The clinical outcome of pembrolizumab for patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a single center, real world study in China

BackgroundThe KEYNOTE-048 and KEYNOTE-040 study have demonstrated the efficacy of pembrolizumab in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC), we conducted this real-world study to investigate the efficacy of pembrolizumab in patients with R/M HNSCC.MethodsThis is a single-center retrospective study conducted in the Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Shanghai, China). Between December 2020 and December 2022, a total of 77 patients with R/M HNSCC were included into analysis. The primary endpoint of the study was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), overall response rate (ORR)and toxicity.Efficacy was assessed according to RECIST version 1.1.SPSS 27.0 and GraphPad Prism 8.0 software were utilized to perform the statistical analysis.ResultsBy the cut-off date (February 28, 2023), the median OS,PFS and ORR were 15.97 months,8.53 months and 48.9% in patients treated with the pembrolizumab regimen in the first line therapy. Among these patients, 17 patients received pembrolizumab with cetuximab,and 18 received pembrolizumab with chemotherapy.We observed no significant differences between two groups neither in median OS (13.9 vs 19.4 months, P=0.3582) nor PFS (unreached vs 8.233 months, P= 0.2807). In the ≥2nd line therapy (n=30), the median OS, PFS and ORR were 5.7 months, 2.58 months and 20% respectively. Combined positive score (CPS) was eligible from 54 patients. For first line therapy, the median OS and PFS were 14.6 and 8.53 months in patients with CPS ≥1, and median OS and PFS were 14.6 and 12.33 months in patients with CPS ≥20. The immune-related adverse events (irAEs) were occurred in the 31 patients (31/77, 40.26%), and the most common potential irAEs were hypothyroidism (25.97%), and pneumonitis (7.79%).ConclusionOur real-world results indicated that pembrolizumab regimen is a promising treatment in patients with R/M HNSC

Station-based average travel distance and its relationship with urban form and land use: an analysis of smart card data in Nanjing City, China

Few studies based on large sample data have examined mobility patterns from a travel distance perspective and investigated the potential influence of urban form and land use on people's daily travel distances. This paper provides additional empirical insights into spatiotemporal urban mobility patterns and their relationship with urban form and land use using station-based average travel distances (ATDs). Drawing on smart card data of the Nanjing metro system, land use data and open source points-of-interest (POIs) data, we apply exploratory spatial data and quantile regression analysis to examine distance patterns and explore the potential effects of urban form and land use calculated at different spatial scales (i.e. 800 m, 2 km and 5 km) on the ATDs. By comparing mobility patterns between weekdays and weekends and for different times of day, our findings highlight that ATDs are not uniformly nor randomly distributed in space. Positive spatial autocorrelation is found for different time segments. The results of OLS and quantile regression models show a positive and robust relationship between ATDs and distances to the city center (DCs). The models also prove that land use mix (especially measured at the 2 km and 5 km scale) significantly affects ATDs, supporting the importance of land use mix in decreasing daily travel distances. No significant relationship is found between ATDs and distances to the nearest subsidiary center (DSCs), while the employment/entertainment-residence balance has a marginal effect on ATDs at relatively large spatial scales (i.e. 2 km, 5 km). Consequently, with respect to reducing the ATDs, we recommend enhancing land use mix and reducing the imbalance between employment/entertainment and residence at larger spatial scales. Potential applications and future research directions are discussed. The findings in the present paper are helpful for guiding urban planning and policy making

Efficient industrial-current-density acetylene to polymer-grade ethylene via hydrogen-localization transfer over fluorine-modified copper

International audienceAbstract Electrocatalytic acetylene semi-hydrogenation to ethylene powered by renewable electricity represents a sustainable pathway, but the inadequate current density and single-pass yield greatly impedes the production efficiency and industrial application. Herein, we develop a F-modified Cu catalyst that shows an industrial partial current density up to 0.76 A cm −2 with an ethylene Faradic efficiency surpass 90%, and the maximum single-pass yield reaches a notable 78.5%. Furthermore, the Cu-F showcase the capability to directly convert acetylene into polymer-grade ethylene in a tandem flow cell, almost no acetylene residual in the production. Combined characterizations and calculations reveal that the Cu δ+ (near fluorine) enhances the water dissociation, and the generated active hydrogen are immediately transferred to Cu 0 (away from fluorine) and react with the locally adsorbed acetylene. Therefore, the hydrogen evolution reaction is surpassed and the overall acetylene semi-hydrogenation performance is boosted. Our findings provide new opportunity towards rational design of catalysts for large-scale electrosynthesis of ethylene and other important industrial raw

A pilot study of camrelizumab with docetaxel and cisplatin for the first line treatment in recurrent/metastatic oral squamous cell carcinoma

Abstract Pembrolizumab with cisplatin and 5‐fluorouracil showed survival benefit but relatively high occurrence of treatment‐related adverse events (TRAEs) for recurrent/metastatic oral squamous cell carcinoma (R/M OSCC). A more tolerable regime is needed. This trial enrolled 20 R/M OSCC patients with previously untreated and PD‐L1 positive. Patients were administered camrelizumab with docetaxel and cisplatin every 3 weeks for six cycles, followed by camrelizumab monotherapy every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was occurrence of grade ≥ 3 TRAEs, secondary endpoints included overall survival (OS), progression‐free survival (PFS), and overall response rate (ORR). 45% patients experienced grade ≥ 3 TRAEs, which the most common were anemia (15%), stomatitis (15%), and neutropenia (10%). The most common potential immune‐related adverse events were reactive cutaneous capillary endothelial proliferation (RCCEP; 60%), hypothyroidism (35%), and pneumonitis (15%). No treatment‐related deaths occurred. The median OS, PFS, and ORR was 14.4 months, 5.35 months, and 40.0% respectively. The study also found RCCEP occurrence, lower FOXP3+ cells, and higher density of intratumor tertiary lymphoid structure were associated with improved efficacy. Our data suggest that camrelizumab with docetaxel/cisplatin as first‐line therapy was well tolerable and had potentially favorite efficacy in PD‐L1‐positive patients with R/M OSCC

A multicenter randomized phase II trial of hyperthermia combined with TPF induction chemotherapy compared with TPF induction chemotherapy in locally advanced resectable oral squamous cell carcinoma

Background Hyperthermia has been reported to cause cancer stage regression, thus providing surgical opportunities in patients with unresectable tumors and improving the quality of life of patients by preserving certain organs. Methods A prospective open-label phase II trial was conducted to evaluate the efficacy of hyperthermia combined with induction chemotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC). Patients received hyperthermia combined with two cycles of 5-fluorouracil, cisplatin, and docetaxel (TPF) induction chemotherapy regimens or TPF induction chemotherapy alone, followed by radical surgery with postoperative radiotherapy. The primary endpoint was the clinical response rate of the induction chemotherapy. The secondary endpoints were overall survival (OS), disease-free survival (DFS), and toxicity. Results A total of 120 patients were enrolled, and 115 patients were included in the clinical response analysis. The clinical response rate was significantly higher in the experimental arm than in the control arm (65.45% vs. 40.00%, p = 0.0088). There were no unexpected toxicities, and hyperthermia and induction chemotherapy did not increase the perioperative morbidity rate. Moreover, there was a significant improvement in DFS, but no significant difference in OS between the two arms. In the subgroup analysis, increased OS and DFS rates were associated with patients with favorable clinical response after induction chemotherapy in the total population, experimental arm, and control arm. Conclusions Our study demonstrates that hyperthermia combined with induction chemotherapy is associated with a high response rate and provides a new treatment option for patients with resectable stage III or IVA OSCC

Microstructure and Mechanical Properties in a Gd-Modified Extruded Mg-4Al-3.5Ca Alloy

In the present study, the microstructure and mechanical properties of a new Mg-4Al-3.5Ca-2Gd (AXE432) alloy are investigated. The microstructure of the as-cast AXE432 alloy consists of α-Mg, C14 (Mg2Ca), and C36((Mg, Al)2Ca) phases. After the heat treatment at 480 °C for 8 h, the C14 with fine lamellar structure changes from narrow stripes to micro-scale particles, and part of the C36 and the C14 dissolve into the α-Mg matrix, with many short needle-shaped C15 (Al2Ca) phase precipitating in the primary a-Mg grains. The AXE432 alloy extruded at a temperature as high as 420 °C exhibits a refined dynamically recrystallized (DRXed) microstructure with grain sizes less than 1.5 ± 0.5 μm and a strong {0001}1¯0> basal texture with a maximum intensity of 5.62. A complex combination of the effects from grain size, texture, second-phase particles, and strain hardening results in balanced mechanical properties, with the tensile yield strength (TYS), ultimate tensile strength (UTS), elongation (El), compressive yield strength (CYS), and ultimate compressive strength (UCS) of 331.4 ± 2.1 MPa, 336.9 ± 3.8 MPa, 16.1 ± 2.3%, 270.4 ± 1.6 MPa and 574.5 ± 12.4 MPa, respectively

Influence of Cu/Mg ratio and content on heat-resistance of Al–Cu–Mg alloys

Heat-resistant Al alloys used in such as aerospace, transportation fields are attracting more and more attention in recent years. Within Al alloy families, Al–Cu–Mg alloys have shown promising heat resistance properties. This work aims to investigate the influence of Cu/Mg ratio and content on the heat resistance of Al–Cu–Mg alloys, based on alloys of Al–4.5Cu–2.5 Mg (referred to as alloy A), Al–4.0Cu–2.2 Mg (alloy B) and Al–4.5Cu–1.6 Mg (alloy C). The alloys A and B possessed approximate Cu/Mg ratio, and they also exhibited nearly identical hardness retention rate during exposure at 200 °C. After 200 h, the rate is ∼75 %, though alloy A showed higher hardness (105 vs. 102 HBW) due to higher Cu, Mg content. In contrast, alloy C with a higher Cu/Mg ratio was less heat-resistant, with hardness retention rate of ∼70.5 % after 200 h exposure. Nano-sized S′(Al2CuMg) precipitate was main strengthening phase for the three alloys. Also, micron and submicron Al2CuMg particles could be formed with increase of Cu and Mg contents, which contributed a lot to yield strength for T6 heat-treated alloys, but slight contribution after exposure at 200 °C for 200 h. The degradation of mechanical properties during heat exposure can be attributed to the transformation and coarsening of S′ precipitates. In alloys with lower Cu/Mg ratio, there was excess Mg dissolved in Al matrix, which reduced Cu solubility in α-Al, and then slowed diffusion flux of Cu element, thus inhibited coarsening of Al2CuMg phase