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
After publication of the PACIFIC trial results,immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer(NSCLC).The PACIFIC trial demonstrat...After publication of the PACIFIC trial results,immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer(NSCLC).The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III NSCLC.This is the first treatment in decades to successfully improve survival in this clinical setting,with manageable toxicity and without deterioration in quality of life.The integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary,coordinated decision-making among lung cancer specialists,bringing new challenges and controversies as well as important changes in clinical work routines.The aim of the present article is to review—from a practical,multidisciplinary perspective—the findings and implications of the PACIFIC trial.We evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 determination.In addition,we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical practice.Finally,we discuss unresolved questions and future challenges.In short,the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.展开更多
Objective:To observe the therapeutic efficacy of Danggui Buxue Decoction No.1(当归补血汤1号,DB1) in treating patients of non-small cell lung cancer(NSCLC) at the peri-operational stage and its impact on the patients i...Objective:To observe the therapeutic efficacy of Danggui Buxue Decoction No.1(当归补血汤1号,DB1) in treating patients of non-small cell lung cancer(NSCLC) at the peri-operational stage and its impact on the patients immune function.Methods:Eighty-two NSCLC patients were randomly assigned to two groups equally,the control group and the test group,they were given conventional treatment,while to the test group, DB1 were given additionally.The observation was conducted by testing the changes of T-lymphocyte subsets,...展开更多
Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The...Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liverdisease(MELD) score helped to reduce waiting list mortality in liver transplantation(LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients' infectious and immunologic risk profiles. The administration of intravenous immunoglobulins(IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.展开更多
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.
文摘After publication of the PACIFIC trial results,immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer(NSCLC).The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III NSCLC.This is the first treatment in decades to successfully improve survival in this clinical setting,with manageable toxicity and without deterioration in quality of life.The integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary,coordinated decision-making among lung cancer specialists,bringing new challenges and controversies as well as important changes in clinical work routines.The aim of the present article is to review—from a practical,multidisciplinary perspective—the findings and implications of the PACIFIC trial.We evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 determination.In addition,we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical practice.Finally,we discuss unresolved questions and future challenges.In short,the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.
文摘Objective:To observe the therapeutic efficacy of Danggui Buxue Decoction No.1(当归补血汤1号,DB1) in treating patients of non-small cell lung cancer(NSCLC) at the peri-operational stage and its impact on the patients immune function.Methods:Eighty-two NSCLC patients were randomly assigned to two groups equally,the control group and the test group,they were given conventional treatment,while to the test group, DB1 were given additionally.The observation was conducted by testing the changes of T-lymphocyte subsets,...
文摘Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liverdisease(MELD) score helped to reduce waiting list mortality in liver transplantation(LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients' infectious and immunologic risk profiles. The administration of intravenous immunoglobulins(IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.
