ALBERT

Description: Background Treatment options for relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) represent an unmet medical need. Apatinib is a new oral tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptor 2 (VEGFR-2) to inhibit tumor angiogenesis, and has shown encouraging anti-tumor effects in multiple solid tumors. Yet clinical evidence of apatinib as a potential treatment choice for RR DLBCL remains rare. In current study, we evaluated the efficacy and safety of Apatinib for patients with RR DLBCL. Methods In this open-label, single-arm, prospective study, we enrolled patients aged 14-70 years with treatment failure of at least two chemotherapeutic regimens using Simon's two stage design. All patients took Apatinib at an initial dose of 500mg on a 4 weeks cycle at home and visited outpatient clinic every 2 cycles to evaluate the efficacy and to record the adverse events. Dose interruptions and reductions were only allowed when there were grade 3 haematological adverse events or grade 2 non-haematological adverse events. We considered objective response rate (ORR) as the primary end point, and progression-free survival (PFS), overall survival (OS) plus duration of response (DoR) as the secondary end point. (This trial was registered at ClinicalTrials.gov, identifier: NCT03376958.) Results From January 2017 to February 2019, we screened 35 and enrolled 32 eligible patients. At the cutoff point (April 2019), we noted 2 (6.3%) complete responses, 12 (37.5%) partial responses and 9 (28.1%) stable diseases, attributing to an ORR of 43.8% and a disease control rate (DCR) of 71.9%. The median PFS was 6.9 months (95%CI 5.8-7.9) and the median OS was 7.9 months (95%CI 7.0-8.7). Kaplan-Meier estimates of PFS and OS are shown in Figure 1. For patients achieved PR, The median DoR was 5.0 months (95%CI 3.5-6.5). At data analysis time, the median duration of follow-up was 8.6 months (95%CI 7.3-9.4), and 16 (50.0%) patients remained on treatment. 21 patients showed tumor shrinkage comparing with their baseline data and the best percentage changes from baseline are shown in Figure 2. The most common grade 3-4 adverse events (AE) were hypertension (12.6%), hand-foot syndrome (9.4%) and leukopenia (6.3%). No Apatinib-related deaths were noted. AEs arose in at least one patient are shown in Table 1. Conclusion With the potential superiority of home administration without frequent hospitalization, apatinib can be an arrow in the bow for RR DLBCL patients considering its favorable efficacy, manageable AEs, improved patient adherence and economic effectiveness. Further investigations into this topic will be of profound significance. Disclosures No relevant conflicts of interest to declare.

Description: Background Extranodal NK/T cell lymphoma (ENKTL) is rare in western countries but rather common in Asia and South America, characterized with Epstein-Barr virus (EBV) infection. Patients with advanced stage (III/IV) ENKTL has a poor survival and low response to conventional CHOP-like chemotherapy, with a 5-year overall survival rate of only 30%. Retrospective study showed that SMILE regimen had a certain effect on ENKTL, but the toxicity limited its further clinical application. More effective treatment regimens are required to be explored for systematic, prospective, controlled, randomized clinical trials. Recently, studies revealed that asparaginase-based combination chemotherapy such as P-Gmox(Pegaspargase, Gemcitabine, Oxaliplatin)is effective in patients of ENKTL. However standard treatment for newly untreated advanced ENKTL is still controversial. We developed a refined chemotherapeutic DDGP (dexamethasone, cisplatin, gemcitabline, and peg-asparaginase) regimen and proceeded a prospective randomized, multicenter and open-label clinical trial to evaluate and compare the efficacy and safety of DDGP with SMILE regimen in patients with newly diagnosed stage III/IV ENKTL in January 2011. Based on the encouraging interim results in 2016(Li, L et al.Clin Cancer Res, 2016), we presented the final results of this clinical investigation (ClinicalTrials.gov, No. NCT01501149). Patients and methods: The study was initiated at 9 centers in China in January 2011. Patients aged 14-70 with newly diagnosed ENKTL in stages III/IV, and ECOG performance score of 0-2 were enrolled. According to a computer-generated randomization schedule, eligible patients were assigned either DDGP regimen (cisplatin 20 mg/m² on day 1-4; dexamethasone 15mg/m2 on d1-5; gemcitabine 800mg/m2 on d1,8; pegaspargase 2500 IU/m2 on d1; 21 days per cycle)or SMILE regimen (methotrexate 2g/m2 on d1; dexamethasone 40mg/m2 on d2-4; ifosfamide 1500mg/m2 on d2-4; L-asparaginase 6000 U/m2 on d3-9; etoposide 100 mg/m2 on d2-4; 21 days per cycle) for up to 6 cycles unless disease progression, unacceptable toxicity or patient rejection. Efficacy was evaluated every two cycles. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall response rate (ORR) and overall survival (OS). In addition we compared the safety and tolerability between DDGP and SMILE regimens. The Kaplan-Merier method was used to evaluate for survival of freedom from events, and the log-rank test was used to evaluate differences among two groups. Results: A total of 87 eligible newly diagnosed advanced ENKTL patients were randomly assigned for the study and 80 patients were included into intention-to-treat population (40 patients in DDGP group and 40 patients in SMILE group). Data were collected from January 2011 to February 2019. Baseline characteristics of the two group patients were well balanced. At median follow-up of 41.5 months, the median PFS and OS in the SMILE group were 6.83 months and 75.2 months, respectively, while the median PFS and OS in the DDGP group have not been reached (Fig 1). The 3-year PFS rate and 5-year OS rate in DDGP group were higher than in SMILE group (56.6% vs. 41.8% for 3-year PFS, P=0.004; 74.3% vs. 51.7% for 5-year OS, P=0.02). No difference of the complete remission (CR) rate was observed between two groups, while overall response rate (ORR) in DDGP group was higher than in SMILE group (90.0% vs. 60.0%, p=0.002) (Table 1). More frequently 3/4 grade hematologic toxicities such as leucopenia and netropenia were observed in SMILE group than in DDGP group (p=0.022, p=0.015). Non-hematologic toxicities included elevated transaminase, mucositis and allergy were higher in SMILE group than in DDGP group(p=0.027, p

Description: It has been reported that backward surface waves of Tamm state can be supported by a multilayered metal–dielectric metamaterial with different partner materials, such as left-handed metamaterial or dissimilar metallic–dielectric metamaterial. In this paper, the transfer-matrix method is employed to reveal that transverse-magnetic (TM)-polarized backward surface waves can be realized by a multilayered metal–dielectric metamaterial in contact with a conventional homogenous dielectric medium. Owing to the strong optical nonlocality, the existence of such backward surface waves is proved to be dependent on the order of the metallic/dielectric layers. The relevant anomalous dispersion relations can also be dramatically engineered by varying the unit-cell thickness and the filling factor. Additionally, the distribution of the energy flow is presented to further unfold the physical mechanism of the backward surface waves. Finally, a numerical simulation of backward surface wave excited by a TM-polarized Gaussian beam based on a prism-coupled configuration is displayed.

Description: Rapid urbanisation and the associated infrastructure development are creating a deficit of conventional construction materials and straining the natural resources. On the other hand, municipal solid waste (MSW) disposal poses a serious environmental problem. Landfilling of MSW is both costly and polluting. Incineration of MSW to generate energy is a commonly adopted approach. However, there are concerns associated with micro pollutants emitted from the combustion process. The carbon footprint of the process and the environmental cost–benefit balancing are disputable. There is clearly a need to adopt cost-effective alternatives to treat MSW. This paper proposes the potential application of “treated” MSW as an ingredient for construction materials. The treatment process involves placing MSW in an autoclave at 150 °C with 5 bars (0.5 MPa), followed by the separation of metals, plastics and glass for recycling purposes. The end-product, which is a semi-organic mixture (referred to as ‘biomass’), is passed through a vortex-oscillation system, which makes it more uniform as a material. Compressive testing of Portland cement-based pastes containing 10% and 15% biomass shows consistency in the results, demonstrating the potential use of biomass in construction materials.

Description: To address sustainability issues by facilitating the use of high-volume fly ash (HVFA) concrete in industry, this paper investigates the early age hydration properties of HVFA binders in concrete and the correlation between hydration properties and compressive strengths of the cement pastes. A new method of calculating the chemically bound water of HVFA binders was used and validated. Fly ash (FA) types used in this study were sourced from Indonesia and Australia for comparison. The water to binder (w/b) ratio was 0.4 and FA replacement levels were 40%, 50% and 60% by weight. Isothermal calorimetry tests were conducted to study the heat of hydration which was further converted to the adiabatic temperature rise. Thermo-gravimetric analysis (TGA) was employed to explore the chemically bound water (WB) of the binders. The results showed that Australian FA pastes had higher heat of hydration, adiabatic temperature rise, WB and compressive strength compared to Indonesian FA pastes. The new method of calculating chemically bound water can be successfully applied to HVFA binders. Linear correlation could be found between the WB and compressive strength.

Description: The aircraft hydraulic system is very important for the actuation system and its failure has led to a number of catastrophic accidents in the past few years. The reasons for hydraulic loss can be leakage, blockage, and structural damage. Fortunately, the development of more electric aircraft (MEA) provides a new means of solving this difficult problem. This paper designs an active fault tolerant control (AFTC) method for MEA suffering from total hydraulic loss and actuation system failure. Two different kinds of scenarios are considered: leakage/blockage and vertical tail damage. With the application of the dissimilar redundant actuation system (DRAS) in MEA, a switching mechanism can be used to change the hydraulic actuation (HA) system into an electro-hydrostatic actuation (EHA) system when the whole hydraulic system fails. Taking account of the gap between HA and EHA, a degraded model is built. As for vertical tail damage, engine differential thrust control is adopted to help regain lateral-directional stability. The engine thrust dynamics are modeled and the mapping relationship between engine differential thrust and rudder deflection is formulated. Moreover, model reference control (MRC) and linear quadratic regulator (LQR) are used to design the AFTC method. Comparative simulation with the NASA generic transportation model (GTM) is carried out to prove the proposed strategy.

Description: Objective:To evaluate the safety, efficacy, and feasibility of rituximab, fotemustine, pemetrexed and dexamethasone (R-FPD) regimen for primary central nervous system lymphoma (PCNSL) patients. Methods:A prospective, single-center, single-arm, phase II clinical trial. Patients with newly diagnosed PCNSL diagnosed from the First Affiliated Hospital of Zhengzhou University from July 2018 to July 2020. R-FPD regimen consisted of rituximab (375 mg/m2 i.v. on D0), fotemustine (100mg/m2 i.v. on D1) ,pemetrexed (600mg/m2 i.v. on D1), and dexamethasone (40 mg i.v. on D1).(NCT04083066) Results: 30 patients were included. After two cycles, the objective response rate(ORR) was 96.4%(27/28,26 PR,1 CR,0 SD,0 PD,2 Censored),the disease control rate(DCR) was 96.4%(27/28); After four cycles, the ORR was 71.4% (15/21, 5PR,10 CR,1SD,5PD,7NR,2 Censored),DCR was 76.2%(16/21). The median progression-free survival (PFS) was 20.3 months (95%CI:5.2--35.4),The median overall survival (OS) was 22.0 months (95%CI:16.1-27.9).The grade III-IV toxicities were mainly leukopenia(17.9%), thrombocypenia(25%) and anemia(10.7%). Conclusion: Fotemustine-based in combination with Rituximab chemotherapy can improve outcomes with the progress free survival and the overall survival benefits, as well as with better tolerability for newly diagnosed PCNSL patients. Keywords: rituximab; primary central nervous system lymphoma; pemetrexed; fotemustine; efficacy Disclosures No relevant conflicts of interest to declare.