Association between bridging therapy and posttransplant outcomes in patients with HCC within Milan criteria: A systematic review and meta-analysis.

Liver transplantation is the curative therapy of choice for patients with early-stage HCC. Locoregional therapies are often employed as a bridge to reduce the risk of waitlist dropout; however, their association with posttransplant outcomes is unclear. We conducted a systematic review using Ovid MEDLINE and EMBASE to identify studies published between database inception and August 2, 2023, which reported posttransplant recurrence-free survival and overall survival among patients transplanted for HCC within Milan criteria, stratified by receipt of bridging therapy. Pooled HRs were calculated for each outcome using the DerSimonian and Laird method for a random-effects model. We identified 38 studies, including 19,671 patients who received and 20,148 patients who did not receive bridging therapy. Bridging therapy was not associated with significant differences in recurrence-free survival (pooled HR: 0.91, 95% CI: 0.77-1.08; I2 =39%) or overall survival (pooled HR: 1.09, 95% CI: 0.95-1.24; I2 =47%). Results were relatively consistent across subgroups, including geographic location and study period. Studies were discordant regarding the differential strength of association by pretreatment tumor burden and pathologic response, but potential benefits of locoregional therapy were mitigated in those who received 3 or more treatments. Adverse events were reported in a minority of studies, but when reported occurred in 6%-15% of the patients. Few studies reported loss to follow-up and most had a risk of residual confounding. Bridging therapy is not associated with improvements in posttransplant recurrence-free or overall survival among patients with HCC within Milan criteria. The risk-benefit ratio of bridging therapy likely differs based on the risk of waitlist dropout.

Resection or ablation versus transarterial therapy for Child-Pugh A patients with a single small hepatocellular carcinoma.

ABSTRACT: Data from a direct comparison of the long-term survival outcomes of surgical resection (SR) or radiofrequency ablation (RFA) versus transarterial therapy in Child-Turcotte-Pugh (CTP)-class A patients with a single small T1/T2 stage hepatocellular carcinoma (HCC) (≤3 cm) are still lacking. This study retrospectively compared the therapeutic outcomes of these treatment types for CTP-A patients with a single small HCC.Using a nationwide Korean registry, we identified 2314 CTP-A patients with SR (n = 722), RFA (n = 731), or transarterial therapy (n = 861) for a single (≤3 cm) T1/T2 stage HCC from 2008 to 2014. The posttreatment overall survival (OS) of transarterial therapy with either SR or RFA were compared using the Inverse Probability of treatment Weighting (IPW). The median follow-up period was 50 months (range 1-107 months).After IPW, the cumulative OS rates after SR or RFA were significantly higher than those after transarterial therapy in all subjects (all P values < .05). The OS rates after SR or RFA were better than those after transarterial therapy in patients with the hepatitis B or C virus (all P values < .05), and in patients aged <65 years (all P values < .05). The cumulative OSs between RFA and transarterial therapy were statistically comparable in patients with a 2 to 3 cm HCC and aged ≥65 years, respectively. For all subjects, the weighted Cox proportional hazards model using IPW provided the adjusted hazard ratios (95% confidence interval) for the OS after SR versus transarterial therapy and after RFA versus transarterial therapy of 0.42 (0.30-0.60) (P < .001) and 0.78 (0.61-0.99) (P = .044), respectively.In CTP-A patients with a single (≤3 cm) T1/T2 HCC, SR or RFA provides a better OS than transarterial therapy, regardless of the HCC etiology (hepatitis B virus or hepatitis C virus), especially in patients with HCC of <2 cm and aged <65 years.

Long-term Outcomes of Transcatheter Arterial Chemoembolization Combined With Radiofrequency Ablation as an Initial Treatment for Early-Stage Hepatocellular Carcinoma.

Importance: The long-term outcomes of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) are not determined. Objective: To report the long-term outcomes of TACE-RFA. Design, Setting, and Participants: This cohort study analyzed long-term follow-up data from a phase 3 randomized clinical trial of adults with early HCC conducted from October 2006 to June 2009. Participants were randomly assigned to the TACE-RFA group or the RFA group in a 1:1 ratio and followed up approximately 6 years after the trial was closed. Data analysis was performed March 2020. Exposure: In the TACE-RFA group, TACE was performed first, and RFA was done 2 weeks later. Main Outcomes and Measures: Overall survival (OS) and recurrence-free survival (RFS). Results: Of 189 patients who were included (mean [SD] age, 54.3 [12.0] years; 146 [77.2%] men), 94 and 95 patients were assigned to the TACE-RFA group and RFA group, respectively, with their baseline characteristics well matched. Three patients in each group were lost to follow-up. The 5-year and 7-year OS rates for the TACE-RFA group vs the RFA group were 52.0% and 36.4% vs 43.2% and 19.4%, respectively (hazard ratio [HR], 0.55; 95% CI, 0.39-0.78; P = .001). The 5-year and 7-year RFS rates for the TACE-RFA group vs the RFA group were 41.4% and 34.5% vs 27.4% and 18.1%, respectively (HR, 0.66; 95% CI, 0.49-0.89; P = .007). On subgroup analysis comparing patients who had tumors larger than 3 cm with those who had tumors 3 cm or smaller, the OS and RFS survival rates in the TACE-RFA group (HR, 3.20; 95% CI, 1.91-5.35, P < .001) were significantly better than those in the RFA group (HR, 2.03; 95% CI, 1.30-3.17; P = .002). Conclusions and Relevance: In this cohort study, combined RFA and TACE was associated with better survival than RFA alone on long-term follow-up. Patients with tumors 3 cm or smaller did not benefit as well as patients with tumors larger than 3 cm from the combined treatment.

Effect of partial splenic embolization on transarterial chemoembolization for hepatocellular carcinoma with hypersplenism.

ABSTRACT: This study retrospectively studied transarterial chemoembolization (TACE) combined with partial splenic embolization (PSE) in the treatment of hepatocellular carcinoma (HCC) with severe hypersplenism.Seventy patients with HCC in Barcelona Clinic Liver Cancer (BCLC) stage B or C with hypersplenism were divided into non-partial splenic embolization group (N-PSE, n = 51) and partial splenic embolization group (PSE, n = 19). The N-PSE group was further divided into N-PSE with mild to moderate hypersplenism (N-PSE-M, 47 cases) and N-PSE with severe hypersplenism (N-PSE-S, 4 cases).In the PSE group, leukocytes, neutrophils, lymphocytes, and platelets were significantly increased (P < .05) and were significantly different from that in the N-PSE group (P < .05). In the N-PSE group, except for a slight increase in neutrophils, other blood cells were decreased, including lymphocytes that were significantly decreased (P < .05). There was no significant difference in the changes of liver function between the 2 groups before and after surgery (P > .05). The analysis showed a significant increase in ascites after 6 months of TACE in the N-PSE group (P < .05). According to the follow-up results, the median overall survival (OS) in the PSE group was 24.47 ±â€Š3.68 (months) and progression-free survival (PFS) was 12.63 ±â€Š4.98 (months). Regardless of OS or PFS, the PSE group was superior to the N-PSE group and its subgroups, with a statistically significant difference in PFS between the N-PSE group and PSE group (P < .05). Moreover, the time of extrahepatic progression was significantly earlier in the N-PSE group than in the PSE group (P < .05). N-PSE-S group had the worst prognosis, and PFS and OS were worse than the other 2 groups, suggesting that PSE in severe hypersplenism may improve PFS and OS.In patients with HCC and severe hypersplenism, TACE should be actively combined with PSE treatment.

Significance of liver resection for intermediate stage hepatocellular carcinoma according to subclassification.

BACKGROUND: Patients diagnosed with Barcelona Clinic Liver Cancer (BCLC) intermediate stage hepatocellular carcinoma (HCC) encompass a broad clinical population. Kinki criteria subclassifications have been proposed to better predict prognoses and determine appropriate treatment strategies for these patients. This study validated the prognostic significance within the Kinki criteria substages and analyzed the role of liver resection in patients with intermediate stage HCC. METHODS: Patients with intermediate stage HCC (n = 378) were retrospectively subclassified according to the Kinki criteria (B1, n = 123; B2, n = 225; and B3, n = 30). We analyzed the overall survival (OS) and treatment methods. RESULTS: The OS was significantly different between adjacent substages. Patients in substage B1 who underwent liver resection had a significantly better prognosis than those who did not, even after propensity score matching (PSM). Patients in substage B2 who underwent liver resection had a significantly better prognosis than those who did not; however, there was no difference after PSM. There was no difference in prognosis based on treatments among patients in substage B3. CONCLUSIONS: The Kinki criteria clearly stratify patients with intermediate stage HCC by prognosis. For substage B1 HCC patients, liver resection provides a better prognosis than other treatment modalities. In patients with substage B2 and B3, an alternative approach is required.

Factors predicting long-term outcomes of early-stage hepatocellular carcinoma after primary curative treatment: the role of surgical or nonsurgical methods.

BACKGROUND: We quantified the elusive effects of putative factors on the clinical course of early hepatocellular carcinoma (HCC) after primary surgical or nonsurgical curative treatment. METHODS: Patients with newly diagnosed early HCC who received surgical resection (SR) or percutaneous radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) from January 2003 to December 2016 were enrolled. The cumulative overall survival (OS) and disease-free survival (DFS) rates were compared. A polytomous logistic regression was used to estimate factors for early and late recurrence. Independent predictors of OS were identified using Cox proportional hazard regression. RESULTS: One hundred twenty-five patients underwent SR, and 176 patients underwent RFA, of whom 72 were treated with TACE followed by RFA. Neither match analysis based on propensity score nor multiple adjustment regression yielded a significant difference in DFS and OS between the two groups. Multivariate analysis showed high AFP (> 20 ng/mL), and multinodularity significantly increased risk of early recurrence (< 1 year). In contrast, hepatitis B virus, hepatitis C virus and multinodularity were significantly associated with late recurrence (> 1 year). Multivariate Cox regression with recurrent events as time-varying covariates identified older age (HR = 1.55, 95% CI:1.01-2.36), clinically significant portal hypertension (CSPH) (HR = 1.97, 95% CI:1.26-3.08), early recurrence (HR = 6.62, 95% CI:3.79-11.6) and late recurrence (HR = 3.75, 95% CI:1.99-7.08) as independent risk factors of mortality. A simple risk score showed fair calibration and discrimination in early HCC patients after primary curative treatment. In the Barcelona Clinic Liver Cancer (BCLC) stage A subgroup, SR significantly improved DFS compared to RFA with or without TACE. CONCLUSION: Host and tumor factors rather than the initial treatment modalities determine the outcomes of early HCC after primary curative treatment. Statistical models based on recurrence types can predict early HCC prognosis but further external validation is necessary.

Impact of preoperative TACE on incidences of microvascular invasion and long-term post-hepatectomy survival in hepatocellular carcinoma patients: A propensity score matching analysis.

BACKGROUND: To study the influence of preoperative transcatheter arterial chemoembolization (TACE) on the incidence of microvascular invasion (MVI) and long-term survival outcomes in hepatocellular carcinoma (HCC) patients. METHODS: Between January 1, 2010 and December 1, 2014, consecutive HCC patients who underwent curative liver resection were enrolled in this study. Univariable and multivariable regression analyses were used to identify independent predictive factors of MVI. Propensity score matching (PSM) was used to compare the incidences of MVI and prognosis between patients who did and did not receive preoperative TACE. Factors associated with Disease-Free Survival (DFS) and Overall survival (OS) were identified using Cox regression analyses. RESULTS: Of 1624 patients, 590 received preoperative TACE. The incidence of MVI was significantly lower in patients with preoperative TACE than those without preoperative TACE (39.15% vs. 45.36%, p = 0.015). After PSM, the incidences of MVI were similar in the two groups (38.85% vs. 41.10%, p = 0.473). Multivariable regression analysis revealed preoperative TACE to have no impact on the incidence of MVI. Before PSM, survival of patients with preoperative TACE was significantly worse than those without preoperative TACE (p = 0.032 for DFS and p = 0.027 for OS). After PSM, the difference became insignificant (p = 0.465 for DFS and p = 0.307 for OS). After adjustment for other prognostic variables in the propensity-matched cohort, preoperative TACE was still found not to be associated with DFS and OS after HCC resection. Both before and after PSM, the prognosis of patients was not significantly different between the two groups for BCLC stages 0, A, and B. CONCLUSIONS: Preoperative TACE did not influence the incidence of MVI and prognosis of patients with HCC who underwent 'curative' liver resection.

Macrophage migration inhibitory factor predicts an unfavorable outcome after transarterial chemoembolization for hepatic malignancies.

Transarterial chemoembolization (TACE) is a therapeutic option for patients with intermediate-stage hepatocellular carcinoma (HCC) or metastatic liver cancers. Identifying those patients who particularly benefit from TACE remains challenging. Macrophage migration inhibitory factor (MIF) represents is an inflammatory protein described in patients with liver cancer, but no data on its prognostic relevance in patients undergoing TACE exist. Here, we evaluate MIF serum concentrations as a potential biomarker in patients undergoing TACE for primary and secondary hepatic malignancies. MIF serum concentrations were measured by multiplex immunoassay in 50 patients (HCC: n = 39, liver metastases: n = 11) before and 1 day after TACE as well as in 51 healthy controls. Serum concentrations of MIF did not differ between patients and healthy controls. Interestingly, in the subgroup of patients with larger tumor size, significantly more patients had increased MIF concentrations. Patients with an objective tumor response to TACE therapy showed comparable concentrations of serum MIF compared to patients who did not respond. MIF concentrations at day 1 after TACE were significantly higher compared to baseline concentrations. Importantly, baseline MIF concentrations above the optimal cutoff value (0.625 ng/ml) turned out as a significant and independent prognostic marker for a reduced overall survival (OS) following TACE: patients with elevated MIF concentrations showed a significantly reduced median OS of only 719 days compared to patients below the cutoff value (median OS: 1430 days, p = 0.021). Baseline MIF serum concentrations are associated with tumor size of intrahepatic malignancies and predict outcome of patients with liver cancer receiving TACE.

Evaluating the predictive power of circulating tumor cells for the prognosis of transarterial chemoembolization treatment on patients with advanced hepatocellular carcinoma.

ABSTRACT: Explore the predictive power of Circulating Tumor Cells (CTCs) for evaluating the prognosis of transarterial chemoembolization (TACE) treatment on advanced hepatocellular carcinoma (HCC) patients, and use it to construct a prediction model.We retrospectively analyzed 43 patients with Barcelona Clinic Liver Cancer stage C HCC who underwent TACE treatment.The survival time of 43 advanced HCC patients were 2 to 60 months, with the median survival time of 12 months, 1-, 3-, and 5-year survival rates were 42.9%, 9.0%, and 3.6%, respectively. The OS of patients with high level of CTCs before TACE (CTC1 > 2) was significantly lower than that of patients with low level of CTCs (8 vs 12 months, P = .040), but there was no significant difference in PFS between the 2 groups (P = .926). Meanwhile, there was no significant difference in OS and PFS between patients with high level CTCs and those with low level CTCs at 1 week and 4 weeks after TACE (P all > .05). In univariate and multivariate Cox regression analysis, the number of lesions and CTC before TACE were the independent influencing factors for prognosis in these patients, and the HR was 3.01 and 1.20, respectively (all P < .05). The area under curve of COX regression model to predict OS increased with the increase of follow-up time, ranging from 0.56 to 0.85.The CTCs number before TACE is an effective biomarker for predicting the OS of advanced HCC patients. The joint prediction model based on CTCs and tumor number can effectively predict the prognosis of patients with advanced HCC.

The clinical characteristics and prognostic factors of combined Hepatocellular Carcinoma and Cholangiocarcinoma, Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma after Surgical Resection: A propensity score matching analysis.

Background: Clinical characteristics and prognosis among combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CC) with HCC and intrahepatic cholangiocarcinoma (ICC) were inconsistent in previous studies. The aim of this study was to compare postoperative prognosis among cHCC-CC, HCC and ICC, and investigated the prognostic risk factor of cHCC-CC after surgical resection. Methods: A total of 1041 eligible patients with pathological diagnosis of cHCC-CC (n=135), HCC (n=698) and ICC (n=208) were enrolled in this study. Univariate and multivariate Cox analysis were applied for assessing important risk factors. cHCC-CC were further 1:1 matched with HCC and ICC on important clinical risk factors. Survival curves of matched and unmatched cohorts were depicted by Kaplan-Meier method with log-rank test. Results: Patients with cHCC-CC had similar rate of sex, age and cirrhosis with HCC (p<0.05) and comparable incidence of hepatitis B or C with ICC (p=0.197). Patients of cHCC-CC had intermediate prognosis between HCC and ICC, with median overall survival (OS) time of cHCC-CC, HCC and ICC of 20.5 months, 35.7 months and 11.6 months (p<0.001). In matched cohorts, the OS of cHCC-CC were worse than HCC (p<0.001) but comparable with ICC (p=0.06), while the disease-free survival (DFS) of cHCC-CC was worse than HCC but better than ICC (p<0.05). And lymph node infiltration and postoperative transarterial chemoembolization (TACE) were independent risk factors of cHCC-CC associated with prognosis. Conclusion: The long term survival of cHCC-CC was worse than HCC but comparable with ICC when matched on albumin level, tumor size, lymph node infiltration, tumor stage and margin. Presence of lymph node infiltration and no postoperative TACE were associated with poor prognosis of cHCC-CC.

Liver Embolisation for Patients with Neuroendocrine Neoplasms: Systematic Review.

BACKGROUND: Liver embolisation is one of the treatment options available for patients diagnosed with neuro-endocrine neoplasms (NEN). It is still uncertain whether the benefits of the various types of embolisation treatments truly outweigh the complications in NENs. This systematic review assesses the available data relating to liver embolisation in patients with NENs. METHODS: Eligible studies (identified using MEDLINE-PubMed) were those reporting data on NEN patients who had undergone any type of liver embolisation. The primary end points were best radiological response and symptomatic response; secondary end-points included progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: Of 598 studies screened, 101 were eligible: 16 were prospective (15.8%). The eligible studies included a total of 5,545 NEN patients, with a median of 39 patients per study (range 5-214). Pooled rate of partial response was 36.6% (38.9% achieved stable disease) and 55.2% of patients had a symptomatic response to therapy when pooled data were analysed. The median PFS and OS were 18.4 months (95% CI 15.5-21.2) and 40.7 months (95% CI 35.2-46.2) respectively. The most common toxicities were found to be abdominal pain (48.8%) and nausea (48.1%). Outcome did not significantly vary depending on the type of embolisation performed. CONCLUSION: Liver embolisation provides adequate symptom relief for patients with carcinoid syndrome and is also able to reach partial response in a significant proportion of patients and a reasonable PFS. Quality of studies was limited, highlighting the need of further prospective studies to confirm the most suitable form of liver embolisation in NENs.

Association of Addition of Ablative Therapy Following Transarterial Chemoembolization With Survival Rates in Patients With Hepatocellular Carcinoma.

Importance: Hepatocellular carcinoma (HCC) is a heterogeneous disease with many available treatment modalities. Transarterial chemoembolization (TACE) is a valuable treatment modality for HCC lesions. This article seeks to evaluate the utility of additional ablative therapy in the management of patients with HCC who received an initial TACE procedure. Objective: To compare the overall survival (OS) and freedom from local progression (FFLP) outcomes after TACE alone with TACE that is followed by an ablative treatment regimen using stereotactic body radiation therapy, radiofrequency ablation, or microwave ablation for patients with HCC. Design, Setting, and Participants: This cohort study of 289 adults at a single urban medical center examined survival outcomes for patients with nonmetastatic, unresectable HCC who received ablative therapies following TACE or TACE alone from January 2010 through December 2018. The Lee, Wei, Amato common baseline hazard model was applied for within-patient correlation with robust variance and Cox regression analysis was used to assess the association between treatment group (TACE vs TACE and ablative therapy) and failure time events (FFLP per individual lesion and OS per patient), respectively. In both analyses, the treatment indication was modeled as a time-varying covariate. Landmark analysis was used as a further sensitivity test for bias by treatment indication. Exposures: TACE alone vs TACE followed by ablative therapy. Main Outcomes and Measures: Freedom from local progression and overall survival. Hypotheses were generated before data collection. Results: Of the 289 patients identified, 176 (60.9%) received TACE only and 113 (39.1%) received TACE plus ablative therapy. Ablative therapy included 45 patients receiving stereotactic body radiation therapy, 39 receiving microwave ablation, 20 receiving radiofrequency ablation, and 9 receiving a combination of these following TACE. With a median (interquartile range) follow-up of 17.4 (9.5-29.5) months, 242 of 512 (47.3%) lesions progressed, 211 in the group with TACE alone and 31 in the group with TACE plus ablative therapy (P < .001). Over 3 years, FFLP was 28.1% for TACE alone vs 67.4% for TACE with ablative therapy (P < .001). The 1-year and 3-year OS was 87.5% and 47.1% for patients with lesions treated with TACE alone vs 98.7% and 85.3% for patients where any lesion received TACE plus ablative therapy, respectively (P = .01), and this benefit remained robust on landmark analyses at 6 and 12 months. The addition of ablative therapy was independently associated with OS on multivariable analysis for all patients (hazard ratio, 0.26; 95% CI, 0.13-0.49; P < .001) and for patients with Barcelona clinic liver cancer stage B or C disease (hazard ratio, 0.31; 95% CI, 0.14-0.69; P = .004). Conclusions and Relevance: Adding ablative therapy following TACE improved FFLP and OS among patients with hepatocellular carcinoma. This study aims to guide the treatment paradigm for HCC patients until results from randomized clinical trials become available.

Transarterial chemoembolization for hepatocellular carcinoma: a bibliometric analysis of the most cited articles.

PURPOSE: Bibliometric analysis is a quantitative assessment of the academic literature in a particular field. The aim of our study was to characterize the 100 top-cited articles regarding transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The 'Web of Science' database was used to identify the leading articles regarding TACE for HCC. We determined the top 100 articles according to citations and performed an analysis on year of publication, authorship, department affiliation, publishing journal, institution and country of origin, subject matter and article type. RESULTS: The top-cited articles received between 92 and 2254 citations (median 283.4). The top 100 papers were published in 32 journals between 1983 and 2016. Cancer, Radiology and Hepatology published the most articles (n = 40). Internal medicine was the department affiliation of the first author in 49%. The country providing the most highly cited articles was Japan (n = 24). CONCLUSION: We performed an analysis of the 100 top-cited articles dealing with TACE for HCC, presenting a detailed list of the most influential and historically significant papers. Japan was the country that produced the most top-cited articles, highlighting its key contribution to this field of the literature.

Demographic and Clinicopathologic Factors of Patients With Hepatocellular Carcinoma in a Safety Net Hospital.

BACKGROUND: Safety net hospitals have historically cared for a disproportionate number of patients of low socioeconomic status, racial and ethnic minorities, and patients with cancer. These innate challenges make safety net hospitals important in understanding how to improve access to cancer care in order to fit the needs of vulnerable patients and ultimately improve their outcomes. The purpose of this study is to characterize the current state and treatment of hepatocellular carcinoma (HCC) at Ben Taub Hospital, a safety net hospital in Houston, Texas. MATERIALS AND METHODS: A retrospective chart review was performed to review the demographic characteristics, clinicopathologic data, treatment strategies, and outcomes of HCC patients at Ben Taub Hospital between January 2012 and December 2014. RESULTS: Two-hundred twenty-six men and 78 women with a mean age of 58 y underwent evaluation. Most (87%) were either uninsured or covered by Medicaid. The majority (69%) of patients presented with advanced (stage 2 or more) disease, with 58% of patients presenting with multiple lesions. Of the 40% that presented with a solitary lesion, the average size was 4.97 cm. Transarterial chemoembolization was used in 37% of patients and sorafenib was given to 26% of patients. Five patients underwent successful transplant. One hundred seventeen (38%) patients died of their disease, 25 patients are alive with no evidence of disease, and 159 patients have been lost to follow-up. CONCLUSIONS: Most patients with HCC presented to this safety net hospital with advanced disease; however, multiple local and systemic treatments were offered. Screening programs to detect HCC at an earlier stage are essential for successful long-term outcomes in a resource-strapped hospital with limited access to liver transplantation.

Survival Outcomes According to Body Mass Index in Hepatocellular Carcinoma Patient: Analysis of Nationwide Cancer Registry Database.

BACKGROUND AND AIMS: Body mass index (BMI) is known to be closely related to the prognosis and mortality of various diseases. The aim of our study was to evaluate differences in post-treatment overall survival (OS) according to BMI with hepatocellular carcinoma (HCC) and to understand the meaning of BMI. Among the records of 10,578 HCC patients registered at the Korean Central Cancer Registry from 2008 through 2014, we selected Barcelona Clinic Liver Cancer (BCLC) 0, A, and B staged HCC patients (n = 4,926). HCC patients showed a good prognosis in the order of overweight, normal weight, obesity, and underweight. However, comparing normal-weight (BMI 18.5-24.9 kg/m2) to overweight (BMI 25-29.9 kg/m2) after propensity score matching (PSM), there was no significant difference in OS (p = 0.153). Overweight males had a better prognosis than normal-weight males (p = 0.014), but, normal-weight females had a better prognosis than overweight. To determine the gender-specific OS differences, we examined the differences according to the HCC treatment type. In males, overweight patients had better OS after transarterial chemoembolization (TACE) (p = 0.039) than normal-weight, but not after surgical resection (p = 0.618) nor radiofrequency ablation (p = 0.553). However, in females, all of those HCC treatments resulted in significantly better OS in normal-weight patients than overweight. In patients with HCC of BCLC stages 0-B, unlike females, overweight males had a better prognosis than normal-weight, especially among TACE-treated patients. Our results carefully suggest that the meaning of normal BMI in patients with HCC may have gender difference.

Stereotactic body radiation therapy vs. radiofrequency ablation in Asian patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Few studies have been conducted to compare the efficacies of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA). Thus, in this multinational study, we compared the effectiveness of SBRT and RFA in patients with unresectable HCC. METHODS: The retrospective study cohort included 2,064 patients treated in 7 hospitals: 1,568 and 496 in the RFA and SBRT groups, respectively. More than half of the patients (56.5%) developed recurrent tumors, mainly after transarterial chemoembolization (44.8%). Propensity score matching was performed to adjust for clinical factors (n = 313 in each group). RESULTS: At baseline, the SBRT group had unfavorable clinical features compared to the RFA group, including BCLC stage (B-C 65% vs. 16%), tumor size (median 3.0 cm vs. 1.9 cm), and frequent history of liver-directed treatment (81% vs. 49%, all p <0.001). With a median follow-up of 27.7 months, the 3-year cumulative local recurrence rates in the SBRT and RFA groups were 21.2% and 27.9%, respectively (p <0.001). After adjusting for clinical factors, SBRT was related to a significantly lower risk of local recurrence than RFA in both the entire (hazard ratio [HR] 0.45, p <0.001) and matched (HR 0.36, p <0.001) cohorts. In subgroup analysis, SBRT was associated with superior local control in small tumors (≤3 cm) irrespective of location, large tumors located in the subphrenic region, and those that progressed after transarterial chemoembolization. Acute grade ≥3 toxicities occurred in 1.6% and 2.6% of the SBRT and RFA patients, respectively (p = 0.268). CONCLUSIONS: SBRT could be an effective alternative to RFA for unresectable HCC, particularly for larger tumors (>3 cm) in a subphrenic location and tumors that have progressed after transarterial chemoembolization. LAY SUMMARY: It is currently not known what the best treatment option is for patients with unresectable hepatocellular carcinoma. Here, we show that stereotactic body radiation therapy provides better local control than radiofrequency ablation, with comparable toxicities. Stereotactic body radiation therapy appears to be an effective alternative to radiofrequency ablation that should be considered when there is a higher risk of local recurrence or toxicity after radiofrequency ablation.

Liver transplantation outcomes after transarterial chemotherapy for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) awaiting liver transplantation is widespread, although evidence that it improves outcomes is lacking and there exist concerns about morbidity. The impact of TACE on outcomes after transplantation was evaluated in this study. METHODS: Patients with HCC who had liver transplantation in the UK were identified, and stratified according to whether they received TACE between 2006 and 2016. Cox regression methods were used to estimate hazard ratios (HRs) for death and graft failure after transplantation adjusted for donor and recipient characteristics. RESULTS: In total, 385 of 968 patients (39·8 per cent) received TACE. Five-year patient survival after transplantation was similar in those who had or had not received TACE: 75·2 (95 per cent c.i. 68·8 to 80·5) and 75·0 (70·5 to 78·8) per cent respectively. After adjustment for donor and recipient characteristics, there were no differences in mortality (HR 0·96, 95 per cent c.i. 0·67 to 1·38; P = 0·821) or graft failure (HR 1·01, 0·73 to 1·40; P = 0·964). The number of TACE treatments (2 or more versus 1: HR 0·97, 0·61 to 1·55; P = 0·903) or the time of death after transplantation (within or after 90 days; P = 0·291) did not alter the outcome. The incidence of hepatic artery thrombosis was low in those who had or had not received TACE (1·3 and 2·4 per cent respectively; P = 0·235). CONCLUSION: TACE delivered to patients with HCC before liver transplant did not affect complications, patient death or graft failure after transplantation.

ANTECEDENTES: La quimioembolización transarterial (transarterial chemoembolization, TACE) en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) se utiliza como puente al trasplante hepático, aunque falta evidencia de que mejore los resultados y la morbilidad relacionada es motivo de preocupación. En este estudio se evaluó el impacto de la TACE en los resultados tras el trasplante para analizar las complicaciones. MÉTODOS: Se identificaron los receptores de trasplante hepático por HCC en el Reino Unido y se estratificaron según si habían recibido TACE entre 2006 y 2016. Se utilizó el método de regresión de Cox para estimar los cocientes de riesgos instantáneos (hazard ratio, HR) para la mortalidad post-trasplante y el fallo del injerto ajustados por las características del donante y del receptor. RESULTADOS: En total, 385 (39,8%) de 968 pacientes recibieron TACE, observándose similar supervivencia del paciente a los 5 años después del trasplante: 75,2% (i.c. del 95%: 68,8% a 80,5%) con TACE y 75,0% (70,5% a 78,8 %) sin TACE. Después de ajustar según las características del donante y del receptor, no hubo diferencias en la mortalidad (HR: 0,96, 0,67 a 1,38; P = 0,82) o en el fallo del injerto (HR: 1,01, 0,73 a 1,40; P = 0,96). El número de tratamientos con TACE (≥ 2 tratamientos TACE HR: 0,97, 0,61 a 1,55; P = 0,90) o el período de tiempo después del trasplante (mortalidad del paciente antes o después de 90 días; P = 0,29) no alteró el resultado. La incidencia de trombosis de la arteria hepática fue baja en aquellos que recibieron TACE o no (1,3% y 2,5%, respectivamente; P = 0,23). El fallo del injerto debido a eventos oclusivos fue similar en el grupo de pacientes que recibieron TACE (8,0% o 11/137) o que no la recibieron (6,7% o 5/75) TACE (P = 0,74). CONCLUSIÓN: La administración de TACE en pacientes con HCC antes del trasplante hepático no influyó en las complicaciones post-trasplante, la mortalidad del paciente o el fallo del injerto.

Applicability of scoring systems predicting outcome of transarterial chemoembolization for hepatocellular carcinoma.

PURPOSE: Several scoring systems have been proposed to predict the outcome of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). However, the application of these scores to a bridging to transplant setting is poorly validated. Evaluation of the applicability of prognostic scores for patients undergoing TACE in palliative intention vs. bridging therapy to liver transplantation (LT) is necessary. METHODS: Between 2008 and 2017, 148 patients with HCC received 492 completed TACE procedures (158 for bridging to transplant; 334 TACE procedures in palliative treatment intention at our center and were analyzed retrospectively. Scores (ART, CLIP, ALBI, APRI, SNACOR, HAP, STATE score, Child-Pugh, MELD, Okuda and BCLC) were calculated and evaluated for prediction of overall survival. ROC analysis was performed to assess prediction of 3-year survival and treatment discontinuation. RESULTS: In patients receiving TACE in palliative intention most scores predicted OS in univariate analysis but only mSNACOR score (p = 0.006), State score (p < 0.001) and Child-Pugh score (p < 0.001) revealed statistical significance in the multivariate analysis. In the bridging to LT cohort only the BCLC score revealed statistical significance (p = 0.002). CONCLUSIONS: Clinical usability of suggested scoring systems for TACE might be limited depending on the individual patient cohorts and the indication. Especially in patients receiving TACE as bridging to LT none of the scores showed sufficiently applicability. In our study Child-Pugh score, STATE score and mSNACOR score showed the best performance assessing OS in patients with TACE as palliative therapy.

Risk factors of mortality in the patients with hepatocellular carcinoma: A multicenter study in Indonesia.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is considered a significant burden, and its associated rate of mortality is increasing. Therefore, a population-based cancer registry is considered an essential element in the baseline and comprehensive analysis of the risk factors associated with HCC. We present a multicenter analysis of HCC registry from 2 hospitals in Indonesia. METHODS: We performed a follow-up on patients with HCC who were admitted between January 2015 and November 2017 in Cipto Mangunkusumo National General Hospital and Dharmais Hospital, Jakarta, Indonesia. Patient's death was considered the primary outcome of the study. A multivariate analysis was conducted using logistic regression, and odds ratio (OR) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 282 patients with HCC included. At the last follow-up, 136 (48.2%) patients had died. Mortality rate was not significantly affected by sex, age, etiology, the presence of cirrhosis, nor surveillance of HCC. Based on the Child-Pugh (CP) classification, the OR increased progressively in CP C patients (OR 1.95; 95% CI 1.08-3.53; P = 0.026). The progressive increase was also found in patients with a higher Barcelona Clinic Liver Cancer stage, and the OR for CP C and D patients were 3.50 (95% CI 1.18-10.38; P = 0.024) and 3.41 (95% CI 1.02-11.41; P = 0.047), respectively. Supportive treatment was the most common treatment modality with an OR of 2.17 (95% CI 1.14-4.16; P = 0.019), and it was associated with the mortality rate of HCC. CONCLUSIONS: The CP classification, Barcelona Clinic Liver Cancer staging system, and treatment modality might predict mortality in patients with HCC. Moreover, other parameters must be further evaluated.

Sequential transcatheter arterial chemoembolization and portal vein embolization versus portal vein embolization alone before major hepatectomy for patients with large hepatocellular carcinoma: An intent-to-treat analysis.

BACKGROUND: Little is known about the value of sequential transcatheter arterial chemoembolization and portal vein embolization compared with portal vein embolization alone before major hepatectomy for large hepatocellular carcinoma. We aimed to compare early and long-term outcomes of these two strategies. METHODS: We included all consecutive patients with large hepatocellular carcinoma (≥50 mm) scheduled for sequential transcatheter arterial chemoembolization and portal vein embolization or portal vein embolization alone before major hepatectomy from January 2005 to December 2015. Comparisons were made on an intent-to-treat basis. RESULTS: A total of 55 patients were included as follows: sequential transcatheter arterial chemoembolization and portal vein embolization (n = 27) and portal vein embolization alone (n = 28). Baseline patient and tumor characteristics were similar in the 2 groups. Downstaging after transcatheter arterial chemoembolization changed the initial strategy in 4 patients who finally underwent liver transplant (n = 1) and limited hepatectomy (n = 3). Overall survival and progression-free survival were better in the transcatheter arterial chemoembolization group compared with the portal vein embolization alone group (3-year overall survival of 60% vs 20%; P = .01 and 3-year progression-free survival of 35% vs 0%; P < .001). The proportion of patients who finally underwent hepatectomy after transcatheter arterial chemoembolization plus portal vein embolization was 91% vs 68% after portal vein embolization alone (P = .08). Hypertrophy of the future remnant liver after portal vein embolization was greater after transcatheter arterial chemoembolization (43% vs 31%, P = 0.03). After resection, the group that received transcatheter arterial chemoembolization and portal vein embolization experienced better progression-free survival compared with portal vein embolization alone (3-year progression-free survival of 28% vs 0%; P = .03). CONCLUSION: Our results suggest that transcatheter arterial chemoembolization before portal vein embolization increases the degree of hypertrophy of the future remnant liver after portal vein embolization and yields improved oncologic outcomes in patients with large hepatocellular carcinomas planned for major hepatectomy.