An overview: Management of patients with advanced hepatocellular carcinoma

Wang, Jincheng; Wu, Rui; Sun, Jin-Yu; Liu, Feifei; Tan, Huabing; Lu, Xiao‐Jie

doi:10.5582/bst.2022.01109

Cited by 10 publications

(6 citation statements)

References 227 publications

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“…Most of the patients with early-stage HCC would undergo curative resection, whereas 50% patients might have disease recurrence within 5 years(Llovet et al 2016 ). Studies have identified risk factors that associated with recurrence after curative resection, including macrovascular/microvascular invasion, tumor size greater than 5 centimeters in diameter, multiple nodes, positive resection margin or resection margin less than 1 centimeter, hepatitis B virus infection and AFP greater than 400ng/L(Imamura et al 2003 ; Wang et al 2020 ; Zeng et al 2022 ). Numerous procedures were explored to decrease the recurrence rate and prolong life span.…”

Section: Discussionmentioning

confidence: 99%

Network meta-analysis of adjuvant treatments for patients with hepatocellular carcinoma after curative resection

Ye,

Wang,

et al. 2023

BMC Gastroenterol

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Purpose The prevention of recurrence for patients with hepatocellular carcinoma after curative resection is still a great challenge in clinical practice. There are numerous studies that trying to search for favorable strategies to decrease the recurrence and prolong life span for these patients, whereas no consensus is reached till now. Herein, we aim to compare the efficacy between different reported treatments by network meta-analysis(NMA). Methods We searched Pubmed, Web of Science and Cochrane Library for abstracts and full-text articles published from database inception through February 2023. All of the random controlled trials(RCTs) were evaluated and collected as eligible studies. The primary outcome was the prevention of recurrence between different procedures. The second outcomes were one-year survival, three-year survival and five-year survival. Results Thirty-two RCTs including 5783 patients were selected, and 12 treatments were classified. Most of the studies were high quality with low bias. Thirty-one studies including 5629 patients were recruited for recurrence analysis. The network meta-analysis showed benefits from transarterial chemoembolization(TACE) + portal vein chemotherapy(PVC)[OR, 2.84 (1.15,6.99)] and internal radiotherapy(IRT) [OR, 2.63 (1.41,4.91)] compared to non-adjuvant(NA) treatment when considering prevention of recurrence. Seventeen studies including 2047 patients were collected for one-year survival analysis. The network meta-analysis showed benefit from TACE[OR, 0.33 (0.14,0.75)] when considering one-year survival. Twenty-one studies including 2463 patients were collected for three-year survival analysis. The network meta-analysis showed TACE [OR, 0.51 (0.30,0.86)], IRT[OR, 0.41 (0.20,0.83)] and dendritic cell(DC) [OR, 0.09 (0.01,0.98)] were better than NA when considering three-year survival. Sixteen studies including 1915 patients were collected for five-year survival analysis. The network meta-analysis didn’t show any benefit from different treatments when considering five-year survival. Other strategies including external radiotherapy(ERT), branched-chain amino acids(BCAA), hepatic artery infusion chemotherapy(HAIC), cytokine-induced killer(CIK), adoptive immunotherapy(AIT), Huaier, interferon(IFN), oral chemotherapy(OCT) and sorafenib(SOR) didn’t show significant benefit regardless of prevention of recurrence or short-, long- time survival. Conclusion This NMA found that TACE + PVC and IRT were considered as the procedures to decrease HCC recurrence rate. TACE, IRT and DC were preferred when considering the extending of life span for post-operative patients with HCC. Large scale of RCTs are needed to verify it.

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Section: Discussionmentioning

confidence: 99%

Network meta-analysis of adjuvant treatments for patients with hepatocellular carcinoma after curative resection

Ye,

Wang,

et al. 2023

BMC Gastroenterol

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“…HCC is the sixth cancer in the world in 2020 and the third leading cause of cancer related death. At present, surgical resection, ablation or liver transplantation are the main treatment methods for liver cancer in clinical practice, which has a good effect on the treatment of early liver cancer [11][12]. However, less than 20% of patients are diagnosed in the early stages of the disease.…”

Section: Discussionmentioning

confidence: 99%

A Novel Differentially Expressed Cuproptosis-Related lncRNAs Signature to predict the prognosis and immune characteristics of hepatocellular carcinoma

Yin

Gao

Sun

et al. 2023

Preprint

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Objective: According to a growing body of research, long non-coding RNAs (lncRNAs) participate in the progress of hepatocellular carcinoma (HCC). Cuproptosis is a distinct kind of programmed cell death, separating it from several other forms of programmed cell death that may be caused by genetic programming. Consequently, our aim was to investigate the relationship between Differentially Expressed Cuproptosis-Related lncRNAs (DECRLs) and clinical outcome and immune characteristics of HCC. Method: The Cancer Genome Atlas (TCGA) database was used to retrieve related data. The GSE101728 dataset was downloaded from the Gene Expression Omnibus (GEO) database. A list of cuproptosis-related genes (CRGs) was obtained from a recently published article in Science. Combined analysis of TCGA dataset and the GSE101728 dataset identified differentially expressed CRGs(DECRGs).We can obtain DECRLs via co-expression. Then, using DECRLs, we developed a risk prediction model using Cox regression analysis and the least absolute shrinkage selection operator (LASSO) regression analysis. To evaluate the diagnostic accuracy of this model, a Kaplan-Meier (K-M) survival analysis and a receiver operating characteristic (ROC) curve analysis were used. Next, principal component analysis (PCA) was carried out.Moreover, the relationships between the risk model and immune characteristics, somatic mutation, and drug sensitivity were also investigated. Finally Real-Time quantitative PCR(RT-qPCR) and Western Blot confirmed the expression of DECRGs or DECRLs in HCC. Results: Three high-risk DECRLs(AL031985.3,AC107959.3,MKLN1-AS) that can guide HCC prognosis and immune microenvironment were obtained through cox regression analysis.Immune functions such as APC co-inhibition,Type-II-IFN-Reponse,Parainflammation,MHC-class-I, and Tumor Immune Dysfunction and Exclusion(TIDE) score, and Tumor Mutation Burden(TMB) were significantly different in high-risk and low-risk groups.Moreover, this research also found that the IC50 values for 87 chemotherapeutic drugs varied widely across patients within high and low-risk groups.The expression of GLS at both mRNA and protein levels was significantly raised in HCC,and that of CDKN2A was dropped in HCC. The mRNA expression level of AL031985.3,AC107959.3 and MKLN1-AS was upregulated in HCC. Conclusion: The proposed 3-DECRLs that can predict clinical prognosis or guide the immune characteristics and drugs that may have a potential curative effect on HCC received in our research may play a major role in patient management and immunotherapy.

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“…Not only is the effective response rate to monotherapy low ( 18 , 19 ), but there is insufficient knowledge of predictive biomarkers of ICI treatment response such as programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and microsatellite instability (MSI) status ( 20 , 21 ). Conversely, some studies have shown that antiangiogenic therapy can enhance the antitumor sensitivity of programmed cell death protein 1 (PD-1)/PD-L1 inhibitors, so antiangiogenic therapy combined with immunotherapy can achieve synergistic antitumor effects ( 22 – 24 ). The results of two multicenter phase III studies (Imbrave150 ( 25 ) and ORIENT32 ( 26 )) showed that overall survival (OS) and progression-free survival (PFS) in the combination therapy group were significantly better than those in the monotherapy group.…”

Section: Introductionmentioning

confidence: 99%

TIDE: adjuvant tislelizumab plus donafenib combined with transarterial chemoembolization for high-risk hepatocellular carcinoma after surgery: protocol for a prospective, single-arm, phase II trial

Wei

et al. 2023

Front. Oncol.

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BackgroundThe high recurrence rate of hepatocellular carcinoma (HCC) after surgery negatively affects the prognosis of patients. There is currently no widely accepted adjuvant therapy strategy for patients with HCC. A clinical study of effective adjuvant therapy is still needed.MethodsIn this prospective, single-arm, phase II clinical trial, an adjuvant regimen of donafenib plus tislelizumab combined with transarterial chemoembolization (TACE) will be used to treat enrolled HCC patients after surgery. Briefly, patients newly diagnosed with HCC by pathological examination who underwent curative resection and had a single tumor more than 5 cm in diameter with microvascular invasion as detected by pathological examination are eligible. The primary endpoint of the study is the recurrence-free survival (RFS) rate at 3 years, and secondary endpoints are the overall survival (OS) rate and the incidence of adverse events (AEs). The planned sample size, 32 patients, was calculated to permit the accumulation of sufficient RFS events in 3 years to achieve 90% power for the RFS primary endpoint.DiscussionVascular endothelial growth factor (VEGF) and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathways regulate the relevant immunosuppressive mechanisms of HCC recurrence. Our trial will evaluate the clinical benefit of adding donafenib plus tislelizumab to TACE in patients with early-stage HCC and a high risk of recurrence.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR2200063003.

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An overview: Management of patients with advanced hepatocellular carcinoma

Cited by 10 publications

References 227 publications

Network meta-analysis of adjuvant treatments for patients with hepatocellular carcinoma after curative resection

Network meta-analysis of adjuvant treatments for patients with hepatocellular carcinoma after curative resection

A Novel Differentially Expressed Cuproptosis-Related lncRNAs Signature to predict the prognosis and immune characteristics of hepatocellular carcinoma

TIDE: adjuvant tislelizumab plus donafenib combined with transarterial chemoembolization for high-risk hepatocellular carcinoma after surgery: protocol for a prospective, single-arm, phase II trial

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