There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessar...There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.展开更多
AIM: To analyze the prognostic factors of 5-year survival and 10-year survival in hepatocellular carcinoma (HCC) patients, and to explore the reasons for longterm survival and provide choice of treatment modalities fo...AIM: To analyze the prognostic factors of 5-year survival and 10-year survival in hepatocellular carcinoma (HCC) patients, and to explore the reasons for longterm survival and provide choice of treatment modalities for HCC patients. METHODS: From January 1990 to October 2012, 8450 HCC patients were included in a prospective database compiled by the Information Center after hospital admission. Long-term surviving patients were included in a 10-year survival group (520 patients) and a 5-year survival group (1516 patients) for analysis. The long-term survival of HCC patients was defined as the survival of 5 years or longer. Clinical and biologic variables were assessed using univariate and multivariate analyses. The survival of patients was evaluated by follow-up data. RESULTS: The long-term survival of HCC patients was associated with the number of lesions, liver cirrhosis and Child-Pugh classification. It was not found to be associated with tumor diameter, histological stage, and pretreatment level of serum α-fetoprotein. The differences in clinical factors between the 5-year survival and the 10-year survival were found to be the number of lesions, liver cirrhosis, Child-Pugh classification, and time elapsed until first recurrence or metastasis. The survival period of different treatment modalities in the patients who survived for 5 years and 10 years showed significant differences: (in order of significance) surgery alone > surgery-transcatheter arterial chemoembolization (TACE) > TACE-radiofrequency ablation (RFA) > TACE alone > surgery-TACE-RFA. The 10-year survival of HCC patients was not associated with the choice of treatment modality.CONCLUSION: This retrospective study elucidated survival outcomes, prognostic factors affecting survival and treatment modalities in HCC patients.展开更多
Background:Macrovascular invasion(MaVI)occurs in nearly half of hepatocellular carcinoma(HCC)patients at diagnosis or during follow-up,which causes severe disease deterioration,and limits the possibility of surgical a...Background:Macrovascular invasion(MaVI)occurs in nearly half of hepatocellular carcinoma(HCC)patients at diagnosis or during follow-up,which causes severe disease deterioration,and limits the possibility of surgical approaches.This study aimed to investigate whether computed tomography(CT)-based radiomics analysis could help predict development of MaVI in HCC.Methods:A cohort of 226 patients diagnosed with HCC was enrolled from 5 hospitals with complete MaVI and prognosis follow-ups.CT-based radiomics signature was built via multi-strategy machine learning methods.Afterwards,MaVI-related clinical factors and radiomics signature were integrated to construct the final prediction model(CRIM,clinical-radiomics integrated model)via random forest modeling.Cox-regression analysis was used to select independent risk factors to predict the time of MaVI development.Kaplan-Meier analysis was conducted to stratify patients according to the time of MaVI development,progression-free survival(PFS),and overall survival(OS)based on the selected risk factors.Results:The radiomics signature showed significant improvement for MaVI prediction compared with conventional clinical/radiological predictors(P<0.001).CRIM could predict MaVI with satisfactory areas under the curve(AUC)of 0.986 and 0.979 in the training(n=154)and external validation(n=72)datasets,respectively.CRIM presented with excellent generalization with AUC of 0.956,1.000,and 1.000 in each external cohort that accepted disparate CT scanning protocol/manufactory.Peel9_fos_InterquartileRange[hazard ratio(HR)=1.98;P<0.001]was selected as the independent risk factor.The cox-regression model successfully stratified patients into the high-risk and low-risk groups regarding the time of MaVI development(P<0.001),PFS(P<0.001)and OS(P=0.002).Conclusions:The CT-based quantitative radiomics analysis could enable high accuracy prediction of subsequent MaVI development in HCC with prognostic implications.展开更多
BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a type of spindle cell sarcoma originating from the peripheral nerve,which usually results in the corresponding nerve sign on magnetic resonance imaging(MRI)...BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a type of spindle cell sarcoma originating from the peripheral nerve,which usually results in the corresponding nerve sign on magnetic resonance imaging(MRI).Patients with MPNST may also have neurofibromatosis type 1.CASE SUMMARY A 78-year-old male was admitted to the hospital due to a tumor in his left knee.He had a previous history of superficial spreading melanoma on the left thigh.Color Doppler ultrasonography showed a hypoechoic mass in the subcutaneous soft tissues of the medial left knee with an abundant rich blood flow.Computed tomography scanning did not show obvious signs of bone destruction,but the skin adjacent to the tumor was slightly thickened.MRI examination revealed that the hypervascular lesion was well-circumscribed,lobulated,invaded the surrounding soft tissues and demonstrated heterogeneous enhancement but lacked an entering and exiting nerve sign.The MRI result indicated the invasiveness of the tumor.The patient underwent a left knee joint mass expanded resection and the first histopathological examination showed a MPNST with positive surgical margins.Therefore,the second extended resection was performed,and the patient had a good outcome in the short term.CONCLUSION MRI is a useful technique for revealing the biological characteristics of MPNST and provides clinical support for evaluation of the surgical area before operation.展开更多
Let G be a simple connected graph with order n.Let L(G)and Q(G)be the normalized Laplacian and normalized signless Laplacian matrices of G,respectively.Letλk(G)be the k-th smallest normalized Laplacian eigenvalue of ...Let G be a simple connected graph with order n.Let L(G)and Q(G)be the normalized Laplacian and normalized signless Laplacian matrices of G,respectively.Letλk(G)be the k-th smallest normalized Laplacian eigenvalue of G.Denote byρ(A)the spectral radius of the matrix A.In this paper,we study the behaviors ofλ2(G)andρ(L(G))when the graph is perturbed by three operations.We also study the properties ofρ(L(G))and X for the connected bipartite graphs,where X is a unit eigenvector of L(G)corresponding toρ(L(G)).Meanwhile we characterize all the simple connected graphs withρ(L(G))=ρ(Q(G)).展开更多
基金The study was supported by National Key Research and Development Program(2018YFA0704100,2018YFA0704104)National Natural Science Foundation of China(81827805,82130060)Jiangsu Provincial Special Program of Medical Science(BE2019750).The funding sources had no role in the writing of the report,or decision to submit the paper for publication.
文摘There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.
基金Supported by Guangdong Province Natural Science Fund,No.10451008901006151
文摘AIM: To analyze the prognostic factors of 5-year survival and 10-year survival in hepatocellular carcinoma (HCC) patients, and to explore the reasons for longterm survival and provide choice of treatment modalities for HCC patients. METHODS: From January 1990 to October 2012, 8450 HCC patients were included in a prospective database compiled by the Information Center after hospital admission. Long-term surviving patients were included in a 10-year survival group (520 patients) and a 5-year survival group (1516 patients) for analysis. The long-term survival of HCC patients was defined as the survival of 5 years or longer. Clinical and biologic variables were assessed using univariate and multivariate analyses. The survival of patients was evaluated by follow-up data. RESULTS: The long-term survival of HCC patients was associated with the number of lesions, liver cirrhosis and Child-Pugh classification. It was not found to be associated with tumor diameter, histological stage, and pretreatment level of serum α-fetoprotein. The differences in clinical factors between the 5-year survival and the 10-year survival were found to be the number of lesions, liver cirrhosis, Child-Pugh classification, and time elapsed until first recurrence or metastasis. The survival period of different treatment modalities in the patients who survived for 5 years and 10 years showed significant differences: (in order of significance) surgery alone > surgery-transcatheter arterial chemoembolization (TACE) > TACE-radiofrequency ablation (RFA) > TACE alone > surgery-TACE-RFA. The 10-year survival of HCC patients was not associated with the choice of treatment modality.CONCLUSION: This retrospective study elucidated survival outcomes, prognostic factors affecting survival and treatment modalities in HCC patients.
基金supported by grants from the National Key R&D Program of China(2017YFA0205200,2017YFC1308701,and 2017YFC1309100)National Natural Science Foundation of China(82001917,81930053,81227901,81771924,81501616,81571785,81771957,and 61671449)the Natural Science Foundation of Guangdong Province,China(2016A030311055 and 2016A030313770)。
文摘Background:Macrovascular invasion(MaVI)occurs in nearly half of hepatocellular carcinoma(HCC)patients at diagnosis or during follow-up,which causes severe disease deterioration,and limits the possibility of surgical approaches.This study aimed to investigate whether computed tomography(CT)-based radiomics analysis could help predict development of MaVI in HCC.Methods:A cohort of 226 patients diagnosed with HCC was enrolled from 5 hospitals with complete MaVI and prognosis follow-ups.CT-based radiomics signature was built via multi-strategy machine learning methods.Afterwards,MaVI-related clinical factors and radiomics signature were integrated to construct the final prediction model(CRIM,clinical-radiomics integrated model)via random forest modeling.Cox-regression analysis was used to select independent risk factors to predict the time of MaVI development.Kaplan-Meier analysis was conducted to stratify patients according to the time of MaVI development,progression-free survival(PFS),and overall survival(OS)based on the selected risk factors.Results:The radiomics signature showed significant improvement for MaVI prediction compared with conventional clinical/radiological predictors(P<0.001).CRIM could predict MaVI with satisfactory areas under the curve(AUC)of 0.986 and 0.979 in the training(n=154)and external validation(n=72)datasets,respectively.CRIM presented with excellent generalization with AUC of 0.956,1.000,and 1.000 in each external cohort that accepted disparate CT scanning protocol/manufactory.Peel9_fos_InterquartileRange[hazard ratio(HR)=1.98;P<0.001]was selected as the independent risk factor.The cox-regression model successfully stratified patients into the high-risk and low-risk groups regarding the time of MaVI development(P<0.001),PFS(P<0.001)and OS(P=0.002).Conclusions:The CT-based quantitative radiomics analysis could enable high accuracy prediction of subsequent MaVI development in HCC with prognostic implications.
文摘BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a type of spindle cell sarcoma originating from the peripheral nerve,which usually results in the corresponding nerve sign on magnetic resonance imaging(MRI).Patients with MPNST may also have neurofibromatosis type 1.CASE SUMMARY A 78-year-old male was admitted to the hospital due to a tumor in his left knee.He had a previous history of superficial spreading melanoma on the left thigh.Color Doppler ultrasonography showed a hypoechoic mass in the subcutaneous soft tissues of the medial left knee with an abundant rich blood flow.Computed tomography scanning did not show obvious signs of bone destruction,but the skin adjacent to the tumor was slightly thickened.MRI examination revealed that the hypervascular lesion was well-circumscribed,lobulated,invaded the surrounding soft tissues and demonstrated heterogeneous enhancement but lacked an entering and exiting nerve sign.The MRI result indicated the invasiveness of the tumor.The patient underwent a left knee joint mass expanded resection and the first histopathological examination showed a MPNST with positive surgical margins.Therefore,the second extended resection was performed,and the patient had a good outcome in the short term.CONCLUSION MRI is a useful technique for revealing the biological characteristics of MPNST and provides clinical support for evaluation of the surgical area before operation.
基金by the National Natural Science Foundation of China(No.11871398)the Natural Science Basic Research Plan in Shaanxi Province of China(Program No.2018JM1032)the Fundamental Research Funds for the Central Universities(No.3102019ghjd003).
文摘Let G be a simple connected graph with order n.Let L(G)and Q(G)be the normalized Laplacian and normalized signless Laplacian matrices of G,respectively.Letλk(G)be the k-th smallest normalized Laplacian eigenvalue of G.Denote byρ(A)the spectral radius of the matrix A.In this paper,we study the behaviors ofλ2(G)andρ(L(G))when the graph is perturbed by three operations.We also study the properties ofρ(L(G))and X for the connected bipartite graphs,where X is a unit eigenvector of L(G)corresponding toρ(L(G)).Meanwhile we characterize all the simple connected graphs withρ(L(G))=ρ(Q(G)).
