Recurrent hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI)-positive primary tumor is at high risk of re-recurrence while treated with radiofrequency ablation (RFA). We aimed to investigate whether neoadjuvant conventional transarterial chemoembolization (cTACE) was effective in reducing re-recurrence after RFA for recurrent HCC patients with MVI-positive primary tumors.

In this retrospective multicenter study, 468 patients with solitary small recurrent HCC (≤3.0cm) underwent RFA alone (n = 322) or with neoadjuvant cTACE (n = 146) between June 2007 and December 2017 were included. Overall survival (OS) and recurrence-free survival (RFS) were compared.

The 1-, 5-year OS rates were 74.8%, 42.5% for RFA with neoadjuvant cTACE group, and 53.5%, 28.7% for RFA group (P < 0.001). The corresponding RFS rates were 51.7%, 24.4% for RFA with neoadjuvant cTACE group, and 36.1%, 9.3% for RFA group (P < 0.001). In subgroup analyses, the OS and RFS for neoadjuvant cTACE group were longer than those for RFA group no matter tumor size > 2cm (HR = 0.52, 95% CI: 0.36-0.77; HR = 0.49, 95% CI: 0.36-0.67) or not (HR = 0.53, 95% CI: 0.32-0.88; HR = 0.65, 95% CI: 0.42-0.98), or the time interval of recurrence from initial treatment ≤ 1 year (HR = 0.53, 95% CI: 0.36-0.77; HR = 0.70, 95% CI: 0.52-0.94) or not (HR = 0.56, 95% CI: 0.34-0.95; HR = 0.39, 95% CI: 0.25-0.62). Multivariable analyses showed that RFA alone (HR = 1.329, P = 0.031; HR = 1.764, P = 0.004) and interval of recurrence from initial treatment > 1 year(HR = 0.642, P = 0.001; HR = 0.298, P = 0.037) were independent prognostic factors of OS and RFS.

Neoadjuvant cTACE could effectively reduce re-recurrence after RFA, and improve the long-term survivals for patients with solitary small recurrent HCC whose primary tumor was MVI-positive. Key pointsFor recurrent hepatocellular carcinoma (HCC) patients whose primary tumor was positive for microvascular invasion, neoadjuvant conventional transarterial chemoembolization (cTACE) with radiofrequency ablation (RFA) achieved better efficacy.Multivariable analyses showed that the interval of recurrence from initial treatment > 1 year and RFA alone were independent prognostic factors of overall survival and recurrence-free survival, respectively.

Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.

Although adjuvant transcatheter arterial chemoembolization (TACE) has been used to prevent recurrence after surgery in patients with hepatocellular carcinoma (HCC), the survival benefits from adjuvant TACE remain controversial. We sought to systematically evaluate the data on the effectiveness of adjuvant TACE for HCC, as well as identify patient populations that might benefit from adjuvant TACE.

The PubMed, Embase, Medline and Cochrane library were systematically searched for studies published before July 2019 that compared adjuvant TACE versus surgery alone for HCC. The study endpoints were overall survival (OS) and disease-free survival (DFS). Patients with large HCC (⩾5 cm), multinodular HCC, microvascular invasion (MVI), or portal vein tumor thrombosis (PVTT) were analyzed in subgroup analyses.

Twenty-four studies with 6977 patients were included in the analytic cohort. The pooled analysis demonstrated that adjuvant TACE was associated with a better OS and DFS [hazard ratio (HR): 0.67 and 0.67, both p < 0.01]. In subgroup analyses, pooled results revealed that adjuvant TACE was associated with an improved OS and DFS in patients with multinodular HCC (HR: 0.79 and 0.31, both p < 0.01), MVI (HR: 0.62 and 0.67, both p < 0.01), or PVTT (HR: 0.49 and 0.58, both p < 0.01), but not among patients with large HCC (⩾5 cm).

Postoperative adjuvant TACE may be effective to improve OS and DFS in patients with multinodular HCC, or HCC with MVI or PVTT. Future randomized controlled trials are needed to better define the benefit of adjuvant TACE in subset patients with HCC.

Hepatocellular carcinoma (HCC) has a recurrence rate of up to 70% in 5 years after resection, detrimentally lowering survival. The role of adjuvant therapy remains controversial; therefore, the aim of this study was to evaluate the disease-free and overall survival of patients with HCC, not candidates for transplantation, undergoing resection and adjuvant hepatic artery infusion therapy vs resection alone. Our meta-analysis showed that adjuvant HAIC improves overall and disease-free survival after resection, especially in tumors ≥7 cm.

Purpose: 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.Experimental Design: In this randomized phase 3 trial, 280 eligible patients were assigned to adjuvant TACE (n = 140) or no adjuvant treatment (control; n = 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.Results: Patients who received adjuvant TACE had a significantly longer RFS than those in the control group [56.0% vs. 42.1%, P = 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%; P = 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; P = 0.01 for RFS; and HR, 0.59; P = 0.04 for OS). There was no grade 3 or 4 toxicity after adjuvant TACE.Conclusions: 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. Clin Cancer Res; 24(9); 2074-81. ©2018 AACR.

Hepatocellular carcinoma (HCC) has high recurrence rate after curative treatment. The aim of the present study was to report our experience with adjuvant use of ¹³¹I-lipiodol after curative treatment of HCC in terms of recurrence and survival in a large cohort of patients with a long follow-up.

All patients treated with ¹³¹I-lipiodol after curative treatment of HCC in two French centers from 1991 to 2009 were included in a retrospective cohort study.

One hundred and six patients were included. The median (range) follow-up was 6 years (0.3-22). Forty-three patients (41%) had cirrhosis. Recurrence-free survival rates at 1, 2, 5, 10, and 20 years were 73, 57, 40, 30, and 14%, respectively. Cirrhosis was an independent predictive factor of recurrence [RR = 1.18, 95% CI (1.11-3.02), p = 0.019]. Overall, survival rates at 1, 2, 5, 10, and 20 years were 90, 83, 59, 37, and 23%, respectively. Prognostic factors were recurrence [RR = 2.73, 95% CI (1.35-5.54); p = 0.005], age over 60 years (RR = 1.91, 95% CI [1.02-3.61]; p = 0.044), and tumor number over 3 [RR = 3.31, 95% CI (1.25-8.77); p = 0.016].

Our results suggest that the effect of ¹³¹I-lipiodol after curative treatment of HCC could be related to a beneficial impact on risk factors of early tumor recurrence. This could be evaluated in further studies using modern radioembolization methods.

Randomised controlled trials (RCTs) with sufficiently high statistical power are not always feasible for patients when the administration of the treatment is burdensome. Nevertheless, useful information concerning the relative effectiveness of the Test and Standard therapies, may be gleaned from under powered trials, non-randomised comparative studies and/or clinician's beliefs: the latter possibly additionally providing some suggestion of the strength of evidence required in order to adopt the Test therapy into clinical practice. In such circumstances, a Bayesian synthesis may be useful in quantifying the evidence of treatment effectiveness. In this article, we aim to present a Bayesian approach for synthesizing the cumulative evidence of the use of adjuvant hepatic intra-arterial iodine-131-lipiodol (I131L) following curative resection in hepatocellular carcinoma (HCC) patients. We constructed a posterior distribution using the information from two small RCTs, three non-randomised comparative studies, three single arm studies and the views of investigators on the use of I131L. This distribution enables calculation of the probability that the Test therapy is more effective than the Standard by a pre-stipulated amount. If this is very high, then for example, one may conclude the Test may replace the Standard therapy. If it is not, then the Standard would be retained for clinical use. Despite a strong early indication of the effectiveness of I131L, the evolving evidence over a 10-year period became more sceptical of its value. Although highly recommended, difficulties of implementing a Bayesian approach in this context are highlighted.

High incidence of intrahepatic recurrence is a major surgical limitation following hepatectomy of hepatocellular carcinoma (HCC). This study was intended to investigate the effects of adjuvant intrahepatic injection of iodine-131-lipiodol on disease recurrence and survival in patients with HCC who underwent resection. A computerized literature search was performed to identify relevant articles. Data synthesis was performed using Review Manager 5.0 software, and results are presented as odds ratio (OR) with 95 % confidence intervals. Two randomized controlled trials and three case-control studies with a total of 334 participants were analyzed. Iodine-131-lipiodol treatment achieved significantly lower rates of intrahepatic recurrence (OR = 0.48, 95 % confidence interval (95 % CI) = 0.30-0.74; P = 0.001) and early recurrence (<2 year) (OR = 0.45, 95 % CI = 0.23-0.89; P = 0.02). Likewise, iodine-131-lipiodol treatment improved both the 5-year disease-free survival and overall survival significantly (OR = 1.85, 95 % CI = 1.13-3.03; P = 0.01; OR = 2.00, 95 % CI = 0.99-4.04; P = 0.05, respectively). Adjuvant intrahepatic injection of iodine-131-lipiodol resulted in a preventive effect on recurrence and improved survival after resection of HCC. Further larger, multi-centred, randomized prospective trial is warranted.

The recurrence rate of hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR) is very high. Many clinical trials have explored the efficacy of several treatment modalities to prevent recurrence, including adjuvant and chemopreventive therapy, but they have often reported contradictory findings. As a result, most liver guidelines and liver seminars do not unequivocally endorse adjuvant or chemopreventive therapy for HCC patients after potentially curative HR. To examine the available evidence on this question, we comprehensively searched PubMed for controlled studies that included a supportive care or placebo control arm, and we used the GRADE system to classify and assess the results.

Prognostic factors of postoperative early and late recurrence in patients with hepatocellular carcinoma (HCC) undergoing curative resection remain to be clarified. The aim of this study was to identify risk factors for postoperative early (≤ 2 year) and late (> 2 year) intrahepatic recurrences in patients with single HCCs without macrovascular invasion.

A total of 280 patients from December 2004 to December 2007 were retrospectively included in this study. Intrahepatic recurrence was classified into early (≤ 2 year) and late (> 2 year) and the Chi-Square test or Fisher's exact test and multivariate logistic regression analysis were performed to determine significant risk factors.

During the follow-up, 124 patients had intrahepatic recurrence, early and late in 82 and 42 patients, respectively. Multivariate logistic regression analysis showed that microvascular invasion (p=0.006, HR: 2.397, 95% CI: 1.290-4.451) was the only independent risk factor for early recurrence, while being female (p = 0.031, HR: 0.326, 95% CI: 0.118-0.901), and having a high degree of cirrhosis (P=0.001, HR: 2.483, 95% CI: 1.417-4.349) were independent risk factors for late recurrence.

Early and late recurrence of HCC is linked to different risk factors in patients with single HCC without macrovascular invasion. This results suggested different emphases of strategies for prevent of recurrence after curative resection, more active intervention including adjuvant therapy, anti-cirrhosis drugs and careful follow-up being necessary for patients with relevant risk factors.

The prevention of tumor recurrence after curative treatment of hepatocellular carcinoma (HCC) is unresolved. Postoperative intraarterial injection of (131)I-labeled lipiodol has been proposed as adjuvant treatment. The aim of this prospective randomized trial was to evaluate if a single dose of postoperative adjuvant intraarterial (131)I-lipiodol (vs. unlabeled lipiodol) could reduce the rate of intrahepatic recurrence at 2 y.

Patients who underwent curative treatment for HCC and recovered within 6 wk were randomly assigned to receive a single 2,200-MBq (131)I-lipiodol dose or a single unlabeled lipiodol dose on a 1:1 basis. Recurrence-free and overall survival rates were analyzed.

Between June 2005 and February 2009, we included 58 patients (median age of 63 y [range, 23-85 y]): 29 received intraarterial (131)I-lipiodol and 29 received lipiodol adjuvant treatment. At 2 y after treatment, the rate of patients with intrahepatic recurrence was 28% in the (131)I-lipiodol group and 56% in the lipiodol group (P = 0.0449). The Kaplan-Meier analysis confirmed this result, with a 2-y recurrence-free survival in the (131)I-lipiodol and lipiodol groups of 73% and 45%, respectively (P = 0.0259). The 5-y recurrence-free survival rates in the (131)I-lipiodol and lipiodol groups were 40% and 0%, respectively (P = 0.0184). The overall and specific survivals were not significantly different between groups (P = 0.9378 and P = 0.1339, respectively). (131)I-lipiodol had no severe toxic effects.

After curative treatment of patients with HCC, one 2,200-MBq dose of intraarterial (131)I-lipiodol significantly decreased the rate of intrahepatic recurrence but failed to improve overall or specific survival.

Although radiotherapy (RT) provides potential benefits for patients with hepatocellular carcinomas (HCCs) that are unsuitable for operation, the specific role of adjuvant RT in HCC after hepatectomy remains ill defined. The current study's aim was to evaluate the safety and efficacy of adjuvant RT for centrally located HCCs after narrow-margin (<1 cm) hepatectomy.

The study included 119 patients with centrally located HCCs who underwent narrow-margin hepatectomy between July 2007 and March 2012. Patients were prospectively randomized to receive adjuvant RT (n = 58) or were assigned to a control group (n = 61). Surgical outcomes, safety, and survival rates were evaluated.

Hepatectomy was successfully performed in all patients. No cases of radiation-induced liver disease were observed. One-, 3-, and 5-year recurrence-free survival rates were 78.1%, 56.5%, and 36.9% in the adjuvant RT group and 72.4%, 40.1%, and 16.0% in the control group, respectively (p = 0.06, log-rank test). Corresponding overall survival rates were 96.2%, 72.6%, 48.4%, and 89.6%, 74.5%, 37.2%, respectively (p = 0.48, log-rank test). One-, 3-, and 5-year recurrence-free survival rates in patients with small-diameter tumors (≤5 cm) were 88.8%, 67.4%, 42.9% in the adjuvant RT group and 82.3%, 42.9%, 21.5% in the control group (p = 0.03, log-rank test). Corresponding overall survival rates were 97.5%, 75.3%, 75.3%, and 94.7%, 84.1%, 65.4%, respectively (p = 0.92, log-rank test).

Adjuvant RT for centrally located HCCs after narrow-margin hepatectomy was technically feasible and relatively safe. No significant between-group difference was observed in recurrence-free and overall survival. The post-hoc subgroup comparison showed that adjuvant RT improved recurrence-free survival considerably, but not overall survival, in patients with small HCCs (≤5 cm). More in-depth studies are needed to validate this finding.