Barcelona Clinic Liver Cancer Stage Research Articles

Prevalence and Risk Factors of Post-chemoembolization Syndrome After Chemo-Embolization for Hepatocellular Carcinoma in Thailand.

The data regarding the incidence of post-embolization syndrome after transarterial chemoembolization for hepatocellular carcinoma in Thailand are scarce. Therefore, this study aimed to determine the prevalence and predictors of post-embolization syndrome after transarterial chemoembolization for hepatocellular carcinoma in Thailand. This retrospective study collected data from patients undergoing transarterial chemoembolization for five years. Post-embolization syndrome was defined as fever and/or abdominal pain, and/or nausea or vomiting that occurred within three days after the transarterial chemoembolization procedure for hepatocellular carcinoma or hospital discharge. Pre-defined predictors for post-embolization syndrome were explored using Poisson regression analysis. Of the 298 patients and 739 transarterial chemoembolization procedures, the incidence of post-embolization syndrome was 68.1% (203/298) and the incidence density was 53.9% (398/739). Tumor size, Barcelona Clinic Liver Cancer stages, and dose of chemotherapy showed no association with the occurrence of PES. However, a model for end-stage liver disease score was the only predictor for post-embolization syndrome [adjusted IRR 0.91 (0.84-0.98); p = 0.01]. There were three patients developing fever after transarterial chemoembolization due to infection. Post-embolization syndrome was common in patients undergoing transarterial chemoembolization for hepatocellular carcinoma. Patients with a lower model for end-stage liver disease scores were at increased risk of post-embolization syndrome. This study highlights the burden of post-embolization syndrome among patients with hepatocellular carcinoma receiving transarterial chemoembolization.

Factors influencing the prognosis patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma undergoing salvage surgery after conversion therapy.

The aim of this study was to investigate the prognostic factors influencing the outcome of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma (HCC) receiving salvage surgery after conversion therapy based on tyrosine kinase inhibitors (TKIs) and anti-programmed death-1 (PD-1) antibodies. From June 2018 to December 2022, patients receiving salvage surgery after conversion therapy based on PD-1 and TKIs at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital were retrospectively recruited for this study. Overall survival (OS) and recurrence-free survival (RFS) were observed as the primary end point in the Cox analysis of prognostic factors among this study. The 6- and 12-month RFS rates were 77.0% and 64.8%, respectively, while the 6-, 12-, 24-, and 36-month OS rates were 98.4%, 93.4%, 76.8%, and 69.8%, respectively. The median OS and RFS were not reached. On multivariable Cox regression analyses, low serum alpha fetoprotein (AFP) level (≤20 ng/mL) after conversion therapy [hazard ratio (HR) 0.186, 95% CI: 0.039-0.887; P=0.035) and microvascular invasion (MVI) grade II (HR 3.054, 95% CI: 1.000-9.329; P=0.050) were independent factors associated with a higher OS and RFS. For patients with Barcelona Clinic Liver Cancer stage C (BCLC-C) HCC, lower AFP level after conversion therapy (<20 ng/mL) and MVI II were associated with a higher OS and lower RFS rate, respectively.

Profil Klinis dan Kesintasan Pasien Karsinoma Sel Hati di Rumah Sakit Rujukan Tersier Indonesia Tahun 2015-2021

Introduction. Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world and Indonesia. This study aimed to describe the clinical presentation and survival rate of HCC patients in Dr. Cipto Mangunkusumo Hospital (RSCM) as the Indonesian tertiary referral hospital in year 2015-2021 Methods. Cohort study was performed in year 2015-2021. Clinical presentations at the time of diagnosis were recorded from electronical health record. All HCC patients were followed up until death. One-year survival based on staging was assessed using log rank test and presented with Kaplan Meier curve. Results. A total of 799 HCC patients were included. Majority of HCC patients were male, 619 patients (77.5%), and aged 55 (SD 11.9) years. Hepatitis B was the major etiology, found in 500 patients (62.6%). Median of alfa feto-protein (AFP) was 1,109 (0.8-3,462,499) ng/ml. At the time of diagnosis, Barcelona Clinic Liver Cancer (BCLC) stage C (37.7%) was the most commonly found. Portal vein thrombosis was found in 205 patients (25.7%). There were 271 (33.9%) HCC patients received curative and palliative treatment, and others had supportive care. One year survival rate of HCC was 61.2%. One year survival rate of HCC based on staging for BCLC A, BCLC B, BCLC C, and BCLC D were 91.1%, 68.6%, 47.6%, and 13.3%, respectively (log-rank test: p&lt;0.001). Conclusion. The majority of patients diagnosed with HCC were at an advanced stage so that the one-year survival is poor.

Integrated exome sequencing and microarray analyses detected genetic defects and underlying pathways of hepatocellular carcinoma

We performed whole exome sequencing (WES) and microarray analysis to detect somatic variants and copy number alterations (CNAs) for underlying mechanisms in a case series of hepatocellular carcinoma (HCC) with paired DNA samples from tumor and adjacent nontumor tissues. Clinicopathologic findings based on Edmondson-Steiner (E-S) grading, Barcelona-Clinic Liver Cancer (BCLC) stages, recurrence, and survival status and their associations with tumor mutation burden (TMB) and CNA burden (CNAB) were evaluated. WES from 36 cases detected variants in the TP53, AXIN1, CTNNB1, and SMARCA4 genes, amplifications of the AKT3, MYC, and TERT genes, and deletions of the CDH1, TP53, IRF2, RB1, RPL5, and PTEN genes. These genetic defects affecting the p53/cell cycle control, PI3K/Ras, and β-catenin pathways were observed in approximately 80% of cases. A germline variant in the ALDH2 gene was detected in 52% of the cases. Significantly higher CNAB in patients with poor prognosis by E-S grade III, BCLC stage C, and recurrence than patients with good prognosis by grade III, stage A, grade III and nonrecurrence was noted. Further analysis on a large case series to correlate genomic profiling with clinicopathologic classifications could provide evidence for diagnostic interpretation, prognostic prediction, and target intervention on involved genes and pathways.

Nomogram to Predict the Long-Term Overall Survival of Early-Stage Hepatocellular Carcinoma after Radiofrequency Ablation

Our objective was to develop a predictive nomogram that could estimate the long-term survival of patients with very early/early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA). For this retrospective study, we enrolled 950 patients who initially received curative RFA for HCC at Barcelona Clinic Liver Cancer (BCLC) stages 0 and A between 2002 and 2016. Factors predicting poor survival after RFA were investigated through a Cox proportional hazard model. The nomogram was constructed using the investigated variables influencing overall survival (OS). After a median follow-up time of 6.25 years, 400 patients had died, and 17 patients had received liver transplantation. The 1-,3-,5-,7-, and 10-year OS rates were 94.5%, 73.5%, 57.9%, 45.7%, and 35.8%, respectively. Multivariate analysis showed that age greater than 65 years, albumin-bilirubin (ALBI) grades 2 and 3, AST-to-platelet ratio index (APRI) greater than 1, tumor size larger than 3 cm, diabetes mellitus, end-stage renal disease, and tumor number greater than 1 were significantly associated with poor OS. The nomogram was constructed using these seven variables. The validation results showed a good concordance index of 0.683. When comparing discriminative ability to tumor, node, and metastasis (TNM), BCLC, and Cancer of the Liver Italian Program (CLIP) staging systems, our nomogram had the highest C-index for predicting mortality. This nomogram provides useful information on prognosis post-RFA as a primary treatment and aids physicians in decision-making.

Factors predictive of clinical outcome in advanced hepatocellular carcinoma patients receiving ramucirumab treatment: A real-world experience.

The aim of this study was to investigate the factors predictive of clinical outcome in advanced hepatocellular carcinoma patients receiving ramucirumab treatment. We conducted a retrospective study using a multi-institutional electronic medical records database in Taiwan. We included advanced HCC patients newly receiving ramucirumab as second-line or beyond systemic therapy between January 2016 and February 2022. The clinical outcomes were median progression-free survival (PFS) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST), overall survival (OS) and adverse events. We applied Kaplan-Meier methods to estimate median PFS and OS. Uni-variable and multi-variable Cox regression models were applied to identify the prognostic factors. We included 39 ramucirumab naive users with a median age of 65.5 (IQR: 57.0-71.0) years and treatment time of 5.0 (3.0-7.0) cycles, of whom 82.1% were male and 84.6% were Barcelona Clinic Liver Cancer (BCLC) stage C. After median follow-up time of 6.0 months, 33.3% of patients' AFP level had decreased more than 20% within 12 weeks. The median PFS and OS were 4.1 months and non-reach, respectively. Moreover, tumor burden beyond the up-to-11 criteria (HR: 2.95, 95% CI: 1.04-8.38) and a decrease in estimated glomerular filtration rate of more than 10% within 12 weeks (HR: 0.31, 0.11-0.88) were significantly related to PFS in the multi-variable analysis. No patient discontinued ramucirumab during the treatment on account of side effects. Ramucirumab was an effective treatment option with good AFP response for advanced HCC patients in real-world experience. Tumor burden beyond the up-to-11 criteria and a decrease in estimated glomerular filtration rate were independent predictive factors for progression-free survival.

Efficacy and safety of regorafenib and PD-1 combined with cryoablation in the treatment of advanced hepatocellular carcinoma after second-line targeted therapy.

e16151 Background: Targeted therapy is the most effective therapeutic approach for middle and late-stage hepatocellular carcinoma (HCC). Regorafenib or PD-1 as a second-line treatment of patients with advanced HCC has achieved good results. Argon-helium cryoablation is one commonly used method for local ablation of liver cancer. Whether systemic therapy combined with local therapy can benefit patients with advanced liver cancer is a hot topic. This study is aimed to investigate the efficacy and safety of regorafenib and PD-1 combined with cryoablation in the treatment of patients with advanced HCC after the failure of second-line targeted treatment. Methods: In this retrospective study, unresectable HCC patients received regorafenib and PD-1combined with cryoablation after the failure of second-line targeted treatment from January 2019 to December 2021 were enrolled. Depending on whether combining local therapy, patients were grouped as RP (regorafenib and PD-1), or RPC groups (regorafenib and PD-1 combined with cryoablation). Objective response rate (ORR), disease control regorafenib rate (DCR), progression free survival (PFS), and safety were recorded. The PFS was defined as the time from the first dose of RP, or from the time of using RPC until disease progression or death. Results: A total of 50 patients were reviewed, including 21 patients in RP group and 29 patients in RCP group. One patient was classified as Barcelona Clinic Liver Cancer (BCLC) stage B and 20 patients were at BCLC stage C in RP group, while one patient was at BCLC stage B and 28 patients were at BCLC stage C in RPC group. The ORR and DCR were 4.8% and 23.8% in PR group respectively, and 31.0% and 69.0% in RPC group respectively. The 6-month PFS rate of RP group and RPC group was 14.3% and 53.6% respectively. Thirteen (61.9%) and eighteen (62.1%) patients experienced adverse events (AEs) in two groups respectively. Two (9.5%) and three (10.7%) patients experienced grade 3 AEs that occurred in RP group and RPC group respectively. The most frequency AE was hand-foot-skin reaction in both groups (58.0% and 50.0%, respectively). No patient discontinued regorafenib and PD-1 due to AE in these two groups. Conclusions: Regorafenib and PD-1 combined with cryoablation showed potential anti-tumor effect and tolerance on unresectable HCC after the failure of second-line targeted treatment. [Table: see text]

Tislelizumab (TIS) versus sorafenib (SOR) in first-line (1L) treatment of unresectable hepatocellular carcinoma (HCC): The RATIONALE-301 European/North American (EU/NA) subgroup.

4082 Background: HCC is one of the most commonly diagnosed cancers globally. Most cases occur in Asia, although a number of patients (pts) are affected in Europe and North America. In the phase 3, open-label RATIONALE-301 trial (NCT03412773), TIS, a PD-1 inhibitor, showed non-inferior overall survival (OS) versus SOR (hazard ratio 0.85, 95% CI: 0.71, 1.02), and a favorable safety profile, in 1L treatment of pts with unresectable HCC. Here, efficacy and safety of TIS versus SOR in the RATIONALE-301 EU/NA subgroup were compared with the overall population (OP). Methods: Systemic therapy-naïve adults with histologically confirmed HCC were randomized (1:1) to receive TIS (200 mg IV Q3W) or SOR (400 mg orally BID) until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was OS; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and duration of response (DoR) by blinded independent review committee per RECIST v1.1, and safety. Results: In the EU/NA subgroup (172/674 pts randomized), at data cutoff (July 11, 2022), median (m) OS follow-up was 37.9 months (mo) (TIS) vs 38.5 mo (SOR). At baseline, fewer pts in the EU/NA subgroup had Barcelona Clinic Liver Cancer (BCLC) Stage C disease (70% vs 78%) and extrahepatic spread (51% vs 62%), and more had a non-viral etiology (60% vs 24%) or underlying HCV infection (28% vs 13%) than in the OP, respectively. Distribution of other baseline characteristics was generally similar between the EU/NA subgroup and the OP. Efficacy data in the EU/NA subgroup were consistent with the OP. Numerically longer mOS and mDoR, higher ORR, and similar mPFS were observed with TIS versus SOR in the EU/NA subgroup. In the EU/NA safety population, incidence of ≥grade 3 treatment-emergent adverse events (TEAEs; 46% vs 66%), ≥grade 3 treatment-related TEAEs (TRAEs; 17% vs 50%), and TRAEs leading to discontinuation (9% vs 15%) was lower with TIS versus SOR, respectively, similar to the OP. Conclusions: In the RATIONALE-301 EU/NA subgroup, mOS of TIS was non-inferior versus SOR, consistent with the findings from the OP. Numerically longer mOS and mDoR, and a higher ORR was seen with TIS versus SOR in the EU/NA subgroup, which had a higher rate of pts with non-viral etiology and a slightly lower number of pts with advanced-stage disease (BCLC Stage C) compared with the OP. Clinical trial information: NCT03412773 . [Table: see text]

Effect of urokinase-type plasminogen activator combined with clinical stage and Barcelona Clinic Liver Cancer stage on the prognosis of patients with hepatocellular carcinoma.

The aim of this investigation is to evaluate the association and potential mechanism between plasminogen activator urokinase (PLAU) and the prognosis of patients with liver hepatocellular carcinoma (LIHC). We verified PLAU expression and its correlation with LIHC patients' prognosis in The Cancer Genome Atlas (TCGA) database. The interaction network for protein-gene was established in the GeneMania database and the STRING database, and the association between PLAU and immune cells was assessed in Tumor Immune Estimation Resource (TIMER) and TCGA databases. The potential physiological mechanism was elucidated by the Gene Set Enrichment Analysis (GSEA) enrichment assessment. Finally, the individual clinical data of 100 LIHC patients were retrospectively evaluated to further analyze the clinical value of PLAU. The PLAU expression in LIHC tissues was greater than in paracancerous tissues, and LIHC patients with low PLAU expression had better disease-specific survival (DSS), overall survival (OS), and progression free interval (PFI) than those with high PLAU expression. In the TIMER database, the PLAU expression was positively associated with six kinds of infiltrating immune cells: CD4+ T, neutrophils, CD8+ T, macrophages, B, and dendritic cells, while GSEA enrichment analysis indicated PLAU may impact the biological activities of LIHC by taking part in MAPK and JAK_STAT signaling pathways, angiogenesis, and P53. There were statistically significant differences in T-stage and Edmondson grading between the two groups of patients with high and low expression of PLAU (P<0.05). The tumor progression rates were 88% (44/50) and 92% (46/50) respectively in the low and high PLAU groups, with early recurrence rates of 60% (30/50) and 72% (36/50), and median PFS of 29.5 and 23 months, respectively. The COX regression analysis showed PLAU expression and CS and Barcelona Clinic Liver Cancer (BCLC) stages were independent prognostic factors affecting tumor progression in LIHC patients. The decreased expression of PLAU can prolong the DSS, OS, and PFI in LIHC patients, and can be utilized as a novel predictive index. PLAU combined with CS staging and BCLC staging has good clinical value in the early screening and prognosis of LIHC. These results reveal an efficient approach for developing anticancer strategies against LIHC.

Impact of risk factors on overall survival (OS) in patients (pts) with unresectable hepatocellular carcinoma (HCC) treated with first-line (1L) tislelizumab (TIS).

4083 Background: TIS is a monoclonal antibody with high affinity and specificity for programmed cell death protein 1. In the phase 3 RATIONALE-301 trial (NCT03412773), TIS demonstrated non-inferior OS versus sorafenib (SOR) as 1L monotherapy for unresectable HCC (median [m] OS 15.9 [TIS] vs 14.1 [SOR] months [mo]; hazard ratio [HR] 0.85), with a favorable safety profile. Certain biomarkers are potential prognostic factors and may impact OS in 1L treatment of unresectable HCC; this exploratory analysis examined the effect of albumin-bilirubin (ALBI) grade, platelet count, platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR) as predictors of OS in RATIONALE-301. Methods: Systemic therapy-naïve adults with histologically confirmed HCC (Barcelona Clinic Liver Cancer Stage C or Stage B that was not amenable to or progressed after loco-regional therapy; Child-Pugh A), with ≥1 measurable lesion per RECIST v1.1, and an ECOG performance status ≤1 were randomized 1:1 to receive TIS (200 mg IV Q3W) or SOR (400 mg orally BID) until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was OS. Results: Overall, 674 pts were randomized (TIS n=342; SOR n=332). At data cutoff (July 11, 2022), minimum study follow-up was 33 mo. Demographic and baseline characteristics for biomarkers were generally balanced across arms. Numerically longer (≥2 mo) mOS was observed in biomarker subgroups ALBI grade 1 vs 2 and NLR ≤3 vs &gt;3 with TIS or SOR, and PLR ≤141 vs &gt;141 with TIS. Both platelet count threshold subgroups were accompanied by a smaller difference (&lt;2 mo) in mOS between biomarker cutoffs, which may indicate limited prognostic value for this biomarker. TIS also demonstrated numerically longer OS versus SOR in the same subgroup categories: ALBI grade 1, PLR ≤141, and NLR ≤3. Conclusions: This analysis suggests that ALBI grade, PLR, and NLR could have prognostic value for OS, irrespective of treatment. TIS demonstrated numerically improved mOS compared with SOR for PLR ≤141 and NLR ≤3, suggesting higher benefit for pts with a more favorable balance between systemic inflammation and immunity. Clinical trial information: NCT03412773 . [Table: see text]

Safety and Efficacy of Drug-Eluting Bead Transarterial Chemoembolization Combined with Lenvatinib and Anti-PD-1 Antibodies for Unresectable Hepatocellular Carcinoma: A Retrospective Analysis.

Drug-eluting bead transarterial chemoembolization (DEB-TACE) has good efficacy in the treatment of unresectable hepatocellular carcinoma (uHCC), with a relatively high objective response rate (ORR) compared to conventional transarterial chemoembolization (cTACE). This study aimed to evaluate the safety and medium-term clinical efficacy of DEB-TACE combined with lenvatinib (LEN) plus PD-1 inhibitors as a triple therapy for the treatment of uHCC. Data of patients with uHCC who received triple therapy of DEB-TACE combined with LEN plus PD-1 inhibitors from January 2019 to June 2021 were analyzed retrospectively. The study endpoints were ORR, progression-free survival (PFS), and treatment-related adverse events based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Thirty-five patients were included in this study, with a median follow-up period of 15 months. The median cycle of DEB-TACE was 1, while that of all forms of TACE procedures per patient was 2. The median administration time of LEN was 7 months, and the median number of PD-1 inhibitor treatment was 4 cycles. The ORR based on mRECIST was 82.9%, disease control rate was 91.4%, and the median time to response was 7 weeks. Among these, the ORR of Barcelona Clinic Liver Cancer (BCLC) stage A reached 100%, while that of BCLC stages B and C reached 84.6% and 78.9%, respectively. The median PFS was 9 months; the mOS was not reached. Fourteen patients (40%) successfully underwent downstaging conversion and surgical resection, 32 patients (91.4%) experienced treatment-related adverse events, and no grade 5-related adverse reactions occurred. DEB-TACE combined with LEN and PD-1 inhibitors has a high ORR and surgical conversion rate in the treatment of uHCC tumors, and the toxicity and side effects were tolerable.

Efficacy and safety of radiotherapy combined with regorafenib for advanced hepatocellular carcinoma: A real-world study from a single center.

e16142 Background: This study aimed to assess the efficacy and safety of radiotherapy (RT) combined with regorafenib as a second or further-line treatment for advanced hepatocellular carcinoma (HCC). Methods: Patients diagnosed with advanced HCC who had received RT combined with concurrent or sequential regorafenib treatment or regorafenib plus anti-PD-1 or anti-PD-L1 immune checkpoint inhibitors (ICIs) in our hospital from April 2018 to August 2022 were reviewed. Progression-free survival (PFS) was the primary endpoint. Overall survival (OS), objective response rate (ORR), disease control rate (DCR) and toxicity were the secondary endpoints. Results: Fifty-four patients were included with a median age of 56 (38-73). Forty-six patients (85.2%) were in Barcelona Clinic Liver Cancer (BCLC) stage C. Thirty-seven patients (68.5%) had portal vein tumor thrombosis and 15 (27.8%) had extrahepatic metastasis. All patients received intensity modulated radiation therapy, while 26 patients were concurrently treated with regorafenib and 28 patients were sequentially treated with regorafenib. The median dose of radiotherapy was 57.2Gy (30-69.8Gy). Anti-PD-1/anti-PD-L1 agents were applied to 31 patients at the use of regorafenib. The median PFS was 11.3 months. The 3-year PFS and OS were 23.8% and 51.9%, respectively. Treatment response after RT was shown. For tumor in in-field of RT, ORR was 75.9% and 92.6% according to RECIST and mRECIST criteria, respectively. No progression was found in in-field of RT. Out-field recurrence in liver and distance metastasis was the main failure pattern. For all lesions, the ORR was 40.7% and DCR was 55.6%, respectively. There was no significant difference of PFS and OS between patients with and without ICIs ( p &gt; 0.05). Univariate analysis showed that alpha-fetoprotein tumor marker level ≥ 1000 ng/ml ( p = 0.049), Albumin-Bilirubin grade ≥ 2 ( p = 0.012) and multiple intrahepatic tumors ( p = 0.031) were the risk factors of lower PFS. Patients were well tolerated to the treatments. The most common grade 3 toxicities were hand-foot syndrome (11.1%), fatigue (3.7%) and hypertension (1.9%). Classical or non-classical radiation-induced liver disease was not noted. Conclusions: Radiotherapy concurrently or sequentially with regorafinib treatment is an effective, well tolerated, and promising regimen in advanced HCC patients. [Table: see text]

Real world impact of hepatocellular carcinoma stage and hepatic function on health-related quality of life.

e16215 Background: Health-Related Quality of Life (HRQoL) is an important prognostic indicator and clinical endpoint for patients with hepatocellular carcinoma (HCC). The relationship between cancer stage, liver function, performance status, and HRQoL in HCC in a real-world clinical setting is not well defined. Methods: A retrospective chart review was undertaken of consecutive patients with HCC treated at our institution's liver multidisciplinary clinic between February 2020 and August 2022. We examined the relationship between Barcelona Clinic Liver Cancer (BCLC) stage, Child Pugh (CP) score, and Eastern Cooperative Oncology Group (ECOG) performance status on HRQoL at diagnosis. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. Results: Fifty-one patients met our inclusion criteria. The median age was 69 and the mean FACT-Hep score was 130.3 ± 20.3. FACT-Hep total and subscales showed no significant association with BCLC stages A, B, and C (p =0.224), except in the Emotional Well Being (EWB) subscale (p =0.001). There was no impact of ECOG performance status on the FACT-Hep scores, except for the Functional Well Being (FWB) subscale (p=0.006). Patients with a CP B had significantly more impairment in FACT-Hep than patients with CP A, including FACT-Hep total score (118.5 ±27.3 versus 134.3 ±23.8; p =0.021) and subscales including the Physical Well Being (p =0.018), FWB (p =0.030), Hepatobiliary Cancer Subscale (p &lt;0.001), and FACT-Hep Trial Outcome Index score (p =0.003). Conclusions: Cancer stage poorly correlates with HRQoL at diagnosis in HCC patients. Impaired liver function reduces overall quality of life in HCC patients. Further large-scale prospective studies should be undertaken which incorporate validated HRQoL tools in the routine assessment of HCC patients. [Table: see text]

Adjuvant therapy with Huatan Sanjie Granules improves the prognosis of patients with primary liver cancer: a cohort study and the investigation of its mechanism of action based on network pharmacology.

Objective: Nowadays, primary liver carcinoma (PLC) is one of the major contributors to the global cancer burden, and China has the highest morbidity and mortality rates in the world. As a well-known Chinese herbal medicine (CHM) prescription, Huatan Sanjie Granules (HSG) has been used clinically for many years to treat PLC with remarkable efficacy, but the underlying mechanism of action remains unclear. Methods: A clinical cohort study was conducted to observe the overall survival of PLC patients with vs. without oral administration of HSG. Meanwhile, the BATMAN-TCM database was used to retrieve the potential active ingredients in the six herbs of HSG and their corresponding drug targets. PLC-related targets were then screened through the Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) network of targets of HSG against PLC was constructed using Cytoscape software. The cell function assays were further carried out for verification. Results: The results of the cohort study showed that the median survival time of PLC patients exposed to HSG was 269days, which was 23days longer than that of the control group (HR, 0.62; 95% CI, 0.38-0.99; p = 0.047). In particular, the median survival time of Barcelona Clinic Liver Cancer stage C patients was 411days in the exposure group, which was 137days longer than that in the control group (HR, 0.59; 95% CI, 0.35-0.96; p = 0.036). Meanwhile, the enrichment analysis result for the obtained PPI network consisting of 362 potential core therapeutic targets suggest that HSG may inhibit the growth of liver cancer (LC) cells by blocking the PI3K-Akt/MAPK signaling pathways. Furthermore, the above prediction results were verified by a series of in vitro assays. Specifically, we found that the expressions TP53 and YWHA2, the targets of the hepatitis B virus signaling pathway, were significantly affected by HSG. Conclusion: HSG shows promising therapeutic efficacy in the adjuvant treatment of PLC.

Impact of first-line systemic therapy with atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.

The study goal was to compare the outcomes of patients with unresectable hepatocellular carcinoma (HCC) who received atezolizumab plus bevacizumab (Atezo/Bev) as either first- or later-line systemic therapy. A total of 430 patients with HCC treated with Atezo/Bev at 22 institutions in Japan were included. Patients treated with Atezo/Bev as first-line therapy for HCC were defined as the first-line group (n=268) while those treated with Atezo/Bev as second- or later-line therapy were defined as the later-line group (n=162). The median progression-free survival times in the first- and later-line groups were 7.7months (95% confidence interval [CI], 6.7-9.2) and 6.2months (95% CI, 5.0-7.7) (P=0.021). Regarding treatment-related adverse events, hypertension of any grade was more common in the first-line group than in the later-line group (P=0.025). Analysis adjusted by inverse probability weighting, including patient and HCC characteristics, showed that the later-line group (hazard ratio, 1.304; 95% CI, 1.006-1.690; P=0.045) was significantly associated with progression-free survival. In patients with Barcelona Clinic Liver Cancer stage B, the median progression-free survival times in the first- and later-line groups were 10.5months (95% CI, 6.8-13.8) and 6.8months (95% CI, 5.0-9.4) (P=0.021). Among patients with a history of lenvatinib therapy, the median progression-free survival times in the first- and later-line groups were 7.7months (95% CI, 6.3-9.2) and 6.2months (95% CI, 5.0-7.7) (P=0.022). The use of Atezo/Bev as first-line systemic therapy in patients with HCC is expected to prolong survival.

The role of routine biopsy of the background liver in the management of hepatocellular carcinoma

We sought to determine the influence of background liver biopsies on hepatocellular carcinoma (HCC) management. The pathology database at a large university hospital was searched between 2013 and 2018 for all instances of when a separate biopsy of the nontumoral liver was performed within 6 months of an HCC biopsy. Patients were evaluated for baseline demographic and clinical characteristics, treatment proposed prior to biopsy, and impact of biopsy results on management. Among the 104 identified cases of paired liver biopsies, 22% were women; the median age was 64 years; and most were of earlier HCC stages at diagnosis (Barcelona Clinic Liver Cancer stages 0-A: 70%). Four patients among 10 in whom cirrhosis status was clinically unclear were confirmed to have cirrhosis on biopsy, and 4 patients did not have cirrhosis despite clinical suspicion. Treatment was altered by the background parenchymal findings for 5 patients (5%): management was less aggressive for 4 patients and more aggressive for 1 patient. A background liver biopsy can significantly impact the management of a small subset of HCC patients, especially those with early disease, and should be considered concurrently with the biopsy of the mass.

Adjuvant TACE may not improve recurrence-free or overall survival in HCC patients with low risk of recurrence after hepatectomy.

To identify whether adjuvant transarterial chemoembolization (TACE) can improve prognosis in HCC patients with a low risk of recurrence (tumor size ≤ 5 cm, single nodule, no satellites, and no microvascular or macrovascular invasions) after hepatectomy. The data of 489 HCC patients with a low risk of recurrence after hepatectomy from Shanghai Cancer Center (SHCC) and Eastern Hepatobiliary Surgery Hospital (EHBH) were retrospectively reviewed. Recurrence-free survival (RFS) and overall survival (OS) were analyzed with Kaplan-Meier curves and Cox proportional hazards regression models. The effects of selection bias and confounding factors were balanced using propensity score matching (PSM). In the SHCC cohort, 40 patients (19.9%, 40/201) received adjuvant TACE, and in the EHBH cohort, 113 patients (46.2%, 133/288) received adjuvant TACE. Compared to the patients without adjuvant TACE after hepatectomy, patients receiving adjuvant TACE had significantly shorter RFS (P=0.022; P=0.014) in both cohorts before PSM. However, no significant difference existed in OS (P=0.568; P=0.082). Multivariate analysis revealed that serum alkaline phosphatase and adjuvant TACE were independent prognostic factors for recurrence in both cohorts. Furthermore, significant differences existed in tumor size between the adjuvant TACE and non-adjuvant TACE groups in the SHCC cohort. There were differences in transfusion, Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage in the EHBH cohort. These factors were balanced by PSM. After PSM, patients with adjuvant TACE after hepatectomy still had significantly shorter RFS than those without (P=0.035; P=0.035) in both cohorts, but there was no difference in OS (P=0.638; P=0.159). Adjuvant TACE was the only independent prognostic factor for recurrence in multivariate analysis, with hazard ratios of 1.95 and 1.57. Adjuvant TACE may not improve long-term survival and might promote postoperative recurrence in HCC patients with a low risk of recurrence after hepatectomy.

Baveno VII criteria identify varices needing treatment in patients with hepatocellular carcinoma of different Barcelona Clinic Liver Cancer stages.

Baveno VII criteria for predicting varices needing treatment (VNT) have not been tested in hepatocellular carcinoma (HCC) population. We evaluated Baveno VII consensus for VNT in HCC patients of different stages according to Barcelona Clinic Liver Cancer (BCLC) stages undergoing curative hepatectomy. This was a prospective cohort study of patients with HCC. Patients underwent transient elastography examination before HCC treatment and received at least one upper endoscopic examination afterwards. Patients were prospectively followed for clinical events including VNT. Six hundred and seventy-three patients (83.1% male, median age 62years) with HCC of BCLC stage 0 (10%), A (57%), B (17%) and C (15%) were recruited and followed for 47months. The median (range) LSM was 10.5 (6.9-20.4) kPa; 74% had LSM≤20kPa and 58% had platelet count ≥150×10/L, respectively. VNT occurred in 51 (7.6%) patients. In patients who fulfilled Baveno VII criteria, that is, LSM≤20kPa and platelet count above 150×10/L, only 11 (1.6%) patients had VNT. In all BCLC stages of HCC, the proportion of patients with VNT was below 5%, which support the validity and applicability of Baveno VII criteria in all BCLC stages of HCC. The Baveno VII criteria are valid and applicable in HCC patients undergoing curative hepatectomy for selecting patients to undergo screening endoscopy for VNT. The validity was consistent across different BCLC stages of HCC.

Development of preoperative and postoperative machine learning models to predict the recurrence of huge hepatocellular carcinoma following surgical resection.

Resection has been commonly utilized for treating huge hepatocellular carcinoma (HCC) with a diameter of ≥10 cm; however, a high rate of mortality is reported due to recurrence. The present study was designed to predict the recurrence following resection based on preoperative and postoperative machine learning models. In total, 1,082 patients with HCC who underwent liver resection in the Eastern Hepatobiliary Surgery Hospital cohort between January 2008 and December 2016 were divided into a training cohort and an internal validation cohort. In addition, 164 patients from Mengchao Hepatobiliary Hospital cohort between January 2014 and December 2016 served as an external validation cohort. The demographic information, and serological, MRI, and pathological data were obtained from each patient prior to and following surgery, followed by evaluating the model performance using the concordance index, time-dependent receiver operating characteristic curves, prediction error cures, and a calibration curve. A preoperative random survival forest (RSF) model and a postoperative RSF model were constructed based on the training set, which outperformed the conventional models, such as the Barcelona Clinic Liver Cancer (BCLC), the 8th edition of the American Joint Committee on Cancer (AJCC 8th) staging systems, and the Chinese stage systems. In addition, the preoperative and postoperative RSF models could also re-stratify patients with BCLC stage A/B/C or AJCC 8th stage IB/II/IIIA/IIIB or Chinese stage IB/IIA/IIB/IIIA into low-risk, intermediate-risk, and high-risk groups in the training and the two validation cohorts. The preoperative and postoperative RSF models were effective for predicting recurrence in patients with huge HCC following hepatectomy.

Prognostic Value of Erythroblastic Leukemia Viral Oncogene Homolog 2 and Neuregulin 4 in Hepatocellular Carcinoma.

Although the roles of erythroblastic leukemia viral oncogene homolog 2 (ERBB2), neuregulin 4 (NRG4), and mitogen-inducible gene 6 (MIG6) in epidermal growth factor receptor signaling in hepatocellular carcinoma (HCC) and other malignancies have been previously investigated, the prognostic value of their serum levels in HCC remains undetermined. In the present study, correlations between serum levels and tumor characteristics, overall survival, and tumor recurrence were analyzed. Furthermore, the prognostic potential of the serum levels of these biomarkers was evaluated relative to that of alpha-fetoprotein. Both ERBB2 and NRG4 correlated with the Barcelona Clinic Liver Cancer stage, ERBB2 correlated with the tumor-maximal diameter, and NRG4 correlated with a tumor number. Cox proportional hazards regression analysis revealed that ERBB2 (hazard ratio [HR], 2.719; p = 0.007) was an independent prognostic factor for overall survival. Furthermore, ERBB2 (HR, 2.338; p = 0.002) and NRG4 (HR, 431.763; p = 0.001) were independent prognostic factors for tumor recurrence. The products of ERBB2 and NRG4 had a better area under the curve than alpha-fetoprotein for predicting 6-month, 1-year, 3-year, and 5-year mortality. Therefore, these factors could be used to evaluate prognosis and monitor treatment response in patients with HCC.