Dataset Information

Downstaging Therapies for Unresectable Hepatocellular Carcinoma Prior to Hepatic Resection: A Systematic Review and Meta-Analysis.

ABSTRACT:

Introduction

Hepatocellular carcinoma (HCC) is a high-grade malignant disease with unfavorable prognosis, and although surgical therapy is necessary, not all patients with HCC are suitable candidates for surgery. Downstaging as preoperative therapeutic strategy, which can convert unresectable HCC into resectable HCC, intends to increase the resection rate and improve prognosis.

Methods

We searched multiple databases updated to December 30, 2020, for studies on transcatheter arterial chemoembolization (TACE), Yttrium 90 microsphere selective internal radiation (SIR)/transcatheter radioembolization (TARE), hepatic arterial infusion (HAI), and systemic treatment as downstaging treatment before resection for patients with unresectable HCC.

Results

A total of 20 comparative and non-comparative studies were finally included in the meta-analysis. The pooled downstaging rate of hepatic resection (HR) was 14% [95% confidence interval (CI) 0.10-0.17] with significant heterogeneity (I ² = 94.51%). The chemotherapy, combination, and non-cirrhosis groups exhibit higher rates of downstaging, but these differences were not significant. For comparative studies, the overall survival (OS) rates of resection after downstaging were far better than those inpatients who received locoregional therapy (LRT) or systemic treatment alone at 1 year (RR 1.87, 95% CI 1.48-2.38), 3 years (RR 5.56, 95% CI 2.55-12.10), and 5 years (RR 5.47, 95% CI 2.22-13.49). In addition, the pooled disease-free survival (DFS) rates in patients undergoing HR after successful downstaging were 78% (95% CI 0.62-0.93) at 1 year, 47% (95% CI 0.25-0.68) at 3 years, and 46% (95% CI 0.32-0.59) at 5 years. The pooled OS rates were 88% (95% CI 0.82-0.95) at 1 year, 64% (95% CI 0.59-0.69) at 3 years, and 42% (95% CI 0.29-0.54) at 5 years.

Conclusions

Downstaging may serve as a screening tool to identify patients who might benefit from surgery. Resection after successful downstaging can improve prognosis.

SUBMITTER: Chen X

PROVIDER: S-EPMC8639517 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background & aimsAccording to the Barcelona Clinic Liver Cancer (BCLC) staging system, hepatic resection and transarterial chemoembolization (TACE) should be recommended in patients with hepatocellular carcinoma (HCC) within and beyond the BCLC stage A, respectively. We conducted a systematic review and meta-analysis to compare the overall survival between HCC patients undergoing hepatic resection and TACE.MethodsPubMed, EMBASE, and Cochrane library databases were searched. All relevant studies were considered, if they reported the survival data in HCC patients undergoing hepatic resection and TACE. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for the comparison of cumulative overall survival. Odds ratios (ORs) with 95%CIs were calculated for the comparison of 1-, 3-, and 5-year survival rates. Subgroup analyses were performed according to the BCLC stages and portal vein tumor thrombus (PVTT). Sensitivity analyses were performed in moderate- and high-quality studies and in studies published after 2005.ResultsFifty of 2029 retrieved papers were included. One, 15, and 34 studies were of high-, moderate-, and low-quality, respectively. The overall meta-analysis demonstrated a statistically significantly higher overall survival in hepatic resection group than in TACE group (HR=0.60, 95%CI=0.55-0.66). Additionally, 1-, 3-, and 5-year survival rates were statistically significantly higher in hepatic resection group than in TACE group (OR=1.82, 95%CI=1.56-2.14; OR=3.09, 95%CI=2.60-3.67; OR=3.48, 95%CI=2.83-4.27). The subgroup meta-analyses confirmed the statistical significance in HCC within the BCLC stage A (HR=0.72, 95%CI=0.64-0.80), in HCC beyond the BCLC stage A (HR=0.60, 95%CI=0.51-0.69), in HCC within the BCLC stage B alone (HR=0.48, 95%CI=0.25-0.90), and in HCC with PVTT (HR=0.78, 95%CI=0.68-0.91). The statistical significance was also confirmed by sensitivity analyses in moderate- and high-quality studies (HR=0.62, 95%CI=0.53-0.71) and in studies published after 2005 (HR=0.59, 95%CI=0.53-0.66).ConclusionsBased on a systematic review and meta-analysis, hepatic resection may be considered in HCC beyond the BCLC stage A. However, given the limitations of study quality, more well-designed randomized controlled trials should be warranted to confirm these findings.

Project description:BackgroundThe aim of the study was to investigate the incidence and spectrum of adverse events in unresectable hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs) or ICI-based combinations.SummaryThe study protocol was prospectively registered on PROSPERO (CRD42022319255). We searched PubMed, EMBASE, and the Cochrane Library for published clinical trials from database inception to April 22, 2022. Studies that included at least one group of unresectable HCC patients treated with ICIs or ICI-based combinations and reported the incidence or spectrum of treatment-related adverse events (trAEs) or immune-related adverse events (irAEs) were eligible. The incidence and spectra of all-grade and grade ≥3 trAEs were the primary outcomes. The profiles of irAEs, the incidence of trAEs leading to treatment discontinuation, and treatment-related mortalities were additional outcomes. We applied random-effects models to pool the incidence and spectra of adverse events. Subgroup analyses and meta-regression were performed. The literature search identified 2,464 records. Twenty studies (4,146 participants with HCC) met the eligibility criteria. The pooled incidences of all-grade trAEs, grade ≥3 trAEs, all-grade irAEs, and grade ≥3 irAEs were 80.1% (95% CI: 73.8-85.2), 35.4% (95% CI: 27.2-44.6), 31.1% (95% CI: 21.0-43.5), and 6.6% (95% CI: 3.6-11.8), respectively. ICIs plus oral targeted agents (all-grade OR = 17.07, 95% CI: 6.05-48.16, p < 0.001; grade ≥3 OR = 9.35, 95% CI: 4.53-19.29, p < 0.001) and ICIs plus intravenous targeted agents (all-grade OR = 4.91, 95% CI: 1.80-13.42, p = 0.003; grade ≥3 OR = 4.21, 95% CI: 1.42-12.48, p = 0.012) were associated with increased trAEs compared with monotherapy. The all-grade trAEs with the highest pooled incidences were reactive capillary endothelial proliferation (49.2%, 95% CI: 26.3-72.3), neutropenia (34.6%, 95% CI: 17.1-57.5), and proteinuria (32.8%, 95% CI: 19.8-49.2). The grade ≥3 trAEs with the highest pooled incidences were hypertension (11.1%, 95% CI: 4.0-29.0), neutropenia (10.5%, 95% CI: 7.0-15.4), and increased aspartate aminotransferase (7.7%, 95% CI: 6.3-9.4). The pooled incidence of trAEs leading to treatment discontinuation was 8.0% (95% CI: 6.0-10.5), and the overall incidence of treatment-related mortalities was 1.1%.Key messagesThis study comprehensively summarized the incidence and spectrum of trAEs in unresectable HCC patients receiving ICIs or ICI-based combinations in clinical trials. The results from this study will provide a useful reference to guide clinical practice.