| The study includes three parts: 1.The impact of radiotherapy on inflammatory factors in unresectable hepatocellular carcinoma and establishment of a nomogram model to predict the prognosis of unresectable hepatocellular carcinoma receiving radiotherapy;2.Efficacy and safety of combining radiotherapy with camrelizumab in unresectable hepatocellular carcinoma: a single-arm trial;3.Efficacy and safety of radiotherapy plus anti-PD-1 versus transcatheter arterial chemoembolization plus sorafenib for unresectable hepatocellular carcinoma: a real-world study.Part 1The impact of radiotherapy on immune parameters in unresectable hepatocellular carcinoma and establishment of a nomogram model to predict the prognosis of unresectable hepatocellular carcinoma receiving radiotherapyObjectives For patients with unresectable hepatocellular carcinoma (u HCC),intensity-modulated radiotherapy(IMRT)has become one of the options for clinical local treatment.Immune parameters,including platelet-to-lymphocyte ratio(PLR),neutrophil-to-lymphocyte ratio(NLR)and systemic immune inflammatory(SII),predict survival in various cancers.This study aimed to determine whether peripheral immune parameters can predict survival in patients with u HCC undergoing IMRT and establish a clinically useful prognostic nomogram for survival prediction.Methods The clinical data of 309 HCC patients were retrospectively analyzed and randomly divided into training(n=216)and validation(n=93)cohorts.PLR,NLR and SII were collected before and after IMRT.Univariate and multivariate Cox analyses were performed to identify independent prognostic factors affecting survival,which were used to generate a nomogram.Results The median survival was 16.3 months,and significant increases in PLR,NLR,and SII were observed after IMRT(P < 0.001).High levels of immune parameters were associated with poor prognosis(P < 0.001);enlarged spleen,Barcelona clinic liver cancer stage(B and C),post-SII,and delta-NLR were independent risk factors for survival and were included in the nomogram,which accurately predicted 3-and 5-year survival.The nomogram was well verified in the validation cohort.Conclusions High levels of immune parameters are associated with poor prognosis in u HCC patients receiving IMRT.Our nomogram accurately predicts the survival of patients with u HCC receiving IMRT.Part 2Efficacy and safety of combining radiotherapy with camrelizumab in unresectable hepatocellular carcinoma: a single-arm trialObjectives Stereotactic body radiotherapy(SBRT)may have significant immunomodulatory effects that enhance tumor response to immune checkpoint inhibitors.This phase 2 clinical trial was conducted to evaluate the safety and efficacy of combining palliative SBRT with camrelizumab(an anti-PD1 monoclonal antibody)in patients with unresectable hepatocellular carcinoma(u HCC).Methods Patients with u HCC,Child-Pugh A/B liver function,and at least one measurable lesion were enrolled between April 2020 and August 2022.Patients were administered 200 mg camrelizumab intravenously from the first day of palliative SBRT and then every 3 weeks.Palliative SBRT was delivered daily over five fractions per week,with a dose range of 30–50 Gy.The primary endpoints were objective response rate(ORR)and safety.This trial was registered at Clinical Trials.gov(NCT04193696).Results Twenty-one patients were enrolled;the median radiation dose was 40 Gy,and the median number of cycles of camrelizumab was five.The ORR was 52.4%.After a median follow-up of 19.7 months,the median progression-free and overall survival were 5.8 and 14.2 months,respectively.The overall survival probability was 85.7% at 6 months,76.2% at 9 months,and 59.9% at 12 months.All grade 3 treatment-related adverse events(TRAEs)occurred in five patients(23.8%)and were manageable.No grade 4/5 TRAEs were observed.Conclusion Palliative SBRT plus camrelizumab showed promising antitumor activity against u HCC.Toxicities were manageable with no unexpected safety issues.This study provides evidence of a new therapeutic method for the treatment of u HCC.Part 3Efficacy and safety of radiotherapy plus anti-PD-1 versus transcatheter arterial chemoembolization plus sorafenib for unresectable hepatocellular carcinoma: a real-world studyObjective The combination of transcatheter arterial chemoembolization(TACE)plus sorafenib prolonged progression-free survival(PFS)and overall survival(OS)than sorafenib or TACE monotherapy for patients with hepatocellular carcinoma(HCC).This study assessed the efficacy and safety of radiotherapy(RT)plus monoclonal antibody against programmed cell death 1(anti-PD-1)versus TACE plus sorafenib for patients with u HCC.Methods Patients with u HCC who treated with RT plus anti-PD-1 and TACE plus sorafenib were enrolled.Objective response rate(ORR),PFS,disease control rate(DCR)and OS were calculated to assess the antitumor response and the treatment-related adverse events(TRAEs)to the safety.Results Between January 2018 to March 2021,37 patients underwent RT plus anti-PD-1 and 41 patients underwent TACE plus sorafenib.The baseline characteristics between the two groups were comparable.The ORR and DCR were significantly higher in the RT+PD-1 group than the TACE plus sorafenib group according to RECIST V1.1(54.05% vs 12.20%,P < 0.001;70.27% vs 46.37%,P = 0.041;respectively)and according to m RECIST(56.76% vs 31.71%,P = 0.039;70.27% vs 46.37%,P = 0.041;respectively).RT plus anti-PD-1 provided significantly better PFS(HR,0.51;95% CI 0.30-0.86;p=0.017)than TACE plus sorafenib.Moreover,patients with RT plus anti-PD-1 had significantly higher 3-,6-,and 9-month OS rates than those with TACE plus sorafenib(97.3% vs 92.30%,P < 0.001;91.89% vs 68.60%,P < 0.001;75.5% vs 60.60%,P < 0.001;respectively).The median OS was more favorable 17.4 months for the RT+PD-1 group and 11.9 months for the TACE plus sorafenib group.No treatment-related death was observed.Grade 3 or more treatment-related adverse events(TRAEs)occurred significantly less in patients in the RT+PD-1 group than the TACE plus sorafenib group(29.7% vs 75.6%,p < 0.001),and all TRAEs were manageable.Conclusions In this real-world study,RT plus anti-PD-1 showed significantly promising efficacy and manageable safety than TACE plus sorafenib in patients with u HCC.Toxicities were manageable,with no unexpected safety signals.The study provides evidence on a new therapeutic method in the treatment of u HCC. |
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