BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibito...BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.展开更多
Background:The development of immunotherapy resistance is associated with a poor prognosis in patients diagnosed with hepatocellular carcinoma(HCC)who are undergoing treatment with immune checkpoint inhibitors(ICI).Th...Background:The development of immunotherapy resistance is associated with a poor prognosis in patients diagnosed with hepatocellular carcinoma(HCC)who are undergoing treatment with immune checkpoint inhibitors(ICI).This study aimed to evaluate the efficacy and safety of subsequent radiotherapy(RT)for patients with advanced-stage HCC who had lesion enlargement or new lesions(NLs)during ICI therapy.Methods:This retrospective observational study enrolled 36 patients with advanced-stage HCC who underwent subsequent RT for lesion enlargement or NLs 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).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),median OFPFS was 7.9 months(95%CI:3.4-12.5 months),and estimated 1-and 2-year LC rates were 67.1%and 31.9%,respectively.The most common treatment-related adverse events(all grades)were diarrhea(33.3%),rash(30.6%),and malaise(27.8%);a total of 14(38.9%)patients developed grade 3-4 AEs.Conclusions:Subsequent RT showed reliable antitumor effects and an acceptable safety profile in patients with advanced-stage HCC who had unsatisfactory response to ICI therapy;therefore,it could serve as an optional salvage strategy.展开更多
Background:A combination of tyrosine kinase inhibitors(TKIs)and anti-PD-1 antibodies with local regional therapy has elicited yield substantial clinical benefits in patients who have hepatocellular carcinoma(HCC)with ...Background:A combination of tyrosine kinase inhibitors(TKIs)and anti-PD-1 antibodies with local regional therapy has elicited yield substantial clinical benefits in patients who have hepatocellular carcinoma(HCC)with extrahepatic metastases.Using this treatment strategy to convert HCC patients with extrahepatic metastases from unresectable to resectable has not yet been reported.Methods:Consecutive hepatocellular carcinoma patients with extrahepatic metastases who received first-line therapy with a combination of TKIs and anti-PD-1 antibodies and at least one local regional therapy were analysed.Results:Nine patients with localized disease who received first-line systemic therapy were enrolled.At baseline,all of them had oligometastatic disease,namely,Barcelona Clinic Liver Cancer stage C(or Chinese Liver Cancer stage IIIB).The most common treatment administered was lenvatinib plus anti-PD-1 antibody and transarterial chemoembolization,and the median time span from systemic therapy to surgery was 3.2(IQR,2.8-6.2)months.Three patients achieved a pathological complete response.Six patients underwent laparoscopic surgery,and the other 3 patients underwent open surgery.After a median follow-up of 10.2(IQR,8.6-20.0)months,7 patients survived without disease recurrence,and 2 experienced tumour recurrence.All patients had any-grade AEs,and 55.6%of the patients experienced grade 3 AEs.Fatigue was the most common AE,followed by elevated aminotransferase levels and hypertension.Conclusions:Stereotactic therapy is a feasible conversion therapy for HCC patients with extrahepatic metastases to become resectable.This is the first study to analyse therapeutic outcomes of patients receiving these therapies for HCC with extrahepatic metastases.展开更多
Gallbladder carcinoma(GBC)is a highly malignant tumor of the digestive system,and the 5-year survival rate of stage IVb is only 2%(1).For unresectable GBC,although the guidelines published by the National Comprehensiv...Gallbladder carcinoma(GBC)is a highly malignant tumor of the digestive system,and the 5-year survival rate of stage IVb is only 2%(1).For unresectable GBC,although the guidelines published by the National Comprehensive Cancer Network(NCCN)in 2019 recommended radiotherapy combined with chemotherapy as the first-line treatment,no promising prognosis has been reported(2).Conversion therapy refers to the achievement of long-term survival by radical surgery in some patients with advanced cancer on the premise that systemic therapy will be effective(3,4).Herein,we reported the case of a 61-year-old male patient with stage IVb GBC who was diagnosed with multiple abdominal,retroperitoneal,mediastinal,and bilateral hilar lymph nodes.The results of follow-up showed that the patient achieved a disease-free survival(DFS)of 11.3 months and overall survival(OS)of 18.1 months after conversion therapy.展开更多
基金Supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,No.2021-I2M-1-061 and 2021-I2M-1-003Chinese Society of Clinical Oncology-Hengrui Cancer Research Fund,No.Y-HR2019-0239+1 种基金Chinese Society of Clinical Oncology-MSD Cancer Research Fund,No.Y-MSDZD2021-0213National Ten-thousand Talent Program.
文摘BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.
基金supported by the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-128)the CAMS Innovation Fund for Medical Sciences (2022-I2M-C&T-A-003)the CSCO-Hengrui Cancer Research Fund (Y-HR2020MS-0415 and Y-HR2020QN-0414).
文摘Background:The development of immunotherapy resistance is associated with a poor prognosis in patients diagnosed with hepatocellular carcinoma(HCC)who are undergoing treatment with immune checkpoint inhibitors(ICI).This study aimed to evaluate the efficacy and safety of subsequent radiotherapy(RT)for patients with advanced-stage HCC who had lesion enlargement or new lesions(NLs)during ICI therapy.Methods:This retrospective observational study enrolled 36 patients with advanced-stage HCC who underwent subsequent RT for lesion enlargement or NLs 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).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),median OFPFS was 7.9 months(95%CI:3.4-12.5 months),and estimated 1-and 2-year LC rates were 67.1%and 31.9%,respectively.The most common treatment-related adverse events(all grades)were diarrhea(33.3%),rash(30.6%),and malaise(27.8%);a total of 14(38.9%)patients developed grade 3-4 AEs.Conclusions:Subsequent RT showed reliable antitumor effects and an acceptable safety profile in patients with advanced-stage HCC who had unsatisfactory response to ICI therapy;therefore,it could serve as an optional salvage strategy.
基金This work was supported by International Science and Technology Cooperation Projects(2016YFE0107100)CAMS Clinical and Translational Medicine Research Funds(2019XK320006)+3 种基金CAMS Innovation Fund for Medical Science(CIFMS)(2017-I2M-4-003 and 2018-I2M-3-001)Beijing Natural Science Foundation(L172055 and 7192158)the Fundamental Research Funds for the Central Universities(3332018032)CSCO-Hengrui Cancer Research Fund(Y-HR2019-0239)and National Ten-thousand Talent Program.
文摘Background:A combination of tyrosine kinase inhibitors(TKIs)and anti-PD-1 antibodies with local regional therapy has elicited yield substantial clinical benefits in patients who have hepatocellular carcinoma(HCC)with extrahepatic metastases.Using this treatment strategy to convert HCC patients with extrahepatic metastases from unresectable to resectable has not yet been reported.Methods:Consecutive hepatocellular carcinoma patients with extrahepatic metastases who received first-line therapy with a combination of TKIs and anti-PD-1 antibodies and at least one local regional therapy were analysed.Results:Nine patients with localized disease who received first-line systemic therapy were enrolled.At baseline,all of them had oligometastatic disease,namely,Barcelona Clinic Liver Cancer stage C(or Chinese Liver Cancer stage IIIB).The most common treatment administered was lenvatinib plus anti-PD-1 antibody and transarterial chemoembolization,and the median time span from systemic therapy to surgery was 3.2(IQR,2.8-6.2)months.Three patients achieved a pathological complete response.Six patients underwent laparoscopic surgery,and the other 3 patients underwent open surgery.After a median follow-up of 10.2(IQR,8.6-20.0)months,7 patients survived without disease recurrence,and 2 experienced tumour recurrence.All patients had any-grade AEs,and 55.6%of the patients experienced grade 3 AEs.Fatigue was the most common AE,followed by elevated aminotransferase levels and hypertension.Conclusions:Stereotactic therapy is a feasible conversion therapy for HCC patients with extrahepatic metastases to become resectable.This is the first study to analyse therapeutic outcomes of patients receiving these therapies for HCC with extrahepatic metastases.
文摘Gallbladder carcinoma(GBC)is a highly malignant tumor of the digestive system,and the 5-year survival rate of stage IVb is only 2%(1).For unresectable GBC,although the guidelines published by the National Comprehensive Cancer Network(NCCN)in 2019 recommended radiotherapy combined with chemotherapy as the first-line treatment,no promising prognosis has been reported(2).Conversion therapy refers to the achievement of long-term survival by radical surgery in some patients with advanced cancer on the premise that systemic therapy will be effective(3,4).Herein,we reported the case of a 61-year-old male patient with stage IVb GBC who was diagnosed with multiple abdominal,retroperitoneal,mediastinal,and bilateral hilar lymph nodes.The results of follow-up showed that the patient achieved a disease-free survival(DFS)of 11.3 months and overall survival(OS)of 18.1 months after conversion therapy.
