An integrated split and dummy gates MOSFET with fast turn-off and reverse recovery characteristics

A power MOSFET with integrated split gate and dummy gate(SD-MOS) is proposed and demonstrated by the TCAD SENTAURUS.The split gate is surrounded by the source and shielded by the dummy gate.Consequently,the coupling area between the split gate and the drain electrode is reduced,thus the gate-to-drain charge(Q_(GD)),reverse transfer capacitance(C_(RSS)) and turn-off loss(E_(off)) are significantly decreased.Moreover,the MOS-channel diode is controlled by the dummy gate with ultra-thin gate oxide t_(ox),which can be turned on before the parasitic P-base/N-drift diode at the reverse conduction,then the majority carriers are injected to the N-drift to attenuate the minority injection.Therefore,the reverse recovery charge(Q_(RR)),time(T_(RR)) and peak current(I_(RRM)) are effectively reduced at the reverse freewheeling state.Additionally,the specific on-resistance(R_(on,sp)) and breakdown voltage(BV) are also studied to evaluate the static properties of the proposed SD-MOS.The simulation results show that the Q_(GD) of 6 nC/cm^(2),the C_(RSS) of 1.1 pF/cm^(2) at the V_(DS) of 150 V,the QRR of 1.2 μC/cm^(2) and the R_(on,sp) of 8.4 mΩ·cm^(2) are obtained,thus the figures of merit(FOM) including Q_(GD) ×R_(on,sp) of50 nC·mΩ,E_(off) × R_(on,sp) of 0.59 mJ·mΩ and the Q_(RR) × R_(on,sp) of 10.1 μC·mΩ are achieved for the proposed SD-MOS.

治疗前外周血炎性标志物对EGFR突变阳性晚期非小细胞肺癌患者的预后价值研究

目的:探讨治疗前外周血炎性标志物在表皮生长因子受体(epidermal growth factor receptor,EGFR)阳性晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者中的预后作用。方法:回顾性分析2015年1月至2018年10月中国人民解放军总医院第五医学中心142例EGFR突变阳性晚期NSCLC患者临床资料。通过受试者工作特征曲线(receiver operating characteristic curve,ROC)确定中性粒细胞与淋巴细胞计数比值(neutrophil-to-lymphocyte ratio,NLR)、血小板与淋巴细胞计数比值(platelet-to-lymphocyte ratio,PLR)、系统免疫炎症指数(systemic immune-inflammation index,SII)和淋巴细胞与单核细胞计数比值(lymphocyte-to-monocyte ratio,LMR)的最佳临界值,应用Kaplan-Meier方法进行生存分析。Cox比例风险模型评估各变量的预测价值。结果:NLR、PLR、SII和LMR的最佳临界值分别为2.60、167.32、687.39和3.13。根据最佳临界值分别将研究对象分为高值组和低值组,高NLR、PLR和SII组的中位无进展生存期(median progression-free survival,mPFS)及中位总生存期(median overall survival,mOS)均显著低于低值组中相应值,高LMR组mPFS及mOS较低LMR组延长。结论:治疗前升高的NLR、PLR、SII和降低的LMR可能与接受靶向治疗的EGFR突变阳性晚期NSCLC患者的不良预后相关。

洛铂联合依托泊苷与顺铂联合依托泊苷一线治疗广泛期小细胞肺癌随机对照临床研究(英文)

Objective: To compare the efficacy and safety of Lobaplatin plus Etoposide (EL) and Cisplatin plus Etoposide (EP) regimens in chemonaive with extensive-stage small-cell lung cancer (SCLC). Methods: Between July 2010 and July 2011, a total of 62 patients with extensive-stage small-cell lung cancer who received initial treatment in our hospital and 309 hospital of PLA. 31 patients were randomly assigned to the EL Group: Lobaplatin was given intravenously at a dose of 30 mg/m2 on day 1 and Etoposide 100 mg/m2 on days 1 to 3 of 21-day cycles for a maximum of six cycles. Another 31 patients were assigned to the EP Group: Cisplatin was given intravenously at a dose of 75 mg/m2 on day 1 and Etoposide 100 mg/m2 on days 1 to 3 of 21-day cycles for a maximum of six cycles. We evaluated the efficacy, overall response rate (ORR), disease control rate (DCR), the progression-free survival (PFS) and toxicity between the patients of the two groups. Results: All 62 patients were eligible. In the EL group, 2 (6.5%) patients had complete response, 20 (64.5%) patients had partial response, 5 (16.1%) patients had stable disease and 4 (12.9%) patients had progress disease. In the EP group, 2 (6.5%) patients had complete response, 22 (70.9%) patients had partial response, 4 (12.9%) patients had stable disease and 3 (9.7%) patients had progress disease. The ORR of EL and EP group were 70.9% and 77.4%, respectively, showing no significant difference (P = 0.562). The DCR of both groups were 87% and 90%, respectively, showing no significant difference (P = 0.688). Median PFS of patients with EL and EP regimens were 5.5 months and 5 months, respectively, showing no significant difference (P = 0.637). Adverse events were observed in all 62 patients. Grade 1 to 4 anemia was higher in the EP group than in EL group, showing significant difference (P = 0.02). Grade 3 and 4 thrombocytopenia was seen in 4 patients (12.9%) in EL group and 1 patient (3.2%) in EP group. Although one patient had platelet transfusion owing to Grade 4 thrombocytopenia in EL group, no significant difference (P = 0.637) were shown. The incidence of nausea/vomiting was higher in the EP group than in the EL group (96.7% vs 51.6%, P = 0.00). Conclusion: The EL regimen is an effective and low-toxicity chemotherapy and no inferior to EP regimen in treatment response, therefore, EL regimen maybe is a good choice for patients with extensive-stage SCLC.

Third-line or above anlotinib in relapsed and refractory small cell lung cancer patients with brain metastases:A post hoc analysis of ALTER1202,a randomized,double-blind phase 2 study

Background:The prognosis of patients with small cell lung cancer(SCLC)and brain metastases(BM)was poor.This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM.Methods:This was a subgroup analysis of the ALTER1202 trial,which was a randomized,placebo-controlled trial aimed to evaluate the role of anlotinib as third-line treatment or above in patients with SCLC.This study included patients with BM at baseline.The efficacy and safety outcomes included progression-free survival(PFS),overall survival(OS),central nervous system(CNS),objective response rate(ORR),CNS disease control rate(DCR),time to CNS progression,and adverse events(AEs).Results:Twenty-one and nine patients with BM were included in the anlotinib and placebo groups,respectively.The median PFS and OS were 3.8 months(95%confidence interval[CI]:1.8-6.1)and 6.1 months(95%CI:4.1-8.0)in the anlotinib group.Anlotinib was associated with a significant improvement in PFS(hazard ratio[HR]=0.15,95%CI:0.04-0.51,p=0.0005)and OS(HR=0.26,95%CI:0.09-0.73,p=0.0061)than placebo.Anlotinib significantly prolonged the time to CNS progression(p<0.0001).The anlotinib group had a higher CNS DCR than placebo(95.2%vs.22.2%,p=0.0001).The most common grade 3 or higher AEs were increased lipase(19.0%),hypertension(14.3%),and hyponatremia(14.3%)in the anlotinib group.Conclusions:Anlotinib proved to have potential CNS activity and a manageable toxicity profile in patients with SCLC and BM,significantly delaying CNS progression.

Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup analysis of a randomized phase 2 study (ALTER1202)

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ≥ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gamma-glutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.