Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line se...Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line second generation EGFR tyrosine kinase inhibitors （TKIs） afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups. Methods： Eligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios （HRs）. All measures were pooled using random- effects models and 95% confidential interval （95% CI） was calculated. Results： A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials （RCTs）, first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy （pooled HR_TKI/Chemo for Del19： 0.82, 95% CI： 0.64- 1.06, P=0.14; pooled HR_TKI/Chemo for L858R： 1.15, 95% CI： 0.85-1.56, P=0.38）. Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference （pooled HR19/21： 0.88, 95% CI： 0.67-1.16, P=0.37）. Conclusions： Among patients with advanced non-small cell hmg cancer （NSCLC） harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.展开更多
Background:Response to immune checkpoint inhibitors(ICIs)is affected by multiple factors.This study aimed to explore whether sites of metastasis are associated with clinical outcomes of ICIs in advanced non-small-cell...Background:Response to immune checkpoint inhibitors(ICIs)is affected by multiple factors.This study aimed to explore whether sites of metastasis are associated with clinical outcomes of ICIs in advanced non-small-cell lung cancer(NSCLC)patients.Methods::The data of NSCLC patients with high programmed death-ligand 1 expression and good performance status receiving first-line ICIs monotherapy from Guangdong Provincial People’s Hospital between May 2019 and July 2020 were retrospectively analyzed.Metastatic sites included liver,bone,brain,adrenal gland,pleura,and contralateral lung.Progression-free survival(PFS)and overall survival(OS)were compared between different metastatic sites and metastatic burden by the Kaplan-Meier method.Organ-specific disease control rate(OSDCR)of different individual metastatic sites was evaluated.Results:Forty NSCLC patients meeting the criteria were identified.The presence of liver metastasis was significantly associated with shorter PFS(3.1 vs.15.5 months,P=0.0005)and OS(11.1 months vs.not reached,P=0.0016).Besides,patients with bone metastasis tend to get shorter PFS(4.2 vs.15.5 months,P=0.0532)rather than OS(P=0.6086).Moreover,the application of local treatment could numerically prolong PFS in patients with brain metastasis(15.5 vs.4.3 months,P=0.1894).More metastatic organs involved were associated with inferior PFS(P=0.0052)but not OS(P=0.0791).The presence of liver metastasis or bone metastasis was associated with more metastatic organs(Phi[φ]:0.516,P=0.001).The highest OSDCR was observed in lung(15/17),and the lowest in the liver(1/4).Conclusions:Metastases in different anatomical locations may be associated with different clinical outcomes and local tumor response to ICIs in NSCLC.ICIs monotherapy shows limited efficacy in patients with liver and bone metastasis,thus patients with this type of metastasis might require more aggressive combination strategies.展开更多
Zr5018Nil1AlTi10Ti5 bulk metallic glass has been rolled at room temperature up to 95% in thickness reduction, and the dependence of microstructure on the strain was investigated. With increasing thickness reduction, t...Zr5018Nil1AlTi10Ti5 bulk metallic glass has been rolled at room temperature up to 95% in thickness reduction, and the dependence of microstructure on the strain was investigated. With increasing thickness reduction, the full width at half maximum （FWHM） and crystallization enthalpy decrease gradually till 80%, and then increase evidently at 95%. It is revealed that the reversible transition between the ordered and disordered atomic configurations was found in the metallic glass as the deformation proceeds, which is further verified by the high-resolution transmission electron microscopy images. The final microstructure in metallic glass during cold-rolling is the net result of two competing processes between shear-induced disordering and diffusion controlled reordering.展开更多
文摘Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line second generation EGFR tyrosine kinase inhibitors （TKIs） afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups. Methods： Eligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios （HRs）. All measures were pooled using random- effects models and 95% confidential interval （95% CI） was calculated. Results： A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials （RCTs）, first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy （pooled HR_TKI/Chemo for Del19： 0.82, 95% CI： 0.64- 1.06, P=0.14; pooled HR_TKI/Chemo for L858R： 1.15, 95% CI： 0.85-1.56, P=0.38）. Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference （pooled HR19/21： 0.88, 95% CI： 0.67-1.16, P=0.37）. Conclusions： Among patients with advanced non-small cell hmg cancer （NSCLC） harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.
基金This study was supported by the National Natural Science Foundation of China(No.82072562 to QZ)the High-Level Hospital Construction Project(No.DFJH201810 to QZ)the GDPH Scientific Research Funds for Leading Medical Talents in Guangdong Province(No.KJ012019428 to QZ).
文摘Background:Response to immune checkpoint inhibitors(ICIs)is affected by multiple factors.This study aimed to explore whether sites of metastasis are associated with clinical outcomes of ICIs in advanced non-small-cell lung cancer(NSCLC)patients.Methods::The data of NSCLC patients with high programmed death-ligand 1 expression and good performance status receiving first-line ICIs monotherapy from Guangdong Provincial People’s Hospital between May 2019 and July 2020 were retrospectively analyzed.Metastatic sites included liver,bone,brain,adrenal gland,pleura,and contralateral lung.Progression-free survival(PFS)and overall survival(OS)were compared between different metastatic sites and metastatic burden by the Kaplan-Meier method.Organ-specific disease control rate(OSDCR)of different individual metastatic sites was evaluated.Results:Forty NSCLC patients meeting the criteria were identified.The presence of liver metastasis was significantly associated with shorter PFS(3.1 vs.15.5 months,P=0.0005)and OS(11.1 months vs.not reached,P=0.0016).Besides,patients with bone metastasis tend to get shorter PFS(4.2 vs.15.5 months,P=0.0532)rather than OS(P=0.6086).Moreover,the application of local treatment could numerically prolong PFS in patients with brain metastasis(15.5 vs.4.3 months,P=0.1894).More metastatic organs involved were associated with inferior PFS(P=0.0052)but not OS(P=0.0791).The presence of liver metastasis or bone metastasis was associated with more metastatic organs(Phi[φ]:0.516,P=0.001).The highest OSDCR was observed in lung(15/17),and the lowest in the liver(1/4).Conclusions:Metastases in different anatomical locations may be associated with different clinical outcomes and local tumor response to ICIs in NSCLC.ICIs monotherapy shows limited efficacy in patients with liver and bone metastasis,thus patients with this type of metastasis might require more aggressive combination strategies.
基金supported by the National Natural Science Foundation of China (No. 50804032)the Natural Science Foundation of Shanxi Province, China (Nos.2011021020-1 and 2012021018-3)the Postgraduate Technology Innovation Project of Taiyuan University of Science and Technology, China (No. 20111002)
文摘Zr5018Nil1AlTi10Ti5 bulk metallic glass has been rolled at room temperature up to 95% in thickness reduction, and the dependence of microstructure on the strain was investigated. With increasing thickness reduction, the full width at half maximum （FWHM） and crystallization enthalpy decrease gradually till 80%, and then increase evidently at 95%. It is revealed that the reversible transition between the ordered and disordered atomic configurations was found in the metallic glass as the deformation proceeds, which is further verified by the high-resolution transmission electron microscopy images. The final microstructure in metallic glass during cold-rolling is the net result of two competing processes between shear-induced disordering and diffusion controlled reordering.
