Barcelona Clinic Liver Cancer Algorithm Research Articles

Liver Resection vs Nonsurgical Treatments for Patients With Early Multinodular Hepatocellular Carcinoma

The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller. To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC. This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023. LR, PRFA, or TACE. Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes. A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE. For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.

Hepatobiliary-phase gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid MRI for pretreatment prediction of efficacy-to-standard-therapies based on Barcelona Clinic Liver Cancer algorithm: an up-to-date review.

Recent advances in systemic therapy have had major impacts on treatment strategies for hepatocellular carcinoma (HCC). The 2022 Barcelona Clinic Liver Cancer (BCLC) guidelines incorporate a new section on clinical decision-making for personalized medicine, although the first treatment suggested by the BCLC guidelines is based on solid scientific evidence. More than ever before, the appropriate treatment strategy must be selected prior to the initiation of therapy for HCC. Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid magnetic resonance imaging (Gd-EOB-DTPA-MRI) is essential for liver imaging and the hepatobiliary phase (HBP) of EOB-MRI reflects the expression of organic anion transporting polypeptide (OATP) transporters. Molecules associated with OATP expression are relevant in the molecular classification of HCC subclasses, and EOB-MRI is becoming increasingly important with advances in the molecular and genetic understanding of HCC. In this review, we describe imaging findings for the pretreatment prediction of response to standard therapies for HCC based on the BCLC algorithm using the HBP of EOB-MRI, with specific attention to the molecular background of OATPs. A more complete understanding of these findings will help radiologists suggest appropriate treatments and clinical follow-ups and could lead to the development of more personalized treatment strategies in the future. CLINICAL RELEVANCE STATEMENT: In the coming era of personalized medicine, HBP of EOB-MRI reflecting molecular and pathological factors could play a predictive role in the therapeutic efficacy of HCC and contribute to treatment selection. KEY POINTS: • Imaging features of hepatobiliary phase predict treatment efficacy prior to therapy and contribute to treatment choice. • Wnt/β-catenin activation associated with organic anion transporting polypeptide expression is involved in the tumor immune microenvironment and chemo-responsiveness. • Peritumoral hypointensity of hepatobiliary phase reflecting microvascular invasion affects the therapeutic efficacy of locoregional to systemic therapy.

Tumor Burden Score and Serum Alpha-fetoprotein Subclassify Intermediate-Stage Hepatocellular Carcinoma

BackgroundResection of Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) remains controversial. While not recommended by the BCLC algorithm, some patients may indeed benefit from hepatectomy. We sought to identify that subset of patients who might derive long-term survival benefit from resection. MethodsIntermediate-stage HCC patients who underwent curative-intent resection were identified from an international multi-institutional database. Factors associated with long-term prognosis were identified using multivariate analysis and a risk score was developed and assessed. ResultsAmong 194 patients, most individuals had two tumors (n = 123, 63.4%) with a median size of 6.0 cm (IQR, 4.0–8.4) for a median tumor burden score (TBS) of 6.5 (IQR, 5.0–9.1); median alpha-fetoprotein (AFP) was 23.9 ng/mL (IQR, 5.0–503.2), and median overall survival (OS) was 69 months (IAR, 60.7–77.3). Factors associated with OS included AFP (referent ≤ 20 ng/mL, > 20 ng/mL: HR 1.78 95%CI, 1.09–2.89) and TBS (referent TBS ≤ 8.0, TBS > 8.0: HR 1.72 95%CI, 1.07–2.75). While 71 (36.6%) patients had neither risk factor, 79 (40.7%) and 44 (22.7%) had 1 or 2, respectively. A simplified score stratified patients relative to recurrence-free survival (RFS) (0: 33.6% vs. 1: 18.0% vs. 2: 14.7%) (AUC 0.60) and recurrence time (i.e., < 6 months after surgery) (0: 21.3% vs. 1: 43.1% vs. 2: 68.6%) (AUC 0.69) (both p < 0.001). Of note, a higher score was also associated with incrementally worse 5-year OS (0: 68.1% vs. 1: 61.0% vs. 2: 29.9%) (AUC 0.62) (p < 0.001). ConclusionLong-term OS and RFS outcomes varied considerably. Using a simple risk score, patients with low AFP and low TBS were identified as the subset of individuals most likely to benefit from resection.

TARE in Hepatocellular Carcinoma: From the Right to the Left of BCLC.

The Barcelona Clinic Liver Cancer (BCLC) system is the most commonly used staging system for hepatocellular carcinoma (HCC) in Western countries. BCLC aims to categorize patients into fivestages with different prognoses and to allocate treatment according to these stages based on the best possible contemporary evidence. Transarterial radioembolization (TARE) has recently entered at the left of the BCLC algorithm (i.e., BCLC 0-A), mainly because of negative phase III trials in BCLC Cstage. TARE has shown a steady increase in nationwide studies over the past 20years and has even been adopted in some tertiary centers as the primary HCC treatment across all BCLC stages. We aimed to review the history of TARE in HCC, starting from advanced HCC and gradually expanding to earlier stages at the left of the BCLC system.

Laparoscopic liver resection for locally advanced tumor

The Barcelona Clinic Liver Cancer (BCLC) staging system categorizes a patient with hepatocellular carcinoma (HCC) according to the characteristics of the tumor, the liver disease, and the performance status of a patient. However, the BCLC algorithm is too conservative in offering resection for advanced HCC, including the locally advanced tumors. As a result, this system recommends systemic therapy for patients with advanced HCC as the first-line treatment with Sorafenib because the portal vein tumor thrombus is often interpreted as metastatic disease. Besides, there are still some uncertainties to categorize HCC with the bile duct invasion and surgical role also indefinite for advanced HCC. A number of international guidelines have excluded the role of surgery for these patients. Nevertheless, multiple studies have found a clear benefit for selected patients and have questioned the appropriateness of published recommendations, in particular concerning the role of liver resection. Usually, en bloc resection of the tumor together with affected structures might show good oncological outcomes & removal of residual microscopic foci. Even though patients with advanced HCC are at high risk of treatment failure, recurrence, and mortality, outcomes of liver resection should be examined and weighed against the lack of any other potentially curative option. Video clips show the 3 cases of laparoscopic liver resection for locally advanced HCC including, huge HCC, HCC with bile duct invasion, and down-staged HCC after TARE. We applied the recently developed laparoscopic surgical skill to remove the advanced HCC to get fewer postoperative complications, less postoperative pain, and shorter hospital stays.

Short article: Endoscopic ultrasound-guided fine-needle aspiration of portal vein thrombosis in patients with chronic liver disease and suspicion of hepatocellular carcinoma.

Differentiation between benign and malignant portal vein thrombosis (PVT) in the setting of a hepatocellular carcinoma (HCC) is of paramount importance. Histological analysis is usually not carried out because of potential severe side effects of the percutaneous approach. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) may be safer and may guide the clinical management of patients with HCC. To describe the feasibility of the EUS-FNA in a series of patients with HCC and PVT. A chart review of patients with PVT was performed from 2014 to 2016 in three tertiary care hospitals of Spain. Patients with chronic liver disease and PVT with a suspicion of HCC referred for EUS-FNA were included. The impact of the EUS-FNA was assessed by comparing staging following the Barcelona Clinic Liver Cancer algorithm (BCLC) before and after EUS-FNA. Of 104 patients with PVT and chronic liver disease, 23 were considered candidates for EUS-FNA. Eight patients were referred for EUS-FNA. The technique was feasible in seven patients and FNA was positive in six patients. No side effects were reported. EUS-FNA upstaged six out of seven (85.7%) patients: one patient BCLC stage B, two patients BCLC stage A, and three patients in whom the HCC was not diagnosed before EUS-FNA of the PVT. A benign PVT was found in the explant of the only patient with a negative PVT. EUS-FNA is a valuable technique in selected patients with chronic liver disease with PVT. It is feasible, safe, and may alter the clinical management in these patients.

Adherence to Barcelona Clinic Liver Cancer guidelines in field practice: Results of Progetto Epatocarcinoma Campania.

The Barcelona Clinic Liver Cancer (BCLC) algorithm is the standard system for clinical management of hepatocellular carcinoma (HCC). Data on adherence to this therapeutic paradigm are scarce. This field practice study aimed to provide a description of HCC cirrhotic patients in Southern Italy, to evaluate the adherence to BCLC guidelines and its impact on patients' survival. We analyzed the region-wide Italian database of Progetto Epatocarcinoma Campania, which includes data of HCC cirrhotic patients, prospectively collected from January 2013 to December 2015 in 16 regional centers. Overall, 1008 HCC patients were enrolled: 70.6% patients received therapies recommended by BCLC algorithm, while 29.4% underwent different treatments. Among patients who were treated in adherence to guidelines, a higher rate of diagnosis on surveillance programs, better liver function, lower rate of alpha-fetoprotein >200ng/mL, more early-stage and monofocal HCC, lower frequency of nodules >5cm, portal vein thrombosis and metastases were observed. The overall survival was evaluated according to HCC stage and no differences between groups and patients managed differently were found. The multivariate analysis showed that non-adherence to treatment guidelines was independently associated to the BCLC stage B, Child-Pugh classes B and C, and the presence of neoplastic thrombosis and metastases. Adherence to BCLC algorithm in field practice was high in early and end-stage HCC patients, but it was poor in intermediate and advanced patients.

A prognostic index for patients within the intermediate stage of hepatocellular carcinoma.

The Barcelona Clinic Liver Cancer algorithm is the most widely used staging system for hepatocellular carcinoma, but the intermediate stage of this classification comprises a very heterogeneous group of patients with different survival probabilities. The aim of our study was to construct a simple prognostic index for identifying subgroups of patients with different prognoses within the intermediate stage. Three-hundred and seven patients were retrospectively analyzed and randomly divided into a training sample (n=205), from which the model was developed, and a test sample (n=102), to independently assess the model's performance. Four variables were retained in the final multivariate model: hepatic failure, number of nodules, α-fetoprotein, and albumin, with hazard ratios equal to 2.22 (95% confidence interval: 1.52-3.24), 1.47 (1.00-2.18), 2.34 (1.56-3.52), and 1.75 (1.26-2.44), respectively. The score system was derived by summing up the linear weights assigned to the four covariates according to the observed regression coefficients. The score ranged between 4 and 13; to avoid sparse-data bias arising from small numbers within strata, only four categories (4-5, 6-7, 8-9, 10-13) were identified. The prognosis worsened significantly with increasing score and the C-index for discriminatory accuracy was equal to 0.66 (95% confidence interval: 0.60-0.72). The score was validated in the test sample (log-rank test P=0.02). Similar results were found when evaluating the score as a continuous variable. The simple prognostic index predicts survival in patients with intermediate-stage hepatocellular carcinoma. This score might help guide treatment selection and patient stratification in clinical studies.

Validity of the Barcelona clinic liver cancer (BCLC) and Hong Kong liver cancer (HKLC) staging system in determining treatment for hepatocellular carcinoma (HCC) in Singapore

Various staging systems have been introduced to stage and guide the therapeutic approach in patients diagnosed with HCC. The goal of our study is to compare paradigms in the HCC staging system, specifically, the BCLC and HKLC system, and to ultimately determine which framework Tan Tock Seng Hospital (TTSH), Singapore, employs more often. Generally, the HKLC algorithm provides a more refined staging and offers more aggressive treatments than the BCLC algorithm. A retrospective analysis was done, in which patients diagnosed with HCC at TTSH between 2010 and 2015 were identified and staged according to both the BCLC and HKLC staging system. The offered treatment was recorded and compared against the recommended treatment algorithm corresponding to each staging framework. Through this comparison, we determined which algorithm was followed by the hospital, if any at all. 779 patients were identified and in 475 (60.8%) cases, either the BCLC or HKLC was followed. 155 (19.9%) patients exclusively used the treatment algorithm recommended by HKLC while 78 (10.0%) patients exclusively followed the treatment algorithm recommended by BCLC. In the cases that exclusively followed the HKLC system, more aggressive treatments were offered than if the BCLC algorithm had been followed instead. In 242 (31.1%) cases, both algorithms recommend the same treatment modality and hence, these patients followed both staging systems. Finally, the treatment offered to 304 (39.0%) patients did not correspond to either of the staging systems. In general, the HKLC staging system was adopted by the hospital in a higher percentage of cases.

Treatment allocation in hepatocellular carcinoma: Assessment of the BCLC algorithm

Background and aims. The Barcelona Clinic Liver Cancer (BCLC) staging system is the algorithm most widely used to manage patients with hepatocellular carcinoma (HCC). We aimed to investigate the extent to which the BCLC recommendations effectively guide clinical practice and assess the reasons for any deviation from the recommendations.Material and methods. The first-line treatments assigned to patients included in the prospective Bern HCC cohort were analyzed.Results. Among 223 patients included in the cohort, 116 were not treated according to the BCLC algorithm. Eighty percent of the patients in BCLC stage 0 (very early HCC) and 60% of the patients in BCLC stage A (early HCC) received recommended curative treatment. Only 29% of the BCLC stage B patients (intermediate HCC) and 33% of the BCLC stage C patients (advanced HCC) were treated according to the algorithm. Eighty-nine percent of the BCLC stage D patients (terminal HCC) were treated with best supportive care, as recommended. In 98 patients (44%) the performance status was disregarded in the stage assignment.Conclusion. The management of HCC in clinical practice frequently deviates from the BCLC recommendations. Most of the curative therapy options, which have well-defined selection criteria, were allocated according to the recommendations, while the majority of the palliative therapy options were assigned to patients with tumor stages not aligned with the recommendations. The only parameter which is subjective in the algorithm, the performance status, is also the least respected.

Primary liver cancer

Primary liver cancer

Does transient elastography (FibroScan®) have a role in decision making in hepatocellular carcinoma?

ObjectivesPortal hypertension has been reported as a negative prognostic factor and a relative contraindication for liver resection. This study considers a possible role of fibrosis evaluation by transient elastography (FibroScan®) and its correlation with portal hypertension in patients with cirrhosis, and discusses the use of this technique in planning therapeutic options in patients with hepatocellular carcinoma (HCC). MethodsA total of 77 patients with cirrhosis, 42 (54.5%) of whom had HCC, were enrolled in this study during 2009–2011. The group included 46 (59.7%) men. The mean age of the sample was 65.2 years. The principle aetiology of disease was hepatitis C virus (HCV)-related cirrhosis (66.2%). Liver function was assessed according to Child–Pugh classification. In all patients liver stiffness (LS) was measured using FibroScan®. The presence of portal hypertension was indirectly defined as: (i) oesophageal varices detectable on endoscopy; (ii) splenomegaly (increased diameter of the spleen to ≥12cm), or (iii) a platelet count of <100000 platelets/mm3. ResultsMedian LS in all patients was 27.9kPa. Portal hypertension was recorded as present in 37 patients (48.1%) and absent in 40 patients (51.9%). Median LS values in HCC patients with and without portal hypertension were 29.1kPa and 19.6kPa, respectively (r=0.26, P<0.04). Liver stiffness was used to implement the Barcelona Clinic Liver Cancer algorithm in decisions about treatment. ConclusionsThe evaluation of liver fibrosis by transient elastography may be useful in the follow-up of patients with cirrhosis and a direct correlation with portal hypertension may aid in the evaluation of surgical risk in patients with HCC and in the choice of alternative therapies.

New Strategies in Hepatocellular Carcinoma: Genomic Prognostic Markers

Accurate prognosis prediction in oncology is critical. In patients with hepatocellular carcinoma (HCC), unlike most solid tumors, the coexistence of two life-threatening conditions, cancer and cirrhosis, makes prognostic assessments difficult. Despite the usefulness of clinical staging systems for HCC in routine clinical decision making (e.g., Barcelona-Clinic Liver Cancer algorithm), there is still a need to refine and complement outcome predictions. Recent data suggest the ability of gene signatures from the tumor (e.g., EpCAM signature) and adjacent tissue (e.g., poor-survival signature) to predict outcome in HCC (either recurrence or overall survival), although independent external validation is still required. In addition, novel information is being produced by alternative genomic sources such as microRNA (miRNA; e.g., miR-26a) or epigenomics, areas in which promising preliminary data are thoroughly explored. Prognostic models need to contemplate the impact of liver dysfunction and risk of subsequent de novo tumors in a patient's life expectancy. The challenge for the future is to precisely depict genomic predictors (e.g., gene signatures, miRNA, or epigenetic biomarkers) at each stage of the disease and their specific influence to determine patient prognosis.

An Evidence-Based Multidisciplinary Approach to the Management of Hepatocellular Carcinoma (HCC): The Alberta HCC Algorithm

Hepatocellular carcinoma (HCC) is one of only a few malignancies with an increasing incidence in North America. Because the vast majority of HCCs occur in the setting of a cirrhotic liver, management of this malignancy is best performed in a multidisciplinary group that recognizes the importance of liver function, as well as patient and tumour characteristics. The Barcelona Clinic Liver Cancer (BCLC) staging system is preferred for HCC because it incorporates the tumour characteristics (ie, tumour-node-metastasis stage), the patient's performance status and liver function according to the Child-Turcotte-Pugh classification, and then links the BCLC stage to recommended therapeutic interventions. However, the BCLC algorithm does not recognize the potential role of radiofrequency ablation for very early stage HCC, the expanding role of liver transplantation in the management of HCC, the role of transarterial chemoembolization in single large tumours, the potential role of transarterial radioembolization with 90Yttrium and the limited evidence for using sorafenib in Child- Turcotte-Pugh class B cirrhotic patients. The current review article presents an evidence-based approach to the multidisciplinary management of HCC along with a new algorithm for the management of HCC that incorporates the BCLC staging system and the authors' local selection criteria for resection, ablative techniques, liver transplantation, transarterial chemoembolization, transarterial radioembolization and sorafenib in Alberta.