AIM: To describe the incidence of cardiovascular mortality(CVM) in survivors of major cancers and identify its trends over the past two decades. METHODS: We used the surveillance, epidemiology and end-results 19 regis...AIM: To describe the incidence of cardiovascular mortality(CVM) in survivors of major cancers and identify its trends over the past two decades. METHODS: We used the surveillance, epidemiology and end-results 19 registry to identify young adults(20-49 years), diagnosed with the following major primary cancers: Lung, breast, liver/intrahepatic bile duct, pancreas, prostate, colorectal, and ovarian from 1990 through 2012 and identified the cumulative incidence of CVM after adjusting for confounding factors. RESULTS: We identified a total of 301923 cancers(breast 173748, lung 38938, colorectal 31722, prostate 22848, ovary 16065, liver 9444, pancreas 9158). A total of 2297(0.8%) of patients had incident CVM. Lung(10-year cumulative CVM 2.4%) and liver(1.73%) cancers had the highest incidence of CVM, while breast(0.6%) and prostate(1.2%) had the lowest CVM mortality, even after multiple adjustments(P < 0.001). Overall, there was a significant improvement in CVM since 1990 [2005-2012 vs 1990-1994, adjusted HR 0.63(0.54-0.72), P < 0.001]. This was driven by improvements in CVM in lung cancers(P = 0.02), breast(P < 0.001), and a trend in ovarian cancer(P = 0.097).There was no statistically significant improvement in CVM among survivors of colorectal, pancreatic, liver, or prostate cancers.CONCLUSION: The risk of CVM differs among different cancers, and is highest among survivors of lung and liver cancers. The incidence of CVM has decreased over the past 2 decades mainly among survivors of lung and breast cancers.展开更多
The accumulated evidence from two decades of randomized controlled trials has not yet resolved the question of how best to monitor colorectal cancer(CRC)survivors for early detection of recurrent and metachronous dise...The accumulated evidence from two decades of randomized controlled trials has not yet resolved the question of how best to monitor colorectal cancer(CRC)survivors for early detection of recurrent and metachronous disease or even whether doing so has its intended effect.A new wave of trial data in the coming years and an evolving knowledge of relevant biomarkers may bring us closer to understanding what surveillance strategies are most effective for a given subset of patients.To best apply these insights,a number of important research questions need to be addressed,and new decision making tools must be developed.In this review,we summarize available randomized controlled trial evidence comparing alternative surveillance testing strategies,describe ongoing trials in the area,and compare professional society recommendations for surveillance.In addition,we discuss innovations relevant to CRC surveillance and outline a research agenda which will inform a more risk-stratified and personalized approach to follow-up.展开更多
Dear editor,Prostate cancer(PCa)remains a major healthcare burden in men globally[1].Most patients present with localized disease,and treatment is recommended based on risk classification systems like the National Com...Dear editor,Prostate cancer(PCa)remains a major healthcare burden in men globally[1].Most patients present with localized disease,and treatment is recommended based on risk classification systems like the National Comprehensive Cancer Network(NCCN)[2].However,these methods are imprecise for estimating metastasis-free survival and prostate cancer-specific mortality and thus biomarkers that can predict tumor aggression are needed[3–5].Several studies have since characterized the molecular landscape of localized PCa in White[4,5]and Black/African-American men[6],but data is lacking in Asian men.The Chinese Prostate Cancer Genome and Epigenome Atlas(CPGEA)reported on the genomic and epigenomic landscape of 208 PCa of men from China[7].Comparative analyses between the CPGEA cohort and data from The Cancer Genome Atlas(TCGA)revealed higher frequencies of Forkhead box A1(FOXA1)and chromodomain-helicase DNA-binding 1(CHD1)mutations,and lower frequencies of phosphatase and tensin homolog(PTEN)mutations and transmembrane protease serine 2-E26 transformationspecific related gene(TMPRSS2-ERG)fusion in Chinese compared with White men[7].These preliminary findings highlight the presence of race-specific differences in molecular phenotypes of PCa.展开更多
Sebaceous carcinoma (SC) of the eyelid is a rare but aggressive malignancy, accounting for 3%—5% of eyelid malignancies in the United States, and up to 35% in Asian populations (Deprez and Uffer, 2009;Xu et al., 2018...Sebaceous carcinoma (SC) of the eyelid is a rare but aggressive malignancy, accounting for 3%—5% of eyelid malignancies in the United States, and up to 35% in Asian populations (Deprez and Uffer, 2009;Xu et al., 2018;Yu et al., 2018). It is frequently mistaken for benign conditions or less aggressive malignancies such as basal cell carcinoma (Muqit et al., 2013), and the effects of delay in diagnosis can be devastating to patients. Aggressive surgical resection is the primary treatment of these tumors and often invoIves orbital exenteration with significant morbidity to patients, and these tumors frequently recur, with local recurrence rate as high as 18%. Importantly, this disease has a high metastatic potential, and there are very limited data guiding systemic treatment options;ultimately 6%—18% of patients diagnosed with SC of the eyelid succumb to metastatic disease (Zurcher et al., 1998;Shields et al., 2004).展开更多
Many cancer types reprogram their metabolism to become addicted to glutamine.One of the critical enzymes in the utilization of glutamine in these cells is glutaminase.CB-839(telaglenastat)is a drug that targets glutam...Many cancer types reprogram their metabolism to become addicted to glutamine.One of the critical enzymes in the utilization of glutamine in these cells is glutaminase.CB-839(telaglenastat)is a drug that targets glutaminase that is currently being evaluated in many clinical trials for efficacy in various cancer types that are known to be driven by glutamine metabolism.Despite its use,there are limited assays available for testing the pharmacodynamic on-target effects of CB-839 on the limited,small-volume patient samples that are obtained in early-phase clinical trials.Thus,we developed an assay based on the cellular thermal shift assay technique using AlphalLlSA technology to show that CB-839 specifically engages glutaminase in colon cancer cell lines in vitro and in minute quantities of mouse xenograft tumors.Notably,we show that this assay detects CB-839 binding to glutaminase in platelets of patients collected while receiving CB-839 on a clinical trial.This assay may be used to study the pharmacodynamic profile of CB-839 in very small tissue samples obtained from patients on a clinical trial and may be useful infuture studies designed to screen other in hibitors of glutaminase.展开更多
Multiple myeloma(MM)remains an incurable,genetically heterogeneous disease characterized by the uncontrolled proliferation of transformed plasma cells nurtured within a permissive bone marrow(BM)microenvironment.Curre...Multiple myeloma(MM)remains an incurable,genetically heterogeneous disease characterized by the uncontrolled proliferation of transformed plasma cells nurtured within a permissive bone marrow(BM)microenvironment.Current therapies leverage the unique biology of MM cells and target the immune microenvironment that drives tumor growth and facilitates immune evasion.Proteasome inhibitors and immunomodulatory drugs were initially introduced to complement and have now supplanted cytotoxic chemotherapy as frontline anti-myeloma agents.Recently,monoclonal antibodies,bispecific antibodies,and chimeric antigen receptor T cells were developed to revamp the immune system to overcome immune suppression and improve patient responses.While current MM therapies have markedly extended patient survival,acquired drug resistance inevitably emerges and drives disease progression.The logical progression for the next generation of MM therapies would be to design and validate agents that prevent and/or overcome acquired resistance to immunotherapies.The complex BM microenvironment promotes resistance to both current anti-myeloma agents and emerging immunotherapies.Myeloma cells are intertwined with a complex BM immune microenvironment that contributes to the development of adaptive drug resistance.Here,we describe recently FDA-approved and investigational anti-myeloma agents that directly or indirectly target the BM microenvironment to prevent or overcome drug resistance.Synergistic effects of anti-myeloma agents may foster the development of rationally-designed drug cocktails that prevent BM-mediated resistance to immunotherapies.展开更多
文摘AIM: To describe the incidence of cardiovascular mortality(CVM) in survivors of major cancers and identify its trends over the past two decades. METHODS: We used the surveillance, epidemiology and end-results 19 registry to identify young adults(20-49 years), diagnosed with the following major primary cancers: Lung, breast, liver/intrahepatic bile duct, pancreas, prostate, colorectal, and ovarian from 1990 through 2012 and identified the cumulative incidence of CVM after adjusting for confounding factors. RESULTS: We identified a total of 301923 cancers(breast 173748, lung 38938, colorectal 31722, prostate 22848, ovary 16065, liver 9444, pancreas 9158). A total of 2297(0.8%) of patients had incident CVM. Lung(10-year cumulative CVM 2.4%) and liver(1.73%) cancers had the highest incidence of CVM, while breast(0.6%) and prostate(1.2%) had the lowest CVM mortality, even after multiple adjustments(P < 0.001). Overall, there was a significant improvement in CVM since 1990 [2005-2012 vs 1990-1994, adjusted HR 0.63(0.54-0.72), P < 0.001]. This was driven by improvements in CVM in lung cancers(P = 0.02), breast(P < 0.001), and a trend in ovarian cancer(P = 0.097).There was no statistically significant improvement in CVM among survivors of colorectal, pancreatic, liver, or prostate cancers.CONCLUSION: The risk of CVM differs among different cancers, and is highest among survivors of lung and liver cancers. The incidence of CVM has decreased over the past 2 decades mainly among survivors of lung and breast cancers.
基金Supported by National Cancer Institute Program Grant,No.5P30 CA043703-21American Cancer Society Mentored Research Scholar Grant,No.124673-MRSG-13-315-01-CPHPS
文摘The accumulated evidence from two decades of randomized controlled trials has not yet resolved the question of how best to monitor colorectal cancer(CRC)survivors for early detection of recurrent and metachronous disease or even whether doing so has its intended effect.A new wave of trial data in the coming years and an evolving knowledge of relevant biomarkers may bring us closer to understanding what surveillance strategies are most effective for a given subset of patients.To best apply these insights,a number of important research questions need to be addressed,and new decision making tools must be developed.In this review,we summarize available randomized controlled trial evidence comparing alternative surveillance testing strategies,describe ongoing trials in the area,and compare professional society recommendations for surveillance.In addition,we discuss innovations relevant to CRC surveillance and outline a research agenda which will inform a more risk-stratified and personalized approach to follow-up.
基金National Medical Research Council Singapore Clinician Scientist Award Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme NCCS Cancer Fund Kua Hong Pak Head and Neck Cancer Research Programme。
文摘Dear editor,Prostate cancer(PCa)remains a major healthcare burden in men globally[1].Most patients present with localized disease,and treatment is recommended based on risk classification systems like the National Comprehensive Cancer Network(NCCN)[2].However,these methods are imprecise for estimating metastasis-free survival and prostate cancer-specific mortality and thus biomarkers that can predict tumor aggression are needed[3–5].Several studies have since characterized the molecular landscape of localized PCa in White[4,5]and Black/African-American men[6],but data is lacking in Asian men.The Chinese Prostate Cancer Genome and Epigenome Atlas(CPGEA)reported on the genomic and epigenomic landscape of 208 PCa of men from China[7].Comparative analyses between the CPGEA cohort and data from The Cancer Genome Atlas(TCGA)revealed higher frequencies of Forkhead box A1(FOXA1)and chromodomain-helicase DNA-binding 1(CHD1)mutations,and lower frequencies of phosphatase and tensin homolog(PTEN)mutations and transmembrane protease serine 2-E26 transformationspecific related gene(TMPRSS2-ERG)fusion in Chinese compared with White men[7].These preliminary findings highlight the presence of race-specific differences in molecular phenotypes of PCa.
基金supported by the merge funding 2016e17, the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicinesupported by the Harrington Physician Scientist Pathway at University Hospitals Cleveland Medical Centerthe Clinical Translational Science Training Program TL1 grant at Case Western Reserve University
文摘Sebaceous carcinoma (SC) of the eyelid is a rare but aggressive malignancy, accounting for 3%—5% of eyelid malignancies in the United States, and up to 35% in Asian populations (Deprez and Uffer, 2009;Xu et al., 2018;Yu et al., 2018). It is frequently mistaken for benign conditions or less aggressive malignancies such as basal cell carcinoma (Muqit et al., 2013), and the effects of delay in diagnosis can be devastating to patients. Aggressive surgical resection is the primary treatment of these tumors and often invoIves orbital exenteration with significant morbidity to patients, and these tumors frequently recur, with local recurrence rate as high as 18%. Importantly, this disease has a high metastatic potential, and there are very limited data guiding systemic treatment options;ultimately 6%—18% of patients diagnosed with SC of the eyelid succumb to metastatic disease (Zurcher et al., 1998;Shields et al., 2004).
基金the Case Comprehensive Cancer Center's K12 award(5K12CA076917-22)the Clinical and Translational Science Collaborative TL1 training grant(1TL1TRO02549-01)+1 种基金NIH grants RO1CA196643,UH2CA223670,P5OCA150964,and P30 CA043703a Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant(SU2C-AACR-DT22-17).Stand Up to Cancer is a program of the Entertainment Industry Foundation.
文摘Many cancer types reprogram their metabolism to become addicted to glutamine.One of the critical enzymes in the utilization of glutamine in these cells is glutaminase.CB-839(telaglenastat)is a drug that targets glutaminase that is currently being evaluated in many clinical trials for efficacy in various cancer types that are known to be driven by glutamine metabolism.Despite its use,there are limited assays available for testing the pharmacodynamic on-target effects of CB-839 on the limited,small-volume patient samples that are obtained in early-phase clinical trials.Thus,we developed an assay based on the cellular thermal shift assay technique using AlphalLlSA technology to show that CB-839 specifically engages glutaminase in colon cancer cell lines in vitro and in minute quantities of mouse xenograft tumors.Notably,we show that this assay detects CB-839 binding to glutaminase in platelets of patients collected while receiving CB-839 on a clinical trial.This assay may be used to study the pharmacodynamic profile of CB-839 in very small tissue samples obtained from patients on a clinical trial and may be useful infuture studies designed to screen other in hibitors of glutaminase.
基金supported by NIH R01(5R01AI139141 to JJD),University Hospitals Cleveland Medical Center/Seidman Cancer Center,and the Case Comprehensive Cancer Center.
文摘Multiple myeloma(MM)remains an incurable,genetically heterogeneous disease characterized by the uncontrolled proliferation of transformed plasma cells nurtured within a permissive bone marrow(BM)microenvironment.Current therapies leverage the unique biology of MM cells and target the immune microenvironment that drives tumor growth and facilitates immune evasion.Proteasome inhibitors and immunomodulatory drugs were initially introduced to complement and have now supplanted cytotoxic chemotherapy as frontline anti-myeloma agents.Recently,monoclonal antibodies,bispecific antibodies,and chimeric antigen receptor T cells were developed to revamp the immune system to overcome immune suppression and improve patient responses.While current MM therapies have markedly extended patient survival,acquired drug resistance inevitably emerges and drives disease progression.The logical progression for the next generation of MM therapies would be to design and validate agents that prevent and/or overcome acquired resistance to immunotherapies.The complex BM microenvironment promotes resistance to both current anti-myeloma agents and emerging immunotherapies.Myeloma cells are intertwined with a complex BM immune microenvironment that contributes to the development of adaptive drug resistance.Here,we describe recently FDA-approved and investigational anti-myeloma agents that directly or indirectly target the BM microenvironment to prevent or overcome drug resistance.Synergistic effects of anti-myeloma agents may foster the development of rationally-designed drug cocktails that prevent BM-mediated resistance to immunotherapies.
