Clinical Application And Prognostic Model Construction Of External Radiotherapy Combined With Immunotherapy In Advanced-stage Hepatocellular Carcinoma

Purpose:Immune checkpoint inhibitors(ICIs)combined with anti-angiogenic therapy have limited efficacy in treating advanced hepatocellular carcinoma(HCC).The synergistic effect from the systemic therapy and radiotherapy(RT)might resolve this problem.We aimed to determine the potential association between ICIs and anti-angiogenic therapy combined with RT and treatment outcomes in patients with advanced-stage HCC.Methods:This retrospective observational study enrolled 76 patients with advanced-stage HCC treated with ICIs and anti-angiogenic therapy in a single center.Propensity score matching(PSM)was utilized to mitigate the selection bias.The primary endpoints were progression-free survival(PFS)and overall survival(OS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),local PFS(LPFS),out-field PFS(OFPFS),and treatment-related adverse events(TRAEs).Results:After PSM,29 matched patient pairs were generated.The median follow-up was 15.5 months,and the RT sites were mainly located on the tumor thrombus(55.2%)and extrahepatic metastatic lesions(48.3%).The median PFS was 8.3 months(95%confidence interval(CI):5.4-11.3)in the RT group and 4.2 months(95%CI:3.4-5.0)in the non-RT(NRT)group(p<0.001).The median OS was not reached in the RT group and 9.7 months(95%CI:4.1-15.3)in the NRT group(p=0.002).The ORR was 75.9%(95%CI:56.5-89.7)in the RT group and 24.1%(95%CI:10.3-43.5)in the NRT group(p<0.001).The DCR was 100%in the RT group and 75.9%(95%CI:56.5-89.7)in the NRT group(p=0.005).The median LPFS and OFPFS was 13.2 months(95%CI:6.3-20.1)and 10.8 months(95%CI:7.0-14.7),respectively.The rates of any grade TRAEs were similar between the two groups.Conclusions:For advanced-stage HCC patients,ICIs and anti-angiogenic therapy combined with RT results in significantly better disease control and survival outcomes than systemic therapy alone.Thus,the triple combination therapy is tolerable and safe.Background:This study aimed to evaluate the efficacy and safety of subsequent radiotherapy(RT)in patients with advanced-stage hepatocellular carcinoma(HCC)who had lesion enlargement or new lesions during immune checkpoint inhibitor(ICI)therapy.Methods:This retrospective observational study enrolled 36 patients with advanced-stage HCC who underwent subsequent RT due to lesion enlargement or new lesions during ICI therapy from two centers.The primary endpoints were progression-free survival(PFS)and overall survival(OS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),1-and 2-year local control(LC)rates,in-field PFS(IFPFS),out-field PFS(OFPFS),and safety.Results:The median follow-up time was 15.3 months.The median PFS was 7.4 months(95%confidence interval[CI]:3.1-11.7 months),and the median OS was 18.8 months(95%CI:17.1-20.5 months).The ORR and DCR were 38.9%and 72.2%,respectively.In addition,the median IFPFS was 17.8 months(95%CI:11.5-24.2 months),the median OFPFS was 7.9 months(95%CI:3.4-12.5 months),and the estimated 1-and 2-year LC rates were 67.1%and 31.9%,respectively.The most common treatment-related adverse events(TRAEs)(all grades)were diarrhea(33.3%),rash(30.6%),and malaise(27.8%);a total of 14(38.9%)patients experienced grade 3-4 AEs.Conclusions:Subsequent RT showed reliable antitumor effects and an acceptable safety profile in advanced-stage HCC patients who had unsatisfactory therapeutic effect of ICI and could serve as an optional salvage strategy.Objective:The objective of this study was to investigate the expression of disulfidptosis genes in patients with hepatocellular carcinoma(HCC)and to evaluate their association with treatment response and prognosis.Methods:Fourteen disulfidptosis-related genes(DRGs)were evaluated systematically,and correlations between transcriptional patterns,prognosis,and clinical characteristics were comprehensively identified.HCC could be divided into two distinct subgroups based on the The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Then,we investigated the prognostic significance of DRG clusters and compared them with other molecular features and clinical indicators.Also,a principal component analysis(PCA)score was developed in order to predict HCC patients’prognosis and immune checkpoint inhibitors(ICIs)’ efficacy.Results:Patients with low expression of DRGs showed longer survival compared to those with high expression.Clinical information and prognosis are associated with two distinct molecular subtypes.Biosynthesis and metabolism were found to be the central enrichment in the enrichment analysis of differential genes associated with prognosis.In order to predict overall survival,we established the PCA score and verified its reliability in HCC patients.Furthermore,we developed a reliable nomogram to facilitate the clinical use of PCA scores.Our analysis revealed a statistically significant upregulation of the immune checkpoint protein programmed death ligand 1 and cytotoxic T-lymphocyte-associated protein 4 in the low PCA score group.Conclusion:Among HCC patients,clinical characteristics,prognosis,and immunotherapy were strongly associated with PCA scores derived from prognostic differential genes in DRG clusters.HCC immunotherapy strategies may be improved with these findings.The majority of patients with hepatocellular carcinoma(HCC)are diagnosed at an intermediate or advanced stage,where curative treatments such as surgical resection,ablation,or liver transplantation are not feasible.As a result,various alternative locoregional therapies have been used to slow disease progression,alleviate symptoms,and delay liver failure.External beam radiotherapy(EBRT),as a classic non-invasive locoregional treatment modality,is gradually being incorporated into the multidisciplinary management of HCC.From initially serving as a salvage therapy for treatment failures to now being considered as an alternative to ablation or surgical treatment options,and from being a palliative treatment for advanced HCC to being combined with other local or systemic therapies such as immunotherapy,the role of EBRT has undergone a significant transformation.This transformation has effectively extended the survival of patients with macroscopic vascular invasion and extrahepatic metastasis,and it is gradually being incorporated into the international treatment guidelines for HCC.This article reviews the current application status of EBRT as a monotherapy or in combination with other treatment modalities in the management of unresectable HCC,and may provide a reference for clinical treatment.