Barcelona Clinic Liver Cancer Stage Research Articles

Adherence to Tumor Board Recommendations in the Treatment of Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a heterogeneous disease that typically arises in the setting of chronic liver disease, making treatment selection complex. Multidisciplinary liver tumor boards (MDLTB) have been shown to improve outcomes in patients with HCC. However, in many cases, patients evaluated by MDLTBs ultimately do not receive the board's recommended treatment. This study aims to assess adherence to MDLTB recommendations for the treatment of HCC, the reasons for non-adherence, and the survival of Barcelona Clinic Liver Cancer (BCLC) Stage A patients treated with curative treatment compared to palliative locoregional therapy. A single-site, retrospective cohort study was conducted of all patients with treatment-naïve HCC who were evaluated by an MDLTB at a tertiary care center in Connecticut between 2013 and 2016, of which 225 patients met inclusion criteria. Investigators conducted a chart review and recorded adherence to the MDLTB's recommendations, and in cases of discordance, evaluated and recorded the underlying cause; investigators assessed MDLTB recommendations' compliance with BCLC guidelines. Survival data was accrued through February 1st of 2022 and analyzed via Kaplan-Meier analysis and multivariate Cox regression. Treatment adherent to MDLTB recommendations occurred in 85.3% of patients (n=192). The majority of non-adherence occurred in the management of BCLC Stage A disease. In cases where adherence was possible but the recommendation was not followed, most discrepancies were whether to treat with curative or palliative intent (20/24), with almost all discrepancies occurring in patients (19/20) with BCLC Stage A disease. For patients with Stage A unifocal HCC, those who received curative therapy lived significantly longer than patients who received palliative locoregional therapy (5.55 years vs 4.26 years, p=0.037). Most forms of non-adherence to MDLTB recommendations were unavoidable; however, treatment discordance in the management of patients with BCLC Stage A unifocal disease may present an opportunity for clinically significant quality improvement.

Radiographic tumor burden score is useful for stratifying the overall survival of hepatocellular carcinoma patients undergoing resection at different Barcelona Clinic Liver Cancer stages

The Barcelona Clinic Liver Cancer (BCLC) staging system has been recommended for prognostic prediction. However, prognosis is variable at different BCLC stages. We aimed to evaluate whether the radiographic tumor burden score (TBS) could be used to stratify prognosis in different BCLC stages. Hepatocellular carcinoma (HCC) patients undergoing liver resection (LR) at BCLC-0, -A, or -B stage in our institution in 2007-2018 were divided into derivation and validation cohorts. Overall survival (OS) was analyzed according to the TBS and BCLC stage. TBS cutoff values for OS were determined with X-tile. Of the 749 patients in the derivation cohort, 138 (18.4%) had BCLC-0, 542 (72.3%) BCLC-A, and 69 (9.2%) BCLC-B HCC; 76 (10.1%) had a high TBS (> 7.9), 477 (63.7%) a medium TBS (2.6-7.9), and 196 (26.2%) a low TBS (< 2.6). OS worsened progressively with increasing TBS in the cohort (p < 0.001) and in BCLC-A (p = 0.04) and BCLC-B (p = 0.002) stages. Multivariate analysis showed that the TBS was associated with OS of patients with BCLC-A (medium vs. low TBS: hazard ratio [HR] = 2.390, 95% CI = 1.024-5.581, p = 0.04; high vs. low TBS: HR = 3.885, 95% CI = 1.443-10.456, p = 0.007) and BCLC-B (high vs. medium TBS: HR = 2.542, 95% CI = 1.077-6.002, p = 0.033) HCC. The TBS could also be used to stratify the OS of patients in the validation cohort (p < 0.001). The TBS could be used to stratify the OS of the entire cohort and BCLC stages A and B of HCC patients undergoing LR.

Liver resection versus transarterial chemoembolisation for the treatment of intermediate hepatocellular carcinoma: a systematic review and meta-analysis.

Transarterial chemoembolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC), according to the updated Barcelona Clinic Liver Cancer (BCLC) staging system. Although growing evidence favours liver resection (LR) over TACE for intermediate-stage HCC, the best treatment option remains controversial. This meta-analysis aimed to compare the overall survival (OS) after LR versus TACE for intermediate-stage HCC. A comprehensive literature review of PubMed, Embase, Cochrane Library, and Web of Science was performed. Studies that compared the efficacy of LR and TACE in patients with intermediate (BCLC stage B) HCC were selected. According to the recent updated BCLC classification, intermediate stage of HCC was defined as follows: (a) four or more HCC nodules of any size, or (b) two or three nodules, but if at least one tumour is larger than 3cm. The main outcome was OS, expressed as the hazard ratio. Nine eligible studies of 3355 patients were included in the review. The OS of patients who underwent LR was significantly longer than that of patients who underwent TACE (hazard ratio=0.52; 95% CI: 0.39-0.69; I2=79%). Prolonged survival following LR was confirmed after sensitivity analysis of five studies using propensity score matching (HR=0.45; 95% CI: 0.34-0.59; I2=55%). Patients with intermediate-stage HCC who underwent LR had a longer OS that those who underwent TACE. The role of LR in patients with BCLC stage B should be clarified in future randomised controlled trials.

Gender survival differences in hepatocellular carcinoma: Is it all due to adherence to surveillance? A study of 1716 patients over three decades.

Hepatocellular carcinoma (HCC) is one of the commonest causes of cancer-related death worldwide. Whether gender is an independent factor for HCC survival is debatable. We studied the influence of gender on the clinical characteristics of HCC and on survival. The study cohort comprised patients with HCC seen in our department from 1988 to 2021. Clinical data were prospectively collected. We studied and compared demography, HCC characteristics, and survival between females and males. Survival analysis was censored on October 31, 2015. There were 1716 HCC patients. 343 (20.0%) were females. Females were significantly older at diagnosis (median 69 vs 62 years, P < 0.001). More females were diagnosed via regular HCC surveillance (37.9% vs 29.6%, P = 0.003). Hence, as expected, females had less-advanced HCC at diagnosis with smaller median tumor diameter (30 vs 39.5 mm, P = 0.038), lower frequency of portal vein tumor thrombus (19.4% vs 33.4%, P < 0.001), less distant metastases (7.7% vs 11%, P = 0.043), and earlier Barcelona Clinic Liver Cancer (BCLC) stages (0/A, 39.7% vs 28.4%, P < 0.001). On multivariable analysis, HCC diagnosis via surveillance but not female gender was an independent predictor of improved HCC survival. In this large cohort of multi-ethnic Asian patients, females with HCC were significantly more adherent to surveillance and hence presented with less advanced HCC with correspondingly better overall survival than males. The gender difference in survival is likely due to females having better adherence to HCC surveillance. Surveillance to diagnose early-stage HCC remains crucial in improving outcomes.

Contrast-enhanced ultrasound liver imaging reporting and data system v2017: patient outcomes after treatment for early-stage hepatocellular carcinoma nodules with category 3-5 and category M.

To evaluate correlation between contrast-enhanced ultrasonography Liver Imaging Reporting and Data System (CEUS LI-RADS; v. 2017) categories (LR 3-5 vs LR-M) and outcomes in patients with early-stage hepatocellular carcinoma (HCC) after initial therapy. In this retrospective study, 272 patients with high risks for HCC and solitary clinically or pathologically confirmed HCC were identified between January 2010 and December 2015. Patients were initially treated by resection and radiofrequency ablation (RFA) according to the Barcelona Clinic Liver Cancer staging system and were followed up until December 31, 2018. Recurrence-free survival (RFS) and overall survival (OS) were compared between nodules assigned as LR 3-5 or LR M according to CEUS LI-RADS v. 2017 by using the Kaplan-Meier curve, log-rank test, and Cox proportional hazard model. Early washout is the key determinating whether a nodule is classed as LR-M. Treatment procedures and LI-RADS category showed an independent correlation with OS and RFS (p < 0.05). LR 3-5 category were more correlated with better OS (88.6 months and 74.2 months, respectively; p = 0.017) compared with LR-M. Surgical resection demonstrated longer OS and RFS than RFA in LR-M patients and longer OS in LR 3-5 patients (p < 0.05). Besides, there was no significantly difference in OS and RFS between two categories in resection (p > 0.05), while for patients treated with RFA, LR 3-5 patients showed significant longer OS and RFS than LR-M patients (p < 0.05). Patients with HCC assigned as LR-M showed worse RFS and OS and surgical resection tended to be a more effective treatment for these patients. Putting forward a theory that CEUS LI-RADS categories could independently predict the outcome for patients with solitary HCC at early-stage after initial treatment.

The adherence to the American Association for the Study of Liver Diseases 2018 guidelines in the management of hepatocellular carcinoma and its impact on survival.

In two Korean and Italian studies, the adherence rate (AR) to ASSLD 2005 guidelines in the management of hepatocellular carcinoma (HCC) was 60%. In a US study, the AR to American Association for the Study of Liver Disease (AASLD) 2005 guidelines was 73.3%, 26.8%, 25.3%, and 58.8% for patients with Barcelona Clinic Liver Cancer (BCLC) Stage A, B, C, and D, respectively, and nonadherence to guidelines was associated with longer overall survival (OS) in patients with BCLC Stage D. Here, we explored the AR to AASLD 2018 guidelines and its impact on OS. Between 2017 and 2019, 148 unique treatment-naïve patients with HCC were identified. Patients were staged according to the BCLC staging system and their AR to AASLD 2018 guidelines was noted. OS was estimated using Kaplan-Meier method. Survivals among patients from different groups was compared using Log-rank test. The overall AR to AASLD 2018 guidelines was 83%. The AR for BCLC Stages 0, A, B, C, and D were 100%, 97%, 77%, 77%, and 38%, respectively. In patients with BCLC Stage D, the OS of patients treated with modalities adherent versus nonadherent to AASLD 2018 guidelines was 0.03 vs. 5.2 months (P = 0.0005). Otherwise, adherence versus nonadherence to AASLD 2018 guidelines showed no statistically significant differences in OS for patients with BCLC Stages 0, A, B, and C. The overall AR to AASLD 2018 guidelines was 83%. Nonadherence to AASLD 2018 guidelines in patients with BCLC Stage D translated into better OS.

Tumor burden in patients with early and intermediate-stage hepatocellular carcinoma undergoing liver resection: a retrospective multicenter study on clinical and oncological outcomes

BackgroundAccording to the Barcelona Clinic Liver Cancer (BCLC) staging system, liver resection (LR) is recommended for early-stage (BCLC-A) hepatocellular carcinoma (HCC) but not for intermediate-stage (BCLC-B). This study aimed to assess the outcomes of LR in these patients using a subclassification tumour burden score (TBS). MethodsAll consecutive patients that underwent LR for BCLC-A and BCLC-B HCC between 01/2010 and 12/2020 in 4 tertiary referral centers were included. Clinical outcomes and overall survival (OS) were assessed in relation to TBS and BCLC stages. ResultsAmong 612 patients included, 562 were classified as BCLC-A and 50 as BCLC-B. The incidence of overall postoperative complications (56.0 vs 41.5%, p = 0.053) and mortality (0 vs 1.6%, p = 1.000) were similar between BCLC-A and BCLC-B patients. OS was significantly higher for BCLC A/low TBS than BCLC B/low TBS (p = 0.009), while patients with medium and high TBS had similar OS, irrespective of BCLC stage (respectively p = 0.103 and p = 0.343). ConclusionsPatients with medium and high TBS had comparable OS and DFS, irrespective of BCLC A or B stage, and postoperative morbidity was comparable. These results highlight the need for refinement of the BCLC staging system, and LR could be considered for selected intermediate stage (BCLC-B) according to the tumour burden.

Survival outcomes in Veterans with hepatocellular carcinoma, with and without HIV infection.

HIV infection has been associated with survival disparities among persons with hepatocellular carcinoma (HCC). However, most studies examining survival do not control for provider- (e.g. type of HCC treatment given) or individual-level factors (e.g. homelessness, substance use) that could impact survival. In this study, we evaluate the effect of HIV status on survival among persons with HCC, in a comprehensive model that accounts for key individual-, provider- and systems-level factors. We conducted a retrospective cohort study of people living with HIV (PLWH) matched 1:1 to HIV-uninfected controls based on age and year of HCC diagnosis in the national Veterans Administration (VA) health system. The primary outcome was survival. We used Cox regression models to evaluate the effect of HIV status on risk of death. This cohort included 200 matched pairs diagnosed with HCC between 2009-2016. A total of 114 PLWH (57.0%) and 115 HIV- patients (57.5%) received guideline-concordant therapy (P = 0.92). Median survival was 13.4 months (95% CI 8.7-18.1) among PLWH and 19.1 months (95% CI 14.6-24.9) for HIV-uninfected patients. In adjusted models, older age, homelessness, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and not receiving any HCC treatment HCC predicted risk of death. HIV status was not associated with risk of death (aHR 0.95 [95% CI 0.75-1.20]; P = 0.65). HIV status was not associated with worse survival among HCC patients, in a single-payer, equal access health care system. These results suggest that HIV infection alone should not exclude PLWH from receiving standard therapy.

A surgical nursing perspective analysis of glucose variability in BCLC stage B-C hepatocellular carcinoma patients with and without T2D within 1 year of hepatectomy: a retrospective cohort study from 2016 to 2020.

Previous research has reported that variability in glucose levels is associated with a variety of patient characteristics in colon cancer. However, relevant research is still lacking in relation to hepatocellular carcinoma (HCC). A total of 95 HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage B-C who underwent liver resection at the Eastern Hepatobiliary Surgery Hospital and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were included in this study. The patients were divided into 2 groups with type 2 diabetes (T2D) and without T2D. The primary outcome variable was blood glucose variability at 1 month and within 1 year of HCC surgery. In this study, the age of patients with T2D was greater than that of patients without T2D (mean age: 70.3±8.45 vs. 60.4±11.27 years, P=0.031). Compared to the patients without T2D, those with T2D had higher blood glucose measurements within 1 month (33 vs. 7) and 1 year (46.5 vs. 22.5, P<0.001) of surgery. The T2D patients and non-T2D patients did not differ in terms of chemotherapy medication or other characteristics. Among the 95 patients with BCLC stage B-C HCC, those with T2D had higher variability in glucose levels (P<0.001) than those without T2D within 1 month of surgery [standard deviation (SD) =46.43 mg/dL, coefficient of variation (CV) =23.5% vs. SD =21.56 mg/dL, CV =13.21%], and within 1 year of surgery (SD =42.49 mg/dL, CV =26.14% vs. SD =20.45 mg/dL, CV =17.36%). A correlation was found between a lower body mass index and higher variability in glucose levels within 1 month of surgery among patients with T2D [SD (r=-0.431, P<0.05) and CV (r=-0.464, P<0.01)]. A higher preoperative blood glucose level in T2D patients was correlated with a higher blood glucose variability within 1 year of surgery (r=0.435, P<0.01). Variability in glucose levels was weakly correlated with the demographic and clinical characteristics of patients who do not have T2D. HCC patients with T2D in BCLC stage B-C showed greater variability in glucose levels within 1 month and 1 year of surgery. Preoperative hyperglycemia, insulin use, and a lower cumulative dose of steroids were clinical features correlated with a higher variability in glucose levels in T2D patients.

Living donor liver transplantation for Barcelona clinic liver cancer (BCLC) intermediate-stage hepatocellular carcinoma.

Barcelona clinic liver cancer (BCLC) stage B (intermediate stage) hepatocellular carcinoma (HCC) is highly heterogeneous; thus, identifying the most effective treatment for individual patients represents a significant clinical challenge. However, transarterial chemoembolization (TACE) is the only recommended treatment option. Therefore, we aimed to investigate the patient characteristics and outcomes of living donor liver transplantation (LDLT) for BCLC stage B HCC. A total of 516 patients with BCLC stage B HCC who underwent LDLT (n=104) or did not undergo LDLT (non-LDLT; n=412) between 2004 to 2018 were analyzed by propensity score matching (PSM; 1:4) analysis. Factors influencing overall survival (OS) and recurrence were analyzed using Cox's proportional hazards models. Patients treated with LDLT achieved better OS than the non-LDLT group, including liver- and non-liver related survival (all P<0.001). Multivariate Cox regression analysis showed age >60 years (P=0.006), a neutrophil-lymphocyte ratio (NLR) >4 (P=0.016) and >3 locoregional therapies (LRT) before LDLT (P<0.001) were independent risk factors for HCC recurrence. In addition, age >60 years (P<0.001) and >3 LRT before LDLT (P=0.001) were independent risk factors for OS. Using a combination of age, NLR, and LRT before liver transplantation (LT), the patients can be divided into low-risk (none of risk), intermediate-risk (one of risk), and high risk (more than two of risk) groups. There were significant differences in the cumulative HCC recurrence (P<0.001) and mortality (P<0.001) rates among the three groups. LDLT may represent a valuable therapeutic option for selected patients with BCLC stage B HCC.

Stage migration as a surrogate of survival in hepatocellular carcinoma treated with transarterial chemoembolization.

Locoregional therapies, including transarterial chemoembolization (TACE), are recommended for the treatment of HCC; however, clinical trials evaluating their effectiveness have been complicated by a lack of validated surrogate outcomes. We aimed to evaluate if stage migration could serve as a potential surrogate of overall survival in patients undergoing TACE. We conducted a retrospective cohort study of adult patients with HCC who underwent TACE as initial therapy from 3 centers in the US from 2008 to 2019. The primary outcome was overall survival from the date of the first TACE treatment, and the primary exposure of interest was Barcelona Clinic Liver Cancer stage migration to a more advanced stage within 6 months of TACE. Survival analysis was completed using Kaplan-Meier and multiple Cox proportional hazard models adjusted by the site. Of 651 eligible patients (51.9% Barcelona Clinic Liver Cancer stage A and 39.6% stage B), 129 (19.6%) patients experienced stage migration within 6 months of TACE. Those with stage migration had larger tumors (5.6 vs. 4.2cm, p < 0.01) and higher AFP levels (median 92 vs. 15ng/mL, p < 0.01). In multivariate analysis, stage migration was significantly associated with worse survival (HR: 2.82, 95% CI: 2.66-2.98), with a median survival of 8.7 and 15.9 months in those with and without stage migration. Other predictors of worse survival included the White race, higher AFP levels, a higher number of tumors, and a larger maximum HCC diameter. Stage migration is associated with increased mortality after TACE in patients with HCC and could serve as a surrogate end point in clinical trials evaluating locoregional therapies such as TACE.

Impact of body mass index in patients receiving atezolizumab plus bevacizumab for hepatocellular carcinoma

BackgroundAtezolizumab plus bevacizumab (Atezo/Bev) is first line-treatment for unresectable hepatocellular carcinoma (HCC). Body mass index (BMI) has demonstrated predictive value for response to immunotherapy in non-HCC cancer types. Our study investigated the effect of BMI on safety and efficacy of real-life use of Atezo/Bev for unresectable HCC.Methods191 consecutive patients from seven centres receiving Atezo/Bev were included in the retrospective study. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in overweight (BMI ≥ 25) and non-overweight (BMI < 25) patients. Treatment-related adverse events (trAEs) were evaluated.ResultsPatients in the overweight cohort (n = 94) had higher rates of non-alcoholic fatty liver disease (NAFLD) and lower rates of Hepatitis B compared to non-overweight cohort (n = 97). Baseline Child–Pugh class and Barcelona Clinic Liver Cancer stage were similar between cohorts, with lower rates of extrahepatic spread in the overweight group. Overweight patients had similar OS compared to non-overweight (median OS 15.1 vs. 14.9 months; p = 0.99). BMI did not influence median PFS (7.1 vs. 6.1 months; p = 0.42), ORR (27.2% vs. 22.0%; p = 0.44) and DCR (74.1% vs. 71.9%; p = 0.46). There were higher rates of atezolizumab-related fatigue (22.3% vs. 10.3%; p = 0.02) and bevacizumab-related thrombosis (8.5% vs. 2.1%; p = 0.045) in the overweight patients, but overall trAEs and treatment discontinuation were comparable between cohorts.ConclusionAtezo/Bev has comparable efficacy in overweight HCC patients, with an increase in treatment-related fatigue and thrombosis. Combination therapy is safe and efficacious to use in overweight patients, including those with underlying NAFLD.

Evaluation of the up-to-7 criterion for determining the treatment of hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage B: a single-center retrospective cohort study.

At present, there are still disputes on the treatment of surgery for patients with stage B hepatocellular carcinoma (HCC). This study sought to investigate whether the up-to-7 criterion could be used to decide the treatment for HCC in Barcelona Clinic Liver Cancer stage B (BCLC-B). We analyzed 340 patients with HCC in BCLC-B who treated with hepatectomy or transcatheter arterial chemoembolization (TACE). Of the 285 HCC patients who underwent hepatectomy, 108 met the up-to-7 criterion and 177 exceeded it. All 55 patients in the TACE group met the up-to-7 criterion. We obtained the tumor status of the patients through inpatient medical records, outpatient medical records, and telephone follow-up of the hospital. We compared overall survival (OS) and progression-free survival (PFS) were compared between patients who met the up-to-7 criterion and who underwent either hepatectomy or TACE. OS and recurrence time were also compared between the patients who were treated with hepatectomy and who either met or exceeded the up-to-7 criterion. Across BCLC-B patients, we compared the OS of patients after surgical treatment between subgroups stratified by tumor number and diameter. Patients who met the up-to-7 criterion had significantly higher OS rates after hepatectomy than TACE (P<0.001). However, the 2 groups did not differ in terms of PFS (P=0.758). Among the patients treated by hepatectomy, the OS rates were significantly higher in patients who met the up-to-7 criterion than in those who exceeded it (P=0.001). The recurrence rates did not differ between patients who met or exceeded the criterion (P=0.662). OS was significantly higher in patients with ≤3 tumors than those with >3 tumors (P=0.001). When we stratified patients with ≤3 tumors based in whether they met or exceeded the up-to-8 to up-to-15 criterion, OS was significantly better among those who met the criterion in all cases. Hepatectomy appears to be associated with better survival than TACE in patients with BCLC-B HCC who meet the up-to-7 criterion, but this criterion is not a strict indication for deciding whether to treat patients with BCLC-B surgically. Tumor number strongly affects the prognosis of BCLC-B patients after hepatectomy.

Image-guided percutaneous locoregional therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the 3rd leading cause of cancer death worldwide. Treatment options include surgical resection, liver transplantation, imageguided percutaneous locoregional options, external beam radiation therapy (EBRT) and systemic therapies. Treatment choice depends on the stage of the disease and patient's characteristics including performance status and liver function. Barcelona Clinic Liver Cancer (BCLC) staging system, with its recent 2022 update, is one of the most widely endorsed staging system. Locoregional therapies (LRT) are recommended for very early stage (BCLC-0), early stage (BCLC-A), and the two first subgroups of intermediate stage (BCLC-B). Image-guided percutaneous locoregional therapies include ablation, mainly thermal ablation with radiofrequency (RFA), microwave ablations (MWA) and cryoablation, transarterial embolization (TAE, also known as bland embolization), transarterial chemoembolization (TACE), drug-eluding beadstransarterial chemoembolization (DEB-TACE), combination of ablation with embolization, transarterial radioembolization (TARE) also known as selective internal radioembolization therapy, and hepatic artery infusion (HAI). While ablation is recognized as a curative therapy, all intra-arterial therapies are considered non-curative options. There is growing evidence that TARE, through radiation segmentectomy, can be considered a curative intent treatment in appropriate selective patients. In this article, we will review indications, complications, and outcomes of locoregional therapies for HCC.

Global Assessment of Predictive Biomarkers in Malian BCLC Stage C Hepatocellular Carcinoma Patients under Mono or Combination Immune Checkpoint Inhibitors Treatment: A Proposed Research Protocol

Background: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, only the advanced stage (stage C) hepatocellular carcinoma (HCC) patient is eligible for systemic treatments. In addition to sorafenib and lenvatinib that represent the standard-of-care options in the first-line treatment, the multikinase inhibitors regorafenib and cabozantinib or ramucirumab, the anti-vascular-endothelial growth factor-2 (VEGF-R2) in the second-line setting but their poor tolerability have brought out the need for new therapeutic strategies, the immune checkpoint inhibitors (ICIs) might represent the most important novelty and the future perspective also in the field of HCC. Therefore, the need to identify predictive biomarkers to select those patients who might actually benefit from ICIs-based treatment is urgently a challenge. Our central hypothesis is that the global assessment of predictive biomarkers could help patient-specific choices for ICIs treatment by developing simplified therapeutic algorithms and novel prognostic index for efficient HCC management. The primary aim of this work will be to globally assess predictive biomarkers in Malian patients with BCLC stage C HCC undergoing treatment with ICIs in mono or in combination.

Navigating through the PD-1/PDL-1 Landscape: A Systematic Review and Meta-Analysis of Clinical Outcomes in Hepatocellular Carcinoma and Their Influence on Immunotherapy and Tumor Microenvironment.

This systematic review aimed to assess the prognostic significance of programmed cell death-ligand 1 (PDL-1) and programmed cell death protein 1 (PD-1) in hepatocellular carcinoma (HCC). Medline, EMBASE, and Cochrane Library database searches were conducted, revealing nine relevant cohort studies (seven PDL-1 and three PD-1). Our meta-analysis showed that PD-1/PDL-1 was a marker of poor survival, regardless of the assessment method (PD-1 overall survival (OS): hazard ratio (HR) 2.40; 95% confidence interval (CI), 1.30-4.42; disease-free survival (DFS): HR 2.12; 95% CI, 1.45-3.10; PDL-1: OS: HR 3.61; 95% CI, 2.75-4.75; and DFS: HR 2.74; 95% CI, 2.09-3.59). Additionally, high level of PD-1/PDL-1 expression was associated with aging, multiple tumors, high alpha-fetoprotein levels, and advanced Barcelona Clinic Liver Cancer stage. This high level significantly predicted a poor prognosis for HCC, suggesting that anti-PD-1 therapy is plausible for patients with HCC. Furthermore, HIF-1 induces PD-1 expression, and PD1lowSOCS3high is associated with a better prognosis. Taken together, combination therapy may be the key to effective immunotherapy. Thus, exploring other markers, such as HIF-1 and SOCS3, along with PD-1/PDL-1 immunotherapy, may lead to improved outcomes.

Prognostic Impact of a Novel Albumin-Platelet Index as Selection Criterion for Hepatic Resection in Intermediate Stage Hepatocellular Carcinoma.

Hepatic resection for Barcelona Clinic Liver Cancer (BCLC) stage B (intermediate-stage) hepatocellular carcinoma (HCC) is not recommended by BCLC treatment algorithms. We sought to develop a new prognostic model for determining appropriate treatment strategies in patients with intermediate-stage HCC. This single-center retrospective study included patients who underwent hepatic resection for HCC between 2000 and 2018. A total of 498 patients were classified according to the BCLC staging system (0, n=116; A, n=319; B, n=63). The predictive impact for surgical outcomes was evaluated using receiver operating characteristic (ROC) curves. Based on a survival outcome probability formula, a new predictive model was established. The preoperative albumin level and platelet count were the strongest diagnostic values in patients with intermediate-stage HCC (areas under the ROC curves, AUCs: 0.710 and 0.676, respectively). Logistic regression analysis provided the albumin-platelet index [API; 156.2×albumin (g/dl)+platelet count (×109/l)] was defined as a new prognostic model for the probability of poor survival. The optimal cutoff value (781.2; AUC 0.755) divided patients with BCLC-B into B1 (>781.2, n=27) and B2 (≤781.2, n=36) categories. Patients in substage B2 had a significantly worse prognosis than patients in other stages (p<0.0001), whereas there was no difference in prognosis between patients in substage B1 and those in other stages. The API stratifies prognosis in patients with intermediate-stage HCC. For subgroup B1, hepatic resection can be considered a radical treatment, even for intermediate-stage HCC.

Impact of skeletal muscle volume on patients with BCLC stage-B hepatocellular carcinoma undergoing sorafenib therapy.

Skeletal muscle volume has been reported to be an important factor that determines overall survival (OS) and post-progression survival (PPS) in patients with hepatocellular carcinoma (HCC). However, the impact of skeletal muscle volume on HCC with Barcelona Clinic Liver Cancer (BCLC) stage B (BCLC-B) remains unclear. We conducted sub-analyses of a previous study on BCLC-B and compared our findings with data on HCC with BCLC stage C (BCLC-C). We retrospectively enrolled 356 patients with HCC (BCLC-B, n= 78; and BCLC-C, n= 278) undergoing sorafenib therapy. Prognostic factors were analyzed using various parameters, including skeletal muscle volume. Muscle volume (MV) depletion was designated as less than the median value of the skeletal muscle index for each gender (cutoff value: 45.0cm2 /m2 for male and 38.0cm2 /m2 for female participants). Both OS and PPS showed no significant differences in patients with non-MV depletion and those with MV depletion in the BCLC-B group (Median OS [MST] 19.3 vs. 13.5 months [p= 0.348]; median PPS 9.7 vs. 10.8 months [p= 0.578]). In the BCLC-C group, patients with non-MV depletion had a significantly longer OS and PPS compared to patients with MV depletion (MST 12.4 vs. 9.0 months [p= 0.001] and median PPS 7.9 vs. 5.4 months [p= 0.002]). Multivariate analysis revealed that MV depletion was an independent prognostic factor of OS and PPS in the BCLC-C group but not in the BCLC-B group. Skeletal muscle volume showed little impact on the clinical outcomes of patients with BCLC-B undergoing sorafenib therapy.

Subclassification of advanced-stage hepatocellular carcinoma with macrovascular invasion: combined transarterial chemoembolization and radiotherapy as an alternative first-line treatment.

The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C. A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points. The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0-4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001). Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

Factors associated with the survival outcomes of patients with untreated hepatocellular carcinoma: An analysis of nationwide data.

In this study, we examined the natural course of untreated hepatocellular carcinoma (HCC) and identified predictors of survival in an area where hepatitis B is the predominant cause of HCC. We identified 1,045 patients with HCC who did not receive HCC treatment and were registered in the Korean Primary Liver Cancer Registry between 2008 and 2014, and were followed-up up to December 2018. Thereafter, we analyzed the clinical characteristics of patients who survived for <12 or ≥12 months. A Cox proportional regression model was used to identify the variables associated with patient survival. The mean age of the untreated patients at HCC diagnosis was 59.6 years, and 52.1% of patients had hepatitis B. Most untreated patients (94.2%) died during the observation period. The median survival times for each Barcelona Clinic Liver Cancer (BCLC) stage were as follows: 31.0 months for stage 0/A (n = 123), 10.0 months for stage B (n = 96), 3.0 months for stage C (n = 599), and 1.0 month for stage D (n = 227). Multivariate Cox regression analysis demonstrated that BCLC stage D (hazard ratio, 4.282; P < 0.001), model for end-stage liver disease (MELD) score ≥10 (HR, 1.484; P < 0.001), and serum alpha-fetoprotein (AFP) level ≥1,000 ng/mL (HR, 1.506; P < 0.001) were associated with poor survival outcomes in patients with untreated HCC. In untreated patients with HCC, advanced stage BCLC, serum AFP level ≥1,000 ng/mL, and MELD score ≥10 were significantly associated with overall survival.