Presence of hepatic vein tumor thrombosis (HVTT) in patients with hepatocellular carcinoma (HCC) is regarded as signaling an extremely poor prognosis. However, little is known about the prognostic impact of surgical treatment for HVTT.Our database of surgical resection for HCC between October 1994 and December 2011 in a tertiary care Japanese hospital was retrospectively analysed. We statistically compared the patient characteristics and surgical outcomes in HCC patients with tumor thrombosis in a peripheral hepatic vein, including microscopic invasion (pHVTT), tumor thrombosis in a major hepatic vein (mHVTT), and tumor thrombosis of the inferior vena cava (IVCTT). Among 1525 hepatic resections, 153 cases of pHVTT, 21 cases of mHVTT, and 13 cases of IVCTT were identified.The median survival time (MST) in the pHVTT and mHVTT groups was 5.27 and 3.95 years, respectively (p=0.77), and the median time to recurrence (TTR) was 1.06 and 0.41 years, respectively (p=0.74). On the other hand, the MST and TTR in the patient group with IVCTT were 1.39 years and 0.25 year respectively; furthermore, the MST of Child-Pugh class B patients was significantly worse (2.39 vs. 0.44 years, p=0.0001). Multivariate analyses revealed IVCTT (risk ratio [RR] 2.54, p=0.024) and R 1/2 resection (RR 2.08, p=0.017) as risk factors for the overall survival.Hepatic resection provided acceptable outcomes in HCC patients with mHVTT or pHVTT when R0 resection was feasible. Resection of HCC may be attempted even in patients with IVCTT, in the presence of good liver function.Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

This article is the first of a series providing guidance for use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system of rating quality of evidence and grading strength of recommendations in systematic reviews, health technology assessments (HTAs), and clinical practice guidelines addressing alternative management options. The GRADE process begins with asking an explicit question, including specification of all important outcomes. After the evidence is collected and summarized, GRADE provides explicit criteria for rating the quality of evidence that include study design, risk of bias, imprecision, inconsistency, indirectness, and magnitude of effect. Recommendations are characterized as strong or weak (alternative terms conditional or discretionary) according to the quality of the supporting evidence and the balance between desirable and undesirable consequences of the alternative management options. GRADE suggests summarizing evidence in succinct, transparent, and informative summary of findings tables that show the quality of evidence and the magnitude of relative and absolute effects for each important outcome and/or as evidence profiles that provide, in addition, detailed information about the reason for the quality of evidence rating. Subsequent articles in this series will address GRADE's approach to formulating questions, assessing quality of evidence, and developing recommendations.Copyright © 2011 Elsevier Inc. All rights reserved.

To retrospectively evaluate the prevalence of extrahepatic collateral artery supply to tumor thrombi of hepatocellular carcinomas (HCCs) invading the inferior vena cava (IVC) and to assess the determining factors.From February 1998 to June 2007, 82 patients with IVC tumor thrombi on computed tomography (CT) underwent angiographic evaluation of their extrahepatic collateral artery supply. Potential determining factors for extrahepatic collateral artery supply to the IVC tumor thrombi included sex, age, Child-Pugh class, history of chemoembolization, tumor factors (ie, size, number, and growth pattern), distance from primary tumor to IVC thrombi, portal vein invasion, and extent of IVC thrombi (ie, occupying more than half the IVC lumen on transverse CT image, completely filling and distending IVC lumen, or extending into the right atrium). Univariate analysis and multiple logistic regression analysis were performed.Fifty-four of the 82 patients (65.9%) had extrahepatic collateral artery supply: 47 from the right inferior phrenic artery, four from the right adrenal artery, two from the right internal mammary artery, and one from the right renal artery. The presence of extrahepatic collateral artery supply to IVC tumor thrombi showed a significant relationship with a history of chemoembolization (P =.001, odds ratio [OR] = 22.4) and distension of IVC by tumor thrombi (P =.005, OR = 9.1).IVC tumor thrombi of HCCs are frequently supplied by extrahepatic collateral arteries, the most common of which is the right inferior phrenic artery. The significant determining factors are a history of chemoembolization and the extent of IVC tumor thrombi.

Because of the rarity of hepatic vein tumor thrombus (HVTT) compared with portal vein tumor thrombus (PVTT) in patients with hepatocellular carcinoma, little is known about this disease entity. The aim of this study was to evaluate the prognosis of each treatment modality for HVTT through an analysis of data collected in a Japanese nationwide survey. We analyzed data for 1,021 Child-Pugh A hepatocellular carcinoma patients with HVTT without inferior vena cava invasion registered between 2000 and 2007. Of these patients, 540 who underwent liver resection (LR) and 481 who received other treatments were compared. Propensity scores were calculated, and we successfully matched 223 patients (49.0% of the LR group). The median survival time in the LR group was 2.89 years longer than that in the non-LR group (4.47 versus 1.58 years, P < 0.001) and 1.61 years longer than that in the non-LR group (3.42 versus 1.81 years, P = 0.023) in a propensity score-matched cohort. After curative resection, median survival times were similar between patients with HVTT in the peripheral hepatic vein and those with HVTT in the major hepatic vein (4.85 versus 4.67 years, P = 0.974). In the LR group, the postoperative 90-day mortality rate was 3.4% (16 patients). In patients without PVTT, the median survival time was significantly better than that in patients with PVTT (5.67 versus 1.88 years, P < 0.001).LR is associated with a good prognosis in hepatocellular carcinoma patients with HVTT, especially in patients without PVTT. (Hepatology 2017;66:510-517).© 2017 by the American Association for the Study of Liver Diseases.

The significance of surgery in the treatment of hepatocellular carcinoma (HCC) extending into the inferior vena cava (IVC)/right atrium (RA) is currently unclear. We sought to clarify whether surgical treatment can improve survival in such patients.A retrospective review was undertaken of patients with HCC and IVC/RA tumor thrombus who were potential candidates for surgery but who were finally treated surgically and nonsurgically between September 2000 and October 2010. The patients were subdivided according to therapeutic modalities, and the results for each group were compared.A total of 56 patients were included in this study. They were divided into three groups. Twenty-five patients underwent hepatectomy plus thrombectomy (surgical group), with minor morbidity and no mortality; the patients in this group had 1-, 3-, and 5-year survival rates of 68.0, 22.5, and 13.5%, respectively, with a median survival of 19 months. Twenty patients were treated with transcatheter arterial chemoembolization, with 1- and 3-year survival rates of 15.0 and 5.0%, respectively (median survival 4.5 months). Eleven patients received symptomatic treatment only, and no one in this group survived longer than 1 year (median survival 5 months). The patients in surgical group survived significantly longer than the patients in the other two groups (p < 0.001).Although technically challenging, surgery for HCC with IVC/RA tumor thrombus can be safely performed and should be considered in patients with resectable primary tumor and sufficient hepatic reservoir because compared with transcatheter arterial chemoembolization or symptomatic treatment, it significantly improved patient survival.

An effective therapeutic option has not yet been established for hepatocellular carcinoma (HCC) invading the hepatic vein (HV) or inferior vena cava (IVC). This study aimed to determine the therapeutic effect of transarterial chemoembolization (TACE) in HCC patients with HV or IVC invasion, and to build a risk prediction model.Data from patients who underwent TACE as a first-line treatment for HCC invading the HV or IVC between 1997 and 2019 were retrospectively evaluated.Data from 296 patients were included (1997-2006 comprised the training cohort, n = 174; 2007-2019 comprised the validation cohort, n = 122). The median post-TACE survival was 7.3 months and an objective tumor response was achieved in 34.1% of patients. Multivariable Cox analysis of the training cohort identified five pretreatment factors (maximal tumor size > 10 cm, infiltrative HCC, combined portal vein invasion, extrahepatic metastasis, and ECOG performance status 1), which were used to create predictive models for overall survival. Median overall survival times in the validation cohort were 14 and 4.2 months for the low (sum of risk score: 0-3)- and high-risk (sum of risk score: 4-7) groups, respectively (p < 0.001). Time-dependent ROC curves for the predictive models for overall survival applied to the validation cohort showed acceptable AUC values (0.723 and 0.667 at 6 months and 1 year).TACE seems effective for selected patients with HCC invading the HV or IVC. The predictive model may help to identify candidates most likely to benefit from TACE.• To develop a risk prediction model for patients with HCC with HV or IVC invasion treated with TACE, five factors were selected from a multivariate Cox regression model for overall survival. • The combination of these factors helped to identify two prognostic categories: low- and high-risk. • The predictive model can help to select candidates who will benefit most from TACE in this patient group.

Systemic therapy such as sorafenib is the standard for Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC); however, the survival benefits are modest especially for HCC with macroscopic vascular invasion (MVI). Transarterial chemoembolization (TACE) plus external beam radiotherapy (RT) is an alternative treatment to sorafenib, with favorable clinical results. We evaluated the outcomes of respiratory-gated RT and TACE in treatment-naïve BCLC stage C HCC patients with MVI and proposed a subclassification model.In this study, 639 patients received TACE plus RT for HCC with MVI as a first-line treatment between January 2010 and December 2015.Main/bilateral portal vein and/or inferior vena cava tumor thrombus was observed in 353 (55.2%) patients. The median radiation dose was 39 Gy (range 24-50) with a 2.5-Gy (2-5) median fraction size. The median overall survival was 10.7 months, with 1- and 2-year survival rates of 46.5% and 23.9%, respectively. In the multivariate analysis, Child-Pugh classification B, tumor size >10 cm, infiltrative/diffuse type, presence of extrahepatic metastasis, alpha-fetoprotein >150,000 ng/mL, and radiation dose ≤40 Gy were significant predictors for poor overall survival. Subclassification of patients into very low, low, intermediate, and high-risk groups showed median survivals of 84.8, 14.7, 10.3, and 5.7 months, respectively (p < 0.001).TACE plus RT is an effective and safe treatment for HCC with MVI and could be considered a first-line treatment option. The subclassification scheme accurately predicted the prognosis of these patients and may be useful for tailored treatment.Copyright © 2019 Elsevier B.V. All rights reserved.

To validate the safety and effectiveness of transarterial chemoembolization (TACE) combination with lenvatinib and sintilimab in treating hepatocellular carcinoma (HCC) patients with inferior vena cava (IVC) and/or right atrium (RA) tumor thrombosis (TT).This study retrospectively analyzed HCC patients with IVC and/or RA TT treated with TACE combined with lenvatinib plus sintilimab. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were calculated to evaluate the anti-tumor efficacy. Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles.A total of 58 patients were screened for eligibility between March 2019 and May 2022. At the time of data collection, 48.2% of patients were still receiving treatment. The median follow-up was 23.5 months. The ORR was 48.3%, the DCR was 91.4%, the median OS was 17.3 months, and the median PFS was 13.0 months. The ORR for IVC/RA TT was 62.1%, DCR was 94.9%, and the median PFS was 14.3 months. 56.9% of patients experienced ≥ grade 3 TRAEs, such as hypertension (10.3%) and elevated liver enzymes (13.8%). No new safety signals were identified. Participants with low levels of serum PCT value had satisfactory prognoses.TACE combination with lenvatinib plus sintilimab is effective in treating HCC with IVC and/or RA TT. The toxicities were manageable, with no unexpected safety signals. The baseline levels of serum PCT might be the predictive biomarkers for the triple combination therapy.© 2023 Ning et al.

This study aims to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) with inferior vena cava/right atrium tumor thrombus (IVC/RATT) treated with lenvatinib and camrelizumab.HCC with IVC/RATT from four hospitals were enrolled in this retrospective study. The patients were divided into RT group and TACE group. Stabilized inverse probability of treatment weighting (sIPTW) was used to minimize bias. The primary endpoints were overall survival (OS) and progression free survival (PFS). The second endpoints were objective response rate (ORR) and disease control rate (DCR). In addition, safety was assessed by treatment-related adverse events (TRAEs) between the two groups.Among 108 patients included in this study, 48 patients in TACE group and 60 patients in RT group. The median follow-up time was 24.8 months. After the application of sIPTW, baseline characteristics were well-balanced between the two groups. Before and after sITPW, the median OS and median PFS in the RT group were significantly longer than in the TACE group. Multivariate Cox analysis showed that RT was an independent prognosis factor of both OS and PFS. There was no significant difference between two groups in overall response, while IVC/RATT response rate of RT group was significantly higher than TACE group. Incidence rate of TRAEs in two groups were similar.In combination with lenvatinib and camrelizumab, RT significantly improves the prognosis of HCC with IVC/RATT compared to TACE, with a comparable safety profile.© 2025. Asian Pacific Association for the Study of the Liver.

Hepatocellular carcinoma with inferior vena cava and/or right atrium tumor thrombus (HCC-IVC/RATT) has a poor prognosis and lacks evidence for standard first-line systemic therapy. This study aims to evaluate the effectiveness and safety of three therapeutic regimens in HCC-IVC/RATT: immune checkpoint inhibitors plus molecular-targeted agents (ICI-MTA), hepatic arterial infusion chemotherapy (HAIC), and their combination (ICI-MTA-HAIC).This multicenter retrospective cohort study included consecutive HCC-IVC/RATT who received ICI-MTA-HAIC, ICI-MTA, or HAIC from June 2015 to December 2023. Propensity score matching (PSM) was used to balance baseline characteristics.A total of 355 patients were included: 209 received ICI-MTA-HAIC, 66 received ICI-MTA, and 80 received HAIC. After PSM, the ICI-MTA-HAIC group showed superior median overall survival (OS) to both the ICI-MTA (18.0 vs. 7.5 months, p < 0.001) and HAIC (18.5 vs. 7.1 months, p < 0.001) groups. The ICI-MTA-HAIC group demonstrated better median progression-free survival (PFS) and objective response rate (ORR) compared to the ICI-MTA (PFS: 9.5 vs. 4.4 months; ORR: 47.0% vs. 21.3%, all p < 0.001) and HAIC (PFS: 9.5 vs. 4.4 months; ORR: 48.8% vs. 21.6%, all p < 0.001) groups. There was no significant difference in OS, PFS, or ORR between the ICI-MTA and HAIC groups (all p > 0.05). Grade 3-4 adverse event rates were 49.8%, 33.3%, and 35.0% for the ICI-MTA-HAIC, ICI-MTA, and HAIC groups, respectively. No unexpected events or treatment-related deaths were observed.ICI-MTA-HAIC was a safe and effective therapy that prolonged the survival of HCC-IVC/RATT compared to ICI-MTA or HAIC.© 2025. Asian Pacific Association for the Study of the Liver.

Both surgery and external‐beam radiotherapy are effective treatments for hepatocellular carcinoma (HCC) patients with inferior vena cava/right atrium (IVC/RA) tumor thrombi. At present, it is not clear which modality is more suitable. We therefore compared outcomes between surgery and radiotherapy for these patients.

Recurrent hepatocellular carcinoma (HCC) with a tumor thrombus (TT) extending into the inferior vena cava (IVC)/right atrium (RA) is generally regarded as a terminal-stage condition and there is no worldwide consensus on the proper management of this situation. In the present study, we report the efficacy of hypofractionated radiotherapy (HFRT) as a salvage treatment for recurrent HCC with IVC/RA TT.We retrospectively reviewed 75 HCC patients with an IVC/RA TT who were referred for HFRT at three institutions between 2008 and 2016. 57 cases had a TT located in the IVC (IVC group), and 18 cases had a TT located in the IVC and RA (IVC + RA group). HFRT was designed to focus on the TT with or without the primary intrahepatic tumors.In all cases, the TT completely disappeared (CR) in 17 patients (22.7%), 55 patients (73.3%) had a partial response (PR), and 3 patients (4.0%) had a stable disease (SD). There were no cases of progressive disease (PD). The 1-, 2-, and 3-year overall survival rates of the 75 patients were 38.7% (29/75), 13.3% (10/75) and 5.3% (4/75), respectively. The overall median survival time was 10 months. The mean survival times for the IVC group and IVC+ RA group were 13.8 ± 1.1 and 11.6 ± 2.5 months, respectively. There was no significant difference in survival between the two groups (p = 0.205). Log-rank test revealed that factors predicting poor survival were Child-Pugh B liver function classification, AFP ≥ 400 μg/L, intrahepatic multiple tumors, distant metastases, only the TT as the target, a biological effective dose (BED) < 55 Gy and no chance of further radiotherapy.HFRT appears to be an effective and reasonable treatment option for recurrent HCC patients with IVC/RA TT. The location of the tumor thrombus, either in IVC or in IVC and RA, is not the factor that influences the efficacy of radiotherapy or survival.

This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies.Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30-65 Gy for planning target volume and 40-65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded.Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level >1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588-20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027-0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up.Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.© 2024 Li et al.

Unresectable hepatocellular carcinoma has a high frequency of vascular invasion and arterial parasitization. Trans-arterial radioembolization using yttrium-90 (Y90) microspheres is a possible treatment option. Paramount to its success is the meticulous angiographic interrogation of tumor feeding arteries and extra-hepatic supply. We describe a patient with tumor invasion of the inferior vena cava with arterial supply from the right inferior phrenic artery, which was exquisitely visualized using intra-arterial computed tomographic angiography (IACTA) during the planning technetium-99m macro aggregated albumin phase. This technique was useful in planning which artery to administer Y90 microspheres into for maximal brachytherapy. Although patient outcome was poor due to significant arterio-portal shunting, we believe that IACTA is a useful adjunct to conventional digital subtraction angiography in planning radioembolization therapy.

Because of the rarity of hepatic vein tumor thrombus (HVTT) in patients with hepatocellular carcinoma (HCC), little is known about HVTT. Thus, the survival benefit of liver resection (LR) versus transcatheter arterial chemoembolization (TACE) for HCC patients with HVTT or inferior vena cava tumor thrombus (IVCTT) remains controversial. We aimed to explore the survival benefits of LR versus TACE for the treatment of these patients.

To clarify the short- and long-term postoperative outcomes and surgical indications for patients accompanied by hepatocellular carcinoma (HCC) with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA).These patients are known to have an extremely poor prognosis; however, the postoperative outcomes have not been fully verified because of the rarity of this disease.We contacted 211 specialized centers in Japan and collected data on liver resection for HCC with TT in the IVC or RA from centers with experience performing surgery for such patients. The patient characteristics, operative procedures, and surgical outcomes were then analyzed.A total of 119 patients from 23 institutions were enrolled; 49 patients had TT in the IVC below the diaphragm (type I), 42 had TT in the IVC above the diaphragm (type II), and 28 had TT entering the RA (type III). The severity and frequency of postoperative complications did not differ among the three groups. There was one surgery-related death in the type III group. The median survival times were 2.47 years in the type I group, 1.77 years in the type II group, and 1.02 years in the type III group. A multivariate analysis identified an indocyanine green retention rate at 15 min >15% and ≥3 tumors as prognostic factors affecting survival, while the use of cardiopulmonary bypass and ≥3 tumors were risk factors for recurrence.As the postoperative prognosis of patients with type I or type II disease and of patients with no risk factors is relatively good, surgery should be considered for these patient populations.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Background: The prognosis for advanced hepatocellular carcinoma (HCC) with tumor thrombi in the inferior vena cava (IVC) or right atrium (RA) is poor, and there is no established effective treatment for this condition. Thus study aimed to evaluate the efficacy of surgical resection and prognosis after surgery for such cases.;Methods: Between January 1990 and December 2012, 891 patients underwent hepatectomy for HCC at our institution. Of these, 13 patients (1.5%) diagnosed with advanced HCC with tumor thrombi in the IVC or RA underwent hepatectomy and thrombectomy. Data detailing the surgical outcome were evaluated and recurrence-free and overall survival rates were calculated using the Kaplan-Meier method.;Results: Seven patients had an IVC thrombus and six had an RA thrombus. Extra-hepatic metastasis was diagnosed in 8 of 13 patients. Surgical procedures included three extended right lobectomies, three extended left lobectomies, five right lobectomies, and two sectionectomies. Right adrenal gland metastases were excised simultaneously in two patients. All IVC thrombi were removed under hepatic vascular exclusion and all RA thrombi were removed under cardiopulmonary bypass (CPB). Four patients (30.8%) experienced controllable postoperative complications, and there was no surgical mortality. The mean postoperative hospital stay for patients with IVC and RA thrombi was 23.6 +/- 12.5 days and 21.2 +/- 4.6 days, respectively. Curative resection was performed in 5 of 13 cases. The 1- and 3-year overall survival rates were 50.4%, and 21.0%, respectively, and the median survival duration was 15.3 months. The 1- and 3-year overall survival rates for patients who underwent curative surgical resection were 80.0% and 30.0%, respectively, with a median survival duration of 30.8 months. All patients who underwent curative resection developed postoperative recurrences, with a median recurrence-free survival duration of 3.8 months. The 1- year survival rate for patients who underwent noncurative surgery and had residual tumors was 29.2%, with a median survival duration of 10.5 months.;Conclusions: Aggressive surgical resection for HCC with tumor thrombi in the IVC or RA can be performed safely and may improve the prognoses of these patients. However, early recurrence and treatment for recurrent or metastatic tumors remain unresolved issues.

Hepatocellular carcinoma (HCC) with tumour thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA) is a rare advanced disease state with a poor prognosis. The aim of this study was to examine survival after surgical resection.Patients with HCC and TT of either the IVC or RA, who underwent liver resection between February 1997 and July 2017, were included. Their short- and long-term outcomes and surgical details were analysed retrospectively.Thirty-seven patients were included; 16 patients had TT in the IVC below the diaphragm, eight had TT in the IVC above the diaphragm, and 13 had TT entering the RA. Twelve patients had advanced portal vein TT (portal vein invasion (Vp) greater than Vp3 and Vp4), ten had bilobar disease, and 12 had extrahepatic disease. There were no in-hospital deaths, although two patients died within 90 days. Median survival did not differ between patients who had resection with curative intent (18·7 months) and those with residual tumour in the lung only (20·7 months), but survival was poor for patients with residual tumour in the liver (8·3 months).Liver resection with thrombectomy for advanced HCC with TT in the IVC or RA is safe and feasible, leading to moderate survival.© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.

Background: Hepatocellular carcinoma (HCC) with hepatic vein invasion (HVI) is classified as advanced stage and palliative management is the primary treatment option. This study compared the long-term outcomes of curative and non-curative treatments in patients of HCC with HVI. Methods: Data were obtained from a retrospective multicenter cohort of the Korean Primary Liver Cancer Registry. We reviewed 18,315 patients newly diagnosed with HCC between 2008 and 2019. After propensity score matching based on the albumin-bilirubin (ALBI) score; tumor number, and tumor size, clinical outcomes were compared between the curative group (n = 42, 29.0%) undergoing surgical resection or local ablation and the non-curative group (n = 103, 71.0%) receiving other treatments. Results: Tumor burdens such as tumor number, maximum tumor size, levels of alpha-fetoprotein (AFP), and protein induced by absence of vitamin K or antagonist-II did not differ significantly between the groups (p = 0.672, p = 0.143, p = 0.153 and p = 0.651, respectively). In long-term outcomes, the overall survival (OS) and cancer-specific survival (CSS) were significantly better in the curative group compared to the non-curative group (p &lt; 0.001, both). Multivariate analysis indicated that non-curative treatment, ALBI grade ≥ 2, and AFP ≥ 400 ng/mL were common risk factors for OS and CSS. Conclusions: Curative-intent treatment has the potential to significantly enhance long-term outcomes in selected patients of HCC with HVI who preserved liver function and performance status.

Indications for liver transplantation for hepatocellular carcinoma are evolving and so-called expanded criteria remain debated. Locoregional therapies are able to downstage hepatocellular carcinoma from beyond to within the Milan criteria. We aimed to investigate the efficacy of liver transplantation after successful hepatocellular carcinoma downstaging.We did an open-label, multicentre, randomised, controlled trial designed in two phases, 2b and 3, at nine Italian tertiary care and transplantation centres. Patients aged 18-65 years with hepatocellular carcinoma beyond the Milan criteria, absence of macrovascular invasion or extrahepatic spread, 5-year estimated post-transplantation survival of at least 50%, and good liver function (Child-Pugh A-B7) were recruited and underwent tumour downstaging with locoregional, surgical, or systemic therapies according to multidisciplinary decision. After an observation period of 3 months, during which sorafenib was allowed, patients with partial or complete responses according to modified Response Evaluation Criteria in Solid Tumors were randomly assigned (1:1) by an interactive web-response system to liver transplantation or non-transplantation therapies (control group). A block randomisation (block size of 2), stratified by centre and compliance to sorafenib treatment, was applied. Liver transplantation was done with whole or split organs procured from brain-dead donors. The control group received sequences of locoregional and systemic treatment at the time of demonstrated tumour progression. The primary outcomes were 5-year tumour event-free survival for phase 2b and overall survival for phase 3. Analyses were by intention to treat. Organ allocation policy changed during the course of the study and restricted patient accrual to 4 years. This trial is registered with ClinicalTrials.gov, NCT01387503.Between March 1, 2011, and March 31, 2015, 74 patients were enrolled. Median duration of downstaging was 6 months (IQR 4-11). 29 patients dropped out before randomisation and 45 were randomly assigned: 23 to the transplantation group versus 22 to the control group. At data cutoff on July 31, 2019, median follow-up was 71 months (IQR 60-85). 5-year tumour event-free survival was 76·8% (95% CI 60·8-96·9) in the transplantation group versus 18·3% (7·1-47·0) in the control group (hazard ratio [HR] 0·20, 95% CI 0·07-0·57; p=0·003). 5-year overall survival was 77·5% (95% CI 61·9-97·1) in the transplantation group versus 31·2% (16·6-58·5) in the control group (HR 0·32, 95% CI 0·11-0·92; p=0·035). The most common registered grade 3-4 serious adverse events were hepatitis C virus recurrence (three [13%] of 23 patients) and acute transplant rejection (two [9%]) in the transplantation group, and post-embolisation syndrome (two [9%] of 22 patients) in the control group. Treatment-related deaths occurred in four patients: two (8%) of 23 patients in the transplantation group (myocardial infarction and multi-organ failure) versus two (9%) of 22 patients in the control group (liver decompensation).Although results must be interpreted with caution owing to the early closing of the trial, after effective and sustained downstaging of eligible hepatocellular carcinomas beyond the Milan criteria, liver transplantation improved tumour event-free survival and overall survival compared with non-transplantation therapies Post-downstaging tumour response could contribute to the expansion of hepatocellular carcinoma transplantation criteria.Italian Ministry of Health.Copyright © 2020 Elsevier Ltd. All rights reserved.

Macrovascular invasion is considered a contraindication to liver transplantation for hepatocellular carcinoma (HCC) due to a high risk of recurrence. The aim of the present multicenter study was to explore the outcome of HCC patients transplanted after a complete radiological regression of the vascular invasion by locoregional therapies and define sub-groups with better outcomes. Medical records of 45 patients were retrospectively reviewed, and imaging was centrally assessed by an expert liver radiologist. In the 30 patients with validated diagnosis of macrovascular invasion, overall survival was 60% at 5 years. Pretransplant alpha-fetoprotein (AFP) value was significantly different between patients with and without recurrence (P = 0.019), and the optimal AFP cutoff was 10ng/ml (area under curve = 0.78). Recurrence rate was 11% in patients with pretransplant AFP < 10ng/ml. The number of viable nodules (P = 0.008), the presence of residual HCC (P = 0.036), and satellite nodules (P = 0.001) on the explant were also significantly different between patients with and without recurrence. Selected HCC patients with radiological signs of vascular invasion could be considered for transplantation, provided that they previously underwent successful treatment of the macrovascular invasion resulting in a pretransplant AFP < 10 ng/ml. Their expected risk of post-transplant HCC recurrence is 11%, and further prospective validation is needed.© 2020 Steunstichting ESOT.

National guidelines on transplant selection have adopted successful downstaging to within Milan criteria (MC) as a viable option for the treatment of hepatocellular carcinoma (HCC) before liver transplant (LT). Recurrence of HCC after LT carries a poor prognosis, and treatment modalities remain challenging.To establish the 10-year outcomes of patients with HCC after LT in a large, multicenter US study based on individual data; provide robust data on the long-term role of downstaging; and evaluate the association of treatment modalities with postrecurrence survival.In this cohort study, a retrospective, multicenter analysis of prospectively collected data was conducted for 2645 adults who had undergone LT for HCC at 5 US academic centers between January 2001 and December 2015. The analysis was performed from May 2019 through June 2021. Outcomes of 341 patients whose disease was downstaged to within MC were compared with those in 2122 patients whose disease was always within MC and 182 patients whose disease was not downstaged. The associations of tumor and treatment factors on postrecurrence survival were analyzed using Cox proportional hazards regression and multivariable logistic regression models.The primary outcome was overall survival for the whole cohort and according to downstaging status. Secondary outcomes were time to recurrence, recurrence-free survival, and recurrence after specific post-LT therapies.Of the 2645 patients studied, the median age was 59.9 years (IQR, 54.7-64.7 years). The majority of the patients were men (2028 [76.7%] vs 617 [23.3%] women). The 10-year post-LT survival and recurrence rates were, respectively, 52.1% and 20.6% among those whose disease was downstaged; 61.5% and 13.3% in those always within MC; and 43.3% and 41.1% in those whose disease was not downstaged. Independent variables associated with downstaging failure were tumor size greater than 7 cm at diagnosis (OR, 2.62; 95% CI, 1.20-5.75; P = .02), more than 3 tumors at diagnosis (OR, 2.34; 95% CI, 1.22-4.50; P = .01), and α-fetoprotein response of at least 20 ng/mL with less than 50% improvement from maximum α-fetoprotein before LT (OR, 1.99; 95% CI, 1.14-3.46; P = .02). Surgically treated patients with recurrent HCC differed in clinicopathologic characteristics and had improved 5-year postrecurrence survival rates (31.6% vs 7.3%; P < .001).In a large, multicenter cohort of patients with HCC successfully downstaged to within MC, 10-year post-LT outcomes were excellent, validating national downstaging policies and showing a clear utility benefit for LT prioritization decision making. Surgical management of HCC recurrence after LT was associated with improved survival in well-selected patients and should be pursued, if feasible.

To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).

Hepatocellular carcinoma (HCC), particularly when accompanied by microvascular invasion (MVI), has a markedly high risk of recurrence after liver resection. Adjuvant immunotherapy is considered a promising avenue. This multicenter, open-label, randomized, controlled, phase 2 trial was conducted at six hospitals in China to assess the efficacy and safety of adjuvant sintilimab, a programmed cell death protein 1 inhibitor, in these patients. Eligible patients with HCC with MVI were randomized (1:1) into the sintilimab or active surveillance group. The sintilimab group received intravenous injections every 3 weeks for a total of eight cycles. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat population. Key secondary endpoints included overall survival (OS) and safety. From September 1, 2020, to April 23, 2022, a total of 198 eligible patients were randomly allocated to receive adjuvant sintilimab (n = 99) or undergo active surveillance (n = 99). After a median follow-up of 23.3 months, the trial met the prespecified endpoints. Sintilimab significantly prolonged RFS compared to active surveillance (median RFS, 27.7 versus 15.5 months; hazard ratio 0.534, 95% confidence interval 0.360-0.792; P = 0.002). Further follow-up is needed to confirm the difference in OS. In the sintilimab group, 12.4% of patients experienced grade 3 or 4 treatment-related adverse events, the most common of which were elevated alanine aminotransferase levels (5.2%) and anemia (4.1%). These findings support the potential of immune checkpoint inhibitors as effective adjuvant therapy for these high-risk patients. Chinese Clinical Trial Registry identifier: ChiCTR2000037655.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.