IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

Effects of Mg-doping temperature on the structural and electrical properties of nonpolar a-plane p-type GaN films

Nonpolar(11–20) a-plane p-type GaN films were successfully grown on r-plane sapphire substrate with the metal–organic chemical vapor deposition(MOCVD) system. The effects of Mg-doping temperature on the structural and electrical properties of nonpolar p-type GaN films were investigated in detail. It is found that all the surface morphology, crystalline quality, strains, and electrical properties of nonpolar a-plane p-type GaN films are interconnected, and are closely related to the Mg-doping temperature. This means that a proper performance of nonpolar p-type GaN can be expected by optimizing the Mg-doping temperature. In fact, a hole concentration of 1.3×10^(18)cm^(-3), a high Mg activation efficiency of 6.5%,an activation energy of 114 me V for Mg acceptor, and a low anisotropy of 8.3% in crystalline quality were achieved with a growth temperature of 990℃. This approach to optimizing the Mg-doping temperature of the nonpolar a-plane p-type GaN film provides an effective way to fabricate high-efficiency optoelectronic devices in the future.

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

Current management of chemotherapy-induced neutropenia in adults:key points and new challenges

Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.

Epitaxial Growth and Characteristics of Nonpolar a-Plane InGaN Films with Blue-Green-Red Emission and Entire In Content Range

Nonpolar(1120)plane In_(x)Ga_(1-x)N epilayers comprising the entire In content(x)range were successfully grown on nanoscale Ga N islands by metal-organic chemical vapor deposition.The structural and optical properties were studied intensively.It was found that the surface morphology was gradually smoothed when x increased from 0.06 to 0.33,even though the crystalline quality was gradually declined,which was accompanied by the appearance of phase separation in the In_(x)Ga_(1-x)N layer.Photoluminescence wavelengths of 478 and 674 nm for blue and red light were achieved for x varied from 0.06 to 0.33.Furthermore,the corresponding average lifetime(τ_(1/e))of carriers for the nonpolar In Ga N film was decreased from 406 ps to 267 ps,indicating that a high-speed modulation bandwidth can be expected for nonpolar In Ga N-based light-emitting diodes.Moreover,the bowing coefficient(b)of the(1120)plane In Ga N was determined to be 1.91 e V for the bandgap energy as a function of x.

Advanced Breast Angiosarcoma Completely Responding to Chemotherapy

Introduction: For patients with anthracycline-resistant metastatic angiosarcoma, currently there is no available standard for second-line therapy and there is a need for novel effective regimens to improve response rates. Case report: We reported here about a case of a primary angiosarcoma of both breasts in a 34-year-old woman presenting lung metastases. At the completion of 3 cycles of the MAID regimen including mesna, adriamycin, ifosfamide and dacarbazine, CT showed progression of the disease (PD). Subsequently second-line chemotherapy was started using GVP regimen consisting of gemcitabine, vincristine and cisplatin. Complete response (CR) of the lung metastases was achieved after 6 treatment cycles. Conclusion: In the absence of an effective therapy among patients with anthracycline-resistant metastatic breast angiosarcoma, a GVP chemo-regimen can be performed as a selective option.

A lateral AlGaN/GaN Schottky barrier diode with 0.36-V turn-on voltage and 10-kV breakdown voltage by using double-barrier anode structure

GaN power electronic devices,such as the lateral AlGaN/GaN Schottky barrier diode(SBD),have received significant attention in recent years.Many studies have focused on optimizing the breakdown voltage(BV)of the device,with a particular emphasis on achieving ultra-high-voltage(UHV,>10 kV)applications.However,another important question arises:can the device maintain a BV of 10 kV while having a low turn-on voltage(V_(on))?In this study,the fabrication of UHV AlGaN/GaN SBDs was demonstrated on sapphire with a BV exceeding 10 kV.Moreover,by utilizing a doublebarrier anode(DBA)structure consisting of platinum(Pt)and tantalum(Ta),a remarkably low Von of 0.36 V was achieved.This achievement highlights the great potential of these devices for UHV applications.

All-optical generation,detection,and manipulation of picosecond acoustic pulses in 2D semiconductor/dielectric heterostructures

Launching,tracking,and controlling picosecond acoustic(PA)pulses are fundamentally important for the construction of ultrafast hypersonic wave sources,ultrafast manipulation of matter,and spatiotemporal imaging of interfaces.Here,we show that GHz PA pulses can be all-optically generated,detected,and manipulated in a 2D layered MoS_(2)∕glass heterostructure using femtosecond laser pump-probe.Based on an interferometric model,PA pulse signals in glass are successfully decoupled from the coexisting temperature and photocarrier relaxation and coherent acoustic phonon(CAP)oscillation signals of MoS_(2)lattice in both time and frequency domains.Under selective interface excitations,temperature-mediated interfacial phonon scatterings can compress PA pulse widths by about 50%.By increasing the pump fluences,anharmonic CAP oscillations of MoS_(2)lattice are initiated.As a result,the increased interatomic distance at the MoS_(2)∕glass interface that reduces interfacial energy couplings can markedly broaden the PA pulse widths by about 150%.Our results open new avenues to obtain controllable PA pulses in 2D semiconductor/dielectric heterostructures with femtosecond laser pump-probe,which will enable many investigations and applications.

基于石墨烯量子点与二硫化钼的双被动调Q激光器研究

为获得脉冲宽度窄、波形对称性好、输出性能稳定的脉冲激光,设计了一种基于石墨烯量子点与二硫化钼的1064 nm双被动调Q激光器。该激光器采用结构简单的线形腔结构,以808 nm LD为抽运源、Nd∶YVO4为增益介质。分别采用水热法和锂离子-插层法获得了石墨烯量子点溶液与二硫化钼溶液。经旋涂、烘干等工艺制备出可饱和吸收体,作为被动调Q器件。相比于单被动调Q激光器,双被动调Q激光器输出的激光脉冲宽度更窄、脉冲波形对称性更好。当抽运功率为12.9 W时,实验测到的调Q激光脉冲宽度为180 ns,重复频率为1085 kHz,信噪比为44 dB,平均输出功率为595 mW。

Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy

Background:Although programmed cell death 1(PD-1)blockade plus chemotherapy can significantly prolong the progression-free survival(PFS)and overall survival(OS)in first-line settings in patients with driver-negative advanced non-small-cell lung cancer(NSCLC),the predictive biomarkers remain undetermined.Here,we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy.Methods:Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone.Tumor immune microenvironmental markers,including PD-1 ligand(PDL1),CD8,CD68,CD4 and forkhead box P3,were assessed using multiplex immunofluorescence(mIF)assays.Kaplan-Meier curveswere used to determine treatment outcome differences according to their expression status.Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations.Results:Responders had significantly higher CD8/PD-L1(P=0.015)or CD68/PD-L1 co-expression levels(P=0.021)than non-responders in the camrelizumab plus chemotherapy group,while no difference was observed in the chemotherapy group.Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS(P=0.002,P=0.024;respectively)and OS(P=0.006,P=0.026;respectively)than those with low co-expression in camrelizumab plus chemotherapy group.When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification,significantly better PFS(P=0.003)and OS(P=0.032)were observed in high co-expression subgroups.The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features.Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression,the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups(both 13.0%vs.0.0%,P=0.023).Notably,enriched PI3K(P=0.012)and cell cycle pathway(P=0.021)were found in the CD8/PD-L1 co-expression group.Conclusion:Tumor immune microenvironmental marker expression,especially CD8/PD-L1 or CD68/PD-L1 co-expression,was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.