Conversion therapy for unresectable hepatocellular carcinoma:Advances and challenges

Recently,the World Journal of Gastrointestinal Oncology published an article entitled“Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of the literature”,in which the authors shared their successful experience with complete surgical resection after multidisciplinary conversion therapy.The study by Chu et al demonstrates the great challenges that the advanced hepatocellular carcinoma(HCC)poses to surgical oncology,reveals the complexity of conversion therapy for unresectable HCC,emphasizes the important role of a multidisciplinary management model in conversion therapy,and enriches our understanding of the dynamics of personalized treatment for different patients.At present,conversion therapy is a hot research topic in the treatment of unresectable HCC,which has brought new hope to many patients with moderately advanced HCC.However,there are still many urgent problems to be solved in conversion therapy.Here,we would like to further discuss the advances and challenges of conversion therapy for unresectable HCC with the authors and the general readers.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Adjuvant therapy for hepatocellular carcinoma:Dilemmas at the start of a new era

Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.

Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

Precision targeting in hepatocellular carcinoma:Exploring ligandreceptor mediated nanotherapy

Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages,but it is often ineffective and suffers from problems such as multidrug resistance,rapid drug clearance,nonspecific targeting,high side effects,and low drug accumulation in tumor cells.In response to these limitations,recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC.This review focuses on recent advances in nanoparticle-based targeted drug delivery systems,with special attention to various receptors overexpressed on HCC cells.These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC.We comprehensively summarize the current understanding of these receptors,their role in nanoparticle targeting,and the impact of such targeted therapies on HCC.By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies,more effective and precise treatment of HCC can be achieved.

Conversion therapy of a giant hepatocellular carcinoma with portal vein thrombus and inferior vena cava thrombus:A case report and review of literature

BACKGROUND The prognosis of hepatocellular carcinoma(HCC)combined with portal and hepatic vein cancerous thrombosis is poor,for unresectable patients the combination of targeted therapy and immune therapy was the first-line recommended treatment for advanced HCC,with a median survival time of only about 2.7-6 months.In this case report,we present the case of a patient with portal and hepatic vein cancerous thrombosis who achieved pathologic complete response after conversion therapy.CASE SUMMARY In our center,a patient with giant HCC combined with portal vein tumor thrombus and hepatic vein tumor thrombus was treated with transcatheter arterial chemoembolization(TACE),radiotherapy,targeted therapy and immunotherapy,and was continuously given icaritin soft capsules for oral regulation.After 7 months of conversion therapy,the patient's tumor shrank and the tumor thrombus subsided significantly.The pathology of surgical resection was in complete remission,and there was no progression in the postoperative follow-up for 7 months,which provided a basis for the future strategy of combined conversion therapy.CONCLUSION In this case,atezolizumab,bevacizumab,icaritin soft capsules combined with radiotherapy and TACE had a good effect.For patients with hepatocellular carcinoma combined with hepatic vein/inferior vena cava tumor thrombus,adopting a high-intensity,multimodal proactive strategy under the guidance of multidisciplinary team(MDT)is an important attempt to break through the current treatment dilemma.

New insights into mechanisms and interventions of locoregional therapies for hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is responsible for a significant number of cancer-related deaths worldwide and its incidence is increasing. Locoregional treatments, which are precision procedures guided by imaging to specifically target liver tumors, play a critical role in the management of a substantial portion of HCC cases. These therapies have become an essential element of the HCC treatment landscape, with transarterial chemoembolization(TACE)being the treatment of choice for patients with intermediate to advanced stages of the disease. Other locoregional therapies, like radiofrequency ablation, are highly effective for small, early-stage HCC. Nevertheless, the advent of targeted immunotherapy has challenged these established treatments. Tyrosine kinase inhibitors(TKIs) and immune checkpoint inhibitors(ICIs) have shown remarkable efficacy in clinical settings. However, their specific uses and the development of resistance in subsequent treatments have led clinicians to reevaluate the future direction of HCC therapy. This review concentrates on the distinct features of both systemic and novel locoregional therapies. We investigate their effects on the tumor microenvironment at the molecular level and discuss how targeted immunotherapy can be effectively integrated with locoregional therapies. We also examine research findings from retrospective studies and randomized controlled trials on various combined treatment regimens, assessing their validity to determine the future evolution of locoregional therapies within the framework of personalized, comprehensive treatment.

Options and survival benefits of conversion therapy for unresectable hepatocellular carcinoma

In the study by Wu et al,patients with unresectable hepatocellular carcinoma were subjected to transarterial chemoembolization(TACE)as a conversion therapy in order to render their tumors suitable for resection.A nomogram was devised and shown to be effective in predicting the survival of these patients.Generalization of the results,however,is questionable since the study subjects consisted of patients who had resection after TACE while excluding patients with the same disease but not suitable for TACE.Immunotherapy can be considered to be an option for conversion therapy.However,markers for determining responses to a conversion therapy and for guiding the decision between TACE and sequential immunotherapy have been lacking.The question of whether effective conversion therapy can truly enhance overall survival remains unanswered.

Improving clinical outcomes of patients with hepatocellular carcinoma:Role of antiviral therapy,conversion therapy,and palliative therapy

In this editorial,I comment on three articles published in the recent issue of the World Journal of Gastrointestinal Oncology.Hepatocellular carcinoma(HCC)is an important public health concern,and there are three articles on the theme of HCC in this issue.I focus on the articles by Mu et al,Chu et al,and Ma et al for this editorial.While these articles may be considered as low-quality evidence,and the results cannot be generalized to non-hepatitis-B or C virus patients,the discussion of the results is important.In addition,though all the articles are from China,the relevance of the results is not minuscule.As resection is the main form of curative treatment modality owing to a donor liver shortage,surgeons need to be aware that preoperative long-course antiviral therapy can improve clinical outcomes by reducing postoperative liver dysfunction and recurrence of HCC following resection.Similarly,patients with super-giant HCC(defined as≥15 cm diameter)should also be carefully considered for liver resection,and if it is unresectable upfront,then a combination of liver-directed therapy and systemic therapy may downstage HCC.If,following downstaging,the patient qualifies for liver resection based on locally prevalent resectability criteria,then such therapy is labelled as conversion(from unresectable to resectable)therapy.In unresectable patients treated by a combination of treatment options,serological markers like neutrophil-to-lymphocyte ratio and alpha-fetoprotein are reported to predict treatment responses,thus enabling personalized medicine.

Pathologic complete response to conversion therapy in hepatocellular carcinoma using patient-derived organoids:A case report

BACKGROUND For primary liver cancer,the key to conversion therapy depends on the effectiveness of drug treatment.Patient-derived tumor organoids have been demonstrated to improve the efficacy of conversion therapy by identifying individualtargeted effective drugs,but their clinical effects in liver cancer remain unknown.CASE SUMMARY We described a patient with hepatocellular carcinoma(HCC)who achieved pathologic complete response(pCR)to conversion therapy guided by the patientderived organoid(PDO)drug sensitivity testing.Despite insufficiency of the remaining liver volume after hepatectomy,the patient obtained tumor reduction after treatment with the PDO-sensitive drugs and successfully underwent radical surgical resection.Postoperatively,pCR was observed.CONCLUSION PDOs contributes to screening sensitive drugs for HCC patients to realize the personalized treatment and improve the conversion therapy efficacy.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Current research status of transarterial therapies for hepatocellular carcinoma

With continuous advancements in interventional radiology,considerable progress has been made in transarterial therapies for hepatocellular carcinoma(HCC)in recent years,and an increasing number of research papers on transarterial therapies for HCC have been published.In this editorial,we comment on the article by Ma et al published in the recent issue of the World Journal of Gastrointestinal Oncology:“Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC”.We focus specifically on the current research status and future directions of transarterial therapies.In the future,more studies are needed to determine the optimal transarterial local treatment for HCC.With the emergence of checkpoint immunotherapy modalities,it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.

From biomarker discovery to combined therapies:Advancing hepatocellular carcinoma treatment strategies

This editorial reviews advances in hepatocellular carcinoma(HCC)treatment,focusing on a triple therapy approach and biomarker discovery.Zhang et al discuss the synergistic potential of transarterial chemoembolization combined with tyrosine kinase inhibitors and PD-1 inhibitors.Meanwhile,Li et al identify protein tyrosine phosphatase non-receptor II(PTPN2)as a biomarker for poor prognosis and immune evasion in HCC.The studies highlight the importance of combined therapies and biomarkers in improving HCC treatment efficacy and patient outcomes,with PTPN2 emerging as a potential therapeutic target.This article supplements the aforementioned studies with more recent research advancements,focusing on the molecular mechanisms and clinical applications of biomarkers.

Impact of baseline body mass index on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy

BACKGROUND Primary liver cancer is the sixth most common cancer worldwide,with hepato-cellular carcinoma(HCC)being the most prevalent form.Despite the current availability of multiple immune or immune combination treatment options,the prognosis is still poor,so how to identify a more suitable population is extremely important.AIM To evaluate the clinical effectiveness of combining lenvatinib with camrelizumab for patients with hepatitis B virus(HBV)-related HCC in Barcelona Clinic Liver Cancer(BCLC)stages B/C,considering various body mass index(BMI)in diffe-rent categories.METHODS Retrospective data were collected from 126 HCC patients treated with lenvatinib plus camrelizumab.Patients were divided into two groups based on BMI:The non-overweight group(BMI<25 kg/m2,n=51)and the overweight/obese group(BMI≥25 kg/m2,n=75).Short-term prognosis was evaluated using mRECIST criteria,with subgroup analyses for non-overweight(BMI:18.5-24.9 kg/m2),overweight(BMI:25-30 kg/m2),and obese(BMI≥30 kg/m2)patients.A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival(OS),leading to the development of a column-line graph model.with subgroup analyses for non-overweight(BMI:18.5-24.9 kg/m2),overweight(BMI:25-30 kg/m2),and obese(BMI≥30 kg/m2)patients.A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival(OS),leading to the development of a column-line graph model.RESULTS Median progression-free survival was significantly longer in the obese/overweight group compared to the non-overweight group.Similarly,the median OS was significantly prolonged in the obese/overweight group than in the non-overweight group.The objective remission rate and disease control rate for the two groups of patients were,respectively,objective remission rate(5.88%vs 28.00%)and disease control rate(39.22%vs 62.67%).Fatigue was more prevalent in the obese/overweight group,while other adverse effects showed no statistically significant differences(P>0.05).Subgroup analysis based on BMI showed that obese and overweight patients had better progression-free survival and OS than non-overweight patients,with obese patients showing the best outcomes.Multifactorial regression analysis identified BCLC grade,alpha-fetoprotein level,portal vein tumor thrombosis,and BMI as independent prognostic factors for OS.The column-line graph model highlighted the importance of BMI as a major predictor of patient prognosis,followed by alpha-fetoprotein level,BCLC classification,and portal vein tumor thrombosis.CONCLUSION BMI is a long-term predictor of the efficacy of lenvatinib plus camrelizumab,and obese/overweight patients have a better prognosis.

Reassessment of palliative surgery in conversion therapy of previously unresectable hepatocellular carcinoma: Two case reports and review of literature

BACKGROUND Most patients with hepatocellular carcinoma(HCC)have lost the opportunity for direct surgery at the time of diagnosis.Transarterial chemoembolization(TACE)combined with immune checkpoint inhibitors or tyrosine kinase inhibitors(TKI)can partially transform some unresectable HCC and improve the prognosis ef-fectively.However,based on the promising prospects of combined targeted and immunotherapy for the effective treatment of HCC,the positive role of palliative surgery in the conversion treatment of advanced HCC urgently needs further in-tensive re-assessment.CASE SUMMARY In this study,we describe two successful cases of"conversion therapy for un-resectable HCC"achieved mainly by palliative surgery combined with TACE plus immunotherapy and TKIs.A 48-year-old patient with newly diagnosed HCC,presenting with a 6-cm mass in the segment VII/VIII of the right liver with mul-tiple intrahepatic metastases,could not undergo one-stage radical surgical resection.He underwent palliative surgery with radiofrequency of metastatic lesions and the palliative resection of the primary mass,and received subsequent TACE treatments twice in the early postoperative period(2 weeks and 6 weeks),in addition to targeted and immune combination therapy with sintilimab injection and oral lenvatinib.No evidence of recurrence was observed during the 11-month follow-up period after surgery.The other patient was a 47-year-old patient with massive HCC(18 cm×15 cm×4.5 cm)in the left liver with severe cirrhosis.The left portal branch was occluded and a tumor thrombus formed,and the tumor partly involved the middle hepatic vein.The patient underwent palliative surgery of left hemihepatectomy(including resection of the middle hepatic vein)for HCC,followed by three TACE procedures and oral TKIs 2 weeks after surgery.Six months later,the re-examination via computed tomography revealed no tumour activity in the remaining right liver,while magnetic resonance imaging revealed slight local tumor enhancement in the caudate lobe of the liver considered,TACE was performed once again,and during the next follow-up of 10 months did not reveal new intrahepatic lesions or distant metastases.CONCLUSION These cases demonstrate that the addition of palliative surgery to conversion therapy in a selected population with a high tumor burden could benefit patients with initially unresectable HCC.

Targeting therapy for hepatocellular carcinoma by delivering microRNAs as exosomal cargo

Exosomes,the smallest extracellular vesicles,have gained significant attention as key mediators in intercellular communication,influencing both physiological and pathological processes,particularly in cancer progression.A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes,with a focus on the origin from which exosomes derive.If information about the mechanisms for delivering exosomes to specific cells is incorporated,the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.

Impact of neoadjuvant multimodal therapy in the setting of locally advanced hepatocellular carcinoma

Immunotherapy and the implementation of more aggressive treatment schemes for locally advanced hepatocellular carcinomas have expanded the boundaries of curative options.Because of these advancements,patients who were once considered beyond the aim of a cure are now eligible for liver transplantation and resection.

Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion

BACKGROUND For resectable hepatocellular carcinoma(HCC),radical hepatectomy is commonly used as a curative treatment.However,postoperative recurrence significantly diminishes the overall survival(OS)of HCC patients,especially with microva-scular invasion(MVI)as an independent high-risk factor for recurrence.While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients,the specific role of adju-vant therapies in those with MVI remains unclear.AIM To conduct a network meta-analysis(NMA)to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen.METHODS A systematic literature search was conducted on PubMed,EMBASE,and Web of Science until April 6,2023.Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included.Hazard ratios(HRs)with 95%confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA.RESULTS Fourteen eligible trials(2268 patients)reporting five different therapies were included.In terms of reducing the risk of recurrence,radiotherapy(RT)[HR=0.34(0.23,0.5);surface under the cumulative ranking curve(SUCRA)=97.7%]was found to be the most effective adjuvant therapy,followed by hepatic artery infusion chemotherapy[HR=0.52(0.35,0.76);SUCRA=65.1%].Regarding OS improvement,RT[HR:0.35(0.2,0.61);SUCRA=93.1%]demonstrated the highest effectiveness,followed by sorafenib[HR=0.48(0.32,0.69);SUCRA=70.9%].INTRODUCTION Hepatocellular carcinoma(HCC)is the sixth most common malignant tumor in the world and ranks third in terms of worldwide malignant tumor mortality rates in 2020[1].Curative treatments for HCC include ablation,radical hepatectomy,and liver transplantation.However,ablation is suitable only for early-stage HCC patients,who represent a small percentage of the overall HCC population.Although liver transplantation serves as the optimal treatment for HCC patients,the scarcity of donor organs restricts the availability of this procedure.Therefore,hepatectomy is the most commonly employed curative treatment for resectable HCC.Unfortunately,the 5-year recurrence rate for patients who undergoing hepatectomy ranges from 50%to 70%[2,3].Recurrence of HCC is associated with several risk factors[4],including single nodule>5 cm,vascular invasion,and multiple nodules.Among these factors,microvascular invasion(MVI)is an independent risk factor for recurrence.MVI is defined as the presence of cancer cells in the lumen of endothelium-lined vessels,typically in the small branches of the portal and hepatic veins of the paracancerous liver tissue,visible only under the microscope[5].Previous studies have shown that among HCC patients who underwent hepatectomy,those with MVI had a higher risk of recurrence and shorter overall survival(OS)than those without MVI[6].Several studies have indicated that adjuvant therapy following curative hepatectomy can prevent recurrence and improve OS in HCC patients with MVI.These postoperative adjuvant therapies include transarterial chemoembolization(TACE)[7],sorafenib[8],hepatic artery infusion chemotherapy(HAIC)[9],and radiotherapy(RT)[10].However,the existing studies mostly compare individual adjuvant therapy with hepatectomy alone.Direct or indirect comparisons between the various adjuvant therapies are lacking.Therefore,we performed the network meta-analysis(NMA)to compare the relative efficacy of each adjuvant therapy to determine the optimal treatment.