The majority of sarcomas are under the influence of a tumor microenvironment that dampens immune activity,resulting in resistance to monoclonal antibodies targeting immune checkpoints and reduced clinical effectivenes...The majority of sarcomas are under the influence of a tumor microenvironment that dampens immune activity,resulting in resistance to monoclonal antibodies targeting immune checkpoints and reduced clinical effectiveness.Preclinical studies indicate that targeting abnormal neoangiogenesis by inhibiting vascular endothelial growth factor receptor(VEGFR)can alter the TME,thereby promoting T cell infiltration and increasing tumor immunogenicity.The REGOMUNE study,a phase II clinical trial,assessed the therapeutic combination of regorafenib,a multityrosine kinase inhibitor that targets VEGFR2 and the PD-L1 blocker avelumab,in individuals with advanced“cold”STS characterized by a lack of mature tertiary lymphoid structures(mTLS).Forty-nine mTLSnegative STS patients were enrolled,including leiomyosarcoma(45%),synovial sarcoma(18%),and other subtypes.The objective response rate was 11.0%(95%CI:4.0%-22.0%),with median progression-free survival and overall survival of 1.8 months(95%CI,1.7-3.5 months)and 15.1 months,respectively.Frequent adverse events included grade 1 or 2 palmar-plantar erythrodysesthesia,fatigue,and diarrhea.On-treatment multiplex immunofluorescence analysis revealed significant increases in CD8+T cell and B cell infiltration and PD1 expression on immune cells.Plasma analysis indicated significant upregulation of soluble PD-L1(sPD-L1)levels and tryptophan consumption.Overall,these results indicate that anti-angiogenic therapy modulates the tumor microenvironment in patients with cold STS and highlight the need for complementary strategies to enhance the functional activity of immune cells in this particular setting.展开更多
Soft-tissue sarcomas(STS)represent a group of rare and heterogeneous tumors associated with several challenges,including incorrect or late diagnosis,the lack of clinical expertise,and limited therapeutic options.Digit...Soft-tissue sarcomas(STS)represent a group of rare and heterogeneous tumors associated with several challenges,including incorrect or late diagnosis,the lack of clinical expertise,and limited therapeutic options.Digital pathology and radiomics represent transformative technologies that appear promising for improving the accuracy of cancer diagnosis,characterization and monitoring.Herein,we review the potential role of the application of digital pathology and radiomics in managing patients with STS.We have particularly described the main results and the limits of the studies using radiomics to refine diagnosis or predict the outcome of patients with soft-tissue sarcomas.We also discussed the current limitation of implementing radiomics in routine settings.Standard management approaches for STS have not improved since the early 1970s.Immunotherapy has revolutionized cancer treatment;nonetheless,immuno-oncology agents have not yet been approved for patients with STS.However,several lines of evidence indicate that immunotherapy may represent an efficient therapeutic strategy for this group of diseases.Thus,we emphasized the remarkable potential of immunotherapy in sarcoma treatment by focusing on recent data regarding the immune landscape of these tumors.We have particularly emphasized the fact that the development of immunotherapy for sarcomas is not an aspect of histology(except for alveolar soft-part sarcoma)but rather that of the tumor microenvironment.Future studies investigating immunotherapy strategies in sarcomas should incorporate at least the presence of tertiary lymphoid structures as a stratification factor in their design,besides including a strong translational program that will allow for a better understanding of the determinants involved in sensitivity and treatment resistance to immune-oncology agents.展开更多
Dear Editor,Sarcomas represent a heterogenous group of tumors accounting for about 1%of cancer in adults and 15%in children[1].However,despite adequate locoregional treatment,up to 40%of patients develop metastatic di...Dear Editor,Sarcomas represent a heterogenous group of tumors accounting for about 1%of cancer in adults and 15%in children[1].However,despite adequate locoregional treatment,up to 40%of patients develop metastatic disease.Drugs used in the advanced setting have very limited efficacy,with a response rate of<10%and progression-free survival of<4 months and are mainly used for palliative purposes[1].It is,therefore,important to monitor individual therapy responses to avoid inefficient therapy and unnecessary toxicity.Such monitoring is currently based on repeated CT imaging which may represent an important burden for patients with advanced disease[2].展开更多
Dear Editor,Surgery remains the cornerstone of treatment for softtissue sarcomas(STS)[1].However,despite adequate locoregional treatment,30%-40%of the patients eventually develop metastases[2,3].Accurate risk assessme...Dear Editor,Surgery remains the cornerstone of treatment for softtissue sarcomas(STS)[1].However,despite adequate locoregional treatment,30%-40%of the patients eventually develop metastases[2,3].Accurate risk assessment is crucial to tailor therapeutic strategies and to identify high-risk patients who may benefit from perioperative chemotherapy.Hence,several efforts have been made to develop prognostic nomograms that enable individual prognosis prediction;representing an important decision-making aid for oncologists and surgeons involved in sarcoma care[4-6].展开更多
To the editor Soft-tissue sarcomas(STS)represent a very heterogeneous group of rare tumors including more than 100 different subtypes[1].Surgery and neo/adjuvant radiation therapy represent the cornerstone of treatmen...To the editor Soft-tissue sarcomas(STS)represent a very heterogeneous group of rare tumors including more than 100 different subtypes[1].Surgery and neo/adjuvant radiation therapy represent the cornerstone of treatment for STS.However,despite an optimal resection of the tumor,up to 40%of patients will develop metastatic relapse and will die from the disease[1].Doxorubicin represents the first-line standard of care for patients with advanced disease since the 1970s,despite several attempts to identify better regimens.The median overall survival(OS)of patients with metastatic disease is<18 months and has only modestly improved over the past 20 years[2].展开更多
基金Institut National du Cancer,from the Association pour la Recherche contre le Cancer and by the Agence Nationale de la Recherche(ANR 21 RHUS 0010).
文摘The majority of sarcomas are under the influence of a tumor microenvironment that dampens immune activity,resulting in resistance to monoclonal antibodies targeting immune checkpoints and reduced clinical effectiveness.Preclinical studies indicate that targeting abnormal neoangiogenesis by inhibiting vascular endothelial growth factor receptor(VEGFR)can alter the TME,thereby promoting T cell infiltration and increasing tumor immunogenicity.The REGOMUNE study,a phase II clinical trial,assessed the therapeutic combination of regorafenib,a multityrosine kinase inhibitor that targets VEGFR2 and the PD-L1 blocker avelumab,in individuals with advanced“cold”STS characterized by a lack of mature tertiary lymphoid structures(mTLS).Forty-nine mTLSnegative STS patients were enrolled,including leiomyosarcoma(45%),synovial sarcoma(18%),and other subtypes.The objective response rate was 11.0%(95%CI:4.0%-22.0%),with median progression-free survival and overall survival of 1.8 months(95%CI,1.7-3.5 months)and 15.1 months,respectively.Frequent adverse events included grade 1 or 2 palmar-plantar erythrodysesthesia,fatigue,and diarrhea.On-treatment multiplex immunofluorescence analysis revealed significant increases in CD8+T cell and B cell infiltration and PD1 expression on immune cells.Plasma analysis indicated significant upregulation of soluble PD-L1(sPD-L1)levels and tryptophan consumption.Overall,these results indicate that anti-angiogenic therapy modulates the tumor microenvironment in patients with cold STS and highlight the need for complementary strategies to enhance the functional activity of immune cells in this particular setting.
基金Agence Nationale de la Recherche-Recherche Hospitalo-Universitaire en sante(RHU)CONDOR programme。
文摘Soft-tissue sarcomas(STS)represent a group of rare and heterogeneous tumors associated with several challenges,including incorrect or late diagnosis,the lack of clinical expertise,and limited therapeutic options.Digital pathology and radiomics represent transformative technologies that appear promising for improving the accuracy of cancer diagnosis,characterization and monitoring.Herein,we review the potential role of the application of digital pathology and radiomics in managing patients with STS.We have particularly described the main results and the limits of the studies using radiomics to refine diagnosis or predict the outcome of patients with soft-tissue sarcomas.We also discussed the current limitation of implementing radiomics in routine settings.Standard management approaches for STS have not improved since the early 1970s.Immunotherapy has revolutionized cancer treatment;nonetheless,immuno-oncology agents have not yet been approved for patients with STS.However,several lines of evidence indicate that immunotherapy may represent an efficient therapeutic strategy for this group of diseases.Thus,we emphasized the remarkable potential of immunotherapy in sarcoma treatment by focusing on recent data regarding the immune landscape of these tumors.We have particularly emphasized the fact that the development of immunotherapy for sarcomas is not an aspect of histology(except for alveolar soft-part sarcoma)but rather that of the tumor microenvironment.Future studies investigating immunotherapy strategies in sarcomas should incorporate at least the presence of tertiary lymphoid structures as a stratification factor in their design,besides including a strong translational program that will allow for a better understanding of the determinants involved in sensitivity and treatment resistance to immune-oncology agents.
文摘Dear Editor,Sarcomas represent a heterogenous group of tumors accounting for about 1%of cancer in adults and 15%in children[1].However,despite adequate locoregional treatment,up to 40%of patients develop metastatic disease.Drugs used in the advanced setting have very limited efficacy,with a response rate of<10%and progression-free survival of<4 months and are mainly used for palliative purposes[1].It is,therefore,important to monitor individual therapy responses to avoid inefficient therapy and unnecessary toxicity.Such monitoring is currently based on repeated CT imaging which may represent an important burden for patients with advanced disease[2].
文摘Dear Editor,Surgery remains the cornerstone of treatment for softtissue sarcomas(STS)[1].However,despite adequate locoregional treatment,30%-40%of the patients eventually develop metastases[2,3].Accurate risk assessment is crucial to tailor therapeutic strategies and to identify high-risk patients who may benefit from perioperative chemotherapy.Hence,several efforts have been made to develop prognostic nomograms that enable individual prognosis prediction;representing an important decision-making aid for oncologists and surgeons involved in sarcoma care[4-6].
基金MSD(Merck Sharp and Dohme)AVENIR.Grant Number:HEART。
文摘To the editor Soft-tissue sarcomas(STS)represent a very heterogeneous group of rare tumors including more than 100 different subtypes[1].Surgery and neo/adjuvant radiation therapy represent the cornerstone of treatment for STS.However,despite an optimal resection of the tumor,up to 40%of patients will develop metastatic relapse and will die from the disease[1].Doxorubicin represents the first-line standard of care for patients with advanced disease since the 1970s,despite several attempts to identify better regimens.The median overall survival(OS)of patients with metastatic disease is<18 months and has only modestly improved over the past 20 years[2].
