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Background: The objective of this study was to construct a risk classification system integrating cell-free Epstein-Barr virus (cfEBV) DNA with T- and N- categories for better prognostication in nasopharyngeal carcinoma (NPC). Methods: Clinical records of 10,149 biopsy-proven, non-metastatic NPC were identified from two cancer centers; this comprised a training ( N = 9,259) and two validation cohorts ( N = 890; including one randomized controlled phase 3 trial cohort). Adjusted hazard ratio (AHR) method using a two-tiered stratification by cfEBV DNA and TN-categories was applied to generate the risk model. Primary clinical endpoint was overall survival (OS). Performances of the models were compared against American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 8th edition TNM-stage classification and two published recursive partitioning analysis (RPA) models, and were validated in the validation cohorts. Results: We chose a cfEBV DNA cutoff of ⩾2,000 copies for optimal risk discretization of OS, disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the training cohort. AHR modeling method divided NPC into six risk groups with significantly disparate survival ( p low); AHR2B, T1N1/T2-3N0 cfEBV DNA ⩾ 2,000 (EBVhigh) and T1-2N2/T2-3N1 EBVlow; AHR3, T1-2N2/T2-3N1 EBVhigh and T3N2/T4N0 EBVlow; AHR4, T3N2/T4 N0-1 EBVhigh and T1-3N3/T4N1-3 EBVlow; AHR5, T1-3N3/T4 N2-3 EBVhigh. Our AHR model outperformed the published RPA models and TNM stage with better hazard consistency (1.35 versus 3.98–12.67), hazard discrimination (5.29 versus 6.69–13.35), explained variation (0.248 versus 0.164–0.225), balance (0.385 versus 0.438–0.749) and C-index (0.707 versus 0.662–0.700). In addition, our AHR model was superior to the TNM stage for risk stratification of OS in two validation cohorts ( p Conclusion: Herein, we developed and validated a risk classification system that combines the AJCC/UICC 8th edition TN-stage classification and cfEBV DNA for non-metastatic NPC. Our new clinicomolecular model provides improved OS prediction over the current staging system.

IMPORTANCE: Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). OBJECTIVE: To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes

Background The authors aimed to investigate the efficacy and safety of apatinib in patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma (NPC). Methods A multicenter, single-arm, prospective phase 2 study was conducted on patients (18-70 years of age) with metastatic or recurrent NPC who had failed chemotherapy. Patients with recurrent disease involving vascular structure invasion were excluded. All enrolled patients received apatinib (500 mg daily) in continuous 4-week cycles until disease progression or development of unacceptable toxicity. The primary end point of this study was objective response rate (ORR), and the secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. This study was registered with ClinicalTrials.gov (NCT03130270). Results Between January 2017 and June 2018, 33 patients were enrolled. At the end of the data collection (May 20, 2020), the 33 patients had completed a total of 261.2 cycles of apatinib. Although 12 patients achieved a partial response, no patient achieved a complete response; thus, the ORR in the 33 patients was 36.4% (95% CI, 19.0%-53.7%). At the end of follow-up (median, 30 months; 95% CI, 24.9-35.1), median OS and median PFS were 16 months (95% CI, 14.6-17.4 months) and 5.0 months (95% CI, 3.6-6.4 months), respectively. The most common adverse events (grade 1/2) were hand-foot syndrome (18 [54.5%]), hypertension (14 [42.4%]), oral ulcer (8 [24.2%]), and proteinuria (4 [12.1%]). Two patients (1 with diabetes and 1 with hypertension) developed cerebral infarction. Grade 3/4 toxicities were uncommon. Conclusions Apatinib shows promising activity, with manageable toxicities, in patients with metastatic or locoregionally recurrent NPC. Further evaluation of apatinib in large-scale studies is warranted. Lay summary Clinical studies on vascular endothelial growth factor receptor (VEGFR)-targeted therapy for recurrent or metastatic nasopharyngeal carcinoma (NPC) are limited. A recent preclinical study that evaluated apatinib in models of NPC showed a high objective response rate and a favorable safety profile. Our data further confirmed good efficacy in patients with lung metastasis. Further studies of the efficacy and safety of apatinib combined with immune checkpoint inhibitors or chemotherapy in NPC is warranted.

The effects of the &gamma, &Prime, Ni3Nb phase on the mechanical properties of Inconel 718 superalloys, with standard heat treatment, hot isostatic pressing + solution treatment + aging, and hot isostatic pressing + direct aging, were characterized by morphological observation, X-ray diffraction, and tensile experiments. The results of the morphological observation revealed that many fine &gamma, precipitates of ~26.49 &plusmn, 1.82 nm in mean size were formed in all samples. However, the relatively coarser &gamma, precipitates formed in the grain boundaries were only observed in the sample treated with hot isostatic pressing + direct aging. The yield strengths of the hot isostatic pressing + direct aging sample at room temperature and at 650 &deg, C both exhibited the maximum values about 993 &plusmn, 5.7 and 811 &plusmn, 12.6 MPa, respectively. The &gamma, precipitate was considered to be the dominant strengthening phase in the sample according to the lattice misfits (&epsilon, ) of &gamma, /&gamma, The strengthening mechanism of the samples can be explained as the coherency strain strengthening of fine &gamma, precipitates. Moreover, due to the coarser &gamma, precipitates in the grain boundaries, dislocation-cut ordered particle strengthening also occurred in the sample after hot isostatic pressing + direct aging treatment.

BACKGROUND: To identify a radiomics signature to predict local recurrence in patients with non-metastatic T4 nasopharyngeal carcinoma (NPC). METHODS: A total of 737 patients from Sun Yat-sen University Cancer Center (training cohort: n = 360; internal validation cohort: n = 120) and Wuzhou Red Cross Hospital (external validation cohort: n = 257) underwent feature extraction from the largest axial area of the tumor on pretreatment magnetic resonance imaging scans. Feature selection was based on the prognostic performance and feature stability in the training cohort. Radscores were generated using the Cox proportional hazards regression model with the selected features in the training cohort and then validated in the internal and external validation cohorts. We also constructed a nomogram for predicting local recurrence-free survival (LRFS). FINDINGS: Eleven features were selected to construct the Radscore, which was significantly associated with LRFS. For the training, internal validation, and external validation cohorts, the Radscore (C-index: 0.741 vs. 0.753 vs. 0.730) outperformed clinical prognostic variables (C-index for primary gross tumor volume: 0.665 vs. 0.672 vs. 0.577; C-index for age: 0.571 vs. 0.629 vs. 0.605) in predicting LRFS. The generated radiomics nomogram, which integrated the Radscore and clinical variables, exhibited a satisfactory prediction performance (C-index: 0.810 vs. 0.807 vs. 0.753). The nomogram-defined high-risk group had a shorter LRFS than did the low-risk group (5-year LRFS: 73.6% vs. 95.3%, P

To process micro-structured surface optical elements without surface damage and subsurface damage in higher efficiency,a numerical control system for Atmospheric Pressure Plasma Processing(APPP) was established.The design of a system platform,APPP process characteristics and numerical control process were investigated.First,according to the principle and requirements of the APPP,the numerical control system composition was presented.Then,by taking the processing of fused silica by He/SF6/O2 as an example,the controllability of the process as well as multi-parameter process characteristics were explored using the plasma torch with a needle electrode,and the removal function under this condition was fitted.Finally,the entire realization process of the numerical control machining for the APPP was proposed.Experimental results indicate that the sine structure with an amplitude of 150 nm and wavelength of 6 mm can be processed on a flat fused silica surface by this system,which verifies the feasibility of the numerical control system and achieves the deterministic processing of complex optical surfaces.

This paper investigates Multirate sampled-data control system optimization design by considering robust stability of linear time-invariant uncertain systems described by affine parameter-dependent model. Extend Lyapunov upper bound robust stability test to develop a new condition for robust stability test of such system and give out a reliable numerical algorithm. For a given compensator F, define the maximum uncertainty set radius that the system is stable with as RSR (robust stability radius). Then convert the RSR calculation problem to a mathematical process of solving an equation by analyzing the robust stability test condition proposed. Solve the equation with Numerical Mathematical methods and get the analytical solution as RSR. At last we can define the RSR as a function of F and achieve F optimization design by a general optimization method to get the biggest RSR. With this F, the system can remain stable with the uncertain parameters vary set being the largest.