New idea for treatment strategies for Barcelona Clinic Liver Cancer stages based on a network meta-analysis.
ABSTRACT: Currently, the Barcelona Clinic Liver Cancer staging (BCLC) system still remains controversies in the management of hepatocellular carcinoma. We are trying to determine the best therapeutic strategy for each BCLC stage through a network meta-analysis and provide a new treatment idea.We conducted a systematic literature search of the PubMed, EMBASE, and Cochrane Library databases and extracted data from randomized controlled trials (RCTs) that compared various strategies. Network meta-analyses were conducted in ADDIS by evaluating different overall survival of each stage. Cumulative probability was used to rank the included strategies. A node-splitting model assessed whether direct and indirect evidence on a specific node was in agreement.Of the 24 included RCTs, 3667 patients were included. Based on the probability P values, the results showed that TACE plus surgical resection (SR) was the first choice for BCLC Stage A (P?=?.38 and P?=?.52 for 3- and 5-year OS, respectively). The application of SR was the best strategy for BCLC Stage B (P?=?.51 and P?=?.95 for 1- and 3-year OS, respectively). For Stage C, whole net connections could not be established in this research, but combined therapy seemed to produce better results based on 3 separated net connections (P?=?.92, P?=?.80, and P?=?.69 for 1-year OS).The updated therapy strategies discussed in this study are recommended. More importantly, we deemed that the recommended strategy for each patient may be subject to adjustment due to individual clinical factors. The applicable scope of each strategy should also be evaluated before application.
Project description:We evaluated the post-treatment overall survival (OS) of elderly hepatocellular carcinoma (HCC) patients.The archived records of 10,578 HCC patients registered at the Korean Central Cancer Registry from 2008 through 2014 were retrospectively analyzed. In this registry, we selected Barcelona Clinic Liver Cancer (BCLC) 0, A, or B staged HCC patients (n = 4744) treated by surgical resection (SR), local ablation therapy (LAT), or locoregional therapy (LRT). OSs in nonelderly (<70 years) and elderly (≥70 years) patients were compared after propensity score matching (PSM).In BCLC 0-A staged HCC, the cumulative OS rates of elderly patients were poorer than those of nonelderly patients after PSM (P < .001), but not in those with BCLC stage B (P > .05). In BCLC 0-A staged elderly patients, OS after SR was significantly better than after LAT (P = .005) or LRT (P < .001). In BCLC B staged elderly patients, SR achieved better OS than LRT (P = .006). Multivariable analysis showed that LAT (hazard ratio [HR] 1.52, P = .048) or LRT (HR, 2.01, P < .001) as compared with SR, and large (>3 cm) tumor size (HR1.49, P = .018) were poor predictors of OS for elderly patients with BCLC stage 0-A, and that LRT (HR, 2.64, P = .042) was a poor predictor for those with BCLC stage B.SR provided a better OS rate than LAT or LRT in elderly HCC patients with BCLC stage 0-A, than LRT in those with BCLC stage B. SR should be considered the first therapeutic option even in elderly HCC patients with these stages.
Project description:Background and Aims: Although previous studies suggested that female patients who underwent curative resection in early-stage hepatocellular carcinoma (HCC) had better survival rates than male patients, it is unclear whether females in different HCC stages actually have survival advantage. This study aimed to investigate whether gender differences in the Barcelona Clinic Liver Cancer (BCLC) classification system contributed to different survival outcomes in hepatitis B virus (HBV)-related HCC. Methods: A retrospective analysis was performed of 1,753 patients diagnosed with HBV-related HCC between January 2008 and June 2017 at the Beijing Ditan hospital. The BCLC stages were classified into BCLC stage 0-B and BCLC stage C-D groups. Factors determining overall survival (OS) and progression-free survival (PFS) were analyzed via univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional-hazards regression models. Results: The cohort consisted of 1,202 BCLC stage 0-B and 551 BCLC stage C-D HBV-related HCC patients. Gender was identified to be an independent risk factor for OS (HR = 0.617; 95% CI, 0.426-0.895; p = 0.011) and PFS (HR = 0.728; 95% CI, 0.558-0.950; p = 0.019) in BCLC stage 0-B HBV-related HCC patients. With respect to OS and PFS, there were significant differences between female and male patients only in BCLC stage 0-B, but not in BCLC stage C-D. The OS and PFS in BCLC stage 0-B for female patients was significantly greater than that for male patients (p = 0.0103, p = 0.0112). Tumor multiplicity and size were independent risk factors for female patients in BCLC stage 0-B, whereas tumor multiplicity, tumor size, HBV-DNA, hemoglobin, total bilirubin, and alpha-fetoprotein levels were independent risk factors for male patients in BCLC stage 0-B. Conclusions: Different outcomes in OS or PFS with respect to gender only exist in BCLC stage 0-B HBV-related HCC patients. Female patients have a better outcome than male patients in BCLC stage 0-B.
Project description:BACKGROUND & AIMS:In 2012, the Barcelona Clinic Liver Cancer (BCLC) system designated a single large hepatocellular carcinoma (SLHCC) (>5 cm) as BCLC stage A rather than stage B. However, a recent study from western countries reported that prognosis following liver resection (LR) among patients with SLHCC was similar to that among patients with BCLC stage B. We aim to evaluate the prognosis following LR among patients with SLHCC from an Asian high-volume liver surgery center. METHODS:Patients who underwent curative-intent LR for histologically proven HCC between 2011 and 2017 were enrolled using an HCC registry database. Overall survival (OS) among patients with BCLC stages 0, A, and B was examined. Patients with a SLHCC were classified as BCLC stage A1. RESULTS:Among 543 patients, 89 (16.4%) were BCLC stage 0, 289 (53.2%) were BCLC stage A, 92 (16.9%) were BCLC stage A1, and 73 (13.4%) were BCLC stage B. The median follow-up was 38 months. The five-year OS rates among patients with BCLC stages 0, A, A1, and B were 83.5%, 83.7%, 77.4%, and 55.4%, respectively (p<0.001). No difference in OS was noted for patients with BCLC stage A versus A1 (p = 0.11), even after adjusting for competing factors (hazard ratio = 0.97, 95% confidence interval = 0.53-1.79; p = 0.93). CONCLUSION:Prognosis following LR among patients with SLHCC was similar to that among patients with BCLC stage A. The prognosis for SLHCC should thus be considered comparable to that for BCLC stage A.
Project description:BACKGROUND:Underlying liver function is a major concern when applying surgical resection for hepatocellular carcinoma (HCC). We aimed to explore the capability of the albumin-bilirubin (ALBI) grade to predict post-hepatectomy liver failure (PHLF) and long-term survival after hepatectomy for HCC patients with different Barcelona Clinic Liver Cancer (BCLC) stages. METHODS:Between January 2010 and December 2014, 338 HCC patients who were treated with liver resection were enrolled. The predictive accuracy of ALBI grade system for PHLF and long-term survival across different BCLC stages was examined. RESULTS:A total of 26 (7.7%) patients developed PHLF. Patients were divided into BCLC 0/A and BCLC B/C categories. ALBI score was found to be a strong independent predictor of PHLF across different BCLC stages by multivariate analysis. In terms of overall survival (OS), it exhibited high discriminative power in the total cohort and in BCLC 0/A subgroup. However, differences in OS between ALBI grade 1 and 2 patients in BCLC B/C subgroup were not significant (P?=?0.222). CONCLUSION:The ALBI grade showed good predictive ability for PHLF in HCC patients across different BCLC stages. However, the ALBI grade was only a significant predictor of OS in BCLC stage 0/A patients and failed to predict OS in BCLC stage B/C patients.
Project description:The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is variable, despite a myriad of prognostic markers. We compared and integrated the established prognostic models, HAP and ART scores, for their accuracy of overall survival (OS) prediction.In both training and validation sets, HAP and ART scores emerged as independent predictors of OS (p<0.01) with HAP achieving better prognostic accuracy (c-index: 0.68) over ART (0.57). We tested both scores in combination to evaluate their combined ability to predict OS. Subgroup analysis of BCLC-C patients revealed favorable HAP stage (p<0.001) and radiological response after initial TACE (p<0.001) as positive prognostic factors.Prognostic scores were studied using multivariable Cox regression and c-index analysis in 83 subjects with Barcelona Clinic Liver Cancer (BCLC) A/B stage from UK and Italy (training set), and 660 from Korea and Japan (validation set), all treated with conventional TACE. Scores were further validated in an separate analysis of patients with BCLC-C stage disease (n=63) receiving initial TACE.ART and HAP scores are validated indices in patients with intermediate stage HCC undergoing TACE. The HAP score is best suited for screening patients prior to initial TACE, whilst sequential ART assessment improves early detection of chemoembolization failure. BCLC-C patients with low HAP stage may be a subgroup where TACE should be explored in clinical studies.
Project description:We aimed to investigate the impact of the controlling nutritional status (CONUT) score, an immuno-nutritional biomarker, on the prognosis of patients with hepatocellular carcinoma (HCC) treated with lenvatinib (LEN). This retrospective study enrolled 164 patients with HCC and treated with LEN (median age 73 years, Barcelona Clinic Liver Cancer (BCLC) stage B/C 93/71). Factors associated with overall survival (OS) were evaluated using multivariate and decision tree analyses. OS was calculated using the Kaplan-Meier method and analyzed using the log-rank test. Independent factors for OS were albumin-bilirubin grade 1, BCLC stage B, and CONUT score <5 (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.58-5.31, p < 0.001). The CONUT score was the most important variable for OS, with OS rates of 70.0% and 29.0% in the low and high CONUT groups, respectively. Additionally, the median survival time was longer in the low CONUT group than in the high CONUT group (median survival time not reached vs. 11.3 months, p < 0.001). The CONUT score was the most important prognostic variable, rather than albumin-bilirubin grade and BCLC stage, in patients with HCC treated with LEN. Accordingly, immuno-nutritional status may be an important factor in the management of patients with HCC treated with LEN.
Project description:Background:Level I evidence supports the use of sorafenib in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma, where heterogeneity in efficacy exists due to varying clinicopathologic features of the disease. Aim:We evaluated whether prior treatment with curative or locoregional therapies influences sorafenib-specific survival. Methods:From a prospective data set of 785 consecutive patients from international specialist centres, 264 patients (34%) were treatment naïve (TN) and 521 (66%) were pre-treated (PT), most frequently with transarterial chemoembolization (n = 413; 79%). The primary endpoint was overall survival (OS) from sorafenib initiation with prognostic factors tested on uni- and multivariate analyses. Results:Median OS for the entire cohort was 9 months; the median sorafenib duration was 2.8 months, with discontinuation being secondary to progression (n = 454; 58%) or toxicity (n = 149; 19%). PT patients had significantly longer OS than TN patients (10.5 vs. 6.6 months; p < 0.001). Compared to TN patients, PT patients had a better Child-Pugh (CP) class (CP A: 57 vs. 47%; p < 0.001) and a lower BCLC stage (BCLC A-B, 40 vs. 30%; p = 0.007). PT status preserved an independent prognostic role (p = 0.002) following adjustment for BCLC stage, ?-fetoprotein, CP class, aetiology, and post-sorafenib treatment status. PT patients were more likely to receive further anticancer treatment after sorafenib (31 vs. 9%; p < 0.001). Conclusion:Patients receiving sorafenib after having failed curative or locoregional therapies survive longer and are more likely to receive further treatment after sorafenib. This suggests an incremental benefit to OS from sequential exposure to multiple lines of therapy, justifying treatment stage migration in eligible patients.
Project description:Introduction:According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, transarterial chemoembolization (TACE) is recommended in patients with hepatocellular carcinoma (HCC) of intermediate stage (BCLC-B), whereas partial hepatectomy (PH) is restricted to early stage A. Expanding the indication for PH to intermediate stage remains debated. Objective:This meta-analysis aimed to analyze short- and long-term outcomes of PH compared to TACE in patients with intermediate-stage HCC. Methods:A meta-analysis was conducted according to PRISMA guidelines. Trials comparing PH with TACE in patients with intermediate-stage HCC were selected. Only patients of BCLC-B stage were included in the analyses. Primary endpoint was overall survival (OS) and secondary endpoint was 90-day postprocedural mortality. Random-effects models were used to analyze time ratios (TRs). Results:Seven eligible trials were analyzed, including 1,730 BCLC-B patients undergoing PH (n = 750) or TACE (n = 980). Comparison of OS between PH and TACE determined a pooled TR of 1.91 (95% CI 1.24-2.94; p < 0.001). Survival rates at 1-, 3-, and 5-year were 85, 60, and 42% after PH, compared to 73, 60, and 20% after TACE (p < 0.001). There was no difference in postprocedural mortality between PH and TACE with rates of 3.7 and 3.4%, respectively (TR 0.95; 95% CI 0.17-5.50; p = 0.879). Conclusions:In patients with intermediate HCC, PH was associated with increased long-term survival compared to TACE, with comparable postprocedural mortality. These results suggest considering PH as treatment option in intermediate HCC and highlight the urgent need to refine the selection of patients with BCLC-B stage who may benefit from PH.
Project description:Cripto-1 could promote tumorigenesis in a wide range of carcinomas, yet little is known in hepatocellular carcinoma (HCC). The expression of Cripto-1 and MMP-9 were assessed by immunohistochemistry in 205 HCC specimens. The correlation between Cripto-1 and MMP-9, clinicopathological/prognostic value in HCC was examined. Cripto-1 overexpression was correlated with larger tumor, TNM stage, BCLC stage and tumor recurrence. In multivariate analyses, Cripto-1 was an independent predictor for overall survival (OS) and time to recurrence (TTR). Cripto-1 expression was increased in TNM and BCLC stage-dependent manner. Cripto-1 overexpression was associated with poor prognosis in patients subgroups stratified by tumor size, tumor differentiation, TNM and BCLC stage. In addition, Cripto-1 was positively correlated with MMP-9 among 205 HCC samples. Patients with Cripto-1 upregulation had poor OS and shorter TTR in low and high aggressiveness groups. Furthermore, Cripto-1 had predictive validity for early and late recurrence in HCC patients. Combination of Cripto-1 and serum AFP was correlated with OS and TTR. In conclusion, Cripto-1 overexpression contributes to aggressiveness and poor prognosis of HCC. Cripto-1/AFP expression could be a potential prognostic biomarker for survival in HCC patients.
Project description:Background:Sorafenib has been recommended as the first-line treatment and shown to prolong the median overall survival (OS) of patients with advanced unresectable hepatocellular carcinoma (HCC). Recently, a growing number of earlier studies showed the application of radiofrequency ablation (RFA) plus sorafenib in patients diagnosed at the advanced-stage HCC. This study aimed to compare the outcomes of RFA plus sorafenib versus sorafenib alone and identify prognostic factors related to OS for BCLC stage C patients with PS 1 but without vascular invasion or extrahepatic spread. Methods:A total of 276 consecutive patients in BCLC stage C with PS 1 but without vascular invasion or extrahepatic spread were enrolled in this retrospective study. Survival analyses were performed using the Kaplan-Meier analysis, and the log-rank test examined the statistical differences between the transarterial chemoembolization (TACE) and sorafenib groups. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS. Results:Based on the Kaplan-Meier curves, patients treated with RFA plus sorafenib showed better OS than those undergoing sorafenib, with respective OS at 1, 3 and 5 years (84.0%, 43.1%, 22.8% vs. 55.6%, 29.6%, 4.8%, Log-rank P<0.001). The univariate analysis and multivariate analysis showed that tumor size, tumor number, treatment method, albumin, bilirubin, and the Child-Pugh score were associated with OS. According to the subgroups analyses based on the tumor size and tumor number, there were significant differences in OS among overall subsets except in patients with tumor number ?4 between RFA plus sorafenib and sorafenib therapy. Conclusions:RFA plus sorafenib provided better prognostic performance than sorafenib, which should be suggested as an alternative treatment modality compared with sorafenib for BCLC stage C patients with PS 1 but without vascular invasion or extrahepatic spread.