BCLC-C Stage Research Articles

Association of serum AFP trajectories and hepatocellular carcinoma outcomes after hepatic arterial infusion chemotherapy: A longitudinal, multicenter study.

This study aims to investigate α-fetoprotein (AFP) trajectories for prediction of survival outcomes after hepatic arterial infusion chemotherapy (HAIC) treatment in large hepatocellular carcinoma (HCC). From May 2014 to June 2020, 889 eligible patients with large HCC underwent HAIC were retrospectively enrolled from five hospitals. A latent class growth mixed (LCGM) model was applied to distinguish potential AFP level dynamic changing trajectories. Inverse-probability-of-treatment weighted (IPTW) analyses were performed to eliminate unmeasured confounders through marginal structural models. Multivariate Cox proportional hazard regression analyses were used to determine the overall survival (OS) in patients with large HCC. Performance of these serum markers for survival prediction was compared by areas under receiver operating characteristic analysis with the Delong test. The median follow-up time was 23.7 (interquartile range, 3.8-115.3). A total of 1009 patients with large HCC, who underwent HAIC with AFP repeatedly measured 3-10 times, were enrolled in the study. Three distinct trajectories of these serum AFP were identified using the LCGM model: high stable (37.0%; n = 373), low stable (15.7%; n = 159), and sharp-falling (47.3%; n = 477). Multivariate Cox proportional hazard regression analyses found that ALBI stage 2-3, BCLC-C stage and high-stable AFP trajectories were associated with OS. AFP trajectories yield the optimal predictive performance in all risk factors. The AFP trajectories based on longitudinal AFP change showed outstanding performance for predicting survival outcomes after HAIC treatment in large HCC, which provide a potential monitoring tool for improving clinical decision-making.

A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma.

Given its heterogeneity and diverse clinical outcomes, precise subclassification of BCLC-C hepatocellular carcinoma (HCC) is required for appropriately determining patient prognosis and selecting treatment. We recruited 2,626 patients with BCLC-C stage HCC from multiple centers, comprising training/test (n=1,693) and validation cohorts (n=933). The XGBoost was chosen for maximum performance among the machine learning (ML) models. Patients were categorized into low-/intermediate-/high-/very high-risk subgroups which were based on the estimated prognosis, and this subclassification was named the CLAssification via Machine learning of BCLC-C (CLAM-C). The areas under the receiver operating characteristic curve of the CLAM-C for predicting the 6-/12-/24-month survival of patients with BCLC-C were 0.800/0.831/0.715, respectively-significantly higher than those of the conventional models, which was consistent in the validation cohort. The four subgroups had significantly different median overall survivals, and this difference was maintained among various patient subgroups and treatment modalities. Immune-checkpoint inhibitors and transarterial therapies were associated with significantly better survival than tyrosine kinase inhibitors (TKIs) in the low- and intermediate-risk subgroups. In cases with first-line systemic therapy, the CLAM-C identified atezolizumab-bevacizumab as the best therapy particularly in the high-risk group. In cases with later-line systemic therapy, nivolumab had better survival than TKIs in the low-to-intermediate-risk subgroup, whereas TKIs had better survival in the high-to-very high-risk subgroup. ML modeling effectively subclassified patients with BCLC-C HCC, potentially aiding treatment allocation. Our study underscores the potential utilization of ML modeling in terms of prognostication and treatment allocation in patients with BCLC-C HCC.

Diagnostic accuracy of serum protein induced by vitamin K absence (PIVKA-II), serum a-fetoprotein and their combination for hepatocellular carcinoma among Caucasian cirrhotic patients with diagnostic or non-diagnostic serum a-fetoprotein levels.

The aim of our study was to evaluate the accuracy of serum biomarkers (AFP/PIVKA-II) and their combination in HCC diagnosis among Caucasian cirrhotic patients. Serum AFP/PIVKA-II levels were evaluated in 218 cirrhotics (163 males, 118 CTP-A, 66 ALBI-I, 111 with varices, 63 with diabetes) with (n = 90) or without (n = 128) HCC. Patients with HCC were categorized to BCLC Stage 0/A (n = 12), B (n = 21), C (n = 48), and D (n = 9). The two groups were comparable for all baseline parameters except for age, platelets, and diabetes presence. Median levels of AFP (239.1 vs. 4.0 ng/mL) and PIVKA-II (4082.7 vs. 45.8 mAU/mL) were both significantly higher in HCC group compared to controls (p < 0.001). AUROC and cutoff value for HCC diagnosis were 88%/12.35 ng/mL (AFP) and 84.4%/677.13 mAU/mL (PIVKA-II), whereas their combination showed better diagnostic accuracy (AUROC = 90.2%). The diagnostic accuracy of each biomarker separately was moderate or good in BCLC-0/A/B and was excellent only for BCLC-C patients (AFP: AUROC = 94.3%, cutoff = 12.35 ng/mL and PIVKA-II: 91.3%, 253.51 mAU/mL) whereas their combination presented quite acceptable results in BCLC-B (AUROC = 92.4%) and BCLC-C (AUROC = 95.7%). Excluding HCC patients with high AFP (above 400 ng/mL), the diagnostic accuracy of each biomarker separately and their combination was moderate/good in all groups, except for their combination in BCLC-C (AUROC = 90.5%). Each biomarker separately showed acceptable accuracy for detecting HCC in cirrhotic patients and excellent for those in BCLC-C stage. The combination of the biomarkers presented excellent results in BCLC-B/C patients. The diagnostic accuracy of PIVKA-II and the combination of the two biomarkers in patients expressing low/non-diagnostic AFP levels was good in BCLC-B and excellent in BCLC-C patients.

Survival benefit of resectability determined by multiple surgeons in BCLC-C stage: a single-center cohort study

Survival benefit of resectability determined by multiple surgeons in BCLC-C stage: a single-center cohort study

Efficacy of atezolizumab-bevacizumab combination therapy early after recurrence of hepatocellular carcinoma following resection or ablation with a curative intent.

The pattern of hepatocellular carcinoma (HCC) recurrence after resection/ablation is intrahepatic and/or systemic. The efficacy of atezolizumab-bevacizumab treatment as early therapy after recurrence has not been extensively evaluated. We evaluated 32 patients (group A) with early HCC recurrence after resection/ablation and 24 patients (group B) initially diagnosed as Barcelona Clinic Liver Cancer (BCLC)-C, all treated with atezolizumab-bevacizumab. Group A was subdivided in group A1 (progression to BCLC-C, n=14) and group A2 (progression to BCLC-B, n=18). Groups A1/A2 were comparable for all baseline parameters. Objective response was observed in 14.3% and 33.3% of patients in groups A1 and A2, respectively. Median overall survival (OS) was impressive and comparable between the 2 groups (22 and 26 months, respectively, P=0.71), as was median progression-free survival (PFS) (15 and 6 months, respectively, P=0.126). Patients categorized in the advanced stage (groups A1/B) were comparable for all baseline characteristics. Median OS was significantly higher in group A1 compared to B (26 vs. 6 months, P<0.001), as was median PFS (6 vs. 3 months, P=0.086). Early initiation of atezolizumab-bevacizumab after recurrence following curative therapy results in impressive survival rates, irrespective of recurrence pattern. Survival of atezolizumab-bevacizumab treated patients who were initially diagnosed in the BCLC-C stage is significantly different from those who recurred to BCLC-C following potentially curative therapies.

A multi-institutional study to predict the benefits of DEB-TACE and molecular targeted agent sequential therapy in unresectable hepatocellular carcinoma using a radiological-clinical nomogram.

Exploring the efficacy of a Radiological-Clinical (Rad-Clinical) model in predicting prognosis of unresectable hepatocellular carcinoma (HCC) patients after drug eluting beads transcatheter arterial chemoembolization (DEB-TACE) to optimize the targeted sequential treatment. In this retrospective analysis, we included 202 patients with unresectable HCC who received DEB-TACE treatment in 17 institutions from June 2018 to December 2022. Progression-free survival (PFS)-related radiomics features were computationally extracted from HCC patients to build a radiological signature (Rad-signature) model with least absolute shrinkage and selection operator regression. A Rad-Clinical model for postoperative PFS was further constructed according to the Rad-signature and clinical variables by Cox regression analysis. It was presented as a nomogram and evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis. And further evaluate the application value of Rad-Clinical model in clinical stages and targeted sequential therapy of HCC. Tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, and radiomics score (Rad-score) were found to be independent risk factors for PFS after DEB-TACE treatment for unresectable HCC, with the Rad-Clinical model being the greatest predictor of PFS in these patients (hazard ratio: 2.08; 95% confidence interval: 1.56-2.78; P < 0.001) along with high 6months, 12months, 18months, and 24months area under the curves of 0.857, 0.810, 0.843, and 0.838, respectively. In addition, compared to the radiomics and clinical nomograms, the Radiological-Clinical nomogram also significantly improved the classification accuracy for PFS outcomes, based on the net reclassification improvement (45.2%, 95% CI 0.260-0.632, p < 0.05) and integrated discrimination improvement (14.9%, 95% CI 0.064-0.281, p < 0.05). Based on this model, low-risk patients had higher PFS than high-risk patients in BCLC-B and C stages (P = 0.021). Targeted sequential therapy for patients with high and low-risk HCC in BCLC-B stage exhibited significant benefits (P = 0.018, P = 0.012), but patients with high-risk HCC in BCLC-C stage did not benefit much (P = 0.052). The Rad-Clinical model may be favorable for predicting PFS in patients with unresectable HCC treated with DEB-TACE and for identifying patients who may benefit from targeted sequential therapy.

Effect of vessels that encapsulate tumor clusters (VETC) on the prognosis of different stages of hepatocellular carcinoma after hepatectomy.

Vessels that encapsulate tumor clusters (VETC) is a newly discovered vascular pattern in hepatocellular carcinoma (HCC), representing high biological aggressiveness. However, it remains unclear whether the prognostic impact of VETC differs in patients with different staged HCC. This study aimed to evaluate the effect of VETC on the prognosis of patients with HCC at different stages after hepatectomy. Patients who underwent hepatectomy for HCC between January 2005 and December 2019 were assessed, and stratified according to their Barcelona Clinic Liver Cancer (BCLC) stage. Overall survival (OS) and disease-free survival (DFS) were compared between patients with and without VETC. Independent risk factors of OS and DFS were determined by multivariable Cox regression analyses. A total of 837 consecutive patients undergoing curative hepatectomy were enrolled, and VETC pattern was found in 339 (40.5%) patients. The incidence of VETC in patients at BCLC-0, BCLC-A, BCLC-B and BCLC-C stage was 17.8%, 40.2%, 53.7% and 66.0%, respectively. In the entire patients, VETC+ patients had significantly lower OS and DFS than VETC- patients. After stratification of patients according to BCLC stage, VETC was associated with worse OS and DFS only in patients at BCLC-A and BCLC-B stages, but not in those at BCLC-0 and BCLC-C stages. Multivariable analyses also revealed that VETC was an independent risk factor for OS and DFS in both the patients at BCLC-A and BCLC-B stages. VETC is associated with poor OS and DFS in patients with HCC at BCLC-A and BCLC-B stage after hepatectomy, but it does not affect the survival of patients with HCC at BCLC-0 and BCLC-C stage after hepatectomy.

Efficacy of Αtezolizumab-Βevacizumab in BCLC-C cirrhotic patients with hepatocellular carcinoma according to the type of disease progression, the type of BCLC-C and liver disease severity.

The aim of our study was to evaluate, under real-life conditions, survival of patients with advanced HCC (BCLC-C), either initially presenting in that stage or migrating from BCLC-A to BCLC-C within 2years after curative LR/RFA, treated either with Atezolizumab-Bevacizumab or TKIs. Sixty-four cirrhotic patients with advanced HCC, who either initially presented as BCLC-C and were treated with Atezo-Bev (group A, N = 23) or TKIs (group B, N = 15) or who migrated from BCLC-A to BCLC-C stage within 2years after LR/RFA and were either treated with Atezo-Bev (group C, N = 12) or TKIs (group D, N = 14), were retrospectively evaluated. The four groups were comparable for all baseline parameters (demographics/platelets/liver disease etiology/diabetes/varices/Child-Pugh stage/ALBI grade) except for CPT score and MELD-Na. Using Cox-regression analysis, we observed that survival of group C after systemic treatment onset was significantly higher compared to group A (HR 3.71, 1.20-11.46, p = 0.02) and presented a trend to statistical significance when compared to group D (HR 3.14, 0.95-10.35, p = 0.06), adjusted for liver disease severity scores. When all BCLC-C patients classified as such due to PS only were excluded from the study, a trend for the same survival benefit in group C was shown, even in the most difficult-to-treat population with extrahepatic disease or macrovascular invasion. Cirrhotic patients with advanced HCC initially diagnosed in BCLC-C, exhibit the worst survival irrespective of treatment schedule, whereas patients progressing to BCLC-C following disease recurrence after LR/RFA, seem to mostly benefit from Atezo-Bev, even patients with extrahepatic disease and/or macrovascular invasion. Liver disease severity seems to drive survival of these patients.

Efficacy of atezolizumab/bevacizumab combination therapy in BCLC-C cirrhotic patients with hepatocellular carcinoma (HCC) according to the type of disease progression.

557 Background: HCC recurs in 70-80% of cases following potentially curative liver resection (LR) or radiofrequency ablation (RFA) and the immune component of the liver microenvironment plays a key role in early recurrence. The aim of our study was to retrospectively evaluate, under real life conditions, the overall survival (OS) of patients with advanced HCC (BCLC-C stage), either initially presented in the advanced stage or migrating from BCLC-A to BCLC-C stage within 2 years after curative LR or RFA, treated either with atezolizumab-bevacizumab (ATZ/BEV) combination or with TKIs sequentially (sorafenib as first line and cabozantinib as second line treatment). Methods: Sixty cirrhotic patients with advanced HCC (53 males, mean age 67y, 35% with diabetes, CPT-A=68.3%/CPT-B=28.3%, mean MELD/Na=11, ALBI grade I=28.3%/ALBI grade II=61.7%, 45% with varices) who either initially presented on the BCLC-C stage and were treated with ATZ/BEV (group A, N=19) or TKIs (group B, N=15) or who migrated from BCLC-A to BCLC-C stage within 2 years after LR or RFA and were treated with ATZ/BEV (group C, N=12) or TKIs (group D, N=14) were evaluated. Results: The four groups were comparable for all the baseline parameters evaluated (age p=0.9, gender p=0.1, platelets p=0.4, chronic liver disease etiology p=0.6, coexistence of diabetes p=0.3, presence of varices p=0.1, CPT stage p=0.1, ALBI grade p=0.3). Median OS was significantly higher for group C patients (mean survival 33.7m, median OS was not reached at the time of evaluation) compared to group D (mOS=27m), group A (mOS=13m) and group B (mOS=8m) patients, as presented in figure 1. It is important to note that the survival after HCC recurrence for group C patients (mean survival=18.2m, median OS was not reached at the time of evaluation) was significantly higher compared to those of group D patients (mOS=9m). Conclusions: Median survival of TKI-treated patients after HCC recurrence is less than 12m and is comparable to survivals observed in patients who initially classified in BCLC-C stage, irrespective of treatment schedule. ATZ/BEV combination therapy significantly prolongs survival in patients after early HCC recurrence, a finding that strongly supports the rationale for adjuvant ATZ/BEV therapy in high risk of recurrence patients.

Effects of Clonorchis sinensis combined with Hepatitis B virus infection on the prognosis of patients with Hepatocellular Carcinoma following Hepatectomy.

This study aimed to determine the impact of co-infection of Clonorchis sinensis (CS) and hepatitis B virus (HBV) on the prognosis of patients with hepatocellular carcinoma (HCC) following hepatectomy. The clinicopathological information of 946 patients with HCC following hepatectomy was retrospectively analyzed. The patients were divided into four groups depending on whether they had CS infection and/or HBV infection: double-negative group (infected with neither CS nor HBV), simple CS group (infected with only CS), simple HBV group (infected with only HBV), and double-positive group (co-infected with CS and HBV). Kaplan-Meier curves were used to evaluate the overall survival (OS) and recurrence-free survival (RFS), while log-rank tests were used to compare survival rates. Further, Cox regression was used to perform both univariate and multivariate survival analyses to identify variables linked to the prognosis of HCC. The median overall survival (OS) and recurrence-free survival (RFS) in the double-positive, simple CS, simple HBV, and double-negative groups were 27 months and 9 months, 20 months and 7 months, 44 months and 12 months, and 42 months and 17 months, respectively. The double-positive group's 1-year, 3-year, and 5-year OS and RFS rates were 79.2% and 46.9%, 62.6% and 28.4%, 47.8%, and 12.2%, respectively. The simple CS group's 1-year, 3-year, and 5-year OS and RFS rates were 86.3% and 41.5%, 56.5% and 27.7%, 50.2%, and 18.5%, respectively. The simple HBV group's 1-year, 3-year, and 5-year OS and RFS rates were 89.8% and 56.0%, 72.5% and 30.5%, 63.8%, and 19.9%, respectively. The double-negative group's 1-year, 3-year, and 5-year OS and RFS rates were 91.5% and 62.3%, 76.1% and 32.9%, 64.0%, and 22.4%, respectively. Further, according to a Cox multivariate analysis, tumor size (> 5cm), Edmonson grade (III-IV), BCLC-C stage, and tumor satellite focus were independent risk factors for RFS and OS in patients with HCC. Patients with HCC and Clonorchis sinensis infection experience a poor prognosis after hepatectomy, regardless of whether they are co-infected with HBV.

Barcelona Clinic Liver Cancer: A Narrative Review

To plan therapies for Hepatocellular Carcinoma (HCC), staging methods are necessary. The most often employed HCC management recommendation is the Barcelona Clinic Liver Cancer (BCLC) staging system. Transarterial Chemoembolisation (TACE) is the go- to therapy for BCLC stage B (intermediate HCC). Numerous studies back the use of TACE in individuals with early and advanced HCC. TACE may be an option for individuals who are not candidates for Radiofrequency Ablation (RFA) or Hepatic Resection (HR) for BCLC stage 0 (very early HCC). TACE with RFA offers superior local tumour suppression than RFA alone in BCLC stage. Patients awaiting liver transplants may benefit from TACE as a bridging treatment. When compared to supportive care approaches, TACE improves survival for BCLC-B patients. Patients with BCLC-C stage HCC are treated in the first instance with sorafenib. The combination of sorafenib and TACE has demonstrated efficacy in slowing the development of tumours. Patients with HCC and portal venous thrombosis have superior survival results with TACE combined with radiation. Taking all of these facts into account, it is obvious that TACE, either alone or in conjunction with other therapies, plays a crucial part in the treatment of HCC at every stage. Patients with HCC should get a variety of treatments, and the best TACE candidates should be chosen using a more accurate patient classification approach.

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma.

Combination atezolizumab/bevacizumab is the gold standard for first-line treatment of unresectable hepatocellular carcinoma (HCC). Our study investigated the efficacy and safety of combination therapy in older patients with HCC. 191 consecutive patients from eight centres receiving atezolizumab and bevacizumab were included. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in older (age ≥ 65 years) and younger (age < 65 years) age patients. Treatment-related adverse events (trAEs) were evaluated. The elderly (n=116) had higher rates of non-alcoholic fatty liver disease (19.8% vs. 2.7%; p < .001), presenting with smaller tumours (6.2cm vs 7.9cm, p=.02) with less portal vein thrombosis (31.9 vs. 54.7%, p=.002), with fewer patients presenting with BCLC-C stage disease (50.9 vs. 74.3%, p=.002). There was no significant difference in OS (median 14.9 vs. 15.1 months; HR 1.15, 95% CI 0.65-2.02 p=.63) and PFS (median 7.1 vs. 5.5 months; HR 1.11, 95% CI 0.54-1.92; p=.72) between older age and younger age. Older patients had similar ORR (27.6% vs. 20.0%; p=.27) and DCR (77.5% vs. 66.1%; p=.11) compared to younger patients. Atezolizumab-related (40.5% vs. 48.0%; p=.31) and bevacizumab-related (44.8% vs. 41.3%; p=.63) trAEs were comparable between groups. Rates of grade ≥3 trAEs and toxicity-related treatment discontinuation were similar between older and younger age patients. Patients 75 years and older had similar survival and safety outcomes compared to younger patients. Atezolizumab and bevacizumab therapy is associated with comparable efficacy and tolerability in older age patients with unresectable HCC.

A novel sub-staging system for prognosis prediction of Barcelona clinic liver cancer C stage hepatocellular carcinoma: 10 years observational study.

e16139 Background: This study sought to propose a novel sub-staging system which could predict prognosis of patients with Barcelona clinic liver cancer (BCLC) C stage Hepatocellular carcinoma (HCC). Methods: Between January 2008 and September 2018, 806 patients with BCLC-C stage HCC were assessed retrospectively. The significance of clinical variables in predicting prognosis were statistical analysis. A prognostic sub-staging system of BCLC-C stage HCC was developed according to prognosis-related factors. The predictive performance was subsequently validated. Results: In training set, tumor burden (TB) &gt;50%, type III/IV portal vein tumor thrombus (PVTT), extrahepatic metastasis (M) and Child-Pugh (CP) B class were independently associated with overall survival (OS). According to those prognosis-related factors, a novel sub-staging system of BCLC-C stage was “linear predictor= TB+PVTT+M+CP”, which had good performance in predicting OS in both training and validation set. The thirtieth percentile and the third quartile of the linear predictor, namely 6 and 12, were selected as cut-off values, stratifying patients into different OS after interventional therapy (IT) or sorafenib therapy (ST), specifically, ≤6: 43.7 months for IT, 32.0 month for ST;＞6 but＜12: 43.7 months for IT, 32.0 month for ST; ≥12: 43.7 months for IT, 32.0 month for ST. Conclusions: The novel sub-staging system of BCLC-C stage HCC may stratify patients for suitable therapy and predict individual survival with favorable performance and discrimination.

Comparing Liver Resection versus Sorafenib in BCLC-C Patients: A National Weighted Multicentric Study in a Real Scenario

Introduction: The treatment of hepatocellular carcinoma (HCC) in BCLC-C stage is still controversial. The aim of the study was to compare the overall survival (OS) of patients treated with surgery (SURG) vs. Sorafenib (SOR) in a national cohort. Methods: BCLC-C patients without extra-hepatic spread were considered. Surgical patients were enrolled from the Hepatocarcinoma-Recurrence-on-the-Liver-Study (HE.RC.O.LE.S.) Register, while Sorafenib patients from the Italian-Liver-Cancer (ITA.LI.CA.) Register. Inverse Probability Weighting (IPW) was used to weight the confounders. Results: Between 2008 and 2019, 478 patients were eligible, 303 in SURG and 175 in SOR group. ECOG PS, presence of cirrhosis, steatosis, Child-score, HBV, HCV, alcohol intake, collateral veins, bilobar disease, localization of the tumor thrombus, number of nodules, age and Charlson Comorbidity index were weighted by IPW to create two balanced pseudo-populations (SURG=374 and SOR=263). After IPW, 1-3-5 years OS was 83.6%, 68.1% and 55.9% and 42.3%, 17.8% and 12.8% for SURG and SOR, respectively (p<0.001, figure 1). Surgery achieved longer OS also in case of ECOG-PS>0, and in any intra-hepatic localization of the tumor thrombus. After adjustment for confounders, being treated by SOR rather than by SURG was an independent predictor of mortality (HR: 4.436; 95%CI: 3.197-6.156; p<0.001), together with a point-increase of the Charlson Index (HR: 1.162; 95%CI: 1.062-1.271; p: 0.010). Conclusions: In BCLC-C patients surgical resection, when feasible, guarantees an increased survival compared to systemic treatment.

Transarterial Chemoembolization Combined with Sorafenib in Patients with BCLC Stage C Hepatocellular Carcinoma.

PurposeTranscatheter arterial chemoembolization (TACE) and targeted therapy have become common methods in the treatment of advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the safety and efficacy of TACE combined with sorafenib (TACE-sorafenib) and TACE alone for the treatment of Barcelona clinical stage C HCC.MethodsThe clinical data of 75 patients with BCLC stage C HCC who received TACE-sorafenib or TACE as the initial treatment were retrospectively analyzed. Tumor response, time to progression (TTP), overall survival (OS), and adverse events were compared at 1 month after surgery in the two groups.ResultsOne month after treatment, the disease control rate in the TACE-sorafenib group was higher than that in the TACE group alone (82.76% and 57.50%, respectively, P = 0.018). The median values of TTP and OS in the TACE-sorafenib group were longer than those in the TACE group (TTP was 7.6 and 3.4 months, respectively, P = 0.002; OS was 13.6 and 6.3 months, respectively, P = 0.041). The cumulative survival time at 3 months, 6 months, and 1 year was higher in the TACE-sorafenib group than in the TACE group (83.5%, 71.2%, 45.7% vs 57.4%, 40.6%, 21.2%). Sorafenib-related side effects such as hypertension, hand-foot syndrome, and oral ulcers were more common than those in the TACE group alone (P<0.05).ConclusionCompared with TACE treatment alone, TACE combined with sorafenib in BCLC-C stage HCC significantly improved disease control rate, TTP, and OS, and no significant increase in adverse reactions was observed.

Real-World Outcomes of Nivolumab in Patients With Unresectable Hepatocellular Carcinoma in an Endemic Area of Hepatitis B Virus Infection.

Real-world results of nivolumab monotherapy against HCC are lacking in the hepatitis B virus (HBV)-endemic, Asia-Pacific regions. Moreover, heterogeneous responses to immune checkpoint inhibitors have rarely been described in advanced HCC. The aim of this study is to evaluate the efficacy and safety of nivolumab monotherapy in a real-world setting in 33 Korean patients with unresectable HCC. In our cohort, twenty-nine patients (88%) showed HBsAg positivity. At the time of nivolumab initiation, 4 among 33 patients (12%) were classified as Barcelona Clinic Liver Cancer (BCLC)-B stage and 29 (88%) as BCLC-C stage, respectively. Prior sorafenib treatment was given to 31 (94%) patients, and 13 (39%) received prior regorafenib treatment. For the liver reserve, patients were classified as Child–Pugh class A (79%) and B (21%), respectively. Grade 3 toxicities occurred in one patient, who developed pneumonitis after 5 cycles of nivolumab treatment. Best overall responses were complete response in 2 patients out of the 33 enrolled patients (6%), partial response in 4 patients (12%) and stable disease in 4 patients (12%). With 29 patients having images for the response evaluation, the objective response rate was 21.4%. The median overall survival (OS) of the cohort was 26.4 weeks (range 2.3–175.1). Achieving objective responses, pre-treatment small tumors (maximal diameter <5 cm) and favorable liver function as assessed by Albumin–Bilirubin grade were significant factors for the favorable OS. Interestingly, differential responses to nivolumab among multiple tumors in a single patient were noted in 6 patients (18%). In these patients, small metastatic tumors were regressed, although their larger tumors did not respond to nivolumab monotherapy. In summary, nivolumab treatment seems clinically efficacious in treating unresectable HCC in an endemic area of HBV infection. Further prospective evaluation is required to overcome the heterogeneous efficacy of nivolumab monotherapy according to the baseline tumor burden.

Impact of baseline and concomitant corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy.

531 Background: The impact of corticosteroid treatment (CT) on the efficacy of immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) is undefined. We evaluated whether CT administered at baseline (bCT) or concurrently to ICI (cCT) influences clinical outcomes of HCC patients treated with ICI. Methods: This retrospective, multi-center observational study was conducted across 9 tertiary academic referral centers collected 341 HCC patients who received ICI across 3 continents between January 1, 2016 and April 1, 2019. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from time of ICI commencement and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1) on 6-8 weekly periodic restaging. Results: Of 331 eligible patients, 254 (76%) had BCLC-C stage HCC and received mostly PD(L)-1 ICI monotherapy (n=250, 85%). Median OS was 12.1 months (95%CI 9.2-15.0 months) and median PFS was 8.1 months (95%CI 6.3-10 months). In total 81 patients (24%) received &gt;10 mg prednisone equivalent daily either as bCT (n=15, 4%) or cCT (n=66, 20%). Indications for CT included procedure/prophylaxis (n=37, 45%), management of irAE (n=31, 37%), cancer-related symptoms (n=5, 2%) or comorbidities (n=8, 3%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in uni- and multi-variable analyses (p&gt;0.05). CT for cancer-related indications predicted for shorter PFS (2.4 vs. 11.3 months, p=0.01), OS (4.5 vs. 12.8 months, p=0.05) and reduced ORR (p=0.03) compared to cancer-unrelated indications. Conclusions: This is the first study to demonstrate that neither bCT nor cCT appear to influence response and OS following ICI in HCC. Worse survival and ORR in CT recipients for cancer-related indications appears driven by the poor prognosis associated with symptomatic HCC.

Myopenia as a significant prognostic factor in BCLC-B intermediate-stage hepatocellular carcinoma treated with sorafenib.

e15639 Background: Tyrosine kinase inhibitors (TKI) are important treatment options for unresectable hepatocellular carcinoma (HCC). The survival benefit of sorafernib was demonstrated not only in advanced stage but also for BCLC-B intermediate stage who are refractory to transcatheter arterial chemoembolization by OPTIMIS study. Skeletal muscle mass depletion (Myopenia) is a poor prognostic factor in HCC treated by resection or loco-reginal ablation, but its effect on survival in TKI treated patients, especially in those within BCLC-B stage remains unclear. The aim of the present study is to elucidate the impact of myopenia on survival among HCC treated with sorafenib, especially in BCLC-B stage. Methods: In 213 patients who started treatment with sorafenib between 2009 and 2016, myopenia at baseline was determined by using skeletal muscle index calculated from CT images of the third lumber vertebra level. The impact of myopenia on survival was analyzed in whole patients, after stratification by BCLC stage, and after matching for backgrounds within BCLC-B patients. Results: The median survival in whole, BCLC-C, and –B was 13.7, 8.7 and 15.2 months, respectively. Myopenia was not a significant prognostic factor in whole patients and in BCLC-C stage. However, among BCLC-B patients (n = 104), survival was significantly better in patients with no myopenia (p = 0.05). Among them, 85 patients who continued sorafenib for more than 8 weeks were extracted and those with or without myopenia were matched for backgrounds by propensity score. Backgrounds including etiology, Child-Pugh score, BMI, AFP and PIVKA-Ⅱwas not different between myopenia (n = 30) and no myopenia group (n = 30) after matching. The overall survival at 6-, 12-, and 24-months was 96%, 74%, and 62% in no myopenia group which was significantly better compared to 89%, 64%, and 28% in myopenia group (p = 0.019). The hazard ratio was 2.12 (95% CI 1.11-4.03). Conclusions: Absence of myopenia predicts favorable outcome in sorafenib treated HCC patients within BCLC-B intermediate stage.

18F-fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment.

Sorafenib, an oral multikinase inhibitor, is a recommended treatment option available for patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). This study aimed to evaluate the performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) for predicting tumour progression during sorafenib treatment. We formed a retrospective cohort comprising patients treated with sorafenib for at least 30days and undergoing 18F-FDG PET/CT within 1month before treatment. For statistical analyses, the tumour-to-liver standardised uptake value (SUV) ratio (TLR) of the most hypermetabolic lesion was measured. Among a total of 35 patients, two obtained partial remission, and 11 showed stable disease after the first response evaluation. Patients with a TLR≥2.9 (n=17) had a median overall survival (OS) of 3.7months after sorafenib treatment, whereas patients with a TLR<2.9 (n=18) had median OS of 12.2months (P<0.001), although the disease control rate was not significantly different between the two groups. Pretreatment TLR≥2.9 (hazard ratio [HR]=6.318, P=0.002) and Child-Pugh class B (HR=4.316, P=0.044) were poor prognostic factors for OS, and a TLR≥2.9 (HR=2.911, P=0.024) was the only poor prognostic factor for progression-free survival in a multivariate analysis. Pretreatment tumour metabolic activity assessed by 18F-FDG PET is an independent prognostic factor for survival in patients with BCLC-C stage HCC receiving sorafenib monotherapy, although it may not predict tumour response to the treatment.

Mo1429 - Prognostic Factors for Survival of BCLC-C Stage Hepatocellular Carcinoma Patients According to Previous Treatments: A Real-Life Experience

Mo1429 - Prognostic Factors for Survival of BCLC-C Stage Hepatocellular Carcinoma Patients According to Previous Treatments: A Real-Life Experience