Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Versus Transarterial Chemoembolization for Large Hepatocellular Carcinoma: A Randomized Phase III Trial.

PURPOSE: In a previous phase II trial, hepatic arterial infusion chemotherapy (HAIC) with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) yielded higher treatment responses than transarterial chemoembolization (TACE) in large unresectable hepatocellular carcinoma. We aimed to compare the overall survival of patients treated with FOLFOX-HAIC versus TACE as first-line treatment in this population. METHODS: In this randomized, multicenter, open-label trial, adults with unresectable hepatocellular carcinoma (largest diameter ≥ 7 cm) without macrovascular invasion or extrahepatic spread were randomly assigned 1:1 to FOLFOX-HAIC (oxaliplatin 130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2,400 mg/m2 for 24 hours, once every 3 weeks) or TACE (epirubicin 50 mg, lobaplatin 50 mg, and lipiodol and polyvinyl alcohol particles). The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received ≥ 1 cycle of study treatment. RESULTS: Between October 1, 2016, and November 23, 2018, 315 patients were randomly assigned to FOLFOX-HAIC (n = 159) or TACE (n = 156). The median overall survival in the FOLFOX-HAIC group was 23.1 months (95% CI, 18.5 to 27.7) versus 16.1 months (95% CI, 14.3 to 17.9) in the TACE group (hazard ratio, 0.58; 95% CI, 0.45 to 0.75; P < .001). The FOLFOX-HAIC group showed a higher response rate than the TACE group (73 [46%] v 28 [18%]; P < .001) and a longer median progression-free survival (9.6 [95% CI, 7.4 to 11.9] v 5.4 months [95% CI, 3.8 to 7.0], P < .001). The incidence of serious adverse events was higher in the TACE group than in the FOLFOX-HAIC group (30% v 19%, P = .03). Two deaths in the FOLFOX-HAIC group and two in the TACE group were deemed to be treatment-related. CONCLUSION: FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma.

Efficacy of combined transarterial radioembolization and sorafenib in the treatment of hepatocarcinoma: A meta-analysis.

BACKGROUND: Adjuvant sorafenib may further enhance the efficacy of transarterial radioembolization for the treatment of hepatocellular carcinoma. AIMS: To evaluate the efficacy and safety of radioembolization plus sorafenib in hepatocellular carcinoma patients. METHODS: With a literature search through October 2020, we identified 9 studies (632 patients). Primary outcome was overall survival. Results were expressed as pooled median, odds ratio, or hazard ratio and 95% confidence intervals. RESULTS: Pooled overall survival after radioembolization plus sorafenib was 10.79 months (95% confidence interval 9.19-12.39) and it was longer in Barcelona Clinic Liver Cancer (BCLC) B (14.47 months, 9.07-19.86) as compared to BCLC C patients (10.22 months, 7.53-12.9). No difference between combined therapy versus radioembolization alone was observed in terms of overall survival (hazard ratio 1.07, 0.89-1.30). Pooled median progression-free survival was 6.32 months (5.68-6.98), with 1-year progression-free survival pooled rate of 38.5% (12.7%-44.2%). No difference in progression-free survival (hazard ratio 0.94, 0.79-1.12) between the two treatments was observed. Pooled rate of severe adverse events was 48.9% (26.7%-71.2%), again with no difference between the two treatment regimens (odds ratio 1.52, 0.15-15.02). CONCLUSIONS: The association of sorafenib does not seem to prolong survival nor delay disease progression in patients treated with radioembolization.

ABO Blood Group Differentials on Survival in Hepatocellular Carcinoma Patients Treated with Chemoembolization.

BACKGROUND: The association between ABO blood group and the prognosis of hepatocellular carcinoma (HCC) remains unclear. We investigated the impact of ABO blood groups as a prognostic factor in HCC patients treated with transarterial chemoembolization (TACE). MATERIALS AND METHODS: We revisited records of all HCC patients who underwent TACE between January 2007 and December 2019 at a tertiary care hospital. The inclusion criteria were HCC patients, Child-Pugh score A5-B7, and treated with TACE monotherapy. The baseline characteristics of each patient were compared against their blood group and the survival analysis was carried out using Cox's regression. With Bonferroni adjustment for multiple comparisons, P-values <.0125 were considered statistically significant. RESULTS: Of 211 eligible patients, the frequencies of blood groups O, A, B, and AB were 89, 54, 56, and 12, respectively. Their respective months of median survival were 41, 20, 21, and 42. After adjustments in the six-and-twelve criteria and Child-Pugh scores, and using blood group O as the referent group, the coefficients (SE) of groups A, B, and AB were 0.69 (0.24), 0.47 (0.23), and 0.49 (0.49), respectively. A significant difference in survival was found only between patients with blood group O vs A (hazard ratio, 2.00; confidence interval, 1.25-3.21). CONCLUSIONS: ABO blood group is associated with the prognosis of HCC patients treated with TACE monotherapy. In our data, patients with blood group O tended to have the best survival. However, only blood group A patients had a significantly shorter survival rate comparing to blood group O.

Chemoembolization for Hepatocellular Carcinoma in Patients With Inferior Vena Caval/Right Atrial Tumor Thrombi Without Hepatic Vein Invasion.

AIM: To clarify the clinical and radiological features of isolated tumor thrombi in the inferior vena cava (IVC)/right atrium in patients with hepatocellular carcinoma (HCC) without hepatic vein invasion. PATIENTS AND METHODS: In this retrospective study, from January 2007 to December 2019, a total of 35,163 chemoembolization sessions were performed in 7,704 patients with HCC. Among them, 10 (0.13%) patients had tumor thrombi in the IVC/right atrium without definitive hepatic vein invasion. Computed tomographic (CT) scans, digital subtraction angiograms, and cone-beam CT images were retrospectively reviewed and interpreted. RESULTS: The tumor thrombi were supplied by the right inferior phrenic artery (n=8) or the right internal mammary artery (n=2). Follow-up CT scans in eight patients showed linear accumulation of iodized oil along the diaphragm, which was presumed to be a thrombosis of the phrenic vein. Retrospective review of formal radiological reports of pre-procedural CT scans revealed that a correct diagnosis of tumor thrombi of the IVC/right atrium was made in only three cases. CONCLUSION: HCC invading the phrenic vein may have tumor thrombi in the IVC/right atrium without hepatic vein invasion.

Brachytherapy with Iodine-125 seeds for treatment of portal vein-branch tumor thrombus in patients with hepatocellular carcinoma.

BACKGROUND: There is currently no widely-accepted consensus for the management of hepatocellular carcinoma with portal vein tumor thrombus. We evaluate the safety and efficacy of ultrasound-guided percutaneous brachytherapy with iodine-125 seeds for the treatment of hepatocellular carcinoma with portal vein-branch tumor thrombus (PVBTT). METHODS: Sixty-nine hepatocellular carcinoma patients with PVBTT were enrolled; 34 received transarterial chemoembolization (TACE) combined with iodine-125 seeds implanted in the PVBTT; 35 were treated with TACE alone. Adverse events, objective response rate, disease control rate, progression-free survival, and overall survival were compared between the two groups. Tumor responses of PVBTT and intrahepatic tumor were correlated. Multivariate and subgroup analyses were conducted for overall survival. RESULTS: No grade 3 or 4 adverse events were recorded, and there was no difference in grade 1 or 2 adverse events between the two groups. Objective response rate and disease control rate for PVBTT were 58.9 and 91.2%, respectively, in the combined treatment group, which were significantly greater than the 5.7 and 54.3% rates, respectively, in the TACE-alone group (both p's ≤ 0.001). Intrahepatic tumor response was positively correlated with the PVBTT response (γ = 0.782, p < 0.01). Survival outcomes were better in the combined treatment group than in the TACE-alone group: the median progression-free survival for PVBTT was 9 months versus 3 months (HR = 0.187 [95% CI: 0.101, 0.345], p < 0.001), and the median overall survival was 11 months versus 7 months (HR = 0.448 [95% CI: 0.265, 0.758], p = 0.003). Multivariate analysis revealed that application of brachytherapy and lower grade PVBTT (Vp1 + Vp2 vs. Vp3) were protective predictors of overall survival. In stratified analysis, the benefit of overall survival was more significant in the subgroup of PVBTT Vp1 + Vp2 rather than in Vp3. CONCLUSIONS: The combination of iodine-125 seed brachytherapy guided by ultrasound and TACE is a convenient, safe, and effective treatment for patients with HCC and PVBTT, conferring a better survival benefit than TACE alone.

Impact of preoperative transcatheter rectal arterial chemoembolization with concurrent chemoradiotherapy on surgery and prognosis of patients with locally advanced rectal cancer.

BACKGROUND AND OBJECTIVES: To analyze and evaluate the impact of preoperative transcatheter rectal arterial chemoembolization (TRACE) with concurrent chemoradiotherapy on surgery and prognosis of locally advanced rectal cancer (LARC). METHODS: A total of 118 patients with LARC were enrolled in this nonrandomized prospective study. They were assigned into the experimental group receiving preoperative TRACE with concurrent chemoradiotherapy (TRACE-CRT group, N = 60) and the control group receiving only neoadjuvant chemoradiotherapy (CRT group, N = 58). All patients underwent surgery after their preoperative treatments. RESULTS: All patients successfully completed the surgical operation. No significant differences were found in sphincter preservation rate and R0 resection rate between TRACE-CRT group and CRT group (p > 0.05). No significant differences were found between the two groups in terms of the perioperative indicators and postoperative complications except mean operation time (165.8 vs. 196.6 min, p < 0.001). Local recurrence occurred in 8 and 5 patients, respectively (p > 0.05). Distant metastasis occurred in 5 and 11 patients, respectively (p < 0.05). CONCLUSIONS: Adding TRACE in the preoperative standard treatment for LARC did not increase perioperative complications. In addition, it has the potential advantage of preventing distant metastasis. It is worthy of further application and promotion in clinical practice.

Comparison of Modified Child-pugh (MCP), Albumin-bilirubin (ALBI), and Child-pugh (CP) score for predicting of survival in Hepatocellular Carcinoma Patients Treated with Transcatheter Arterial Chemoembolization.

BACKGROUND: Both modified Child-Pugh (MCP) and Albumin-bilirubin (ALBI) grade were reported that simpler, more objective and evidence-based alternative to the Child-Pugh (CP) class for assessing liver function. AIMS: To investigate whether the MCP and ALBI grade could better evaluate the liver reserve of Hepatocellular Carcinoma (HCC) patients treated with TACE (transcatheter arterial chemoembolization) than CP grade. METHODS: Three hundred seventy-six consecutive HCC patients treated with TACE between December 2007 and October 2011 were enrolled. The baseline characteristics and clinical information were collected. Homogeneity and discriminatory ability were compared between the MCP grade and ALBI class or CP grade. RESULTS: Compared with the CP and ALBI, the MCP grade had a higher predictive accuracy for overall survival (OS) in terms of homogeneity and discriminatory ability. Most of the HCC patients had CP class A disease (84.0%) at presentation, and within this CP class, although the ALBI grade revealed two clear and nonoverlapping groups, the MCP grade revealed three clearly different prognostic groups. Both in the ALBI grade 1 or ALBI grade 2 group, the MCP grade still showed a significant progressive decrease in OS from the smallest to the largest grades, but the CP class was unsatisfactory in stratifying these patients. CONCLUSIONS: The stratification ability and prognostic predictive power of the MCP grade for HCC patients treated with TACE may be better than that of the ALBI grade or CP class.

Downstaging Outcomes for Hepatocellular Carcinoma: Results From the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) Consortium.

BACKGROUND & AIMS: United Network of Organ Sharing (UNOS) has adopted uniform criteria for downstaging (UNOS-DS) of hepatocellular carcinoma (HCC) before liver transplantation (LT), but the downstaging success rate and intention-to-treat outcomes across broad geographic regions are unknown. METHODS: In this first multiregional study (7 centers, 4 UNOS regions), 209 consecutive patients with HCC undergoing downstaging based on UNOS-DS criteria were prospectively evaluated from 2016 to 2019. RESULTS: Probability of successful downstaging to Milan criteria and dropout at 2 years from the initial downstaging procedure was 87.7% and 37.3%, respectively. Pretreatment with lectin-reactive α-fetoprotein ≥10% (hazard ratio, 3.7; P = .02) was associated with increased dropout risk. When chemoembolization (n = 132) and yttrium-90 radioembolization (n = 62) were compared as the initial downstaging treatment, there were no differences in Modified Response Evaluation Criteria In Solid Tumors response, probability of or time to successful downstaging, waiting list dropout, or LT. Probability of LT at 3 years was 46.6% after a median of 17.2 months. In the explant, 17.5% had vascular invasion, and 42.8% exceeded Milan criteria (understaging). The only factor associated with understaging was the sum of the number of lesions plus largest tumor diameter on the last pre-LT imaging, and the odds of understaging increased by 35% per 1-unit increase in this sum. Post-LT survival at 2 years was 95%, and HCC recurrence occurred in 7.9%. CONCLUSION: In this first prospective multiregional study based on UNOS-DS criteria, we observed a successful downstaging rate of >80% and similar efficacy of chemoembolization and yttrium-90 radioembolization as the initial downstaging treatment. A high rate of tumor understaging was observed despite excellent 2-year post-LT survival of 95%. Additional LRT to reduce viable tumor burden may reduce tumor understaging.

Treatment efficacy and safety of regorafenib plus drug-eluting beads-transarterial chemoembolization versus regorafenib monotherapy in colorectal cancer liver metastasis patients who fail standard treatment regimens.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of regorafenib plus drug-eluting beads-transarterial chemoembolization (DEB-TACE) versus regorafenib monotherapy in colorectal cancer liver metastases (CRLM) patients who failed standard treatment regimens. METHODS: Totally, 76 eligible CRLM patients were analyzed, among which 42 patients received regorafenib monotherapy (as regorafenib group) and 34 patients received regorafenib plus DEB-TACE (as regorafenib plus DEB-TACE group). RESULTS: Objective response rate (35.3% versus 7.1%, P = 0.002) and disease control rate (76.5% versus 47.6%, P = 0.011) were both increased in regorafenib plus DEB-TACE group compared with regorafenib group; meanwhile, negative conversion rate of carcinoembryonic antigen (66.7% versus 28.6%, P = 0.008) after treatment was elevated in regorafenib plus DEB-TACE group compared with regorafenib group. Notably, progression-free survival (PFS) (median value: 7.6 versus 4.1 months, P < 0.001) and overall survival (OS) (median value: 15.7 versus 9.2 months, P < 0.001) were both higher in regorafenib plus DEB-TACE group compared with regorafenib group. Furthermore, liver function indexes (alanine transaminase, aspartate aminotransferase, and cholinesterase levels) after treatment were all similar between the two groups (all P > 0.05). In addition, the occurrences of upper abdominal distending pain (P < 0.001), nausea and vomiting (P = 0.002) and fever (P = 0.002) were higher in regorafenib plus DEB-TACE group compared with regorafenib group, while the majority of these adverse events were mild and tolerable. CONCLUSIONS: Regorafenib plus DEB-TACE is superior to regorafenib monotherapy regarding treatment response, PFS and OS, while induces tolerable post-embolization syndrome in CRLM patients who fail standard treatment regimens.

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.

Hepatic Toxicity After Selective Chemoembolization Is Associated With Decreased Survival Among Patients With Hepatocellular Carcinoma.

OBJECTIVE. The purpose of this study was to identify risk factors for and outcomes of hepatotoxicity after selective chemoembolization of hepatocellular carcinoma. MATERIALS AND METHODS. This retrospective study included 182 patients (136 men and 46 women; median age, 63 years [interquartile range, 57-70 years]) who underwent 338 consecutive doxorubicin drug-eluting bead (DEB) chemoembolization procedures between 2011 and 2014. Outcomes were assessed until November 2019. In 97% of procedures, two or fewer segments were targeted. The Barcelona Clinic Liver Cancer (BCLC) stage was 0 or A for 77 procedures (22.8%), B for 75 (22.2%), C for 122 (36.1%), and D for 64 (18.9%). Hepatotoxicity was defined as worsened ascites or encephalopathy or as grade 3 or 4 elevations in liver function test results, creatinine levels, or the international normalized ratio within 30 days. Risk factors were assessed by univariate and multivariable generalized estimating equations. Transplant-free survival was assessed using Cox proportional hazard models. RESULTS. Hepatotoxicity was observed after 84 of 338 procedures (24.9%) performed for 70 of 182 patients (38.5%) and was irreversible for 40 procedures (11.8%). On multivariable analysis, risk factors for irreversible toxicity included Child-Pugh class C liver function (odds ratio [OR], 4.4; 95% CI, 1.0-19.0; p = .04), BCLC stage C (OR, 5.0; 95% CI, 1.6-16.0; p = .006) or D (OR, 7.4; 95% CI, 2.1-25.5; p = .002) disease, TIPS or hepatofugal portal venous flow (OR, 6.3; 95% CI, 2.3-17.0; p < .001), and a serum α-fetoprotein level of 200 ng/mL or greater (OR, 2.6; 95% CI, 1.1-6.1; p = .03). Irreversible toxicity was associated with reduced transplant-free survival among patients who were ineligible for liver transplant (hazard ratio, 2.5; standard error, 0.42; p = .03). CONCLUSION. Irreversible hepatotoxicity was common after selective chemoembolization in patients with advanced stage disease, an elevated serum α-fetoprotein level, or reduced hepatic portal venous perfusion, and it may hasten death among patients who are ineligible for liver transplant.

Changing trends in hepatocellular carcinoma management: Results from a nationwide database in the last decade.

OBJECTIVE: The therapeutic strategies for hepatocellular carcinoma (HCC) have greatly expanded in recent years. However, the actual usage of each of these treatments in clinical routine remains unknown. Here, we analysed the distribution and changes of the main surgical and radiological therapeutic procedures nationwide during the last decade. METHODS: Retrospectively, analysis of the data on all >18-year-old patients with a diagnosis of HCC identified in the French Program for the Medicalization of Information Systems database that contains all discharge summaries from all French hospitals. The number and percentage of the therapeutic procedures performed from January 2010 to December 2019 were extracted. RESULTS: A total of 68,416 therapeutic procedures were performed in 34,000 HCC patients. Whereas HCC incidence remained stable, the annual number of procedures frankly increased over the decade (from 4267 to 8042). Trans-arterial chemoembolization was the most frequently performed technical procedure, with a double-digit annual growth from 2010 (n = 1932) to 2015 (n = 4085), before stabilization from 2016. Selective internal radiation therapy displayed the highest increase in the decade (+475%). Among curative treatments, the annual number of percutaneous tumour ablations more than doubled in 10 years, till representing 64% of curative treatments in cirrhotic patients in 2019. Surgical tumour resections showed a 1.5-fold increase in 10 years, due to the great increase in minimally invasive approaches, whereas the proportion of open resection progressively decreased. CONCLUSION: Minimally invasive procedures have gained major importance in HCC management during the last decade. Percutaneous thermal ablation has emerged as the first curative treatment performed for patients with HCC.

Outcome of TACE treatment in HIV infected patients with hepatocellular carcinoma.

The surgical treatment and transcatheter arterial chemoembolization (TACE) rate of human immunodeficiency virus (HIV)-infected hepatocellular carcinoma (HCC) patients is relatively low in West China. For various reasons, most patients do not receive timely surgical treatment. Upon transfer to an infectious disease centralized hospital, they were already classified in the Barcelona Clinic Liver Cancer (BCLC)-B stage. A total of 2249 BCLC-B HCC patients were analyzed. The eligible population was divided into three groups for analysis of survival and prognostic factors; These were 21 HIV infected (HIV+) HCC patients treated with TACE (TACE+), 1293 non-HIV-infected (HIV-) HCC patients treated with TACE, and 150 HIV- HCC patients who only receive medication (TACE-) as a second control group. After 1:2 matching, 1- and 2-year survival of HIV+ TACE+ and HIV- TACE+ groups was 64.3% and 76.5% (P = 0.453) and 45.5% vs. 50.0% (P = 0.790) respectively. We also compared one and two-year survival between HIV+ TACE+ and HIV- TACE-. One-year overall survival was 64.3% vs. 45.7% (P = 0.097) and 2-year survival was 45.5% vs. 7.1% (P = 0.004). Multivariate analysis showed that the most important prognostic factors for survival were serum alpha-fetoprotein (AFP) and Child-Pugh score and tumor size, while HIV status had no significant effect on prognosis statistically. CD4 levels below 200 may increase the risk of opportunistic infection after surgery, but after anti-infection and systematic supportive therapy, it has no effect on survival. HIV+ patients should have the same treatment opportunities as HIV- patients. If the patient's immune status permits, we suggest that early TACE treatment should be administered to BCLC-B HCC patients, regardless of HIV infection.

Prognostic value of serum HIF-1α change following transarterial chemoembolization in hepatocellular carcinoma.

Transarterial chemoembolization (TACE) induces a change in serum HIF-1α level in patients with hepatocellular carcinoma (HCC). This study investigated the prognostic value of change in serum HIF-1α following TACE treatment in HCC patients. A total of 61 hepatocellular carcinoma patients treated with TACE were included. Peripheral blood samples were collected within 1 week before and after TACE to determine the serum levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) by enzyme-linked immunosorbent assay (ELISA). Serum HIF-1α change was calculated as follows: ∆HIF-1α = (HIF-1α (pre-TACE) - HIF-1α (post-TACE))/HIF-1α (pre-TACE). Likewise, serum VEG-F change was calculated as follows: ∆VEG-F = (VEG-F (pre-TACE) - VEG-F(post-TACE))/VEG-F (pre-TACE). Based on the cutoffs (0.25) determined by the maximum Youden's index in receiver operating characteristic analysis, the patients were grouped into the low ∆HIF-1α group (< 0.25) and the high ∆HIF-1α group (> 0.25). After TACE treatment, HIF-1α was significantly decreased (pre-TACE 1901.62 vs. post-TACE 621.82 pg/ml, P < 0.01) but VEGF-A was significantly increased (pre-TACE 60.80 vs. post-TACE 143.81 pg/ml, P < 0.01). Multivariate logistic regression analysis demonstrated that ∆HIF-1α was a prognostic factor (OR = 58.09, 95% CI: 1.59-2127.32, P = 0.027) for the TACE treatment response. Furthermore, multivariate Cox regression analysis revealed that ∆HIF-1α was a prognostic factor for progression-free survival (PFS) (HR = 0.30, 95% CI: 0.14-0.66, P = 0.003) and overall survival (OS) (estimated HR = 0.38, 95% CI: 0.16-0.93, P = 0.034). Kaplan-Meier survival analysis showed that the high ∆HIF-1α group was more likely to have longer PFS (log-rank test, P = 0.004) and OS (log-rank test, P = 0.002) than the low ∆HIF-1α group. The change in serum HIF-1α level following TACE is a prognostic factor associated with the TACE treatment response, PFS, and OS in HCC patients following TACE.

Analysis of Patient Outcome after Non-curative Resection for Hepatocellular Carcinoma Using Nationwide Survey Data in Japan.

BACKGROUND: Non-curative (debulking) hepatic resection for hepatocellular carcinoma (HCC) is occasionally applied for selected cases with bulky tumors or for oncologic emergency cases; however, the clinical usefulness of this procedure has not yet been fully evaluated. The aim of the present study was to evaluate the patient outcomes of non-curative hepatic resections for HCC using data from bi-annual nationwide surveys conducted in Japan. METHOD: Data of 1084 non-curative hepatic resections for HCC were collected. The patient outcomes were compared with those of curative resections, transcatheter arterial chemoembolization (TACE), and hepatic arterial infusion chemotherapy (HAIC). RESULTS: Patient survival after the non-curative resection was poorer than that after curative resection (P < 0.001) and was especially dismal in cases with extrahepatic tumor spread (lymph node metastasis, peritoneal seeding, or distant metastasis). As compared to cases receiving TACE without surgery, non-curative resections for multiple intrahepatic tumors were applied to cases with advanced tumors with good liver functional reserve. The survival outcomes were significantly more favorable in the TACE group, but the results became similar after propensity score matching of the patients. The survival outcome of patients receiving non-curative resections was better than that of cases treated by HAIC, with median survival times of 26.0 months and 10.0 months, respectively. CONCLUSION: The indications for non-curative hepatic resection in patients with HCC should be judged cautiously, especially in patients with extrahepatic tumor spread. This treatment approach may be beneficial for selected patients with intermediate- or advanced-stage HCC limited in liver and with good liver functional reserve.

γ-Glutamyltranspeptidase as a Prognostic Biomarker in Advanced Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.

PURPOSE: To evaluate the prognostic value of pretreatment serum γ-glutamyltransferase (GGT) level in patients with advanced hepatocellular carcinoma (HCC) receiving transarterial chemoembolization. MATERIALS AND METHODS: This retrospective study included 140 patients (123 male, 17 female; mean age, 56.9 y ± 12.0; range, 22.0-82.0 y) with Barcelona Clinic Liver Cancer class C HCC who received first-line conventional chemoembolization between December 2013 and March 2018. Patients were divided into low and high GGT groups based on a cutoff value calculated with a receiver operating characteristic curve. Overall survival (OS) was compared between groups by log-rank test. Univariate and multivariate survival analyses were performed. RESULTS: The optimal cutoff values of GGT were 119.5 U/L in men and 175.0 U/L in women. The 6-, 9-, and 12-mo OS rates were 81.7%, 72.4%, and 62.9%, respectively, for patients in the low GGT group (n = 44) and 58.8%, 35.7%, and 28.8%, respectively, for patients in the high GGT group (n = 96; P < .001). Multivariable Cox regression analysis identified high pretreatment serum GGT level (hazard ratio [HR], 2.71; 95% confidence interval [CI], 1.67-4.40; P < .001), multiple tumors (HR, 3.05; 95% CI, 1.23-7.53; P = .02), and performance of target treatment (ie, sorafenib; HR, 0.41; 95% CI, 0.24-0.72; P = .002) or ablation (HR, 0.35; 95% CI, 0.18-0.66; P = .001) as independent prognostic factors for OS. CONCLUSIONS: Pretreatment serum GGT level was an independent prognostic factor for OS in patients with advanced HCC treated with chemoembolization, suggesting that GGT is a useful prognostic biomarker for advanced HCC.

Response rate and safety in patients with hepatocellular carcinoma treated with transarterial chemoembolization using 40-µm doxorubicin-eluting microspheres.

PURPOSE: To evaluate the response rate and safety of superselective drug-eluting beats transarterial chemoembolization (DEB-TACE) with doxorubicin-loaded 40-µm microspheres in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and forty-one treatments with doxorubicin-loaded 40-µm microspheres in 83 patients between 2012 and 2017 were retrospectively evaluated. Images of the treated lesions were analyzed before and after each treatment according to mRECIST (modified Response Evaluation Criteria in Solid Tumors). Therapy response (complete response [CR] + partial response [PR]) and disease control (CR + PR + stable disease [SD]) rates were determined, and the correlation between the longitudinal axis (longest diameter of the tumor) and volume was investigated using a newly developed software for systematic tumor response assessment. Additional endpoints were progression-free survival (PFS) and time to progression (TTP). RESULTS: In the target tumors, a therapy response rate of 63.1% and a disease control rate of 95.7% were achieved. There was a good correlation between the measurement of the longitudinal axis and volume of the measured lesion (r value, 0.954). The median PFS was 2.23 months, and the median TTP was 5.91 months. The serious adverse event rate (SAE) was 10.64%. CONCLUSION: Superselective DEB-TACE with 40-µm sized Embozene Tandem™ can be considered an effective and safe treatment, given the number of procedure-related complications.

Prognostic impact of adjuvant chemolipiodolization and treatment frequency on patients with hepatocellular carcinoma after hepatectomy: Prospective study with historical control group.

BACKGROUND: Reducing or minimizing metastatic recurrence is a consideration in prolongation of survival of patients with hepatocellular carcinoma. We previously proposed single adjuvant chemolipiodolization (ACL) as a possible adjuvant treatment. The current study aims to further improve prognosis by performing ACL three times (sequential-ACL). METHODS: We examined the prognostic impact of sequential-ACL compared with our historical cohort groups: resection alone (non-ALC) and single-ACL. We evaluated recurrence-free survival (RFS), recurrence pattern, and overall survival. Multivariate prognostic analyses were used to adjust baseline bias between three treatment groups. RESULTS: Non-ACL (n = 64), single-ACL (n = 137), and sequential-ACL (n = 95) showed 40, 54, and 62% of two-year RFS rates (P = 0.03 and P = 0.007 compared with non-ACL). Recurrence pattern beyond Milan criteria was frequently observed in the non-ACL group (P = 0.003). Five-year overall survival rates of these three groups were 53, 69, and 77% (P = 0.02 and 0.002 compared with non-ACL). Single- and sequential-ACL were selected as independent favorable factors for five-year overall survival; their hazard ratios (95% confidence interval) were 0.61 (0.37-0.99) and 0.48 (0.26-0.86). However, compared with single-ACL, there was no additional prognostic effects of sequential-ACL. CONCLUSIONS: Single- and sequential-ACL treatment both showed better RFS and overall survival with minimized recurrence patterns than resection alone. There was not sufficient additional benefit by sequential-ACL, however, over single-ACL. Single-ACL might therefore be appropriate as an adjuvant therapy.

Comparison of Drug-Eluting Embolics versus Conventional Transarterial Chemoembolization for the Treatment of Patients with Unresectable Hepatocellular Carcinoma: A Cost-Effectiveness Analysis.

PURPOSE: To compare the cost-effectiveness of using doxorubicin-loaded drug-eluting embolic (DEE) transarterial chemoembolization versus that of using conventional transarterial chemoembolization for patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A decision-analysis model was constructed over the lifespan of a payer's perspective. The model simulated the clinical course, including periprocedural complications, additional transarterial chemoembolization or other treatments (ablation, radioembolization, or systemic treatment), palliative care, and death, of patients with unresectable HCC. All clinical parameters were derived from the literature. Base case calculations, probabilistic sensitivity analyses, and multiple two-way sensitivity analyses were performed. RESULTS: In the base case calculations for patients with a median age of 67 years (range for conventional transarterial chemoembolization: 28-88 years, range for DEE-transarterial chemoembolization: 16-93 years), conventional transarterial chemoembolization yielded a health benefit of 2.11 quality-adjusted life years (QALY) at a cost of $125,324, whereas DEE-transarterial chemoembolization yielded 1.71 QALY for $144,816. In 10,000 Monte Carlo simulations, conventional transarterial chemoembolization continued to be a more cost-effective strategy. conventional transarterial chemoembolization was cost-effective when the complication risks for both the procedures were simultaneously varied from 0% to 30%. DEE-transarterial chemoembolization became cost-effective if the conventional transarterial chemoembolization mortality exceeded that of DEE-transarterial chemoembolization by 17% in absolute values. The two-way sensitivity analyses demonstrated that conventional transarterial chemoembolization was cost-effective until the risk of disease progression was >0.4% of that for DEE-transarterial chemoembolization in absolute values. Our analysis showed that DEE-transarterial chemoembolization would be more cost-effective if it offered >2.5% higher overall survival benefit than conventional transarterial chemoembolization in absolute values. CONCLUSIONS: Compared with DEE-transarterial chemoembolization, conventional transarterial chemoembolization yielded a higher number of QALY at a lower cost, making it the more cost-effective of the 2 modalities.

Effectiveness of stereotactic body radiotherapy for portal vein tumor thrombosis in patients with hepatocellular carcinoma and underlying chronic liver disease.

AIM: Stereotactic-body radiotherapy (SBRT) is a treatment option for portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC). Here, we report on our experience of treating PVTT using SBRT in patients with concomitant underlying chronic liver disease. METHODS: This study included 24 patients. The initial prescription dose was 45 Gy in three fractions in 17 (70.8%) patients, but it was modified in the remaining seven (29.2%) patients, with the dose ranging from 39 to 42 Gy in 3-4 fractions. After SBRT, transarterial chemoembolization (TACE) was performed in 16 (66.7%) patients. RESULTS: Of the 24 patients, 2 (8.3%) showed complete response, while 11 (45.8%) showed partial response. After a median follow-up of 8.4 months (range: 2.6-56.5 months), the 1-year overall survival (OS) and the median survival were 67.5% and 20.8 months, respectively. Both combined SBRT and TACE and grade ≥3 hepatic toxicity affected the 1-year OS (SBRT alone vs SBRT + TACE: 14.6% vs 71.4%, P < .001; presence of hepatic toxicity vs absence: 0% vs 81.1%, P = .002). CONCLUSIONS: Overall, SBRT, especially in combination with TACE, is an effective treatment for patients with HCC and PVTT. An optimal dose schedule must be followed to reduce hepatic toxicity while maintaining tumor response.