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PURPOSE ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079 ), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor ( EGFR) mutation-positive resected stage II-IIIA (N1-N2) non–small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results. METHODS From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data. RESULTS Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% ( P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP ( P = .316) and 5y DFS rates were 22. 6% and 23.2% ( P = .928), respectively. CONCLUSION Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.

With the rapid development of power-electronics-enabled power systems, the new converter-based generators are deteriorating the small-signal stability of the power system. Although the numerical differentiation method has been widely used for approximately calculating the eigenvalue sensitivities, its accuracy has not been carefully investigated. Besides, the ele-ment-based formulation for computing closed-form eigenvalue sensitivities has not been used in any commercial software due to the average efficiency, complicated formulation, and error-prone characteristics. Based on the matrix calculus, this paper proposes an easily manipulated formulation of the closed-form eigenvalue sensitivities with respect to the power generation. The distinguishing feature of the formulation is that all the formulas consist of vector and matrix operations, which can be performed by developed numerical algorithms to take full advantages of architectural features of the modern computer. The tests on WSCC 3-machine 9-bus system, New England to-ma-chine 39-bus system, and IEEE 54-machine 118-bus system show that the accuracy of the proposed formulation is superior to the numerical differentiation method and the efficiency is also greatly improved compared to the element-based closed-form formulation. The proposed formulation will be helpful to perform a more accurate and faster stability analysis of a power grid with converter-based devices.

Background The purpose of this study was to analyze the clinical characteristics and prognostic survival of patients with neuroendocrine tumors of the thymus (NETTs), and to develop and validate a nomogram model for predicting the prognosis of patients. Methods We conducted a retrospective analysis of patients with neuroendocrine tumors of the thymus in the Surveillance, Epidemiology, and End Results (SEER) database in the United States between 1988 and 2016. Cox scale risk regression analysis, the Kaplan‐Meier method and log‐rank test were used to carry out the significance test to determine the independent prognostic factors, from which a nomogram for NETTs was established. C‐index and calibration curve were used to evaluate the prediction accuracy of the model. External validation of the nomogram was performed using data from our center. Results A total of 254 patients with NETTs were collected in the SEER database. In the multivariable analysis, T stage, tumor grade, surgery, and chemotherapy were found to be independent factors affecting the prognosis of patients (all P, The neuroendocrine tumors of the thymus is a rare invasive tumor with a poor prognosis, and visualization models are needed to provide patients with appropriate individualized treatment strategies.In this study, we established and validated a new Nomogram model to predict the survival of patients with neuroendocrine tumors of the thymus.

Cr2+:ZnSe materials have attracted much attention as candidates for mid-infrared laser source either in the form of polycrystalline powders, or bulk ceramics, single crystals and nano-materials. In this work, a novel method for synthesizing Cr2+:ZnSe polycrystalline by direct reaction of Zn–Cr alloy and element Se (DRAE) was proposed. The zinc alloy containing 0.1 at% Cr was prepared by dissolving Cr in zinc liquid in a closed quartz ampoule. X-ray diffraction (XRD) results showed that the synthesized Cr2+:ZnSe polycrystalline was with a Zinc-blend structure. X-ray photoelectron spectroscopy (XPS) spectra showed that there was no un-reacted element of Zn, or Se. Cr2+ ions successfully and uniformly doped into ZnSe crystal lattice, which is confirmed by the diffuse reflectance spectrum, Raman spectrum and mid-infrared photoluminescence spectra. Furthermore, the sample showed excellent mid-infrared properties without luminescence quenching in the region 1800–3000 nm, and the decay-time was about 5 μs. The as-synthesized Cr2+:ZnSe polycrystalline meets the requirement for the preparation of mid-infrared ceramic or single crystals. These results indicate that the novel strategy of DRAE is valid for the synthesis of other transition metal doped ZnSe materials.

Background This study investigated the prognostic impact of (neo‐)adjuvant radiation therapies in early stage esophageal cancer. Methods A retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database was conducted from 2004 to 2016. Patients with pathologically staged T1‐4N0M0 esophageal cancer were divided into two treatment groups: (i) neoadjuvant radiotherapy followed by surgery; and (ii) upfront esophagectomy followed by adjuvant radiotherapy. Propensity scored match and Cox proportional hazards model were used to identify covariates associated with overall survival and cancer‐specific survival. Results There were 821 patients selected, of whom 588 (71.6%) received neoadjuvant radiotherapy and 233 (28.4%) received adjuvant radiotherapy. For the entire cohort, neoadjuvant radiotherapy was associated with a significantly benefit in five‐year survival outcomes compared with adjuvant radiotherapy (P, In this population‐based study, we indicated that the addition of neoadjuvant RT for pT3‐4N0 diseases followed by esophagectomy was associated with improved cancer‐specific survival in patients with tumor lengths 5 cm and squamous cell carcinoma. The identification of higher‐risk patients for neoadjuvant therapy would be expected to yield better results than taking a uniform approach to this population, to avoid unnecessary and possibly harmful treatment in node‐negative diseases.

Background The impact of neoadjuvant chemoradiotherapy (nCRT) on early stage esophageal cancer is unknown. Here, we compared the outcomes after esophagectomy alone or nCRT plus surgery for clinically staged node‐negative esophageal cancer. Methods We searched the Surveillance, Epidemiology, and End Results database for patients with clinically node‐negative (cN0) esophageal cancer from 2004 to 2016 who underwent surgery alone or nCRT plus surgery. Propensity score matching and Cox regression analysis were used to identify covariates associated with overall survival and cancer‐specific survival. Results A total of 1587 patients were retrospectively identified, of whom 49.8% (n = 791) received nCRT and 80.2% (n = 1273) were truly node‐negative diseases. For the entire cohort, surgery alone was associated with a statistically significant but modest absolute increase in survival outcomes (P, This study focuses on the use of neoadjuvant chemoradiotherapy to esophageal carcinoma patients with clinically staged node‐negative (cN0) status. Finally, compared with surgery alone, cN0 esophageal cancer with falsely node‐negative (pN+) or localized truly node‐negative (pT3‐4N0) gain a significant survival benefit from neoadjuvant chemoradiation. However, neoadjuvant chemoradiation plus surgery was associated with decreased survival for early‐staged true node‐negative (pT1‐2N0) patients. Despite the inherent limitations, this population‐based study allows for a robust analysis of patients with cN0 esophageal carcinoma and the benefits of neoadjuvant chemoradiation when stratified by nodal and tumor status, and this finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN0 disease.

The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II–IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy., Adjuvant gefitinib improves outcomes in non-small cell lung cancer (NSCLC) patients compared to chemotherapy, but not in all cases. Here, the authors find genomic biomarkers of response to gefitinib in NSCLC patients from the ADJUVANT trial, and propose a score to stratify them by potential benefit from the treatment.

Iron-doped ZnTe (Fe2+:ZnTe) crystal can be used as promising gain media for mid-infrared laser. However, there are few studies in the optical properties of Fe2+:ZnTe crystal from mid-infrared to ultraviolet. In this work, large size Fe2+:ZnTe bulk crystal (the concentration of Fe ions is about 1019 cm−3) with a dimension of Φ30 mm × 50 mm was grown by the temperature gradient solution growth (TGSG) method. The luminescence and optical properties of Fe2+:ZnTe from terahertz wave to ultraviolet wave have been studied. The evaluated refractive index of Fe2+:ZnTe crystal is approximately 2.5–3.0 at the frequency range of 0.5–2.0 THz range. And its band gap is estimated to be about 2.24 eV. It is noted that strong absorptions at the wavelength of 2.8–4.7 μm and 705 nm were observed. Based on the experimental results, the energetic positions of Fe2+ center such as 3T1, 5T2, 5E in ZnTe crystal were proposed.

ZnTe crystal is a promising electro-optical crystal materials applied for THz generation and detection. However, there is still a big challenge to obtain large sized high quality ZnTe crystals. In this work, large sized ZnTe bulk crystals with Φ30 mm × 150 mm were grown by the traveling solvent melting zone (TSMZ) method. With the characterization of the optical and electrical properties of as-grown ZnTe crystals, the band gap (2.22 eV), high IR transmittance (around 60%), high resistivity (3.5 × 103 Ω·cm), low density (1.3 × 105 cm−2) and small sizes (3 μm - 5 μm) of Te inclusions in ZnTe crystals, low etch pit densities (1.5 × 105 cm−2), high peak intensity to FWHM ratio (2.5 × 104) of the LO peak in the Raman spectra were obtained. Furthermore, the THz transmission spectra was measured and the maximum transmittance is more than 40% at the range of 0.3 - 3 THz. Based on these results, high quality and large aspect ratio ZnTe bulk crystals can be obtained by the TSMZ technique. Our work has greatly facilitated the application of ZnTe crystals in THz device.

BackgroundGastric cancer is one of the most common malignancies worldwide. Although the diagnosis and treatment of this disease have substantially improved in recent years, the five-year survival rate of gastric cancer is still low due to local recurrence and distant metastasis. An in-depth study of the molecular pathogenesis of gastric cancer and related prognostic markers will help improve the quality of life and prognosis of patients with this disease. The purpose of this study was to identify and verify key SNPs in genes with prognostic value for gastric cancer.MethodsSNP-related data from gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA) database, and the functions and pathways of the mutated genes were analyzed using DAVID software. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized by Cytoscape software, and molecular complex detection (MCODE) was used to screen the PPI network to extract important mutated genes. Ten hub genes were identified using cytoHubba, and the expression levels and the prognostic value of the central genes were determined by UALCAN and Kaplan-Meier Plotter. Finally, quantitative PCR and Western blotting were used to verify the expression of the hub genes in gastric cancer cells.ResultsFrom the database, 945 genes with mutations in more than 25 samples were identified. The PPI network had 360 nodes and 1616 edges. Finally, cytoHubba identified six key genes (TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4), and their expression levels were closely related to the survival rate of gastric cancer patients.ConclusionOur results indicate that TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4 may be key genes for the development and prognosis of gastric cancer. Our research provides an important bioinformatics foundation and related theoretical foundation for further exploring the molecular pathogenesis of gastric cancer and evaluating the prognosis of patients.

Background This study aimed to identify variables associated with anastomotic leakage after esophagectomy and established a tool for anastomotic leakage prediction. Methods Twenty-six preoperative and postoperative variables were retrospectively collected from esophageal cancer patients who were treated with radical esophagectomy from January 2018 to June 2020 in the Affiliated Hospital of Qingdao University. SPSS Version 23.0 and Empower Stats software were used for establishing a nomogram after screening relevant variables by univariate and multivariate Logistic regression analyses. The established nomogram was identified by depicting the receiver operating characteristic (ROC) curves and calibration curve, which was verified by 1,000 bootstrap resamples method. Results A total of 604 eligible esophageal cancer patients were included, of which 51 (8.4%) patients had anastomotic leakage. Multivariate Logistic regression analysis showed that smoking, anastomotic location, anastomotic technique, prognostic nutritional index (PNI) and ASA score were independent risks of anastomotic leakage. The area under curve (AUC) of ROC in the established nomogram was 0.764 (95% CI, 0.69-0.83). The internal validation confirmed that the nomogram had a great discrimination ability (AUC =0.766). Depicted calibration curve demonstrated a well-fitted prediction and observation probability. In addition, the decision curve analysis concluded that the newly established nomogram is significant for clinical decision-making. Conclusions This nomogram provided the individual prediction of anastomotic leakage for esophageal cancer patients after surgery, which might benefit treatment results for patients and clinicians, as well as pre-and postoperative intervention strategy-making.

Locally advanced thymic tumor usually invades adjacent great vessels, while the optimal treatment strategy for vessels resection and prosthetic replacement is still in controversial. We hereby present our series of patients undergoing autologous pericardial angioplasty for thymic malignancies. For invasive thymic tumors involving the superior vena cava (SVC), the replacement vessel was prepared by autologous pericardium and placed between the right atrium and distal left innominate vein stump to establish a SVC bypass. Then, the distal right innominate vein and proximal SVC were blocked, and the thymic tumor and involved vessel were completely resected, followed by SVC reconstruction using pericardium. We retrospectively analyzed the clinical characteristics and short-term outcomes of six related patients with autologous pericardial angioplasty. Due to the homologous advantages of autologous pericardial transplantation, those patients didn’t need to receive anticoagulant therapy during the perioperative period, so as to avoid the occurrence of hemorrhage, embolism and other graft-related complications. There were no postoperative long-term thoracic drainage (>7 days), anastomotic bleeding, reconstructed vascular stenosis, embolism or even secondary thoracotomy and other related complications occurred in this case series. The application of autologous pericardium for the replacement of mediastinal great vessels in the surgery of locally advanced thymoma is a safe and effective technique. Compared with former artificial materials, such as polytetrafluoroethylene synthetic prosthesis, autologous pericardial transplantation avoids the occurrence of high risk graft-related complications such as postoperative hemorrhage and vascular stenosis, and its clinical application prospect is worth expecting.

Histologically node negative esophageal squamous cell carcinoma (pN0 ESCC) after radical resection still carries a significant risk of recurrence, especially in high-risk patients. Our previous study showed that the risk of recurrence was associated with tumor location and cell differentiation, as well as the presence of lymphovascular invasion. Most recurrence occurs within two years after surgery. There is still a lack of knowledge on the risks or potential benefits of postoperative adjuvant therapies for high-risk pN0 ESCC patients. This study was designed to evaluate the efficacy and toxicity of adjuvant therapies after radical surgery in high-risk patients with pN0 ESCC. This study is a multicenter, prospective, controlled randomized trial, which will compare the differences between either adjuvant chemotherapy or adjuvant radiotherapy and surgery alone for high-risk pN0 ESCC. Patients in group A will receive three cycles of adjuvant chemotherapy with paclitaxel and cisplatin, patients in group B will receive adjuvant radiotherapy with intensity-modulated radiation of 50 Gy, and patients in group C (the control) will receive surgery alone. The primary endpoint is three-year disease-free survival. Secondary endpoints include toxicity of adjuvant therapies and five-year overall survival. One hundred and sixty-two patients in each group are required and a total of 486 patients will finally be enrolled into the study. This will be the first randomized trial to investigate the necessity or potential benefit of postoperative adjuvant therapies for high-risk pN0 ESCC patients.

OBJECTIVES Video-assisted thoracoscopic surgery (VATS) has been increasingly used in the management of thymic epithelial tumours. However, its oncological efficacy remains to be proved. The purpose of this study is to compare the oncological outcomes following thoracoscopic versus open surgery in the case-matched groups of patients with early-stage thymic tumours from the Chinese Alliance for Research in Thymomas (ChART) retrospective database. METHODS Between 1994 and 2012, a total of 1087 patients who underwent surgery for UICC (Union for International Cancer Control) pathological Stage I tumours from the ChART retrospective database were recruited for this study. A propensity score-matched analysis was used to compare the long-term outcomes in patients who received VATS or open surgery. RESULTS VATS resection was performed in 271 patients (24.9%) and open surgery in 816 patients (75.1%). Before propensity score matching, the VATS group had a smaller tumour size (P = 0.002), lower grade histology (P = 0.034), lower T stage (P < 0.001) and less adjuvant therapy (P < 0.001). Propensity score matching by gender, myasthenia gravis, tumour size, histological classification, pathological T stage, extent of thymectomy, adjuvant radiotherapy and adjuvant chemotherapy identified 110 patients in each group. After matching, there was no significant difference in patient demographics, tumour characteristics or adjuvant therapy. All matched patients had R0 resection. Overall survival, disease-free survival and cumulative incidence of recurrence were only predicted by WHO histology, but not by surgical approach, in both univariable and multivariable analyses. There was no significant difference in the overall survival (85.7% vs 93.1%, P = 0.539), disease-free survival (92.5% vs 91.9%, P = 0.773), cumulative incidence of recurrence (7.1% vs 5.8%, P = 0.522) and improvement rate of myasthenia gravis (83.3% vs 88.2%, P = 0.589) between the 2 groups. CONCLUSIONS This propensity score-matched study suggests that VATS and open surgeries are associated with similar oncological outcomes for Stage I thymic epithelial tumours. Minimally invasive surgery might be an acceptable surgical approach for early-stage thymic malignancies.

In the recent two decades, Cr2+:ZnSe crystals have been widely used as a gain media for 2∼3 μm mid-infrared lasers. However, it still remains a huge challenge for researchers to meet more and more requirements on the crystals with high qualities and large sizes. In this work, one Cr2+:ZnSe single crystal with a diameter of about 15 mm was successfully grown by chemical vapor transporting (CVT) with NH4Cl in a closed quartz ampoule without any seed. The transmission of as-grown crystal is up to 70% in the UV-VIS-NIR region and is with an intense characteristic absorption of Cr2+ near 1770 nm. The X-ray photoelectron spectroscopy (XPS) shows that the incorporation of chlorine anions does not significantly affect the valence distribution of components in the crystal. The mid-infrared photoluminescence spectra show a strong and broad emission band centered at 2400 nm with a width of 600 nm under the 1770 nm laser excitation at room temperature. The calculated cross sections of absorption and emission were 1.31×10−18 and 1.4×10−18 cm2, respectively. The measured photoluminescence decay time was about 6.9 μs at room temperature. It is confirmed that the method of CVT with NH4Cl is suitable for the growth of Cr2+:ZnSe single crystals, which are expected to have a promising prospect in mid-infrared laser applications in further.

To compare the predictive effect of the Masaoka-Koga staging system and the International Association for the Study of Lung Cancer (IASLC)/the International Thymic Malignancies Interest Group (ITMIG) proposal for the new TNM staging on prognosis of thymic malignancies using the Chinese Alliance for Research in Thymomas (ChART) retrospective database.From 1992 to 2012, 2,370 patients in ChART database were retrospectively reviewed. Of these, 1,198 patients with complete information on TNM stage, Masaoka-Koga stage, and survival were used for analysis. Cumulative incidence of recurrence (CIR) was assessed in R0 patients. Overall survival (OS) was evaluated both in an R0 resected cohort, as well as in all patients (any R status). CIR and OS were first analyzed according to the Masaoka-Koga staging system. Then, they were compared using the new TNM staging proposal.Based on Masaoka-Koga staging system, significant difference was detected in CIR among all stages. However, no survival difference was revealed between stage I and II, or between stage II and III. Stage IV carried the highest risk of recurrence and worst survival. According to the new TNM staging proposal, CIR in T1a was significantly lower comparing to all other T categories (P0.05) and there is a significant difference in OS between T1a and T1b (P=0.004). T4 had the worst OS comparing to all other T categories. CIR and OS were significantly worse in N (+) than in N0 patients. Significant difference in CIR and OS was detected between M0 and M1b, but not between M0 and M1a. OS was almost always statistically different when comparison was made between stages I-IIIa and stages IIIb-IVb. However, no statistical difference could be detected among stages IIIb to IVb.Compared with Masaoka-Koga staging, the IASLC/ITMIG TNM staging proposal not only describes the extent of tumor invasion but also provides information on lymphatic involvement and tumor dissemination. Further study using prospectively recorded information on the proposed TNM categories would be helpful to better grouping thymic tumors for predicting prognosis and guiding clinical management.

Thymic tumors are relatively rare malignancies comparing to other solid tumors in the chest (1). Its incidence is estimated to be at 3.93 per 1,000,000, which is about 1/00 of lung cancer and 1/25 of esophageal cancer in China. And it appears to be higher than that reported from North America, which is only 2.14 per 1,000,000 according to the SEER database. However, in the SEER database, the incidence rate was much higher in Asians (3.74 per 1,000,000) than in Caucasians (1.89 per 1,000,000) and close to the data from China. This implicates that there might be some ethnical and generic difference in thymic tumors. In the meantime, both these two registrations record only ‘malignant tumors’ that are clinically advanced diseases. A large part of early stage, low grade lesions are considered ‘benign tumors’ and thus, not registered. Therefore, the actual incidence of thymic tumors is much under-estimated. With the increasing use of screening for other malignancies such as lung cancer, it can be expected that more early stage thymic tumors would be discovered.

Objective: Fatty acid desaturase 1 is a member of the fatty acid desaturase, which is related to a number of diseases. However, its role in cancers remains unclear. This study was to explore the clinical importance of FADS1 expression in non-small-cell lung cancer (NSCLC). Materials and Methods: Immunochemistry was used to evaluate FADS1 expressions in 216 paraffin-embedded specimens. The expression of FADS1 was divided into high and low groups. The clinical and prognostic significance of FADS1 expression was analyzed statistically by Kaplan-Meier estimate and Cox regression model. Results: FADS1 overexpressed in normal bronchial mucosa compared with non-small-cell lung cancer. Reduced FADS1 expression was associated with tumor size (P=0.023) and histological grade (P

Slug, a member of the Snail family of transcriptional factors, is a newly identified suppressive transcriptional factor of E-cadherin. The present study investigated the expression pattern of Slug in thymomas to evaluate its clinical significance. Immunohistochemistry was used to investigate the expression pattern of the Slug protein in archived tissue sections from 100 thymoma and 60 histologically normal thymus tissue samples. The associations between Slug expression and clinicopathological factors, such as prognosis, were analyzed. Positive expression of Slug was detected in a greater proportion of thymoma samples [51/100 (51%) patients, P

Background: Immunotherapy has played an increasingly important role in the treatment of non-small-cell lung cancer (NSCLC) and it was approved for the first-line treatment of advanced lung cancer. PD-L1 expression and TMB are two important immunotherapy biomarkers, however, the relationship between PD-L1 expression, TMB and clinical features is still unclear. Methods: A total of 205 Chinese NSCLC patients (pts) including 120 males and 85 females with a median age of 61.5 years (range 31-84) were enrolled. Tumor stage was evaluated according to the 8th edition of the AJCC/UICC TNM staging system for NSCLC. FFPE tumor and matched blood samples were collected for NGS based 450[[Unsupported Character - Codename ­]]gene panel assay. TMB was assessed by standard NGS algorithms. TMB data (median: 5.4 muts/Mb, range 0.8-68.9 muts/Mb) from 206 lesions were provided for analysis. 172, 16 and 18 lesions tissues were analyzed for PD[[Unsupported Character - Codename ­]]L1 expression by IHC with 22C3, 28-8 and ZR3 antibodies, respectively. Results: According to TNM staging system, pts were divided into stage I (44 pts), stage II (20 pts), stage III (40 pts) and stage IV (101 pts). The pathological types of pts are adenocarcinoma (69.4%), squamous cell carcinoma (18.4%) and other types (12.1%). 34.5% of lesions were positive for PD-L1 expression (TPS≥1%), including 25.7% PD-L1(TPS≥10%) and 16.5% PD-L1(TPS≥50%) respectively. Significant differences between males and females were observed in PD-L1 expression (TPS≥1%: 40.8% vs. 25.6%, p Conclusion: In this study, we found the most commonly used two biomarkers for immune checkpoint inhibitors, PD-L1 expression and TMB, may be correlated with gender, stage and pathological type of NSCLC patients. There is also a weak correlation between these two biomarkers. Exploring the relationship between immune biomarkers and clinical features may better guide in screening more suitable patients for immune checkpoint blockade. Citation Format: Yang Yu, Xinglong Fan, Yucheng Wei, Zimin Liu, Zuping Lian, Hongxia Han, Ming Yao, Kai Wang. Correlation analysis between PD-L1 expression, TMB and clinical characteristics in Chinese non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4056.

In this paper we establish the existence and multiplicity of solutions for a class of partially superquadratic elliptic systems by using the Morse theory.

OBJECTIVES Lymphatic involvement is believed to be relatively rare in thymic epithelial tumours. The incidence and prognostic significance of nodal metastases are still unclear. The goal of this study was to define the incidence and prognostic relevance of nodal metastasis in patients with thymic epithelial tumours, using a nationwide retrospective database of the Chinese Alliance for Research in Thymomas. METHODS Patients who underwent upfront surgical resection without preoperative therapy were enrolled for the study. The International Thymic Malignancies Interest Group proposal of a new staging system for thymic epithelial tumours was used to redefine the pathological stage. The incidence of nodal metastasis and its relationship with clinicopathological characteristics and its impact on survival were examined accordingly. RESULTS A total of 1617 patients were enrolled in this study. Lymph node metastasis was identified in 35 patients (2.2%). No nodal involvement was found in type A, AB or B1 thymomas. The incidence of nodal metastasis in thymoma (B2/B3) and thymic carcinoma was 1.3% and 7.9%, respectively, and it was most commonly seen in patients with neuroendocrine thymic tumours (16.7%, P

To study the role of postoperative chemotherapy and its prognostic effect in Masaoka-Koga stage III and IV thymic tumors.Between 1994 and 2012, 1,700 patients with thymic tumors who underwent surgery without neoadjuvant therapy were enrolled for the study. Among them, 665 patients in Masaoka-Koga stage III and IV were further analyzed to evaluate the clinical value of postoperative chemotherapy. The Kaplan-Meier method was used to obtain the survival curve of the patients divided into different subgroups, and the Cox regression analysis was used to make multivariate analysis on the factors affecting prognosis. A Propensity-Matched Study was used to evaluate the clinical value of chemotherapy.Two-hundred and twenty-one patients were treated with postoperative chemotherapy, while the rest 444 cases were not. The two groups showed significant differences (P0.05) regarding the incidence of myasthenia gravis, World Health Organization (WHO) histological subtypes, pathological staging, resection status and the use of postoperative radiotherapy. WHO type C tumors, incomplete resection, and postoperative radiotherapy were significantly related to increased recurrence and worse survival (P0.05). Five-year and 10-year disease free survivals (DFS) and recurrence rates in patients who underwent surgery followed by postoperative chemotherapy were 51% and 30%, 46% and 68%, comparing with 73% and 58%, 26% and 40% in patients who had no adjuvant chemotherapy after surgery (P=0.001, P=0.001, respectively). In propensity-matched study, 158 pairs of patients with or without postoperative chemotherapy (316 patients in total) were selected and compared accordingly. Similar 5-year survival rates were detected between the two groups (P=0.332).Pathologically higher grade histology, incomplete resection, and postoperative radiotherapy were found to be associated with worse outcomes in advanced stage thymic tumors. At present, there is no evidence to show that postoperative chemotherapy may help improve prognosis in patients with Masaoka-Koga stage III and IV thymic tumors.

The present study investigated the role of miR-141 regulation of eukaryotic initiation factor-4E (EIF4E) expression in docetaxel chemoresistance of human non-small cell lung cancer (NSCLC). The expression of miR-141 in docetaxel chemoresistant patients with NSCLCs was markedly higher than those of non-docetaxel chemoresistant patients with NSCLCs. The expression of EIF4E in docetaxel chemoresistant patients with NSCLCs was markedly lower than those of non-docetaxel chemoresistant patients with NSCLCs. Downregulation of miR-141 suppressed cell proliferation, induced cell death and increased caspase-3 activity in H1299 or H2009/docetaxel cells. Downregulation of miR-141 also increased the protein expression of EIF4E, VEGF, c-Myc and Bax in H1299 or H2009/docetaxel cells. Conversely, up-regulation of miR-141 promoted cell proliferation, inhibited cell death and caspase-3 activity in H1299 or H2009/docetaxel cell. Upregulation of miR-141 suppressed EIF4E, VEGF, c-Myc protein expression and inhibited Bax in H1299 or H2009/docetaxel cells. Thus, the present study is the first to show the induction of miR-141/EIF4E expression in an acquired model of docetaxel chemoresistant patients with NSCLCs. This serves as a mechanism of acquired docetaxel chemoresistant patients with NSCLCs, possibly through direct interactions with VEGF, c-Myc, and Bax, therefore presenting a potential therapeutic target for the treatment of docetaxel chemoresistant patients with NSCLCs.

BACKGROUND To evaluate the surgical outcomes of tumor resection with or without total thymectomy for thymic epithelial tumors (TETs) using the Chinese Alliance for Research in Thymomas (ChART) retrospective database. METHODS Patients without preoperative therapy, who underwent surgery for early-stage (Masaoka-Koga stage I and II) tumors, were enrolled for the study. They were divided into thymectomy and thymomectomy groups according to the resection extent of the thymus. Demographic and surgical outcomes were compared between the two patients groups. RESULTS A total of 1,047 patients were enrolled, with 796 cases in the thymectomy group and 251 cases in the thymomectomy group. Improvement rate of myasthenia gravis (MG) was higher after thymectomy than after thymomectomy (91.6% vs. 50.0%, P

BACKGROUND Postoperative radiotherapy (PORT) for thymic tumor is still controversial. The object of the study is to evaluate the role of PORT for stage I to III thymic tumors. METHODS The Chinese Alliance for Research in Thymomas (ChART) was searched for patients with stage I to III thymic tumors who underwent surgical resection without neoajuvant therapy between 1994 and 2012. Univariate and multivariate survival analyses were performed. Cox proportional hazard model was used to determine the hazard ratio for death. RESULT From the ChART database, 1,546 stage I to III patients were identified. Among these patients, 649 (41.98%) received PORT. PORT was associated with gender, histological type (World Health Organization, WHO), thymectomy extent, resection status, Masaoka-Koga stage and adjuvant chemotherapy. The 5-year and 10-year overall survival (OS) rates and disease-free survival (DFS) rates for patients underwent surgery followed by PORT were 90% and 80%, 81% and 63%, comparing with 96% and 95%, 92% and 90% for patients underwent surgery alone (P=0.001, P

To study the incidence and pattern of lymph node metastases in thymic malignancies.This multicenter prospective observational trial with intentional lymph node dissection was carried out by the Chinese Alliance for Research in Thymomas (ChART). Data on patients with thymic tumors without pretreatment were collected prospectively. Results from this prospective study were then compared with those from a previously reported ChART retrospective study.Among 275 patients, metastasis was detected in 41 nodes (3.04%) in 15 patients (5.5%). The rate of lymph node metastasis was 2.1% (5/238) in patients with thymomas, 25% (6/24) in those with thymic carcinomas, and 50% (4/8) in those with neuroendocrine tumors (P .001). The rate of lymph node metastasis in category T1 to T4 tumors was 2.7% (6/222) in T1, 7.7% (1/13) in T2, 18.4% (7/38) in T3, and 50% (1/2) in T4 (P .001). Nodal involvement was significantly higher compared with the ChART retrospective study (5.5% vs 2.2%; P = .002), although the 2 groups were comparable in terms of tumor stage and histology. Metastasis was found in N1 nodes in 13 patients (86.7%) and in N2 nodes in 8 patients (53.3%); 6 patients (40%) had simultaneous N1/N2 diseases and 6 (40%) had multistation involvement. Based on World Health Organization histological classification and Union for International Cancer Control T category, patients were divided into a low-risk group (1/192; 0.5%) with T1-2 and type A-B2 diseases and a high-risk group (14/83; 16.9%) of category T3 and above or histology B3 and above tumors for nodal metastasis (P .001). On multivariate analysis, type B3/thymic carcinoma/neuroendocrine tumors, category T3 or above, and N2 dissection predicted a greater likelihood of finding nodal metastasis.Lymph node involvement in thymic malignancies is more common than previously recognized, especially in tumors with aggressive histology and advanced T category. Intentional lymph node dissection increases the detection of nodal involvement and improves accuracy of staging. In selected high-risk patients, systemic dissection of both N1and N2 nodes should be considered for accurate tumor staging.

In this paper, we show the existence of nontrivial critical point for a class of strongly indefinite asymptotically quadratic functional without compactness, by using the technique of penalized functionals and an infinite dimensional Morse theory developed by Kryszewski and Szulkin. Two applications are given to Hamiltonian systems and elliptic systems.

BackgroundThe response to cytotoxic chemotherapy varies greatly in patients with advanced non-small cell lung cancer (NSCLC), and molecular markers may be useful in determining a preferable therapeutic approach for individual patients. This retrospective study was performed to evaluate the predictive value of ribonucleotide reductase regulatory subunit M1 (RRM1) on the therapeutic efficacy of platinum-based chemotherapy in patients with NSCLC.MethodsPatients with advanced NSCLC who received platinum doublet chemotherapy (n = 229) were included in this retrospective study, and their clinical outcomes were analyzed according to RRM1 expression.ResultsIn patients receiving gemcitabine-based therapy, the disease control rate (DCR) and progression-free survival (PFS) of patients with RRM1-negative tumors were significantly higher than in patients with RRMI-positive tumors (P = 0.041 and P = 0.01, respectively), and multivariate analysis showed that RRM1 expression was an independent prognostic factor (P = 0.013). No similar differences were found in patients receiving docetaxel- or vinorelbine-based therapy. In RRM1-positive patients, the DCRs for docetaxel and vinorelbine were higher than for gemcitabine (P = 0.047 and P = 0.047, respectively), and docetaxel and vinorelbine showed a longer PFS than gemcitabine-based chemotherapy (P = 0.012 and P = 0.007). No similar differences were found among patients with RRM1-negative tumors.ConclusionsNegative RRM1 expression in advanced NSCLC is associated with a higher response rate to gemcitabine-based chemotherapy. In patients with RRM1-positive tumors, docetaxel and vinorelbine showed a higher therapeutic efficacy than gemcitabine-based therapy. Additional prospective studies are needed to investigate the predictive meaning of RRM1 in the response to chemotherapy.

OBJECTIVE: To evaluate whether external suction is more advantageous than water seal in patients undergoing selective pulmonary resection (SPR) for lung neoplasm. SUMMARY OF BACKGROUND DATA: Whether external suction should be routinely applied in postoperative chest drainage is still unclear, particularly for lung neoplasm patients. To most surgeons, the decision is based on their clinical experience. METHODS: Randomized control trials were selected. The participants were patients undergoing SPR with lung neoplasm. Lung volume reduction surgery and pneumothorax were excluded. Suction versus non-suction for the intervention. The primary outcome was the incidence of persistent air leak (PAL). The definition of PAL was air leak for more than 3-7 days. The secondary outcomes included air leak duration, time of drainage, postoperative hospital stay and the incidence of postoperative pneumothorax. Studies were identified from literature collections through screening. Bias was analyzed and meta-analysis was used. RESULTS: From the 1824 potentially relevant trials, 6 randomized control trials involving 676 patients were included. There was no difference between external suction and water seal in decreasing the incidence of PAL [95% confidence interval (CI) 0.81-2.16; z = 1.10; P = 0.27]. Regarding secondary outcomes, there were no differences in time of drainage (95% CI-0.36-1.56, P = 0.22), postoperative hospital stay (95% CI -.31-.54, P = 0.87) or incidence of postoperative pneumothorax (95% CI 0.18-.02, P = 0.05) between external suction and water seal. CONCLUSIONS: For participants, no differences are identified in terms of PAL incidence, drainage time, length of postoperative hospital stay or incidence of postoperative pneumothorax between external suction and water seal. The bias analysis should be emphasized. To the limitations of the bias and methodological differences among the included studies, we have no recommendation on whether external suction should be routinely applied after lung neoplasm SPR. More high-quality randomized controlled trials are needed. SYSTEMATIC REVIEW REGISTRATION: None.