LPFS, local progression-free survival; PFS, progression-free survival; OS, overall survival; TACE-RFA, transarterial chemoembolization combined with radiofrequency ablation; TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI, transarterial chemoembolization plus radiofrequency ablation and iodine-125 seed implantation\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4258024/v1/d08accc449e9da3dfb1fed7c.jpg"},{"id":60752348,"identity":"dbc90ade-057a-4ac4-b1fd-41a1040a7ba7","added_by":"auto","created_at":"2024-07-20 21:46:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5567051,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4258024/v1/4d37d932-7c7e-4606-83d8-d0ff63990c7a.pdf"},{"id":55008787,"identity":"3f61ed21-eaf3-4b45-a063-69e5c1ea9507","added_by":"auto","created_at":"2024-04-19 19:09:00","extension":"docx","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":30889,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4258024/v1/f76e8541d79e8357c25bd478.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Transarterial chemoembolization plus radiofrequency ablation and iodine-125 seed implantation for hepatocellular carcinoma in high-risk locations: a propensity score-matched analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide (Sung et al. \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Radiofrequency ablation (RFA) has been accepted as an effective alternative to surgery in the management of small- to intermediate-sized (\u0026le;\u0026thinsp;5 cm) HCCs (Wang et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Bai et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Lee et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). However, for RFA of HCCs in high-risk locations (tumors close to the diaphragm, large vessels, liver capsule, gallbladder, gastrointestinal tract, or kidney), it is difficult to achieve an effective and safe ablation periphery with a 1 cm surgical margin beyond the tumor confinement for protecting these adjacent critical structures from heat damage, which thus often leads to a local tumor recurrence. Attempts have been made to address this issue, such as RFA combined with transarterial chemoembolization (TACE) or iodine-125 (\u003csup\u003e125\u003c/sup\u003eI) seed implantation (Lin et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Chen et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). However, the local tumor recurrence rates and patients\u0026rsquo; long-term survival are still not satisfactory (Chen et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Cao et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Thus, there is a pressing clinical need to develop a more effective treatment strategy to improve the effect of RFA on HCCs in high-risk locations.\u003c/p\u003e \u003cp\u003eDue to its minimal invasiveness, safety, and effectiveness, \u003csup\u003e125\u003c/sup\u003eI seed implantation is a favourable therapy for some solid malignant tumors, including HCC (Strnad et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Monk et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Choudhury et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Several previous studies (Lin et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Chen et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Li et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) reported that \u003csup\u003e125\u003c/sup\u003eI seed implantation could further improve the effects of TACE or RFA on HCCs. To the best of our knowledge, there was no report of the triple-combination treatment (TACE\u0026thinsp;+\u0026thinsp;RFA\u0026thinsp;+\u0026thinsp;\u003csup\u003e125\u003c/sup\u003eI seed implantation) for HCC in high-risk locations.\u003c/p\u003e \u003cp\u003ePercutaneous RFA and \u003csup\u003e125\u003c/sup\u003eI seed implantation procedures were usually performed under ultrasound or computed tomography (CT) guidance (Chen et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Hong et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). However, for HCCs in high-risk locations, ultrasound-guided percutaneous RFA or \u003csup\u003e125\u003c/sup\u003eI seed implantation is challenging for poor tumor visualization or suboptimal electrode path due to the overlapped ribs, lung, gallbladder, or gastrointestinal tract, which may result in incomplete RFA, thermal injury to the surrounding organs, or uneven distribution of \u003csup\u003e125\u003c/sup\u003eI seed in tumors. Although CT imaging usually provides a clearer visualization for such HCCs compared with ultrasound imaging, a CT-guided puncture may result in injury to the diaphragm, blood vessels, gastrointestinal tract, or gallbladder for lack of real-time dynamic imaging. So a real-time and accurate imaging guidance strategy is needed for RFA and \u003csup\u003e125\u003c/sup\u003eI seed implantation in the treatment of HCCs in high-risk locations.\u003c/p\u003e \u003cp\u003eIn the present study, patients with HCC in high-risk locations were first treated with TACE, followed by RFA and \u003csup\u003e125\u003c/sup\u003eI seed implantation treatments (TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI), which were performed under ultrasound plus CT guidance, and the clinical data of these patients were retrospectively analyzed. The purpose of this study was to evaluate whether this therapy could lead to better tumor control and patients\u0026rsquo; survival compared with TACE plus RFA (TACE-RFA) for HCC in high-risk locations, and provide a more effective and safe treatment strategy in the management of this type of HCC.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and patient selection\u003c/h2\u003e \u003cp\u003eFrom January 2010 to June 2023, the clinical data of 126 HCC patients who received the treatment of TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI or TACE-RFA in our center was retrospectively analyzed. The clinical outcomes between the two treatment groups were compared after propensity score matching (PSM) analysis. Meanwhile, a subgroup analysis according to tumor size (\u0026le;\u0026thinsp;3 cm and 3\u0026ndash;5 cm) was performed to compare the effects of these two different treatments in the two subgroups. This retrospective study was conducted in accordance with the Declaration of Helsinki, and was approved by the Ethics Committee of our institution (approval number: UHCT-IEC-SOP-012-01-01), which waived the need for written informed consent. The report of this study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies (\u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e).\u003c/p\u003e \u003cp\u003e The inclusion criteria of this study were as follows: (1) patients were diagnosed with HCC according to the European Association for the Study of the Liver or American Association for the Study of Liver Disease guidelines (Heimbach et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Galle et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2018\u003c/span\u003e); (2) patients with HCC in high-risk locations, which were defined as these located\u0026thinsp;\u0026lt;\u0026thinsp;5 mm of vital structures, such as the diaphragm, large vessels, liver capsule, gallbladder, gastrointestinal tract, and kidneys (Hsieh et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2019\u003c/span\u003e); (3) a solitary HCC (\u0026le;\u0026thinsp;5.0 cm) or multiple (up to three) HCC lesions (each \u0026le;\u0026thinsp;3.0 cm); (4) patients were not eligible for surgical resection or liver transplantation; (5) the procedures of RFA and \u003csup\u003e125\u003c/sup\u003eI seed implantation were performed under combined ultrasound/CT guidance; (6) no vascular invasion or no extrahepatic metastasis; (7) Eastern Cooperative OncologyGroup (ECOG) performance status 0; (8) Child-Pugh class A or B; (9) blood platelet count\u0026thinsp;\u0026gt;\u0026thinsp;40\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L. The exclusion criteria of this study were as follows: (1) before TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI or TACE-RFA treatment, patients received other treatments for HCC, such as stereotactic body radiotherapy, chemotherapy, and liver transplantation, et al.; (2) patients were accompanied by other malignancies; (3) patients were accompanied by severe cardiac and renal dysfunction; (4) the clinical data of patients were incomplete or lost to follow-up.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTACE procedure and ultrasound plus CT-guided RFA and \u003csup\u003e125\u003c/sup\u003eI seed implantation\u003c/h2\u003e \u003cp\u003eAll the patients received TACE treatment before RFA and \u003csup\u003e125\u003c/sup\u003eI seed implantation procedures, and the TACE procedures were performed as described in our previous study (Kan et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). RFA was performed 5\u0026ndash;10 days after TACE. Before RFA treatment, laboratory examinations, such as complete blood count, liver and renal function, and prothrombin time, were performed to assess whether the patients fulfilled the RFA treatment criteria. The RFA procedures were performed with a RITA 1500 generator (RITA Medical Systems Inc., Mountain View, USA) and a 14-gauge multiple electrode (Rita Medical Systems, Mountain View, California, USA) under combined ultrasound/CT guidance, as described in our previous study (Kan et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). The analgesia was conducted by local injection of 5 mL of 2% lidocaine and intravenous administration of 50\u0026ndash;100 mg of a flurbiprofen axetil injection (Tide Pharmaceutical Co., Ltd., Beijing, China).\u003c/p\u003e \u003cp\u003eThe procedures of \u003csup\u003e125\u003c/sup\u003eI seed implantation were performed within 7 days after RFA treatment. The \u003csup\u003e125\u003c/sup\u003eI seeds were implanted in the insufficient ablation tumor magin or the highly suspected zone of residual viable tumors. The number and distribution of \u003csup\u003e125\u003c/sup\u003eI seed were determined by the Treatment Planning System (TPS) (HGGR300, Hokai Medical Instruments Co., Ltd., Zhuhai, China). An interstitial needle (17-gauge, hollow needles, 15 cm long) was inserted into the site close to the tumor under ultrasound guidance, and then CT images were used to precisely guide the placement of the interstitial needle. A Mick applicator (Mick Radionuclear Instruments, Bronx, NY) was then sequentially attached to the distal end of each needle to place the \u003csup\u003e125\u003c/sup\u003eI seed (0.7 millicuries per seed) into the tumor, spaced approximately 1 cm apart along the needle track. After \u003csup\u003e125\u003c/sup\u003eI seed implantation, a CT scan was performed again to assess the \u003csup\u003e125\u003c/sup\u003eI seed position and the presence of major complications, and the images were transmitted to TPS for dose verification.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eFollow-up\u003c/h3\u003e\n\u003cp\u003eContrast-enhanced CT or contrast-enhanced magnetic resonance imaging (MRI) of the chest and liver, blood tests such as liver and kidney function, blood routine, and tumor markers were performed at each follow-up. The first follow-up was conducted 4\u0026ndash;6 weeks after the initial treatment, and then the patients were reviewed every 3 months during the first year and every 6 months thereafter. Repeated TACE, RFA, or \u003csup\u003e125\u003c/sup\u003eI seed implantation was used to treat the recurrent or residual tumors. The follow-up of this study ended on November 30, 2023.\u003c/p\u003e \u003cp\u003eIn the present study, local tumor progression was defined as the appearance of any viable tumor within 1 cm from the ablated margin of tumors on CT/MRI images during follow-up, and intrahepatic tumor progression was defined as the occurrence of a new tumor within the liver, except for local tumor progression. Local progression-free survival (LPFS) was defined as the time from the initial TACE to local tumor progression or death from any cause. Progression-free survival (PFS) was defined as the time from the initial TACE to local, intrahepatic, distant tumor progression, or death from any cause. Overall survival (OS) was defined as the time from the initial TACE to any cause of the patients\u0026rsquo; death. Tumor assessments were conducted by two radiologists with more than 10 years of experience (X.L. and B.L.), and reviewed by an independent radiologist (X.K.).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePropensity score matching analysis\u003c/h2\u003e \u003cp\u003eA PSM analysis was conducted to reduce the potential biases that may have originated from differences in the baseline characteristics of patients in the present study. The baseline characteristics, including age, gender, Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, tumor size, tumor number, ascites, hepatitis B virus infection, and serum α-fetoprotein level, were matched in our model. A one-to-one matching without replacement was applied, and the value of the caliper was 0.05.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eThe \u003cem\u003ex\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e test and Mann-Whitney U test were used for comparison of the baseline characteristics between the two groups. The LPFS, PFS, and OS between the two groups were estimated by the Kaplan-Meier method and compared by the log-rank test. The uni- and multi-variate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with the LPFS, PFS, and OS. The variables with a \u003cem\u003ep\u003c/em\u003e value\u0026le;0.1 in the uni-variate analysis were entered into a multi-variate analysis. All the statistical analyses were performed using SPSS (Version 26, Chicago, Illinois, USA) or R Foundation for Statistical Computing software (Version 4.3.1, Vienna, Austria). The statistical significance was two-tailed, and a \u003cem\u003ep\u003c/em\u003e value less than 0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStudy population, technical success rate, and safety\u003c/h2\u003e \u003cp\u003eAs described in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, 126 patients with HCC in high-risk locations were enrolled in this study, including 70 patients in the TACE-RFA group and 56 patients in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group, and 46 pairs of patients were matched after the PSM analysis. The baseline characteristics of patients between the two groups were balanced after the PSM analysis, which were shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. All of the TACE, RFA, or \u003csup\u003e125\u003c/sup\u003eI seed implantation procedures of the 46 pairs of patients were successfully performed, and there was no occurrence of major complications or procedure-related deaths. The median follow-up period was 43.5 months (range, 31\u0026ndash;68 months). One representative case of TACE-RFA-125I therapy for HCC in high-risk locations is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe patients\u0026rsquo; baseline characteristics between the TACE-RFA and TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI groups before and after PSM analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eBefore PSM\u003c/p\u003e \u003cp\u003e(Median, IQR; No., %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eAfter PSM\u003c/p\u003e \u003cp\u003e(Median, IQR; No., %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTACE-RFA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTACE-RFA-\u003csup\u003e125\u003c/sup\u003eI\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTACE-RFA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTACE-RFA-\u003csup\u003e125\u003c/sup\u003eI\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (54\u0026ndash;69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (56\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.443\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61 (54\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e59 (53\u0026ndash;68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.356\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.765\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (90.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (82.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39 (84.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40 (87.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (17.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (15.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (13.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eChild-Pugh class\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.026*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.216\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (64.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (82.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42 (91.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e38 (82.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (35.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (17.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8 (17.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCLC stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.936\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.676\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (45.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (46.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21 (45.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (54.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (53.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25 (54.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTumor size (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.498\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.677\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (54.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (48.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24 (52.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22 (47.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (45.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (51.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22 (47.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24 (52.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTumor number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.846\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.901\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (67.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35 (76.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35 (76.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (15.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (19.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (17.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (15.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAscites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.014*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.503\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (89.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40 (87.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e42 (91.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (13.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHBV infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.302\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (5.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66 (94.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (89.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42 (91.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e42 (91.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAFP (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.832\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e≦\u0026thinsp;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (44.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27 (58.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28 (60.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (55.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19 (41.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18 (39.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: TACE, transarterial chemoembolization; RFA, radiofrequency ablation; PSM, propensity score matching; IQR, interquartile range; No., Number; BCLC, Barcelona Clinic Liver Cancer; HBV, hepatitis B virus; AFP, α-fetoprotein\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e*\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to indicate statistical significance\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eThe tumor recurrence rates between the two groups after PSM\u003c/h2\u003e \u003cp\u003eThe 1-, 2-, 3-, 4-, and 5-years of local recurrence rates in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group and TACE-RFA group were 0%, 11.1%, 16.9%, 16.9%, 20.1%, and 6.5%, 15.8%, 33.2%, 46.1%, 46.1%, respectively. The overall recurrence rates (including local, intrahepatic distant, and extrahepatic recurrences) at 1-, 2-, 3-, 4-, and 5-years were 2.1%, 24.4%, 38.5%, 53.8%, and 61.5% in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group and 17.5%, 40%, 66.1%, 81.1%, and 90.9% in the TACE-RFA group, respectively. Both the local and overall recurrence rates in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group were significantly lower than those in the TACE-RFA group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.037, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eThe local progression-free survival between the two groups after PSM analysis\u003c/h2\u003e \u003cp\u003eThe 1-, 2-, 3-, 4-, and 5-years LPFS rates in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group were 100%, 82.4%, 74.8%, 63.5%, and 54%, respectively, which were significantly higher than those of 91.3%, 69.4%, 50.7%, 29.4%, and 26.7% in the TACE-RFA group, respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). The uni- and multi-variate analyses demonstrated that the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI treatment, tumor size\u0026le;\u0026thinsp;3 cm, a solitary HCC, and BCLC stage A were the protective factors for patients\u0026rsquo; LPFS (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe uni- and multi-variate analyses of LPFS between the TACE-RFA and TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI groups after PSM analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.99 (0.97\u0026ndash;1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.710\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment method\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTACE-RFA-\u003csup\u003e125\u003c/sup\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTACE-RFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.32 (1.30\u0026ndash;4.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.005*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.35 (1.79\u0026ndash;6.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.17 (0.78\u0026ndash;6.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBV infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.87 (0.37\u0026ndash;2.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.752\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.27 (3.24\u0026ndash;12.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.56 (1.14\u0026ndash;5.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.022**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.66 (1.48\u0026ndash;4.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.84 (1.49\u0026ndash;5.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCLC stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.84 (3.50\u0026ndash;13.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.80 (1.69\u0026ndash;8.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFP (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.80 (0.45\u0026ndash;1.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.445\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAscites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.50 (0.64\u0026ndash;3.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.349\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild-Pugh class\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.83 (1.77\u0026ndash;8.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.85 (1.15\u0026ndash;7.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.024**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: LPFS, local progression-free survival; TACE, transarterial chemoembolization; RFA, radiofrequency ablation; PSM, propensity score matching; HR, hazard ratio; CI, confidence interval; Ref, reference; HBV, hepatitis B virus; BCLC, Barcelona Clinic Liver Cancer; AFP, α-fetoprotein\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e*\u003cem\u003ep\u003c/em\u003e value\u0026le;0.1 in uni-variate analysis were included in multi-variate analysis, **\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to indicate statistical significance in multi-variate analysis\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eThe progression-free survival between the two groups after PSM analysis\u003c/h2\u003e \u003cp\u003eThe 1-, 2-, 3-, 4-, and 5-years PFS rates in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group were 97.8%, 69.3%, 53.7%, 38.2%, and 31.8%, respectively, which were significantly higher than those of 84.8%, 54.3%, 29.3%, 16.3%, and 7.2% in the TACE-RFA group, respectively, and the median PFS in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group was also significantly longer than that of the TACE-RFA group (42.0 months vs. 29.0 months, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). The uni- and multi-variate analyses indicated that the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI treatment, tumor size\u0026le;\u0026thinsp;3 cm, a solitary HCC, BCLC stage A, and absence of ascites were the protective factors for patients\u0026rsquo; PFS (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe uni- and multi-variate analyses of PFS between the TACE-RFA and TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI groups after PSM analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.01 (0.98\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.656\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment method\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTACE-RFA-\u003csup\u003e125\u003c/sup\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTACE-RFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.07 (1.28\u0026ndash;3.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.003*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.96 (1.75\u0026ndash;5.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.07 (0.98\u0026ndash;4.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.057*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.25 (0.56\u0026ndash;2.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.583\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBV infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.70 (0.72\u0026ndash;4.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.34 (2.89\u0026ndash;9.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.67 (1.25\u0026ndash;5.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.011**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.39 (1.38\u0026ndash;4.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.002*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.98 (2.06\u0026ndash;7.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCLC stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.44 (3.83\u0026ndash;14.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.90 (2.57\u0026ndash;13.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFP (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.74 (0.46\u0026ndash;1.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.228\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAscites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.72 (1.79\u0026ndash;7.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.93 (1.34\u0026ndash;6.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.007**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild-Pugh class\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.96 (0.95\u0026ndash;4.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.067*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.08 (0.46\u0026ndash;2.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.862\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: PFS, progression-free survival; TACE, transarterial chemoembolization; RFA, radiofrequency ablation; PSM, propensity score matching; HR, hazard ratio; CI, confidence interval; Ref, reference; HBV, hepatitis B virus; BCLC, Barcelona Clinic Liver Cancer; AFP, α-fetoprotein\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e*\u003cem\u003ep\u003c/em\u003e value\u0026le;0.1 in uni-variate analysis were included in multi-variate analysis, **\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to indicate statistical significance in multi-variate analysis\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eThe overall survival between the two groups after PSM analysis\u003c/h2\u003e \u003cp\u003eAt the end of follow-up, 28.3% (13/46) patients in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group and 56.5% (26/46) patients in the TACE-RFA group died. The 1-, 2-, 3-, 4-, and 5-years OS rates were 100%, 93.4%, 80.7%, 74.9%, and 64.7% in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group, respectively, which were significantly higher than those of 97.8%, 78%, 68.6%, 51.1%, and 45.3% in the TACE-RFA group, respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). The uni- and multi-variate analyses showed that the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI treatment, tumor size\u0026le;\u0026thinsp;3 cm, a solitary HCC, BCLC stage A, and Child-Pugh class A were the protective factors for patients\u0026rsquo; OS (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe uni- and multi-variate analyses of OS between the TACE-RFA and TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI groups after PSM analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.98 (0.95\u0026ndash;1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment method\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTACE-RFA-\u003csup\u003e125\u003c/sup\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTACE-RFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.34 (1.20\u0026ndash;4.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.013*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.60 (2.11\u0026ndash;10.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.47 (0.76\u0026ndash;8.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBV infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.21 (0.43\u0026ndash;3.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.713\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.76 (5.07\u0026ndash;27.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.46 (2.68\u0026ndash;20.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.66 (1.38\u0026ndash;5.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.004*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.44 (1.66\u0026ndash;7.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCLC stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.38 (3.71\u0026ndash;18.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.40 (1.30\u0026ndash;8.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.013**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFP (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.23 (0.65\u0026ndash;2.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.532\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAscites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.13 (0.40\u0026ndash;3.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.819\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild-Pugh class\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.79 (2.83\u0026ndash;16.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.84 (2.00\u0026ndash;17.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: OS, overall survival; TACE, transarterial chemoembolization; RFA, radiofrequency ablation; PSM, propensity score matching; HR, hazard ratio; CI, confidence interval; Ref, reference; HBV, hepatitis B virus; BCLC, Barcelona Clinic Liver Cancer; AFP, α-fetoprotein\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e*\u003cem\u003ep\u003c/em\u003e value\u0026le;0.1 in uni-variate analysis were included in multi-variate analysis, **\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to indicate statistical significance in multi-variate analysis\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eThe subgroup analyses by tumor size after PSM\u003c/h2\u003e \u003cp\u003eIn the subgroup analysis of patients with tumor size\u0026le;\u0026thinsp;3 cm, the 1-, 2-, 3-, 4-, and 5-years LPFS, PFS, and OS rates in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group (LPFS rates: 100%, 92.9%, 89.1%, 85.3%, and 72.5%; PFS rates: 100%, 85.7%, 74.7%, 53.1%, and 44.2%; OS rates: 100%, 100%, 96.3%, 92.4%, and 79.8%, respectively) were all significantly better than those in the TACE-RFA group (LPFS rates: 100%, 80%, 69.4%, 44.9%, and 44.9%; PFS rates: 93.3%, 70%, 45.2%, 25.1%, and 11.2%; OS rates: 96.7%, 93.3%, 89.9%, 75%, and 66.5%, respectively) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.040, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA-C). Meanwhile, the median PFS in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group was significantly longer than that in the TACE-RFA group (50.0 months vs. 34.0 months, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAs described in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD-F, in the subgroup analysis of patients with tumor size\u0026thinsp;\u0026gt;\u0026thinsp;3 cm and \u0026le;\u0026thinsp;5 cm, the 1-, 2-, and 3-years LPFS and OS rates in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group (LPFS rates: 100%, 82.6%, and 49.1%; OS rates: 100%, 82.6%, and 48.7%, respectively) were significantly higher than those in the TACE-RFA group (LPFS rates: 75%, 48.6%, and 13.9%; OS rates: 93.8%, 48.1%, and 24.8%, respectively) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011, respectively). The 1-, 2-years PFS rates in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group (PFS rates: 94.4%, 42.4%, respectively) were also significantly higher than those in the TACE-RFA group (PFS rates: 56.3%, 25%, respectively) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011). In addition, the median LPFS, PFS, and OS in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group were significantly longer than that of in the TACE-RFA group (median LPFS: 36.0 months vs. 23.0 months, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034; median PFS: 23.0 months vs. 17.0 months, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011; median OS: 36.0 months vs. 23.0 months, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn recent years, the application of \u003csup\u003e125\u003c/sup\u003eI seed implantation in the treatment of some malignant solid tumors extended the indication of brachytherapy, and the therapeutic effectiveness was proven to be preferable, such as in HCC (Chen et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2014\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). The results of our study showed that, for patients with HCC\u0026thinsp;\u0026le;\u0026thinsp;5 cm in high-risk locations, the tumor control and patients\u0026rsquo; survival in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group were significantly better than those in the TACE-RFA group. Meanwhile, the results of our study showed that the treatment method of TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI was an independent protective factor for tumor control and patients\u0026rsquo; survival outcomes. These outcomes supported the hypothesis that adding \u003csup\u003e125\u003c/sup\u003eI seed implantation therapy on the basis of TACE-RFA can further improve the effect of TACE-RFA on unresectable HCC (\u0026le;\u0026thinsp;5 cm) in high-risk locations.\u003c/p\u003e \u003cp\u003eFor unresectable HCC\u0026thinsp;\u0026le;\u0026thinsp;5 cm, TACE-RFA or TACE in combination with microwave ablation (TACE-MWA) was a favourable treatment. A previous study (Shibata et al. \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2009\u003c/span\u003e) reported the OS rates at 1-, 2-, 3-, and 4-years after TACE-RFA for patients with HCCs\u0026thinsp;\u0026lt;\u0026thinsp;3 cm were 100%, 100%, 84.8%, and 72.7%, respectively, and the recurrence-free survival rates at 1-, 2-, 3-, and 4-years were 71.3%, 59.9%, 48.8%, and 36.6%, respectively. Meanwhile, a randomized controlled trial (Zaitoun et al. \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) reported that 93 patients with HCC ranging from 3 to 5cm received TACE-MWA treatment, the recurrence rate at 1 year was 22.47%, and the median OS was 24 months. Compared with these studies, our study focused on HCCs in high-risk locations, the treatment effects of which are usually inferior to those of HCCs in non-high-risk locations under the same treatment. However, in the present study, the results of our study were comparable or superior to those of studies, which indicated TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI was an excellent treatment strategy for patients with unresectable HCC (\u0026le;\u0026thinsp;5 cm) in high-risk locations.\u003c/p\u003e \u003cp\u003eThe possible potential mechanisms of TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI for HCC are as follows: (1) the tumor-killing effect of hyperthermia and radiotherapy complement each other. The tumor cells in the S phase of the cell cycle are less sensitive to radiotherapy, but respond relatively better to hyperthermia. Meanwhile, the sensitivity of anoxic tumor cells to radiotherapy is lower, but that to hyperthermia is relatively stable (Hall et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Nishimura et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2015\u003c/span\u003e); (2) radiofrequency hyperthermia could increase the vasodilation and vascular permeability in the treated peritumoral area, which could increase the oxygen supply of this area, and subsequently improve the treatment effect of radiotherapy on HCC (Wang et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Dabbagh et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2015\u003c/span\u003e); (3) the RFA treatment could trigger the systemic anti-tumor immune response, and subsequently enhance the anti-tumor effect of radiotherapy (Hong et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2014\u003c/span\u003e); (4) TACE treatment could embolize the tumor blood vessels and reduce the influence of heat-sink effect (Kim et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Choe et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2014\u003c/span\u003e); (5) the deposition of lipiodol in the tumor after TACE treatment can be used as a marker, which helps to achieve a precise RFA and iodine-125 seed implantation treatment. Based on these potential mechanisms, the triple combination treatment (TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI) strategy was used for unresectable HCC in high-risk locations in the present study.\u003c/p\u003e \u003cp\u003eMWA of HCC is becoming increasingly popular as MWA allows for a larger ablation zone in a relatively short time. However, for MWA of HCC in high-risk locations, this feature may cause thermal injury to the adjacent important structures of HCC, such as the biliary and gastrointestinal tracts. Compared to MWA, RFA has the characteristic of a slower heating rate, and thus it may reduce the risk of thermal damage to the surrounding tissues of ablated tumors. Therefore, in the present study, we used RFA instead of MWA for HCC. In addition, in this study, RFA and \u003csup\u003e125\u003c/sup\u003eI seed implantation were performed under ultrasound plus CT guidance, which could provide a real-time and accurate imaging guidance. It not only avoided blood vessels and other important tissues from injuries during puncture, but also facilitated the precise placement of the radiofrequency electrode and \u003csup\u003e125\u003c/sup\u003eI seeds. We believed these were the main reasons for the absence of major complications and procedure-related deaths in our study.\u003c/p\u003e \u003cp\u003eOur study had limitations. This is a single center and retrospective study. Although a PSM analysis was performed to reduce the potential selection bias, it could not be completely avoided. So a prospective multi-center randomized controlled trial is necessary to confirmed the results of this study.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eCompared with TACE-RFA treatment, TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI should be a more effective therapy for patients with unresectable HCC (\u0026le;\u0026thinsp;5 cm) in high-risk locations. TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI under ultrasound plus CT guidance is an excellent and safe treatment strategy for this type of unresectable HCC, and is worth of clinical promotion and application.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAckonwledgements:\u003c/strong\u003e None.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe study was conducted according to the Declaration of Helsinki. Informed consent was waived for the retrospective type of this study. The information of all participants is maintained with confidentiality. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis study was supported by the\u0026nbsp;grants of National Natural Science Foundation of China (Nos. 82372069 and 82072041) and the Outstanding Youth Foundation of Hubei Province, China (2023AFA107).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003eG.Z. and Y.R.: Data analysis, preparation of original draft, visualization, writing and editing. J.L., Y.C., and F.X.: Visualization, writing and editing. C.Z. and B.L.: Conceptualization, reviewing and editing. X. K.: Conceptualization, reviewing, editing, and funding acquisition.X.K. and C.Z.: Guarantor.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e The data that support the study findings are available upon reasonable request from the corresponding authors\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e The study received approval from the Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Approval no.: UHCT-IEC-SOP-012-01-01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u0026nbsp;\u003c/strong\u003eThe requirement for obtaining written consent was waived because of the retrospective design of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish:\u0026nbsp;\u003c/strong\u003eThe authors affirm that the human research participant provided informed consent for publication of the images in Fig. 2 A-E.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBai X-M, Cui M, Yang W, et al (2021) The 10-year Survival Analysis of Radiofrequency Ablation for Solitary Hepatocellular Carcinoma 5 cm or Smaller: Primary versus Recurrent HCC. 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J Hepatol 61:1304\u0026ndash;1311. https://doi.org/10.1016/j.jhep.2014.07.026\u003c/li\u003e\n\u003cli\u003eChen L, Kan X, Sun T, et al (2020) Transarterial chemoembolization combined with iodine 125 seeds versus transarterial chemoembolization combined with radiofrequency ablation in the treatment of early- and intermediate-stage hepatocellular carcinoma. Bmc Gastroenterol 20:205. https://doi.org/10.1186/s12876-020-01355-3\u003c/li\u003e\n\u003cli\u003eChen M-L, Li H-L, Guo C-Y, et al (2022) Radiofrequency ablation combined with transarterial chemoembolization in treatment of hepatocellular carcinoma adjacent to the second hepatic hilus. Abdom Radiol (NY) 47:423\u0026ndash;430. https://doi.org/10.1007/s00261-021-03304-4\u003c/li\u003e\n\u003cli\u003eChen Z, Fu X, Qiu Z, et al (2023) CT-guided 125I brachytherapy for hepatocellular carcinoma in high-risk locations after transarterial chemoembolization combined with microwave ablation: a propensity score-matched study. 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Int J Hyperthermia 31:375\u0026ndash;385. https://doi.org/10.3109/02656736.2015.1006268\u003c/li\u003e\n\u003cli\u003eGalle PR, Forner A, Llovet JM, et al (2018) EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 69:182\u0026ndash;236. https://doi.org/10.1016/j.jhep.2018.03.019\u003c/li\u003e\n\u003cli\u003eHall SK, Ooi EH, Payne SJ (2015) Cell death, perfusion and electrical parameters are critical in models of hepatic radiofrequency ablation. Int J Hyperthermia 31:538\u0026ndash;550. https://doi.org/10.3109/02656736.2015.1032370\u003c/li\u003e\n\u003cli\u003eHeimbach JK, Kulik LM, Finn RS, et al (2018) AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 67:358\u0026ndash;380. https://doi.org/10.1002/hep.29086\u003c/li\u003e\n\u003cli\u003eHong D, Zhou Y, Wan X, et al (2021) Brachytherapy with Iodine-125 seeds for treatment of portal vein-branch tumor thrombus in patients with hepatocellular carcinoma. BMC Cancer 21:1020. https://doi.org/10.1186/s12885-021-08680-0\u003c/li\u003e\n\u003cli\u003eHong M, Jiang Z, Zhou Y-F (2014) Effects of thermotherapy on Th1/Th2 cells in esophageal cancer patients treated with radiotherapy. Asian Pac J Cancer Prev 15:2359\u0026ndash;2362. https://doi.org/10.7314/apjcp.2014.15.5.2359\u003c/li\u003e\n\u003cli\u003eHsieh Y-C, Limquiaco JL, Lin C-C, et al (2019) Radiofrequency ablation following s and pleural effusion creation may improve outcomes for hepatocellular carcinoma in high-risk locations. Abdom Radiol 44:1141\u0026ndash;1151. https://doi.org/10.1007/s00261-018-1831-6\u003c/li\u003e\n\u003cli\u003eKan X, Wang Y, Han P, et al (2019) Combined ultrasound/computed tomography guidance in percutaneous radiofrequency ablation after transarterial chemoembolization for hepatocellular carcinoma in the hepatic dome. Cancer Manag Res 11:7751\u0026ndash;7757. https://doi.org/10.2147/CMAR.S212127\u003c/li\u003e\n\u003cli\u003eKim JW, Kim JH, Won HJ, et al (2012) Hepatocellular carcinomas 2-3 cm in diameter: transarterial chemoembolization plus radiofrequency ablation vs. radiofrequency ablation alone. Eur J Radiol 81:e189-193. https://doi.org/10.1016/j.ejrad.2011.01.122\u003c/li\u003e\n\u003cli\u003eLee DH, Lee MW, Kim PN, et al (2021) Outcome of No-Touch Radiofrequency Ablation for Small Hepatocellular Carcinoma: A Multicenter Clinical Trial. Radiology 301:229\u0026ndash;236. https://doi.org/10.1148/radiol.2021210309\u003c/li\u003e\n\u003cli\u003eLi J, Zhang L, Xie Q, et al (2019) 125I seeds implantation for treating residual hepatocellular carcinoma located beneath the diaphragm after transcatheter arterial chemoembolization. Brachytherapy 18:420\u0026ndash;425. https://doi.org/10.1016/j.brachy.2018.12.008\u003c/li\u003e\n\u003cli\u003eLin Z-Y, Chen J, Deng X-F (2012) Treatment of hepatocellular carcinoma adjacent to large blood vessels using 1.5T MRI-guided percutaneous radiofrequency ablation combined with iodine-125 radioactive seed implantation. Eur J Radiol 81:3079\u0026ndash;3083. https://doi.org/10.1016/j.ejrad.2012.05.007\u003c/li\u003e\n\u003cli\u003eMonk BJ, Toita T, Wu X, et al (2023) Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. Lancet Oncol 24:1334\u0026ndash;1348. https://doi.org/10.1016/S1470-2045(23)00479-5\u003c/li\u003e\n\u003cli\u003eNishimura S, Saeki H, Nakanoko T, et al (2015) Hyperthermia combined with chemotherapy for patients with residual or recurrent oesophageal cancer after definitive chemoradiotherapy. Anticancer Res 35:2299\u0026ndash;2303\u003c/li\u003e\n\u003cli\u003eShibata T, Isoda H, Hirokawa Y, et al (2009) Small hepatocellular carcinoma: is radiofrequency ablation combined with transcatheter arterial chemoembolization more effective than radiofrequency ablation alone for treatment? Radiology 252:905\u0026ndash;913. https://doi.org/10.1148/radiol.2523081676\u003c/li\u003e\n\u003cli\u003eStrnad V, Polg\u0026aacute;r C, Ott OJ, et al (2023) Accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy compared with whole-breast irradiation with boost for early breast cancer: 10-year results of a GEC-ESTRO randomised, phase 3, non-inferiority trial. Lancet Oncol 24:262\u0026ndash;272. https://doi.org/10.1016/S1470-2045(23)00018-9\u003c/li\u003e\n\u003cli\u003eSung H, Ferlay J, Siegel RL, et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209\u0026ndash;249. https://doi.org/10.3322/caac.21660\u003c/li\u003e\n\u003cli\u003eWang K, Tavakkoli F, Wang S, Vafai K (2015) Analysis and analytical characterization of bioheat transfer during radiofrequency ablation. J Biomech 48:930\u0026ndash;940. https://doi.org/10.1016/j.jbiomech.2015.02.023\u003c/li\u003e\n\u003cli\u003eWang Q, Tang M, Zhang S (2021) Comparison of radiofrequency ablation and surgical resection for hepatocellular carcinoma conforming to the Milan criteria: a meta-analysis. ANZ J Surg 91:E432\u0026ndash;E438. https://doi.org/10.1111/ans.16560\u003c/li\u003e\n\u003cli\u003eZaitoun MMA, Elsayed SB, Zaitoun NA, et al (2021) Combined therapy with conventional trans-arterial chemoembolization (cTACE) and microwave ablation (MWA) for hepatocellular carcinoma \u0026gt;3-\u0026lt;5\u0026thinsp;cm. Int J Hyperthermia 38:248\u0026ndash;256. https://doi.org/10.1080/02656736.2021.1887941\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"radiofrequency ablation, transarterial chemoembolization, iodine-125 seed, hepatocellular carcinoma, high-risk locations","lastPublishedDoi":"10.21203/rs.3.rs-4258024/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4258024/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u0026amp; aims:\u003c/strong\u003e The effect of transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) (TACE-RFA) for hepatocellular carcinoma (HCC) in high-risk locations is not satisfactory. The aim of this study was to compare the clinical outcomes of TACE-RFA plus iodine-125 (\u003csup\u003e125\u003c/sup\u003eI) seed implantation (TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI) therapy with those of TACE-RFA for unresectable HCC (≤5 cm) in high-risk locations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eFrom January 2010 to June 2023, the clinical data of 126 patients with unresectable HCC (≤5 cm) in high-risk locations who received TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI or TACE-RFA treatment were retrospectively analyzed. The clinical outcomes between the two groups were compared after propensity score matching (PSM) analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eForty-six pairs of patients were matched. The local progression-free survival rates at 1-, 2-, 3-, 4-, and 5-years were 100%, 82.4%, 74.8%, 63.5%, and 54% in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group, which were significantly higher than 91.3%, 69.4%, 50.7%, 29.4%, and 26.7% in the TACE-RFA group, respectively (\u003cem\u003ep \u003c/em\u003e= 0.004). The median progression-free survival in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group was significantly longer than that in the TACE-RFA group (\u003cem\u003ep\u003c/em\u003e = 0.002). The overall survival rates at 1-, 2-, 3-, 4-, and 5-years were 100%, 93.4%, 80.7%, 74.9%, and 64.7% in the TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI group, which were significantly higher than 97.8%, 78%, 68.6%, 51.1%, and 45.3% in the TACE-RFA group, respectively (\u003cem\u003ep \u003c/em\u003e= 0.011). There was no occurrence of major complications or procedure-related deaths in the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eCompared with\u003cstrong\u003e \u003c/strong\u003ethe\u003cstrong\u003e \u003c/strong\u003eTACE-RFA treatment, TACE-RFA-\u003csup\u003e125\u003c/sup\u003eI should be a \u0026nbsp;more effective treatment strategy for patients with unresectable HCC (≤5 cm) in high-risk locations.\u003c/p\u003e","manuscriptTitle":"Transarterial chemoembolization plus radiofrequency ablation and iodine-125 seed implantation for hepatocellular carcinoma in high-risk locations: a propensity score-matched analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-19 19:08:55","doi":"10.21203/rs.3.rs-4258024/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a08f1860-b1cb-4096-92c7-422d72d45f34","owner":[],"postedDate":"April 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-20T21:38:27+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-19 19:08:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4258024","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4258024","identity":"rs-4258024","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}