Background:Liquid biopsy-based biomarkers,including circulating tumor DNA(ctDNA)and blood tumor muta-tional burden(bTMB),are recognized as promising predictors of prognoses and responses to immune checkpoint inhibitor...Background:Liquid biopsy-based biomarkers,including circulating tumor DNA(ctDNA)and blood tumor muta-tional burden(bTMB),are recognized as promising predictors of prognoses and responses to immune checkpoint inhibitors(ICIs),despite insufficient sensitivity of single biomarker detection.This research aims to determine whether the combinatorial utility of longitudinal ctDNA with bTMB analysis could improve the prognostic and predictive effects.Methods:This prospective two-center cohort trial,consisting of discovery and validation datasets,enrolled unre-sectable locally advanced non-small-cell lung cancer(LA-NSCLC)patients and assigned them to chemoradiother-apy(CRT)or CRT+consolidation ICI cohorts from 2018 to 2022.Blood specimens were collected pretreatment,4 weeks post-CRT,and at progression to assess bTMB and ctDNA using 486-gene next-generation sequencing.DynamicΔbTMB was calculated as post-CRT bTMB minus baseline bTMB levels.Decision curve analyses were performed to calculate Concordance index(C-index).Results:One hundred twenty-eight patients were enrolled.In the discovery dataset(n=73),patients treated with CRT and consolidation ICI had significantly longer overall survival(OS;median not reached[NR]vs 20.2 months;P<0.001)and progression-free survival(PFS;median 25.2 vs 11.4 months;P=0.011)than those without ICI.Longitudinal analysis demonstrated a significant decrease in ctDNA abundance post-CRT(P<0.001)but a relative increase with disease progression.Post-CRT detectable residual ctDNA correlated with significantly shorter OS(median 18.3 months vs NR;P=0.001)and PFS(median 7.3 vs 25.2 months;P<0.001).For patients with residual ctDNA,consolidation ICI brought significantly greater OS(median NR vs 14.8 months;P=0.005)and PFS(median 13.8 vs 6.2 months;P=0.028)benefit,but no significant difference for patients with ctDNA clearance.DynamicΔbTMB was predictive of prognosis.Patients with residual ctDNA and increasedΔbTMB(ΔbTMB>0)had significantly worse OS(median 9.0 vs 23.0 months vs NR;P<0.001)and PFS(median 3.4 vs 7.3 vs 25.2 months;P<0.001).The combinatorial model integrating post-CRT ctDNA withΔbTMB had optimal predictive effects on OS(C-index=0.723)and PFS(C-index=0.693),outperforming individual features.In the independent validation set,we confirmed residual ctDNA predicted poorer PFS(median 50.8 vs 14.3 months;P=0.026)but identified more consolidation ICI benefit(median NR vs 8.3 months;P=0.039).The combined model exhibited a stable predictive advantage(C-index=0.742 for PFS).Conclusions:The multiparameter assay integrating qualitative residual ctDNA testing with quantitativeΔbTMB dynamics improves patient prognostic risk stratification and efficacy predictions,allowing for personalized con-solidation therapy for LA-NSCLC.展开更多
This study focuses on the development and analysis of a real-time updated operations strategy of a distributed energy system(DES).Owing to the relevant Chinese policy of electrical transmission and distribution,combin...This study focuses on the development and analysis of a real-time updated operations strategy of a distributed energy system(DES).Owing to the relevant Chinese policy of electrical transmission and distribution,combined cooling,heating,and power system(CCHP)and photovoltaic(PV)systems are not currently allowed.However,with the Chinese supply-side power grid reform,the permissions for connections between DESs and utilities are gradually evolving.By performing building simulation and using mixed integer linear programming(MILP),a real-time updated operation strategy of a DES is established.Then,considering the DES from Tianjin Eco-city as a case study,a comparative analysis between this updated strategy and the current operation strategy is performed by evaluating three factors:economic efficiency,energy consumption,and CO2 emission.The results show that the updated strategy can reduce 29.12%of electricity time-of-use cost,10.11%of total fuel consumption,and 18.40%of CO2 emission during the cooling season.Besides,a method of“rolling load forecasting”for DES by using Support vector regression machine(SVR)is proposed and discussed.The testing shows that the Mean Absolute Percentage Error(MAPE)is below 7.5%.And when the training sample is large,the particle swarm optimization algorithm can be used to shorten the modeling time of the air conditioning load forecasting model.展开更多
基金funded by National Natural Sciences Foundation Key Program(grant number:82173348)Chinese Academy of Medical Sci-ences Innovation Fund for Medical Sciences(grant number:2021-1-I2M-1-012)the Special Research Fund for Central Universities,Peking Union Medical College(grant number:3332023133).
文摘Background:Liquid biopsy-based biomarkers,including circulating tumor DNA(ctDNA)and blood tumor muta-tional burden(bTMB),are recognized as promising predictors of prognoses and responses to immune checkpoint inhibitors(ICIs),despite insufficient sensitivity of single biomarker detection.This research aims to determine whether the combinatorial utility of longitudinal ctDNA with bTMB analysis could improve the prognostic and predictive effects.Methods:This prospective two-center cohort trial,consisting of discovery and validation datasets,enrolled unre-sectable locally advanced non-small-cell lung cancer(LA-NSCLC)patients and assigned them to chemoradiother-apy(CRT)or CRT+consolidation ICI cohorts from 2018 to 2022.Blood specimens were collected pretreatment,4 weeks post-CRT,and at progression to assess bTMB and ctDNA using 486-gene next-generation sequencing.DynamicΔbTMB was calculated as post-CRT bTMB minus baseline bTMB levels.Decision curve analyses were performed to calculate Concordance index(C-index).Results:One hundred twenty-eight patients were enrolled.In the discovery dataset(n=73),patients treated with CRT and consolidation ICI had significantly longer overall survival(OS;median not reached[NR]vs 20.2 months;P<0.001)and progression-free survival(PFS;median 25.2 vs 11.4 months;P=0.011)than those without ICI.Longitudinal analysis demonstrated a significant decrease in ctDNA abundance post-CRT(P<0.001)but a relative increase with disease progression.Post-CRT detectable residual ctDNA correlated with significantly shorter OS(median 18.3 months vs NR;P=0.001)and PFS(median 7.3 vs 25.2 months;P<0.001).For patients with residual ctDNA,consolidation ICI brought significantly greater OS(median NR vs 14.8 months;P=0.005)and PFS(median 13.8 vs 6.2 months;P=0.028)benefit,but no significant difference for patients with ctDNA clearance.DynamicΔbTMB was predictive of prognosis.Patients with residual ctDNA and increasedΔbTMB(ΔbTMB>0)had significantly worse OS(median 9.0 vs 23.0 months vs NR;P<0.001)and PFS(median 3.4 vs 7.3 vs 25.2 months;P<0.001).The combinatorial model integrating post-CRT ctDNA withΔbTMB had optimal predictive effects on OS(C-index=0.723)and PFS(C-index=0.693),outperforming individual features.In the independent validation set,we confirmed residual ctDNA predicted poorer PFS(median 50.8 vs 14.3 months;P=0.026)but identified more consolidation ICI benefit(median NR vs 8.3 months;P=0.039).The combined model exhibited a stable predictive advantage(C-index=0.742 for PFS).Conclusions:The multiparameter assay integrating qualitative residual ctDNA testing with quantitativeΔbTMB dynamics improves patient prognostic risk stratification and efficacy predictions,allowing for personalized con-solidation therapy for LA-NSCLC.
基金This study was supported by Scientific Research Project of Science and technology Commission of Shanghai Municipality(Grant No.18DZ1202700).
文摘This study focuses on the development and analysis of a real-time updated operations strategy of a distributed energy system(DES).Owing to the relevant Chinese policy of electrical transmission and distribution,combined cooling,heating,and power system(CCHP)and photovoltaic(PV)systems are not currently allowed.However,with the Chinese supply-side power grid reform,the permissions for connections between DESs and utilities are gradually evolving.By performing building simulation and using mixed integer linear programming(MILP),a real-time updated operation strategy of a DES is established.Then,considering the DES from Tianjin Eco-city as a case study,a comparative analysis between this updated strategy and the current operation strategy is performed by evaluating three factors:economic efficiency,energy consumption,and CO2 emission.The results show that the updated strategy can reduce 29.12%of electricity time-of-use cost,10.11%of total fuel consumption,and 18.40%of CO2 emission during the cooling season.Besides,a method of“rolling load forecasting”for DES by using Support vector regression machine(SVR)is proposed and discussed.The testing shows that the Mean Absolute Percentage Error(MAPE)is below 7.5%.And when the training sample is large,the particle swarm optimization algorithm can be used to shorten the modeling time of the air conditioning load forecasting model.
