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Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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Signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： Si-yang Liu Song Dong xue-ning yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong Yan Li-Xu Yan Qiang Nie Hai-Yan Tu Bin-Chao Wang Jin-Ji yang Qing Zhou Hong-Rui Li Ke Liu Wendy Wu Si-yang Maggie Liu Wen-Zhao Zhong Yi-Long Wu Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis FuzhouChina Berry Oncology Corporation FuzhouChina Chinese Thoracic Oncology Group(CTONG) GuangzhouChina Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 expression.Eligible patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK alterations.Patients received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 expression.The primary endpoint was the major pathological response(MPR).Key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and EFS.Fifty-two patients were enrolled,with 46 undergoing surgeries.The MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,respectively.Thirteen(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant treatment.Patients with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–vs.ctDNA+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

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Erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage IIIA-N2 EGFR-mutant non-small-cell lung cancer:final overall survival analysis of the EMERGING-CTONG 1103 randomised phase II trial

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1310-1317页

作者： Wen-Zhao Zhong Hong-Hong Yan Ke-Neng Chen Chun Chen Chun-Dong Gu Jun Wang xue-ning yang Wei-Min Mao Qun Wang Gui-Bin Qiao Ying Cheng Lin Xu Chang-Li Wang Ming-Wei Chen Xiao-Zheng Kang Wan-Pu Yan Ri-Qiang Liao Jin-Ji yang Xu-Chao Zhang Si-yang Liu Qing Zhou Yi-Long Wu Guangdong Provincial People’s Hospital Guangdong Academy of Medical Sciences510080 GuangzhouChina Peking University Cancer Hospital and Institute 100142 BeijingChina Fujian Medical University Union Hospital 350001 FuzhouChina First Affiliated Hospital of Dalian Medical University 116011 DalianChina Peking University People’s Hospital 100044 BeijingChina Zhejiang Cancer Hospital 310022 HangzhouChina Zhongshan Hospital 200032 ShanghaiChina Guangzhou Liuhuaqiao Hospital 510000 GuangzhouChina Jilin Provincial Tumor Hospital 130012 ChangchunChina Jiangsu Cancer Institute and Hospital 210009 NanjingChina Tianjin Medical University Cancer Institute and Hospital 300060 TianjinChina First Affiliated Hospital of Xi’an Jiaotong University 710061 Xi’anChina

EMERGING-CTONG 1103 showed improved progression-free survival(PFS)with neoadjuvant erlotinib vs.chemotherapy for patients harbouring EGFR sensibility mutations and R0 resected stage IIIA-N2 non-small cell lung cancer(NSCLC)(NCT01407822).Herein,we report the final results.Recruited patients were randomly allocated 1:1 to the erlotinib group(150 mg/day orally;neoadjuvant phase for 42 days and adjuvant phase to 12 months)or to the GC group(gemcitabine 1250 mg/m2 plus cisplatin 75 mg/m2 intravenously;2 cycles in neoadjuvant phase and 2 cycles in adjuvant phase).Objective response rate(ORR),complete pathologic response(pCR),PFS,and overall survival(OS)were assessed along with safety.Post hoc analysis was performed for subsequent treatments after disease recurrence.Among investigated 72 patients(erlotinib,n=37;GC,n=35),the median follow-up was 62.5 months.The median OS was 42.2 months(erlotinib)and 36.9 months(GC)(hazard ratio[HR],0.83;95%confidence interval[CI],0.47-1.47;p=0.513).The 3-and_(5-y)ear OS rates were 58.6%and 40.8%with erlotinib and 55.9%and 27.6%with GC(p_(3-y)=0.819,p_(5-y)=0.252).Subsequent treatment was administered in 71.9%and 81.8%of patients receiving erlotinib and GC,respectively;targeted therapy contributed mostly to OS(HR,0.35;95%CI,0.18-0.70).After disease progression,the ORR was 53.3%,and the median PFS was 10.9 months during the EGFR-TKI rechallenge.During postoperative therapy,grade 3 or 4 adverse events(AEs)were 13.5%in the erlotinib group and 29.4%in the GC group.No serious adverse events were observed.Erlotinib exhibited clinical feasibility for resectable IIIA-N2 NSCLC over chemotherapy in the neoadjuvant setting.

关键词： neoadjuvant cisplatin chemotherapy

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A lobe-specific lymphadenectomy protocol for solitary pulmonary nodules in non-small cell lung cancer

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Chinese Journal of Cancer Research 2015年第6期27卷 538-544页

作者： xue-ning yang Ze-Rui Zhao Wen-Zhao Zhong Qiang Nie Ri-Qiang Liao Song Dong Division of Surgery Department of Pulmonary Oncology Guangdong Lung Cancer Institute Guangdong General Hospital and Guangdong Academy of Medical Sciences

Background： We want to establish a lobe-specific mediastinal lymphadenectomy protocol for solitary pulmonary nodules （SPNs） in non-small cell lung cancer （NSCLC）. Methods： We retrospectively analyzed 401 patients with pathological diagnoses of NSCLC who underwent lobectomy, bilobectomy, or pneumonectomy with systematic lymphadenectomy from March 2004 to June 2011 in our hospital. All of the patients enrolled had a SPN preoperatively. Information about the primary tumor location, lymph node metastasis, and other baseline data were collected. Stepwise logistic regression was used to identify the key factors indicating non-regional mediastinal lymph node metastases （NRM）. Results： Of the primary tumors, 117, 39, 74, 104, and 67 were in the right upper lung （RUL）, right middle lung （RML）, right lower lung （RLL）, left upper lung （LUL）, and left lower lung （LLL）, respectively. Stepwise regression showed that #2,4, #10,11, and #10,11 as well as #7 was the key lymph node station for RUL, LUL, and lower lobes： #2,4 [odds ratio （OR）=28.000, 95% confidence interval （CI）： 2.917-268.790, P=0.004] for RUL, #10,11 （OR=31.667, 95% CI： 2.502-400.833, P=0.008） for LUL, #10,11 （OR=19.540, 95% CI： 4.217-90.541, P〈0.001） and #7 （OR=7.395, 95% CI： 1.586-34.484, P=0.011） for lower lobes, respectively. Patients with tumors 〉2 cm rarely had NRM without primary regional mediastinal involvement. Conclusions： With rigid consideration, a lobe-specific lymphadenectomy is feasible in practice. This protocol can be used when the lobe-specific key nodes are negative in intraoperative frozen sections, especially for NSCLC diagnosed as SPN 〈2 cm preoperatively.

关键词： Lung cancer surgery lymph nodes selective dissection lobe-specific

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Comparison of three mathematical prediction models in patients with a solitary pulmonary nodule

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Chinese Journal of Cancer Research 2014年第6期26卷 647-652页

作者： Xuan Zhang Hong-Hong Yan Jun-Tao Lin Ze-Hua Wu Jia Liu Xu-Wei Cao xue-ning yang From Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer Guangdong General Hospital & Guangdong Academy of Medical Sciences Jinan University the 2nd Clinical College Shenzhen people’s hospital

Background： Effective methods for managing patients with solitary pulmonary nodules（SPNs） depend critically on the predictive probability of malignancy.Methods： Between July 2009 and June 2011, data on gender, age, cancer history, tumor familial history, smoking status, tumor location, nodule size, spiculation, calcification, the tumor border, and the final pathological diagnosis were collected retrospectively from 154 surgical patients with an SPN measuring 3-30 mm. Each final diagnosis was compared with the probability calculated by three predicted models—the Mayo, VA, and Peking University（PU） models. The accuracy of each model was assessed using area under the receiver operating characteristics（ROC） and calibration curves.Results： The area under the ROC curve of the PU model [0.800; 95% confidence interval（CI）： 0.708-0.891] was higher than that of the Mayo model（0.753; 95% CI： 0.650-0.857） or VA model（0.728; 95% CI： 0.623-0.833）; however, this finding was not statistically significant. To varying degrees, calibration curves showed that all three models overestimated malignancy.Conclusions： The three predicted models have similar accuracy for prediction of SPN malignancy, although the accuracy is not sufficient. For Chinese patients, the PU model may has greater predictive power.Background： Here, we introduced our short experience on the application of a new CUSA Excel ultrasonic aspiration system, which was provided by Integra Lifesciences corporation, in skull base meningiomas resection.Methods： Ten patients with anterior, middle skull base and sphenoid ridge meningioma were operated using the CUSA Excel ultrasonic aspiration system at the Neurosurgery Department of Shanghai Huashan Hospital from August 2014 to October 2014. There were six male and four female patients, aged from 38 to 61 years old（the mean age was 48.5 years old）. Five cases with tumor located at anterior skull base, three cases with tumor on middle skull base, and two cases with tumor on sphenoid ridge.Results： All the patents received tot

关键词： Solitary pulmonary nodule（SPN） benign and malignant model comparison

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Single nucleotide polymorphisms of MAGE-A3 gene and its clinical implications in Chinese patients with non-small cell lung cancer(NSCLC)

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Chinese Journal of Cancer Research 2015年第3期27卷 301-308页

作者： xue-ning yang Ling Huang Yu Chen She-Juan An Xu-Chao Zhang Ri-Qiang Liao Jian Su Yi-Long Wu Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong General Hospital& Guangdong Academy of Medical Sciences

Background： Available study revealed advanced tumors have a higher expression rate of MAGE-A3 gene which has a lot of single nucleotide polymorphism（SNP） loci with polymorphisms. This study aimed to analyze the allele frequency of SNP loci in MAGE-A3 gene and investigate the relationship between MAGE-A3 gene polymorphisms and clinical factors.Methods： Tumor samples of a cohort of 191 NSCLC patients were collected. EGFR m RNA expression were detected by q RT-PCR. SNPs in whole length of MAGE-A3 gene were detected by direct sequencing. Frequencies of the SNPs were correlated to gene expression, mutation status of EGFR and clinical factors.Results： Sequencing analysis confirmed that allele frequencies of genotypes on SNP loci rs5970360, rs5925210, rs5970361, rs5925211 and rs35123853 were CC（0.681）/CT（0.319）, CC（0.660）/CG（0.340）, CC（0.681）/CA（0.319）, AA（0.984）/AT（0.016） and GG（1.000）/GA（0.000）, respectively, which were different from the frequencies and genotypes of MAGE-A3 in SNP database. Chi-square tests showed the EGFR mR NA expression level had significant correlation with the genotypes of SNP loci rs5970360 and rs5925210. But all frequencies of each MAGE-A3 SNPs were not found significantly different between EGFR mutant and wild type patients. MAGE-A3 gene polymorphisms had no significant effects on survival of NSCLC patients.Conclusions： Chinese patients with NSCLC had different SNP patterns of MAGE-A3 in comparison with those in international SNP database. These MAGE-A3 SNP loci might have not prognostic significance. MAGE-A3 SNP loci rs5970360 and rs5925210 might be predictive for EGFR m RNA expression levels and helpful to the selection of patients for epidermal growth factor receptor（EGFR） targeted immunotherapy.

关键词： MAGE-A3 epidermal growth factor receptor （EGFR） non-small cell lung cancer （NSCLC） single nucleotide polymorphism （SNP）

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Different dissecting orders of the pulmonary bronchus and vessels during right upper lobectomy are associated with surgical feasibility and postoperative recovery for lung cancer patients

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Chinese Journal of Cancer 2017年第10期36卷 468-477页

作者： Hao-Ran Zhai xue-ning yang Qiang Nie Ri-Qiang Liao Song Dong Wei Li Ben-Yuan Jiang Jin-Ji yang Qing Zhou Hai-Yan Tu Xu-Chao Zhang Yi-Long Wu Wen-Zhao Zhong Graduate School Southern Medical University Guangdong Lung Cancer Institute Guangdong General Hospital&Guangdong Academy of Medical Sciences

Background: Right upper lobectomy(RUL) for lung cancer with di erent dissecting orders involves the most vari?able anatomical structures, but no studies have analyzed its e ects on postoperative recovery. This study compared the conventional surgical approach, VAB(dissecting pulmonary vessels first, followed by the bronchus), and the alter?native surgical approach, a BVA(dissecting the posterior ascending arterial branch first, followed by the bronchus and vessels) on improving surgical feasibility and postoperative recovery for lung cancer patients.Methods: According to the surgical approach, consecutive lung cancer patients undergoing RUL were grouped into a BVA and VAB cohorts. Their clinical, pathologic, and perioperative characteristics were collected to compare periop?erative outcomes.Results: Three hundred one patients were selected(109 in the a BVA cohort and 192 in the VAB cohort). The mean operation time was shorter in the a BVA cohort than in the VAB cohort(164 vs. 221 min, P 0.05). The median disease?free survival was comparable for all patients in the two cohorts(not arrived vs. 41.97 months) and for patients with disease recurrences(13.25 vs. 9.44 months)(both P > 0.05). The recurrence models in two cohorts were also comparable for patients with local recurrences(6.4% vs. 7.8%), distant metastases(10.1% vs. 8.3%), and both(1.8% vs. 1.6%)(all P > 0.05).Conclusions: Dissecting the right upper bronchus before turning over the lobe repeatedly and dissecting veins via the a BVA approach during RUL would promote surgical feasibility and achi

关键词： Lung cancer Dissecting order Video-assisted thoracic surgery Pulmonary veins Bronchus

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Neoadjuvant immune checkpoint inhibitor plus chemotherapy in rare tracheal tumors

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Cancer Communications 2021年第11期41卷 1243-1245页

作者： Ben-Yuan Jiang Jia-Tao Zhang Li-Xu Yan Xiang-Peng Chu Qiang Nie Jian-Xiu Cui xue-ning yang Wen-Zhao Zhong Yi-Long Wu Guangdong Provincial People’s Hospital Guangdong Key Laboratory of Lung Cancer Translational MedicineGuangdong Lung Cancer InstituteSouth China University of Technology&Guangdong Academy of Medical SciencesGuangzhouGuangdong 510080P.R.China Department of Pathology Guangdong Provincial People’s HospitalGuangzhouGuangdong 510080P.R.China Department of Anaesthesiology Guangdong Provincial People’s HospitalGuangzhouGuangdong 510080P.R.China

Dear Editor,Primary malignant tumors of the trachea account for 0.01%-0.4%of all cancer cases[1].Due to their locally aggressive growth,surgical resection including carinal resection and airway reconstruction was most frequently applied for these diseases[2].However,tracheal surgery is technically challenging and is associated with high rates of operative morbidity and mortality.Effective neoadjuvant treatment is expected to reduce the tumor load and lessen the extent of resecting primary tracheal tumors.However,evidence regarding neoadjuvant treatment for tracheal tumors remains relatively scarce and platinumbased doublet chemotherapy remains the standard in this setting.Immune checkpoint inhibitors are a promising approach to neoadjuvant treatment.

关键词： chemotherapy operative treatment

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Spectral properties and energy of weighted adjacency matrix for graphs with a degree-based edge-weight function

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Acta Mathematica Sinica,English Series 2024年

作者： xue Liang LI ning yang Center for Combinatorics and LPMC Nankai University

Let G be a graph and di denote the degree of a vertex vi in G, and let f(x, y) be a real symmetric function. Then one can get an edge-weighted graph in such a way that for each edge vivj of G, the weight of vivj is assigned by the value f(di, dj). Hence, we have a weighted adjacency matrix Af(G) of G, in which the ij-entry is equal to f(di, dj) if vivj ∈ E(G) and 0 otherwise. This paper attempts to unify the study of spectral properties for the weighted adjacency matrix Af(G) of graphs with a degree-based edge-weight function f(x, y). Some lower and upper bounds of the largest weighted adjacency eigenvalue λ1 are given, and the corresponding extremal graphs are characterized. Bounds of the energy Ef(G) for the weighted adjacency matrix Af(G) are also obtained. By virtue of the unified method, this makes many earlier results become special cases of our results.

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The response of structure and nitrogen removal function of the biofilm on submerged macrophytes to high ammonium in constructed wetlands

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Journal of Environmental Sciences 2024年第8期142卷 129-141页

作者： xue Jiang Mengmeng Wang Shunqing yang Di He Fei Fang Liuyan yang State Key Laboratory of Pollution Control and Resource Reuse School of the EnvironmentNanjing UniversityNanjing 210023China School of Resources and Environment Anqing Normal UniversityAnqing 246133China

The ammonium exceedance discharge from sewage treatment plants has a great risk to the stable operation of subsequent constructed wetlands(CWs).The effects of high ammonium shocks on submerged macrophytes and epiphytic biofilms on the leaves of submerged macrophytes in CWs were rarely mentioned in previous studies.In this paper,the 16S rRNA sequencing method was used to investigate the variation of the microbial communities in biofilms on the leaves of Vallisneria natans plants while the growth characteristics of V.natans plants were measured at different initial ammonium concentrations.The results demonstrated that the total chlorophyll and soluble sugar synthesis of V.natans plants decreased by 51.45%and 57.16%,respectively,and malondialdehyde content increased threefold after8 days if the initial NH_(4)^(+)-N concentration was more than 5 mg/L.Algal density,bacterial quantity,dissolved oxygen,and pH increased with high ammonium shocks.The average removal efficiencies of total nitrogen and NH_(4)^(+)-N reached 73.26%and 83.94%,respectively.The heat map and relative abundance analysis represented that the relative abundances of phyla Proteobacteria,Cyanobacteria,and Bacteroidetes increased.The numbers of autotrophic nitrifiers and heterotrophic nitrification aerobic denitrification(HNAD)bacteria expanded in biofilms.In particular,HNAD bacteria of Flavobacterium,Hydrogenophaga,Acidovorax,Acinetobacter,Pseudomonas,Aeromonas,and Azospira had higher abundances than autotrophic nitrifiers because there were organic matters secreted from declining leaves of V.natans plants.The analysis of the nitrogen metabolic pathway showed aerobic denitrification was the main nitrogen removal pathway.Thus,the nitrification and denitrification bacterial communities increased in epiphytic biofilms on submerged macrophytes in constructed wetlands while submerged macrophytes declined under ammonium shock loading.

关键词： Ammonium shock loading Biofilm Autotrophic nitrifiers Heterotrophic nitrification aerobic denitrification bacteria Submerged macrophyte

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Pathway Planning of Nuclear Power Development Incorporating Assessment of Nuclear Event Risk

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Journal of Modern Power Systems and Clean Energy 2024年第2期12卷 500-513页

作者： Xinxin yang Yusheng xue Bin Cai School of Electrical Engineering Southeast UniversityNanjingChinaand they are also with State Grid Electric Power Research Institute(NARI Group Corporation)NanjingChina State Key Laboratory of Smart Grid Protection and Operation Control NanjingChina State Grid Electric Power Research Institute(NARI Group Corporation) NanjingChina

The nuclear event risk(NER)is an important and disputed factor that should be reasonably considered when planning the pathway of nuclear power development(NPD)to assess the benefits and risks of developing nuclear power more objectively.This paper aims to explore the impact of nuclear events on NPD pathway planning.The influence of nuclear events is quantified as a monetary risk component,and an optimization model that incorporates the NER in the objective function is proposed.To optimize the pathway of NPD in the lowcarbon transition course of power supply structure evolution,a simulation model is built to deduce alternative NPD pathways and corresponding power supply evolution scenarios under the constraint of an exogenously assigned carbon emission pathway(CEP);moreover,a method is proposed to describe the CEP by superimposing the maximum carbon emission space and each carbon emission reduction(CER)component,and various CER components are clustered considering the emission reduction characteristics and resource endowments of different power generation technologies.A case study is conducted to explore the impact of NER and its risk valuation uncertainty on NPD pathway planning.The method presented in this paper allows the impact of nuclear events on NPD pathway planning to be quantified and improves the level of coordinated optimization of benefits and risks.

关键词： Low-carbon transition power supply structure evolution nuclear power development(NPD) quantitative analysis nuclear event risk evaluation

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