Predictive value of random forest prediction model based on postoperative adjuvant transcatheter arterial chemoembolization therapy for survival of hepatocellular carcinoma patients with microvascular invasion: a retrospective cohort study

Objective To systematically review the clinical effectiveness of combined postoperative adjuvant transcatheter arterial chemoembolization (TACE) with portal vein chemotherapy (PVC) versus TACE alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). Methods Databases including PubMed, Embase, Cochrane Library, Medline, Web of Science, CNKI, China Biology Medicine, Wan Fang and VIP were searched from Jan 1st 2000 to Jun 30th 2019 for eligible studies on clinical effectiveness of combined postoperative adjuvant TACE with PVC versus TACE alone in patients with HCC and PVTT. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoint was adverse events. These endpoints were evaluated by odds ratio (OR) and 95% confidence interval (CI) using Review Manager 5.3 software. Results Nine studies with 642 patients were enrolled in this meta-analysis. There were 323 patients in the TACE group and 319 patients in the TACE plus PVC group. The pooled OR for the 1-, 2-, and 3-year OS were all significantly better in the TACE plus PVC group than the TACE group (1-year OS, OR=2.20, 95% CI: 1.53-3.17; 2-year OS, OR=2.44, 95% CI: 1.69-3.53; 3-year OS, OR=2.30, 95% CI: 1.52-3.46) (all P 0.05). Conclusion Postoperative adjuvant TACE combined with PVC for patients with HCC and PVTT was safe and effective, and was significantly better than TACE alone in long-term prognosis. Large-scale, multi-center, prospective studies are needed to support the conclusion. Key words: Carcinoma, hepatocellular; Portal vein tumor thrombosis; Transarterial chemoembolization; Portal vein chemotherapy; Meta-analysis

Objective To evaluate the clinical value of postoperative adjuvant transcatheter arterial chemoembolization(TACE) on the prognosis of hepatocellular carcinoma(HCC) patients after radical hepatectomy using a prospective cohort study.Methods A total of 220 HCC patients underwent radical hepatectomy from Jan.2008 to Dec.2008 and 104 were recruited in the present study.Fifty-six patients(TACE group) received adjuvant TACE one month after hepatectomy,and 48(control group) did not receive any adjuvant therapies.Follow-up was done regularly.The disease-free survival(DFS) time and total survival(TS) were statistically analyzed.Results The median DFS time in TACE group was significantly shorter than that in the control group(11 months vs 13 months,P=0.005).The 1-year,2-year and 3-year recurrence rates were 50%,85.7%,and 89.3% in TACE group and 46.8%,58.3%,and 62.5% in the control group(P=0.005),respectively.Multivariate COX regression analysis indicated that TACE,AFP,intact tumor peplos,liver cirrhosis,vascular invasion and tumor Edmondson-Steiner grade were the risk factors for recurrence(P0.05).The median TS time periods in TACE group and control group were 29(4-41) months and 24(5-59) months(P=0.789),respectively.The 1-year,2-year and 3-year survival rates were 85.6%,59.5%,and 36.5% in TACE group and 75%,50%,and 41.7% in the control group(P=0.789),respectively.Multivariate COX regression analysis indicated that AFP,intact tumor peplos and tumor Edmondson-Steiner grade were correlated with the total survival of patients(P0.05).Conclusion Adjuvant TACE can not improve DFS and TS of HCC patients after radical hepatectomy,and it may even contribute to a poor prognosis.Therefore more attention should be paid in choosing treatment strategy.

BackgroundThe aim of this study was to evaluate the clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC).MethodsData 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.ResultsThe 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 3-year 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).ConclusionsPostoperative 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.

Effects of adjuvant transcatheter arterial chemoembolization (TACE) for intrahepatic cholangiocarcinoma (ICC) radical surgery have never been evaluated. A retrospective analysis was conducted on 125 ICC patients who had undergone operations with curative intent in Shanghai Eastern Hepatobiliary Surgery Hospital from July 2002 to December 2003. Of these patients, 53 underwent adjuvant TACE (TACE group) and 72 did not (non-TACE group). Adjuvant TACE was performed one time 1.5-2.0 months after the operation. Follow-up was performed at a median of 18 months (range 3-96 months). There was no significant recurrence-free survival (RFS) difference between the TACE and non-TACE groups (P = 0.659). The 1-, 3-, and 5-year overall survival (OS) rates were 69.8, 37.7, and 28.3%, respectively, for the TACE group and 54.2, 25.0, and 20.8%, respectively, for the non-TACE group (P = 0.045). Among 54 patients with a recurrence time of ≤ 3 months, the OS rate of the TACE group was better than that of the non-TACE group (P < 0.001). For 59 patients with a recurrence time later than the median RFS, no significant RFS difference was found between the TACE and non-TACE groups (P = 0.681). These results indicate that TACE could not delay recurrence but could prolong the OS of patients with early recurrence. Adjuvant TACE after radical surgery was associated with better survival among the ICC patients with early recurrence.

The aim of this study was to investigate whether postoperative adjuvant transcatheter arterial chemoembolization (TACE) treatment in wide- and narrow-margin groups could improve the long-term prognosis of patients with hepatocellular carcinoma (HCC). A total of 670 patients with HCC who underwent radical hepatectomy from January 2016 to December 2017 were enrolled, including 397 patients and 273 patients in the wide- and narrow-margin groups. Recurrence-free survival (RFS) and overall survival (OS) outcomes were compared in the wide-margin and narrow-margin groups with and without adjuvant TACE postoperatively, respectively. Propensity score matching (PSM) analysis was used to match patients between TACE and no TACE groups in a 1:1 ratio. The wide-margin resection was associated with better RFS and OS rates than narrow-margin resection for patients with HCC. Patients with postoperative adjuvant TACE had a better RFS and OS than patients without postoperative adjuvant TACE in the narrow-margin group and reduced the intrahepatic recurrence rate (39.1% vs. 52.6%, P = .036) and the local recurrence rate in the liver (11.2% vs. 21.4%, P = .032). But postoperative adjuvant TACE did not alter recurrence and survival outcomes in the wide-margin group. Similar results were noted after propensity score matching (PSM). The wide-margin resection had better RFS and OS than the narrow-margin resection for patients with HCC. Postoperative adjuvant TACE was associated with reduced recurrence and improved OS after narrow-margin resection, but was not effective in the wide-margin resection.

The aim of this study was to evaluate the clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC) with microscopic venous invasion. Data from 76 patients with HCC who underwent hepatectomy with or without postoperative adjuvant TACE between July 2005 and August 2010 were retrospectively reviewed. Kaplan-Meier method was used to compare survival between the groups and prognostic factors were evaluated by Cox proportional hazard model. The 1-, 3- and 5-year disease- free survival rates were 76.3%, 44.5% and 31.8%, respectively, for the adjuvant TACE group (35 patients) and 60.1%, 39.3% and 21.5%, respectively, for the control group (41 patients). The 1-, 3- and 5-year overall survival rates were 88.6%, 67.2% and 42.3%, respectively, for the TACE group and 77.5%, 58.0% and 40.5%, respectively, for the control group. Although improving trends of both disease-free survival and overall survival were observed in adjuvant TACE group, there was no significant difference between the two groups (p>0.05). Cox regression analysis revealed that tumor size and differentiation were significant independent prognostic factors. Postoperative adjuvant TACE may improve 1, 3 and 5 year disease-free and overall survival rates of HCC patients with microscopic venous invasion but no statistical significance was found. It can be used as a preventative treatment but not a routine procedure for such patients.

To evaluate the effect of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on the prognosis of hepatocellular carcinoma (HCC) patients with or without risk factors for the residual tumor. From January 1995 to December 1998, 549 consecutive HCC patients undergoing surgical resection were included in this research. There were 185 patients who underwent surgical resection with adjuvant TACE and 364 patients who underwent surgical resection only. Tumors with a diameter more than 5 cm, multiple nodules, and vascular invasion were defined as risk factors for residual tumor and used for patient stratification. Kaplan-Meier method was used to analyze survival curve and Cox proportional hazard model was used to evaluate the prognostic significance of adjuvant TACE. In the patients without any risk factors for the residual tumor, the 1-, 3-, 5-year survival rates were 93.48%, 75.85%, 62.39% in the control group and 97.39%, 70.37%, 50.85% in the adjuvant TACE group, respectively. There was no significant difference in the survival between two groups (P = 0.3956). However, in the patients with risk factors for residual tumor, postoperative adjuvant TACE significantly prolonged the patients' survival. There was a statistically significant difference in survival between two groups (P = 0.0216). The 1-, 3-, 5-year survival rates were 69.95%, 49.86%, 37.40% in the control group and 89.67%, 61.28%, 44.36% in the adjuvant TACE group, respectively. Cox proportional hazard model showed that tumor diameter and cirrhosis, but not the adjuvant TACE, were the significantly independent prognostic factors in the patients without risk factors for residual tumor. However, in the patients with risk factors for residual tumor adjuvant TACE, and also tumor diameter, AFP level, vascular invasion, were the significantly independent factors associated with the decreasing risk for patients' death from HCC. Postoperative adjuvant TACE can prolong the survival of patients with risk factors for residual tumor, but can not prolong the survival of patients without risk factors for residual tumor.

BackgroundHigh rates of postoperative tumor recurrence contribute to poor outcome in hepatocellular carcinoma (HCC). Here, we investigated whether circulating tumor cells (CTCs) status can predict the benefit of adjuvant transcatheter arterial chemoembolization (TACE) in patients with HCC.MethodsThe retrospective study enrolled 344 HCC patients with preoperative CTCs analysis. Clinical outcomes including recurrence and survival were compared between those who received and who did not receive adjuvant TACE. Similar comparisons were made for patients stratified according to CTC status (CTC‐negative [CTC = 0], n = 123; CTC‐positive [CTC ≥ 1], n = 221). Propensity score matching (PSM) strategy was adopted to offset differences between two groups.ResultsIn the study cohort as a whole or in CTC‐negative cohort, there were no observable differences in overall survival (OS) or time to recurrence (TTR) between TACE and control group (P > .05). In CTC‐positive patients, PSM generated 64 patient pairs, and patients with adjuvant TACE had significantly better clinical outcomes (OS: not reached vs 36.4 months, P < .001; TTR: 45.8 vs 9.8 months, P < .001). Adjuvant TACE significantly reduced early recurrence (≤2 years) (64.1% vs 31.7%, P < .001) in CTC‐positive patients. Notably, adjuvant TACE influenced TTR and OS even in subgroups of CTC‐positive patients with low risk of recurrence according to traditional evaluation.ConclusionsPreoperative CTC status could serve as an indicator for the administration of adjuvant TACE in HCC patients. Adjuvant TACE benefits CTC‐positive HCC patients mainly by reducing early recurrence.

The survival benefit of postoperative adjuvant transcatheter arterial chemoembolization (TACE) remains controversial. We aim to investigate the survival effect of postoperative adjuvant TACE on the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients (stage B, the Barcelona Clinic Liver Cancer staging). Sixty consecutive HBV-related HCC patients (stage B) from February 2006 to May 2009 undergoing surgical resection were included in this study. Of these 60 patients, 34 patients underwent surgery only (Group A) and 26 patients underwent surgery plus TACE (Group B). We followed-up until May 2013. Overall survival rates as well as prognostic factors were analyzed by the Kaplan-Meier method, the log-rank test or Cox's proportional hazard model. All patients' data were collected from the hospital medical records, which were described precisely after accurate clinical samples detection. The 1-, 2-, and 3-year overall survival rates in surgery-only group were 58.8, 32.4 and 12.6%, and the rates in surgery plus TACE group were 73.1, 61.5, and 48.9%, respectively (P = 0.033). The median survival time of the two groups after surgery and surgery plus TACE was 15.0 months [95% confidence interval (CI) 10.714-19.286] and 35.0 months (95% CI 20.974-49.026). In multivariate analysis, hemoglobin, HBeAg, peripheral blood regulatory T cells and tumor size were independent prognostic elements for HBV-related HCC patients (stage B). Postoperative adjuvant TACE improves the survival of patients with HBV-related HCC (stage B) after curative resection compared to surgery only.

Cytokine-induced killer (CIK) cells have high anti-tumor activity for hepatocellular carcinoma (HCC). Whether CIK cell therapy can eradicate residual cancer cells and prevent or postpone tumor relapse after transcatheter arterial chemoembolization (TACE) should be testified. This study was to evaluate the efficacy of CIK cell therapy combined with TACE on HCC. A total of 146 consecutive patients with unresectable HCC were divided into combination group (72 patients treated with CIK cell therapy combined with TACE) and TACE group (74 patients treated only with TACE). The progression-free survival (PFS) and overall survival (OS) were analyzed. The 6-month, 1-year, and 2-year PFS rates were 72.2%, 40.4%, 25.3% in combination group, and 34.8%, 7.7%, 2.6% in TACE group. The median time to progression was 11 months [95% confidence interval (CI), 8-14 months] in combination group and 5 months (95% CI, 4-7 months) in TACE group. The estimated 6-month, 1-year, and 2-year OS rates were 90.3%, 71.9%, 62.4% in combination group, and 74.6%, 42.8%, 18.8% in TACE group. The median OS was 31 months (95% CI, 27-35 months) in combination group and 10 months (95% CI, 7-13 months) in TACE group. The times of TACE, ECOG performance status, and CIK cell therapy were independent prognostic factors for PFS and OS. Adjuvant immunotherapy with CIK cells could greatly improve the efficacy of TACE on HCC, and plays an important role in prolonging the PFS and OS of HCC patients after TACE.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world. Transcatheter arterial chemoembolization (TACE) was commonly used for HCC patients postoperatively. However, the survival benefits of adjuvant TACE were controversial due to the extensive heterogeneity of HCC. Hence, there is a critical need to explore potential biomarkers that can predict the clinical response to TACE. The AMP-activated protein kinase (AMPK) is a highly conserved heterotrimeric serine/threonine kinase that plays a central role in linking metabolism and cancer development. In this study, we aimed at evaluating the association of pAMPKα (Thr172) status with clinical outcomes in HCC patients treated with or without postoperative adjuvant TACE.pAMPKα (Thr172) expression was assessed using immunohistochemical analysis in a cohort of 378 Chinese HCC patients who had undergone tumor resection. Kaplan–Meier analysis and multivariate Cox proportional hazards models were used to study the impact on clinical outcomes.High pAMPKα (Thr172) expression was associated with improved disease-free and overall survival and was an independent prognostic factor for overall survival by multivariate analysis. Furthermore, low pAMPKα (Thr172) expression level was correlated with high percentage of OV6+ tumor-initiating cells (T-ICs) in HCC specimens.To our knowledge, it can be demonstrated for the first time that pAMPKα (Thr172) status is associated with response to postoperative adjuvant TACE. High pAMPKα (Thr172) level in HCC may serve as a positive predictor of survival in HCC patients undergoing TACE.

BackgroundThe role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC.MethodsInformation for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected. Patients were divided into adjuvant TACE and observation groups according to whether they received adjuvant TACE or not. The recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after propensity score matching (PSM).ResultsOf the 225 patients enrolled, the median time of HCC recurrence was 11 months (IQR, 6–16 months). After repeated surgery or radiofrequency ablation (RFA) for recurrent tumors, 45 patients (20%) received adjuvant TACE while the remaining 180 (80%) didn’t. There were no significant differences in RFS (P = 0.325) and OS (P = 0.072) between adjuvant TACE and observation groups before PSM. There were also no significant differences in RFS (P = 0.897) and OS (P = 0.090) between the two groups after PSM. Multivariable analysis suggested that multiple tumors, liver cirrhosis, and RFA were independent risk factors for the re-recurrence of HCC.ConclusionAdjuvant TACE after repeated resection or ablation for early recurrent HCCs was not associated with a long-term survival benefit in this single-center cohort.

To develop a model for predicting the overall survival (OS) of hepatocellularcarcinoma (HCC) patients after transarterial chemoembolization (TACE) on the basis of multisequence MRI radiomic features and clinical variables. The DCE-MRI and clinical data of 116HCC patients treated with TACE for the first time were retrospectively analyzed. The included patients were randomly divided into training and validation cohorts at a ratio of 7:3. Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors that affect the OS of patients with HCC after TACE. Radiomic features were extracted from the sequences of FS-T2W images and arterial-phase (A) and portal venous-phase (P) axial DCE-MR images. The LASSO method was used to select the best radiomic features. Logistic regression was used to establish a radiomic model of each sequence, a joint model of MRI features (M model) combined the radiomic features of all the sequences, and a radiomic-clinical model (M-C model) that integrated the radiomic signatures and clinically independent predictors. The diagnostic performance of each model was evaluated as the area under the receiver operating characteristic (ROC) curve (AUC). The Child-Turcotte-Pugh (CTP) score and neutrophil-to-lymphocyte ratio (NLR) -platelet-to-lymphocyte ratio (PLR) were found to be independent risk factors that affect the OS of patients with HCC treated with TACE. The AUCs of the FS-T2WI, A, P, M, and M-C models for predicting the OS of HCC patients after TACE treatment were 0.779, 0.803, 0.745, 0.858 and 0.893, respectively, in the training group and 0.635, 0.651, 0.644, 0.778 and 0.803, respectively, in the validation group. The M-C model had the best predictive performance. Multiparameter MRI-based radiomic features may be helpful for predicting OS after TACE treatment in HCC patients. The inclusion of clinical indicators such as inflammation scores can improve the predictive performance.

Objective To observe the clinical curative effet and survival condition of sorafenib for patients with advanced hepatocellular carcinoma. Methods Sixty-six patients with hepatocellular carcinoma during January 2013 to January 2015 in Chang′an Hospital were included. All patients were randomly divided into transcatheter arterial chemoembolization (TACE) group (n=33) and sorafenib+ TACE group (n=33) according to the random digital table method. Followed up for 2 years, we observed the clinical curative effect, including 6-months survival rate, 1-year survival rate, the changes of serum alpha fetoprotein level before and after the treatment, survival time and related adverse reactions. Results The disease control rate of sora-fenib+ TACE group was 84.85% (28/33), which was significantly higher than that of TACE group (60.61%, 20/33), and the difference was statistically significant (χ2=4.889, P=0.027). The median survival time of patients with sorafenib+ TACE group was 20.30 months, which was longer than that of TACE group (12.50 months), and the difference was statistically significant (χ2=29.570, P=0.000). The 6-months and 1-year survival rates in patients with sorafenib+ TACE group were 93.93% and 75.76%, respectively, which were significantly higher than those of TACE group (84.85%, 51.52%). The rate of 1-year recurrence and metastasis of sorafenib+ TACE group was 21.21%, which was lower than that of TACE group (39.39%), and the difference was statistically significant (χ2=2.908, P=0.041). After 6 months treatment, the serum level of alpha fetoprotein in patients with sorafenib+ TACE group was (1 911.53±457.86)ng/ml, which was signi-ficantly lower than that of TACE group [(2 979.83±842.71)ng/ml], and the difference was statistically significant (t=11.996, P=0.001). The median survival time of patients with Child-Pugh A was significantly longer than that of patients with Child-Pugh B (20.50 months vs. 13.95 months), with a significant difference (χ2=3.973, P=0.046). Patients in sorafenib+ TACE group and TACE group had adverse reactions including nausea, vomiting and abnormal liver function, and there was significant difference in the incidence of untoward effects (87.88% vs. 60.61%; χ2=6.418, P=0.011). Conclusion The application of sorafenib the-rapy in the treatment of advanced hepatocellular carcinoma based on TACE can effectively improve the disease control rate, prolong the survival time of patients and improve the survival rate of patients. Key words: Carcinoma, hepatocellular; Drug therapy; Prognosis; Sorafenib

4580 Background: Surgical resection was the main treatment for hepatocellular carcinoma (HCC) in China. Multiple clinical studies had demonstrated that the overall survival (OS) of the surgical resection group was significantly better than the transcatheter arterial chemoembolization (TACE) or radiotherapy group even for HCC patients with BCLC stage B or C. There was no standard adjuvant therapy for HCC patients to decrease the post-operative tumor relapse. For HCC patients with high recurrence risk, TACE significantly reduced tumor recurrence, prolonged the disease free survival (DFS) and OS, and was recommended as the adjuvant therapy. However, its effect is not very satisfactory. The purpose of this study was to assess the efficacy and safety of lenvatinib in combination with TACE versus TACE alone as adjuvant therapy in HCC patients with high recurrence risk after resection. Methods: This is a muti-center prospective cohort study. The criteria of HCC patients with high postoperative recurrence risk included: accompanied with gross vascular or bile duct invasion (tumor thrombi in portal vein, hepatic vein or bile duct); or tumor rupture or invasion of adjacent organs; or grade 2 of microvascular invasion (MVI) (M2) along with the tumor number more than 3 or the maximum diameter of tumor larger than 8cm or tumor showed invasive growth with unclear boundaries and imcomplete capsules. The patients were divided into two groups, the lenvatinb (8mg qd for weights &lt; 60kg and 12mg qd for weights≥60kg) in combination with TACE (Len+TACE) group and the TACE group. Results: A total of 90 patients were enrolled into the study, while 45 patients in the Len+TACE group and 45 in TACE group. The media age was 52 years (range from 23 to 73 years). Most patients were males (82.2%) and 66 patients had HBV background (73.3%). There were no significant differences between the two groups in the baseline clinicopathological characteristics including gender, age, HBV background, liver cirrhosis, liver function, tumor characteristic and AFP level. The media DFS was 12.0 months (95% CI 8.0-NA) in the Len+ TACE group, which was longer than that of TACE group (8.0 months, 95% CI 6.0-12.0, P = 0.0359; HR 0.5, 95% CI 0.3-1.0). The most common grade 3 or 4 adverse events were hypertension (11.1%) and diarrhea (7.7%) in the Len+TACE group. Conclusions: Lenvatinib in combination with TACE was effective and safe as adjuvant therapy, which can prolong the DFS of HCC patients with high recurrence risk after resection. Clinical trial information: NCT03838796 .