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Analysis of the efficacy of adjuvant transarterial chemoembolization after curative hepatectomy in hepatocellular carcinoma with satellite nodules
YU Wang-jin, MENG Fan-zheng, AN Ze-yang, ZHANG Shen-yu, WANG Yong-shuai, SONG Hua-chuan, SONG Rui-peng
Chinese Journal of Practical Surgery ›› 2025, Vol. 45 ›› Issue (11) : 1295-1301.
PDF(3494 KB)
PDF(3494 KB)
Analysis of the efficacy of adjuvant transarterial chemoembolization after curative hepatectomy in hepatocellular carcinoma with satellite nodules
Objective To evaluate the therapeutic efficacy of postoperative adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with satellite nodules after curative resection. Methods A retrospective analysis was performed on clinical data of 107 HCC patients with satellite nodules who underwent curative hepatectomy at the First Affiliated Hospital of the University of Science and Technology of China between January 1, 2018, and January 1, 2024. 51 patients underwent hepatectomy alone (control group), and 56 patients received postoperative adjuvant TACE (TACE group). The log-rank test was used to compare recurrence-free survival (RFS) and overall survival (OS) between groups. Cox regression analyses were applied to identify prognostic factors for RFS and OS, and univariate Cox proportional hazards models were used for subgroup analyses of RFS and OS. Results The median RFS duration in the TACE group was longer than that in the control group [14.72 (95%CI 9.49-27.96) months vs. 5.72 months (95%CI 4.40-9.53), P=0.006], with a 45.0% reduction in recurrence risk (HR=0.550, 95%CI 0.358-27.96). The 1- and 2-year RFS rates in the TACE group were 55.36% and 28.57%, respectively, compared to 29.41% and 11.76% in the control group. The median OS of the TACE group was longer than that in the control group (P=0.034), with a 48.4% reduction in mortality risk (HR=0.516, 95%CI 0.276-0.962), At the end of follow-up, the median OS had not been reached in the TACE group, whereas it was 69.88 months (95%CI 22.14-NR) in the control group.Multivariate Cox analysis indicated that Edmondson-Steiner grade Ⅲ/Ⅳ (HR=1.82, 95%CI 1.11-2.96, P=0.017) and postoperative adjuvant TACE (HR=0.45, 95%CI 0.28-0.72, P<0.001) were independent prognostic factors for RFS. Alpha-fetoprotein >400 μg/L (HR=2.05, 95%CI 1.09-3.83, P=0.025), Edmondson-Steiner grade Ⅲ/Ⅳ (HR=2.28, 95%CI 1.20-4.31, P=0.012), and postoperative adjuvant TACE (HR=0.43, 95%CI 0.22-0.82, P=0.011) were independent prognostic factors for OS. Pain and elevated transaminase levels were the most common adverse effects in the TACE group, generally mild and manageable. Conclusion Postoperative adjuvant TACE can effectively prolong early recurrence-free survival and overall survival in HCC patients with satellite nodules.
hepatocellular carcinoma / satellite nodules / postoperative adjuvant therapy / transarterial chemoembolization
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The aim of this study was to estimate probabilities of achieving the statistical cure from hepatocellular carcinoma (HCC) with hepatic resection (HR) and liver transplantation (LT).
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樊嘉, 王征. 从《原发性肝癌诊疗指南(2024年版)》更新看我国肝癌综合治疗新进展[J]. 中国实用外科杂志, 2024, 44(09):984-987.DOI:10.19538/j.cjps.issn1005-2208.2024.09.03.
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The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.
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中华人民共和国国家卫生健康委员会医政司. 原发性肝癌诊疗指南(2024年版)[J]. 中国实用外科杂志, 2024, 44(4):361-386.DOI:10.19538/j.cjps.issn1005-2208.2024.04.01.
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Background: The aim of this study was to evaluate the clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC). Methods: Data from 117 patients with HCC who underwent hepatectomy between December 2010 and February 2014 were retrospectively reviewed. In total, 55 patients underwent surgical resection only (group A), and 62 patients underwent surgical resection with adjuvant TACE (group B). The perioperative clinical indicators, postoperative sequential treatment, and follow-up were compared between the two groups of patients. The Kaplan-Meier method was used to compare survival between the groups, and prognostic factors were evaluated by a Cox proportional hazard model. Results: The two groups showed no significant difference in age, gender, preoperative A-fetoprotein (AFP) values, preoperative Child-Pugh score, hepatitis B virus(HBV) DNA levels, duration of surgery, hepatectomy technique, albumin values 1-week postoperative, postoperative complications, duration of postoperative hospital stay, cirrhosis, tumor size, tumor differentiation, tumor encapsulation, satellite nodules, or microvascular infiltration. Cox regression analysis revealed that tumor size, satellite nodules, and microvascular infiltration were significantly independent prognostic factors (P = 0.001, 0.002, and 0.001). Of the 117 patients, the 1-, 2-, and 3-year disease-free survival rates were 64.5, 50.0, and 41.9 %, respectively, for group B (62 patients) and 45.5, 36.4, and 30.9 %, respectively, for group A (55 patients). Although improving trends of disease-free survival were observed in the adjuvant TACE group, there was a significant difference in postoperative 1-year survival between the two groups (P = 0.04) but no significant difference in postoperative 2-and 3year survival. In patients with tumor size >5 cm, the 1-, 2-, and 3-year disease-free survival rates were 41.7, 25.0, and 12.5 %, respectively, for group B and 11.8, 0, and 0 %, respectively, for group A. There was a significant difference in postoperative 1-and 2-year survival between the two groups (P = 0.04 and 0.03, respectively) but no significant difference in postoperative 3-year survival. In patients with microvascular infiltration, the 1-, 2-, and 3-year disease-free survival rates were 42.3, 26.9, and 15.4 %, respectively, for group B and 12.5, 4.2, and 0 %, respectively, for group A. There was a significant difference between the two groups (P = 0.02, 0.03, and 0.045, respectively). In patients with satellite nodules, the 1-, 2-, and 3-year disease-free survival rates were 50.0, 50, and 40 %, respectively, for group B and 17.6, 0, and 0 %, respectively, for group A. There was a significant difference between the two groups (P = 0.04, 0.01, and 0.03, respectively). In patients with tumor size <= 5 cm, without satellite nodules, or without microvascular infiltration, there was no significant difference between the two groups in the 1-, 2-, or 3-year disease-free survival rates. Of 117 patients overall, 18 (15.4 %) developed hepatitis B virus reactivation: 2 (3.6 %) patients in group A and 16 (25.8 %) patients in group B. There was a significant difference between the two groups (P = 0.000). Of these patients, one (1.8 %) patient in group A and five (8.1 %) patients in group B developed hepatitis due to hepatitis B virus reactivation. There was a significant difference between the two groups (P = 0.000). Conclusions: Postoperative adjuvant TACE can improve the 1-year disease-free survival rate of HCC patients. Postoperative adjuvant TACE may improve 2-and 3-year disease-free survival rates, but no statistical significance was found. For patients with tumor size >5 cm, postoperative adjuvant TACE can improve 1-and 2-year disease-free survival rates, and postoperative adjuvant TACE may improve the 3-year disease-free survival rate. For HCC patients with tumor size <= 5 cm, postoperative adjuvant TACE may improve the 1-, 2-, and 3-year disease-free survival rates, but no statistical significance was found. For patients with microvascular infiltration or satellite nodules, postoperative adjuvant TACE can improve the 1-, 2-, and 3-year disease-free survival rates. For patients without microvascular infiltration or without satellite nodules, postoperative adjuvant TACE cannot improve 1-, 2-, or 3-year disease-free survival rates. For patients with tumor size >5 cm with microvascular infiltration or with satellite nodules, postoperative adjuvant TACE was suggested. Hepatitis B virus reactivation can occur in patients with postoperative adjuvant TACE; thus, antiviral treatment was suggested for these patients.
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The survival benefit of adjuvant transarterial chemoembolization (TACE) in patients with hepatectomy for hepatocellular carcinoma (HCC) after hepatectomy remains controversial. We aimed to investigate the survival efficacy of adjuvant TACE after hepatectomy for HCC.1491 patients with HCC who underwent hepatectomy between January 2018 and September 2021 at four medical centers in China were retrospectively analyzed, including 782 patients who received adjuvant TACE and 709 patients who did not receive adjuvant TACE. Propensity score matching (PSM) (1:1) was performed to minimize selection bias, which balanced the clinical characteristics of the two groups.A total of 1254 patients were enrolled after PSM, including 627 patients who received adjuvant TACE and 627 patients who did not receive adjuvant TACE. Patients who received adjuvant TACE had higher disease-free survival (DFS, 1-,2-, and 3-year: 78%-68%-62% vs. 69%-57%-50%, p < 0.001) and overall survival (OS, 1-,2-, and 3-year: 96%-88%-80% vs. 90%-77%-66%, p < 0.001) than those who did not receive adjuvant TACE (Median DFS was 39 months). Among the different levels of risk factors affecting prognosis [AFP, Lymphocyte-to-monocyte ratio, Maximum tumor diameter, Number of tumors, Child-Pugh classification, Liver cirrhosis, Vascular invasion (imaging), Microvascular invasion, Satellite nodules, Differentiation, Chinese liver cancer stage II-IIIa], the majority of patients who received adjuvant TACE had higher DFS or OS than those who did not receive adjuvant TACE. More patients who received adjuvant TACE accepted subsequent antitumor therapy such as liver transplantation, re-hepatectomy and local ablation after tumor recurrence, while more patients who did not receive adjuvant TACE accepted subsequent antitumor therapy with TACE after tumor recurrence (All p < 0.05).Adjuvant TACE may be a potential way to monitor early tumor recurrence and improve postoperative survival in patients with HCC.© 2023. The Author(s).
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The survival of patients with hepatocellular carcinoma (HCC) recurrence after curative resection is usually poor. We sought to evaluate the safety and efficacy of adjuvant transarterial chemoembolization (TACE) in HBV-related HCC patients with an intermediate (a single tumor larger than 5 cm without microvascular invasion) or high risk (a single tumor with microvascular invasion, or two or three tumors) of recurrence. In this randomized phase 3 trial, 280 eligible patients were assigned to adjuvant TACE ( = 140) or no adjuvant treatment (control; = 140) groups. The primary endpoint was recurrence-free survival (RFS); secondary endpoints included overall survival (OS) and safety. Multivariable Cox-proportional hazards model was used to determine the independent impact of TACE on patients' outcomes. Patients who received adjuvant TACE had a significantly longer RFS than those in the control group [56.0% vs. 42.1%, = 0.01; HR, 0.68; 95% confidence interval (CI), 0.49-0.93]. Patients in the adjuvant TACE group had 7.8% higher 3-year OS rate than the control group (85.2% vs. 77.4%; = 0.04; HR, 0.59; 95% CI, 0.36-0.97). The impact of adjuvant TACE on RFS and OS remained significant after controlling for other known prognostic factors (HR, 0.67; = 0.01 for RFS; and HR, 0.59; = 0.04 for OS). There was no grade 3 or 4 toxicity after adjuvant TACE. For patients with HBV-related HCC who had an intermediate or high risk of recurrence after curative hepatectomy, our study showed adjuvant TACE significantly reduced tumor recurrence, improved RFS and OS, and the procedure was well tolerated..©2018 American Association for Cancer Research.
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To explore the effect of lipiodolized transarterial chemoembolization (lip-TACE) in hepatocellular carcinoma (HCC) patients at different risk of recurrence after curative resection.One thousand nine hundred and twenty-four consecutive HCC patients who underwent curative resection were retrospectively analyzed. Patients who underwent resection only were classified into control group, while those received adjuvant lip-TACE were classified into intervention group. Patients were further stratified into 4 groups, that is, tumor ≤5 cm with low or high risk factors, as well as tumor >5 cm with low or high risk factors for recurrence. Tumor number and microscopic tumor thrombus were defined as risk factors for recurrence. The effect of adjuvant lip-TACE on early (<2 year) or late (≥2 year) recurrence was evaluated.There was no significant difference in recurrence curve between intervention group and control group in each stratum. Adjuvant lip-TACE showed an overall survival benefit in patients with tumor >5 cm and presenting high risk factors, mainly for those with time to recurrence (TTR) <2 years after operation. For them, the median survival was 17 months in the intervention group and 11 months in the control group (P = 0.010). For patients who were confirmed to be recurrence-free at 2 years after operation, it had the negative effect for survival (HR = 1.75, P = 0.004).Adjuvant lip-TACE had no preventive effect on recurrence, but may be of benefit to detect early recurrence.
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Certain patients with hepatocellular carcinoma with portal vein tumor thrombus could benefit from surgical resection, and postoperative adjuvant therapy may lower the incidence of tumor recurrence.To compare the efficacy and safety of sorafenib plus transarterial chemoembolization vs sorafenib alone as postoperative adjuvant therapy for patients with hepatocellular carcinoma with portal vein tumor thrombus.This was a phase 3, multicenter, randomized clinical trial conducted in 5 hospitals in China. A total of 158 patients were enrolled and randomized from October 2019 to March 2022, with a median follow-up of 28.4 months. Portal vein tumor thrombus was graded by the Cheng classification. Eligible patients with hepatocellular carcinoma with Cheng grade I to III portal vein tumor thrombus (ie, involving segmental or sectoral branches, right- or left-side branch, or main trunk of portal vein) were included.Patients were randomly assigned 1:1 to receive transarterial chemoembolization with sorafenib or sorafenib alone as postoperative adjuvant therapy. Sorafenib treatment was started within 3 days after randomization, with an initial dose of 400 mg orally twice a day. In the transarterial chemoembolization with sorafenib group, transarterial chemoembolization was performed 1 day after the first administration of sorafenib.The primary end point was recurrence-free survival. Efficacy was assessed in the intention-to-treat population and safety was assessed in patients who received at least 1 dose of study treatment.Of 158 patients included, the median (IQR) age was 54 (43-61) years, and 140 (88.6%) patients were male. The median (IQR) recurrence-free survival was significantly longer in the transarterial chemoembolization with sorafenib group (16.8 [12.0-NA] vs 12.6 [7.8-18.1] months; hazard ratio [HR], 0.57; 95% CI, 0.39-0.83; P = .002). The median (IQR) overall survival was also significantly longer with transarterial chemoembolization with sorafenib than with sorafenib alone (30.4 [20.6-NA] vs 22.5 [15.4-NA] months; HR, 0.57; 95% CI, 0.36-0.91; P = .02). The most common grade 3/4 adverse event was hand-foot syndrome (23 of 79 patients in the transarterial chemoembolization with sorafenib group [29.1%] vs 24 of 79 patients in the sorafenib alone group [30.4%]). There were no treatment-related deaths in either group. The transarterial chemoembolization with sorafenib group did not show additional toxicity compared with the sorafenib monotherapy group.In this study, the combination of sorafenib and transarterial chemoembolization as postoperative adjuvant therapy in patients with hepatocellular carcinoma with portal vein tumor thrombus resulted in longer recurrence-free survival and overall survival than sorafenib alone and was well tolerated.ClinicalTrials.gov Identifier: NCT04143191.
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