Objective:Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis.This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.Methods:Patients with HE...Objective:Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis.This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.Methods:Patients with HER2-negative breast cancer,who were pre-treated with anthracycline or taxanes in a neoadjuvant,adjuvant,or metastatic setting,and had treatment failure after at least one prior chemotherapy regimen in the metastatic setting were enrolled.Anlotinib was administered at 12 mg daily for 14 days in a 21-day cycle until disease progression or unacceptable toxicity occurred.Simultaneously,5–10 m L of venous blood was collected to perform circulating tumor DNA(ct DNA)testing every 2 treatment cycles.The primary endpoint was the objective response rate(ORR).Secondary endpoints included the disease control rate(DCR),progression-free survival(PFS),overall survival,safety,and biomarkers.Results:Twenty-six eligible patients were enrolled,with a median age of 56(30–75)years.The median follow-up time was 10.5 months.The ORR was 15.4%,the DCR was 80.8%,and the median PFS was 5.22 months(95%confidence interval 2.86–6.24).Fourteen(53.8%)patients survived for more than 10 months.The changes in the detectable ct DNA variant allele frequency were consistent with the tumor response.The most common treatment-related adverse events were hypertension(57.7%),thyroidstimulating hormone elevation(34.6%),and hand-foot syndrome(23.1%).Conclusion:Anlotinib showed objective efficacy with tolerable toxicity in heavily pre-treated,metastatic HER2-negative breast cancer.The dynamic changes in the ct DNA variant allele fraction may be predictive of the tumor response.展开更多
Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment o...Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS.展开更多
Urban parks are an important part of urban ecosystems and play an important role in biodiversity conservation.However,it is still unclear how park characteristics aff ect plant diversity which could hinder the conserv...Urban parks are an important part of urban ecosystems and play an important role in biodiversity conservation.However,it is still unclear how park characteristics aff ect plant diversity which could hinder the conservation of urban biodiversity due to the ineff ective design of urban parks.The diversity of woody plants in 33 parks of Changchun,China,was measured with plot measurements and linked with urban park characteristics(e.g.,size and age of the park)to uncover the relationship between them.The results show that urban woody plant species were abundant,with 98 species belonging to 51 genera and 26 families in the snow climate city of Changchun.The variation in woody plant diversity was largely explained by internal patch characteristics(e.g.,size,age,shape),and external factors surrounding the park(e.g.,land use type and socioeconomic level)accounted for only 16.0%in our study.For internal patch characteristics,older urban parks with larger areas demonstrated a richer level of plant diversity and increased nonlinearly with increasing park area.The threshold size signifi cantly aff ecting plant diversity variation was approximately 30 ha.Plant diversity had positive linear relationships with the ages of urban parks,supporting the legacy eff ect.In addition,woody plant diversity nonlinearly decreased with increasing park shape index,which suggested that the plant diversity could also be increased by optimizing the park shape.Regarding the external factors surrounding parks,the spatial distribution of woody plant diversity varied greatly from the urban center to the suburbs.House prices around the park had positive linear relationships with woody plant diversity in parks,supporting the luxury eff ect.However,building and road proportions,and green space proportion had no relationship with plant diversity in parks.This study can provide a robust reference for enriching plant diversity in urban parks,thus improving the development of urban sustainable cities.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81672634)National Key Research and Development Program of China(Grant No.2018YFC0115204)+2 种基金Capital Health Development Scientific Research Project(Grant No.2018-2-4023)Clinical Translation and Medical Research Fund of Chinese Academy of Medical Sciences(Grant No.12019XK320071)Peking Union Medical College Graduate Innovation Fund(Grant No.2018-1002-02-25)。
文摘Objective:Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis.This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.Methods:Patients with HER2-negative breast cancer,who were pre-treated with anthracycline or taxanes in a neoadjuvant,adjuvant,or metastatic setting,and had treatment failure after at least one prior chemotherapy regimen in the metastatic setting were enrolled.Anlotinib was administered at 12 mg daily for 14 days in a 21-day cycle until disease progression or unacceptable toxicity occurred.Simultaneously,5–10 m L of venous blood was collected to perform circulating tumor DNA(ct DNA)testing every 2 treatment cycles.The primary endpoint was the objective response rate(ORR).Secondary endpoints included the disease control rate(DCR),progression-free survival(PFS),overall survival,safety,and biomarkers.Results:Twenty-six eligible patients were enrolled,with a median age of 56(30–75)years.The median follow-up time was 10.5 months.The ORR was 15.4%,the DCR was 80.8%,and the median PFS was 5.22 months(95%confidence interval 2.86–6.24).Fourteen(53.8%)patients survived for more than 10 months.The changes in the detectable ct DNA variant allele frequency were consistent with the tumor response.The most common treatment-related adverse events were hypertension(57.7%),thyroidstimulating hormone elevation(34.6%),and hand-foot syndrome(23.1%).Conclusion:Anlotinib showed objective efficacy with tolerable toxicity in heavily pre-treated,metastatic HER2-negative breast cancer.The dynamic changes in the ct DNA variant allele fraction may be predictive of the tumor response.
基金funded by the National Natural Science Foundation of China(Grant No.81472753 and 81672634)。
文摘Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS.
基金supported by the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2020237 and 2019234)the National Natural Science Foundation of China(Grant No.42171109 and 32130068).
文摘Urban parks are an important part of urban ecosystems and play an important role in biodiversity conservation.However,it is still unclear how park characteristics aff ect plant diversity which could hinder the conservation of urban biodiversity due to the ineff ective design of urban parks.The diversity of woody plants in 33 parks of Changchun,China,was measured with plot measurements and linked with urban park characteristics(e.g.,size and age of the park)to uncover the relationship between them.The results show that urban woody plant species were abundant,with 98 species belonging to 51 genera and 26 families in the snow climate city of Changchun.The variation in woody plant diversity was largely explained by internal patch characteristics(e.g.,size,age,shape),and external factors surrounding the park(e.g.,land use type and socioeconomic level)accounted for only 16.0%in our study.For internal patch characteristics,older urban parks with larger areas demonstrated a richer level of plant diversity and increased nonlinearly with increasing park area.The threshold size signifi cantly aff ecting plant diversity variation was approximately 30 ha.Plant diversity had positive linear relationships with the ages of urban parks,supporting the legacy eff ect.In addition,woody plant diversity nonlinearly decreased with increasing park shape index,which suggested that the plant diversity could also be increased by optimizing the park shape.Regarding the external factors surrounding parks,the spatial distribution of woody plant diversity varied greatly from the urban center to the suburbs.House prices around the park had positive linear relationships with woody plant diversity in parks,supporting the luxury eff ect.However,building and road proportions,and green space proportion had no relationship with plant diversity in parks.This study can provide a robust reference for enriching plant diversity in urban parks,thus improving the development of urban sustainable cities.
