Expert consensus on the detection and clinical application of tumor mutational burden 认领 引用

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作者 Zhenying Guo Chunwei Xu +168 位作者 Shirong Zhang Yue Hao Xiaotong Hu Ming Zhao Chan Xiang Yingshi Piao Pingli Sun Xueping Xiang Jing Zhao Huanwen Wu Weixing Li Jinpu Yu Jingping Yuan Shuangshuang Wang Cong Wang Yun Gu Bingjian Lv Liping Zhang Yueping Liu Xiaobin Cui Weizhong Gu Yining Li Wei Wang Wenjun Yang Weiguo Long Jingjing Xiang Hong Mou Biao Liu Huajuan Ruan Yubin Wang Yongjie Zhu Feng Wang Zhonghua Wang Xiaomin Feng Xing Liu Peng Li Min Deng Bin Lian Lili Mao Qian Wang Wenxian Wang Zhengbo Song Ziming Li Wenzhao Zhong Zhijie Wang Shengxiang Ren Wenfeng Fang Yongchang Zhang Jingjing Liu Xiuyu Cai Anwen Liu Wen Li Ping Zhan Hongbing Liu Tangfeng Lv Liyun Miao Lingfeng Min Yu Chen Yu Zhang Feng Wang Zhansheng Jiang Gen Lin Long Huang Xingxiang Pu Rongbo Lin Weifeng Liu Chuangzhou Rao Dongqing Lv Zongyang Yu Peng Shen Xiaoyan Li Chuanhao Tang Chengzhi Zhou Junping Zhang Junli Xue Hui Guo Qian Chu Rui Meng Jingxun Wu Rui Zhang Jin Zhou Zhengfei Zhu Yongheng Li Hong Qiu Fan Xia Yuanyuan Lu Xiaofeng Chen Rui Ge Enyong Dai Yu Han Jian Zhang Yinghua Ji Xianbin Liang Hongmei Zhang Xuelei Ma Xuewen Liu Yu Yao Peng Luo Weiwei Pan Fei Pang Fan Wu Dejian Gu Li Wang Liping Wang Youcai Zhu Li Lin Weiwen Li Xinqing Lin Jing Cai Ling Xu Jisheng Li Xiaodong Jiao Kainan Li Jia Wei Huijing Feng Lin Wang Yingying Du Wang Yao Xuefei Shi Xiaomin Niu Dongmei Yuan Yanwen Yao Yinbin Zhang Binbin Song Wenfeng Li Jianfei Fu Hong Wang Mingxiang Ye Dong Wang Zhaofeng Wang Qing Ji Yuan Fang Qing Wei Zhen Wang Bin Wan Donglai Lv Xiaofeng Li Shengjie Yang Jing Kang Jiatao Zhang Chao Zhang Lin Shi Yina Wang Bihui Li Zhang Zhang Ke Wang Zhefeng Liu Nong Yang Lin Wu Xiaobing Chen Gu Jin Zhongwu Li Miao Li Guansong Wang Jiandong Wang Meiyu Fang Yong Fang Xiaojia Wang Jing Chen Yiping Zhang Xixu Zhu Yi Shen Shenglin Ma Biyun Wang Lu Si Yong Song Yuanzhi Lu Aijun Liu Yuchen Han 《Cancer Biology & Medicine》 SCIE CAS CSCD 2026年第2期218-246,共29页

As an emerging biomarker,tumor mutational burden(TMB)has attracted increasing attention from clinicians in predicting the efficacy of tumor immunotherapy.Currently,TMB is detected primarily by whole-exome sequencing o... As an emerging biomarker,tumor mutational burden(TMB)has attracted increasing attention from clinicians in predicting the efficacy of tumor immunotherapy.Currently,TMB is detected primarily by whole-exome sequencing or targeted panel sequencing on high-throughput sequencing platforms.However,the lack of uniformity in detection methods,threshold settings,and reporting formats,as well as the significant differences in TMB values among different cancer types,have hindered the standardized application of this biomarker in clinical practice.This consensus focuses on the definition,standardization of detection,clinical significance,and limitations of TMB,and provides consensus recommendations for the clinical application of TMB in real-world practice in China.This consensus is aimed at helping clinicians and laboratory personnel understand the clinical significance and testing standards of TMB,promoting more accurate interpretation of test results,and improving patient care. 展开更多

关键词 Biomarkers tumor mutational burden tumor immunotherapy targeted panel sequencing whole-exome sequencing

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Prediction model for endpoint and product composition of copper-converter smelting based on CNN-GAT algorithm collaboration 认领 引用

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作者 Yunhao Qiu Mingzhou Li +4 位作者 Jindi Huang Zhiming He Wenfeng Fang Lihua Zhong Wu Xu 《International Journal of Minerals,Metallurgy and Materials》 SCIE EI CAS CSCD 2026年第4期1187-1200,共14页

The endpoint timing of copper-converter blowing directly affects the quality of blister copper,furnace stability,and blowing efficiency.Therefore,enhancing the digitalization and intelligence levels of this process ha... The endpoint timing of copper-converter blowing directly affects the quality of blister copper,furnace stability,and blowing efficiency.Therefore,enhancing the digitalization and intelligence levels of this process has significant practical importance.This study employed a deep learning algorithm that integrated a convolutional neural network(CNN)and graph attention network(GAT).It utilized CNNs to extract image features from the cooling samples of high-temperature melts.Subsequently,by fusing these image features with various production condition data and constraints through the GAT,a model was constructed to determine the best endpoint and predict the product composition.This model could predict the main elemental content of furnace products and estimate the required blowing time.A dataset comprising 5172 production parameters and images of high-temperature cooling samples from a furnace was established.The model was trained and validated using this dataset,and the results indicated that the model achieved endpoint judgment accuracies of 96.73%and 97.85%for the slag-making and copper-making periods,respectively,on the test set.The average prediction error for the composition across four cycles of copper-converter blowing was as low as 0.705wt%,and the average error in estimating the required blowing time was only 1.94 min.The results of this study provide new methods and insights for the development of intelligent endpoint judgment technologies for copper-converter blowing. 展开更多

关键词 endpoint judgment of copper-converter blowing composition prediction convolutional neural networ graph attention network

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Expert consensus on the diagnosis and treatment of non-small cell lung cancer with MET alteration 认领 引用 被引量：1

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作者 Huijing Feng Yang Xia +106 位作者 Wenxian Wang Chunwei Xu Qian Wang Zhengbo Song Ziming Li Jinpu Yu Wenzhao Zhong Zhijie Wang Yongchang Zhang Jingjing Liu Shirong Zhang Xiuyu Cai Anwen Liu Wen Li Ping Zhan Hongbing Liu Tangfeng Lyu Liyun Miao Lingfeng Min Gen Lin Long Huang Jingping Yuan Zhansheng Jiang Xingxiang Pu Chuangzhou Rao DongqingLyu Zongyang Yu Xiaoyan Li Chuanhao Tang Chengzhi Zhou Qi Mei Hui Guo Qian Chu Rui Meng Xuewen Liu Jingxun Wu Jin Zhou Zhengfei Zhu Weiwei Pan Fei Pang Meizhen Hu Kai Wang Fan Wu Bingwei Xu Ling Xu Liping Wang Youcai Zhu Jisheng Li Yanru Xie Xinqing Lin Jing Cai Lin Wang Yingying Du Wang Yao Xuefei Shi Xiaomin Niu Dongmei Yuan Yanwen Yao Jing Kang Jiatao Zhang Chao Zhang Wenbin Gao Jianhui Huang Yinbin Zhang Pingli Sun Hong Wang Mingxiang Ye Dong Wang Zhaofeng Wang Yue Hao Zheng Wang Bing Wan Donglai Lyu Xiaodong Jiao Lin Shi Gang Lan Shengjie Yang Yanhong Shang Yina Wang Bihui Li Gang Jin Kang Zheng Jun Ma Wenfeng Li Zhang Zhang Zhongwu Li Yuan Li Zhefeng Liu Xuelei Ma Nong Yang Lin Wu Qiming Wang Guansong Wang Zhuan Hong Jiandong Wang Meiyu Fang Yong Fang Xixu Zhu Yi Shen Ke Wang Xiubao Ren Yiping Zhang Shenglin Ma Junping Zhang Yong Song Wenfeng Fang Yuanzhi Lu 《Cancer Biology & Medicine》 SCIE CAS CSCD 2025年第3期237-265,共29页

Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant... Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations. 展开更多

关键词 Mesenchymal-epithelial transition factor MET exon 14 skipping mutation MET amplification non-small cell lung cancer precision medicine targeted therapy tyrosine kinase

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A multicenter,retrospective.epidemiologic survey of the clinical features and management of bone metastatic disease in China 认领 引用 被引量：22

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作者 Yunpeng Yang Yuxiang Ma +7 位作者 Jin Sheng Yan Huang Yuanyuan Zhao Wenfeng Fang Shaodong Hong Ying Tian Cong Xue Li Zhang 《Chinese Journal of Cancer》 2016年第5期223-228,共6页

Background:Bone metastases are common in patients with advanced cancer.Bisphosphonates(BPs) could prevent or delay the development of skeleton-related events(SREs).The present study aimed to identify the clinical feat... Background:Bone metastases are common in patients with advanced cancer.Bisphosphonates(BPs) could prevent or delay the development of skeleton-related events(SREs).The present study aimed to identify the clinical features of and treatment strategies for Chinese patients with bone metastases.Methods:Consecutive cancer patients who had bone metastases and received BP treatment were enrolled.A questionnaire was developed to collect the patients' clinical data,as well as information on the diagnosis and management of bone metastases.Physicians' awareness of the guidelines and knowledge of the application of BP were also assessed.Results:A total of 3223 patients with lung cancer(36.5%),breast cancer(30.9%),prostate cancer(8.5%),and gastrointestinal cancer(5.7%) were included in this study.The sites of bone metastases were the thoracic spine(56.0%),lumbar spine(47.1%),ribs(32.6%),and pelvis(23.2%).The SRE frequency was the highest in patients with multiple myeloma(36.6%),followed by those with lung cancer(25.9%),breast cancer(20.2%),prostate cancer(18.2%),and gastrointestinal cancer(17.3%).Irradiation to the bone was the most frequent SRE(58%in lung cancer patients,45%in breast cancer patients,and 48%in prostate cancer patients).Our survey also showed that 45.5%of patients received BP within 3 months after their diagnosis of bone metastases,whereas the remaining 54.5%of patients did not receive BP treatment until at least 3 months after their diagnosis of bone metastases.The SRE frequency in the former group was significantly lower than that in the latter group(4.0%vs.42.3%,P < 0.05).In patients with more than 6 months of continuous BP treatment,the mean time to the first SRE was significantly longer than that in patients with less than 6 months of continuous BP treatment(7.2 vs.3.4 months,P < 0.05).In addition,12.2%of the physicians were not aware of the efficacy of BP in preventing and delaying SRE.Only half(52.3%) of the physicians agreed that the BP treatment should persist for at least 6 months unless it was intolerable.Conclusions:Our study suggested that prompt and persistent BP treatment was associated with a reduced risk of SREs.However,our survey also revealed that the proper application of BP was not as common as expected in China. 展开更多

关键词 Bisphosphonates, Bone metastases, Skeleton-related events, Chinese cancer patients

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帕博利珠单抗治疗晚期非小细胞肺癌安全性和有效性的真实世界研究 认领 引用 被引量：5

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作者 万宁 王冰 +10 位作者 郭娅 何梓健 杨晨 杨宁 卢丽清 梁虹艺 萧伟斌 杨丹丹 陈卓佳 方文峰 梁蔚婷 《中国肺癌杂志》 CAS CSCD 北大核心 2024年第10期745-754,共10页

背景与目的帕博利珠单抗(Pembrolizumab,PEM)治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)在临床试验中被证实有效,但这些试验是基于按照特定标准筛选的患者群体,因此这些结果是否能够代表真实世界中患者的普遍情况,仍然值... 背景与目的帕博利珠单抗(Pembrolizumab,PEM)治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)在临床试验中被证实有效,但这些试验是基于按照特定标准筛选的患者群体,因此这些结果是否能够代表真实世界中患者的普遍情况,仍然值得讨论。本研究旨在基于真实世界数据评估PEM治疗晚期NSCLC的有效性和安全性。方法回顾性收集接受PEM治疗的晚期NSCLC患者的真实世界数据,使用倾向性评分匹配消除组间差异,评估PEM与化疗的有效性和安全性。结果在倾向性评分匹配后的450例患者中PEM组和化疗组任何等级不良事件发生率分别为79.87%和86.71%,≥3级不良事件发生率分别为4.03%和7.31%。PEM组和化疗组的客观缓解率分别为48.63%和36.00%(P=0.011),中位无进展生存期分别为15.5和8.8个月(P<0.001),中位总生存期分别为未达到和26.2个月(P<0.001)。结论PEM治疗晚期NSCLC在实际临床应用中显示出较好的生存率和可接受的安全性。 展开更多

关键词 真实世界数据 帕博利珠单抗 肺肿瘤 安全性 有效性

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International guidelines on the diagnosis and treatment of NUT carcinoma 认领 引用 被引量：2

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作者 Yu Zhang Qi Zhang +171 位作者 Yue Hao Jia Luo Yingshi Piao Wenxian Wang Zhengbo Song Ziming Li Luka Brcic Aijun Liu Jinpu Yu Yasuhiro Tsutani Wenzhao Zhong Wenfeng Fang Zhijie Wang Shengxiang Ren Athanasios G.Papavassiliou Yongchang Zhang Jingjing Liu Shirong Zhang Xiuyu Cai Ayten Kayi Cangir Anwen Liu Wen Li Filippo Lococo Ping Zhan Hongbing Liu Tangfeng Lv Liyun Miao Lingfeng Min Helmut Popper Yu Chen Jingping Yuan Feng Wang Zhansheng Jiang Gen Lin Long Huang Xingxiang Pu Rongbo Lin Kalevi Kairemo Weifeng Liu Chuangzhou Rao Dongqing Lv Zongyang Yu Ashrafian Leanne Xiaoyan Li Chuanhao Tang Hifzur R.Siddique Chengzhi Zhou Junping Zhang Junli Xue Vishal Shelat Hui Guo Qian Chu Rui Meng Fatemeh Ardeshir Jingxun Wu Rui Zhang Jin Zhou Robert A.Kratzke Zhengfei Zhu Yongheng Li Hong Qiu Fan Xia Fiorella Calabrese Yang Xia Alessandro Wasum Mariani Yuanyuan Lu Xiaofeng Chen Mark A.Klein Rui Ge Enyong Dai Axel H.Schönthal Yu Han Zhenying Guo Jian Zhang Yinghua Ji Xianbin Liang Hongmei Zhang Xuelei Ma Marco Chiappetta Xuewen Liu Francoise Galateau Salle Yu Yao Malgorzata Szolkowska Weiwei Pan Fei Pang Fan Wu Stefan B.Watzka Liping Wang Youcai Zhu Li Lin Aparna Sharma Jianfei Tu Xinqing Lin Jing Cai Ling Xu Jisheng Li Xiaodong Jiao Kainan Li Marjorie G.Zauderer Jia Wei Huijing Feng Lin Wang Yingying Du Wang Yao Elizabeth Dudnik Xuefei Shi Xiaomin Niu Dongmei Yuan Yanwen Yao Jianhui Huang Yue Feng Yinbin Zhang Binbin Song Wenfeng Li Jianfei Fu Marina K.Baine Pingli Sun Hong Wang Mingxiang Ye Dong Wang Zhaofeng Wang Jing Wu Yunyun Yang Yuan Fang Zhen Wang Bin Wan Donglai Lv Huafei Chen Shengjie Yang Jing Kang Jiatao Zhang Chao Zhang Lin Shi Yina Wang Mohamed Emam Sobeih Bihui Li Bin Lian Lili Mao Zhang Zhang Ke Wang Zhongwu Li Zhefeng Liu Nong Yang Lin Wu Xiaobing Chen Gu Jin Miao Li Guansong Wang Thomas U.Marron Jiandong Wang Sanjay Popat Meiyu Fang Yong Fang Daniel Mansilla Yuan Li Xiaojia Wang Jing Chen Yiping Zhang Xixu Zhu Yi Shen Shenglin Ma Aaron S.Mansfield Biyun Wang Lu Si Anja C.Roden Bjørn H.Grønberg Yong Song Geoffrey I.Shapiro Christopher A.French Yuanzhi Lu Qian Wang Chunwei Xu 《The Innovation》 EI 2026年第1期111-126,共16页

1(NUTM1)gene rearrangements(15q14).In 1991,two independent research teams reported NC cases characterized by the t(15;19)translo-cation.1,2 In vitro studies by French et al.3 led to the pivotal discovery of NC in 2003... 1(NUTM1)gene rearrangements(15q14).In 1991,two independent research teams reported NC cases characterized by the t(15;19)translo-cation.1,2 In vitro studies by French et al.3 led to the pivotal discovery of NC in 2003 as a distinct disease entity driven by the fusion of bromodo-main and extraterminal domain(BET)protein 4(BRD4)and NUTM1.In 2004,the World Health Organization(WHO)classified tumors with t(15;19)translocation as a thymic malignancy and designated it“NUT midline carcinoma,”due to its predominant occurrence in midline organs.4 However,subsequent reports revealed NC’s emergence in numerous nonmidline organs,leading to its reclassification as the independent entity“NUT carcinoma of the thorax”by the WHO in 2015.5 NC exhibits rapid progression and profound resistance to conventional radiotherapy and chemotherapy. 展开更多

关键词 t BRD vitro studies translocation nut carcinoma thorax thymic malignancy nut midline carcinoma NUTM

Rare transformation from lung adenocarcinoma to sarcomatoid carcinoma mediates resistance to inhibitors targeting different driver oncogenes 认领 引用

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作者 Lanlan Pang Weitao Zhuang +5 位作者 Yihua Huang Jun Liao Mengjuan Yang Li Zhang Yaxiong Zhang Wenfeng Fang 《Journal of the National Cancer Center》 CSCD 2025年第1期75-81,共7页

Background:Phenotypic transition is a common resistance mechanism of targeted therapy.While transformations from lung adenocarcinoma(LUAD)to small-cell lung cancer or squamous-cell carcinoma have been extensively stud... Background:Phenotypic transition is a common resistance mechanism of targeted therapy.While transformations from lung adenocarcinoma(LUAD)to small-cell lung cancer or squamous-cell carcinoma have been extensively studied,the conversion into sarcomatoid carcinoma(SC)is rarely reported.Methods:Genetic and histological examinations were systematically performed on tumor re-biopsy samples ob-tained from patients with advanced EGFR-mutant LUAD who progressed on EGFR-tyrosine kinase inhibitors(TKIs).EGFR wild-type patients were also identified who underwent the rare transformation from adenocarci-noma to SC following the ineffectiveness of inhibitors that target distinct driver oncogenes.Furthermore,we also retrospectively collected 42 cases diagnosed with primary pulmonary SC as a comparison cohort to comprehen-sively characterize the biological events and clinical outcomes of transformed SC.Results:The sarcomatoid transformation mediated drug resistance in 2.5%and 4.8%of patients after failure on the first/second,and third-generation EGFR-TKIs.Transformation of sarcomatoid carcinoma is characterized by a higher frequency of TP53,RB1,and MET genetic alterations compared to cases lacking histological transforma-tion;the PI3K signaling pathway was also significantly activated.Fifteen individuals were identified with a rare transition from adenocarcinoma to SC,consisting of seven cases with EGFR-activating mutations and eight cases without EGFR mutations.All sarcomatoid-transformed samples not only retained their original driver mutations but also shared specific genetic alterations with primary LUAD.Moreover,transformed sarcomatoid carcinomas mimic the primary SC in terms of immunochemical and molecular features.Conclusions:The transformation from lung adenocarcinoma to SC is a resistance mechanism wildly applied to inhibitors targeting different driver oncogenes.Immunotherapy plus chemotherapy shows potential to benefit patients with sarcomatoid transformation and warrants further study in larger cohorts. 展开更多

关键词 Histological transformation Drug resistance Sarcomatoid carcinoma Immunotherapy

Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial 认领 引用 被引量：22

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作者 Yunpeng Yang Jie Min +17 位作者 Nong Yang Qitao Yu Ying Cheng Yanqiu Zhao Manxiang Li Hong Chen Shou’an Ren Jianying Zhou Wu Zhuang Xintian Qin Lejie Cao Yan Yu Jian Zhang Jianxing He Jifeng Feng Hao Yu Li Zhang Wenfeng Fang 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2023年第9期4338-4345,共8页

Anaplastic lymphoma kinase(ALK)rearrangements are present in about 5–6%of non-small cell lung cancer(NSCLC)cases and associated with increased risks of central nervous system(CNS)involvement.Envonalkib,a novel ALK in... Anaplastic lymphoma kinase(ALK)rearrangements are present in about 5–6%of non-small cell lung cancer(NSCLC)cases and associated with increased risks of central nervous system(CNS)involvement.Envonalkib,a novel ALK inhibitor,demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study.This phase III trial(ClinicalTrials.gov NCT04009317)investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases.Totally 264 participants were randomized 1:1 to receive envonalkib(n=131)or crizotinib(n=133).Median independent review committee(IRC)-assessed progression-free survival(PFS)times were 24.87(95%confidence interval[CI]:15.64–30.36)and 11.60(95%CI:8.28–13.73)months in the envonalkib and crizotinib groups,respectively(hazard ratio[HR]=0.47,95%CI:0.34–0.64,p<0.0001).IRC-assessed confirmed objective response rate(ORR)was higher(81.68%vs.70.68%,p=0.056)and duration of response was longer(median,25.79[95%CI,16.53–29.47]vs.11.14[95%CI,9.23–16.59]months,p=0.0003)in the envonalkib group compared with the crizotinib group.In participants with baseline brain target lesions,IRC-assessed CNS-ORR was improved with envonalkib compared with crizotinib(78.95%vs.23.81%).Overall survival(OS)data were immature,and median OS was not reached in either group(HR=0.84,95%CI:0.48–1.47,p=0.5741).The 12-month OS rates were 90.6%(95%CI,84.0%–94.5%)and 89.4%(95%CI,82.8%–93.6%)in the envonalkib and crizotinib groups,respectively.Grade≥3 treatment-related adverse events were observed in 55.73%and 42.86%of participants in the envonalkib and crizotinib groups,respectively.Envonalkib significantly improved PFS and delayed brain metastasis progression in advanced ALK-positive NSCLC. 展开更多

关键词 crizotinib randomized cancer

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QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study 认领 引用 被引量：15

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作者 Yan Huang Yunpeng Yang +12 位作者 Yuanyuan Zhao Hongyun Zhao Ningning Zhou Yaxiong Zhang Likun Chen Ting Zhou Gang Chen Ting Wu Lu Lu Shilin Xue Xiaoyan Kang Li Zhang Wenfeng Fang 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2024年第2期797-806,共10页

First-line chemoimmunotherapy(with or without bevacizumab)has improved outcomes in advanced non-small cell lung cancer(NSCLC).Here,this open-label,multi-cohort phase II study(NCT05329025)was done to investigate the sa... First-line chemoimmunotherapy(with or without bevacizumab)has improved outcomes in advanced non-small cell lung cancer(NSCLC).Here,this open-label,multi-cohort phase II study(NCT05329025)was done to investigate the safety and efficacy of QL1706(a single bifunctional MabPair product against PD-1 and CTLA-4)and chemotherapy with or without bevacizumab in this population.Patients were enrolled into five different cohorts based on genotype(cohorts 1-4,epidermal growth factor receptor[EGFR]wild-type;cohort 5,EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors[TKIs]).Between June 11,2021 and December 29,2021,91 patients were enrolled.Most frequent treatment-related adverse events(TRAEs)included decreased appetite(60[65.9%]),anemia(60[65.9%]),infusion-related reactions(48[52.7%]),and pruritus(44[48.4%]).Grade≥3 TRAEs occurred in 30(33.0%)patients.Twenty-seven(45%)patients with wild-type EGFR achieved partial response(PR)(objective response rate[ORR]=45%)and had a median progression-free survival(mPFS)of 6.8 months(95%CI:5.2-9.7).For 31 patients harboring mutated EGFR,17(54.8%)achieved PR(ORR=54.8%),with an mPFS of 8.5 months(95%CI:5.72-not evaluable).Overall,QL1706 plus chemotherapy,regardless of having bevacizumab,was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line setting.Moreover,QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy,demonstrating a potential for treating this population. 展开更多

关键词 bevacizumab chemotherapy phase

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The ACTIVE study protocol:apatinib or placebo plus gefitinib as first-line treatment for patients with EGFR-mutant advanced non-small cell lung cancer(CTONG1706) 认领 引用 被引量：10

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作者 Zhonghan Zhang Fan Luo +7 位作者 Yang Zhang Yuxiang Ma Shaodong Hong Yunpeng Yang Wenfeng Fang Yan Huang Li Zhang Hongyun Zhao 《Cancer Communications》 SCIE 2019年第1期607-614,共8页

Background:Gefitinib,as the first epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)approved for the treatment of advanced non-small cell lung cancer(NSCLC),has been proved to significantly improve ... Background:Gefitinib,as the first epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)approved for the treatment of advanced non-small cell lung cancer(NSCLC),has been proved to significantly improve the progression-free survival(PFS)in the first-line setting but suffers from resistance 7-10 months after treatment initia-tion.Apatinib(YN968D1),a potent vascular endothelial growth factor receptor(VEGFR)2-TKI,specifically binds to VEGFR2 and leads to anti-angiogenetic and anti-neoplastic effect.Concurrent inhibition of VEGFR and EGFR path-ways represents a rational approach to improve treatment responses and delay the onset of treatment resistance in EGFR-mutant NSCLC.This ACTIVE study aims to assess the combination of apatinib and gefitinib as a new treatment approach for EGFR-mutant NSCLC as a first-line setting.Methods:This multicenter,randomized,double-blind,placebo-controlled phase III study(NCT02824458)has been designed to assess the efficacy and safety of apatinib or placebo combined with gefitinib as a first-line treatment for patients with EGFR-mutant advanced NSCLC.A total of 310 patients with EGFR-mutation(19del or 21L858R),pathological stage IIIB to IV non-squamous NSCLC were to be enrolled.The primary endpoint is investigator assessment of PFS,and the secondary endpoints include independent radiological central(IRC)-confirmed PFS,overall survival(OS),objective response rate(ORR),disease control rate(DCR),time to progressive disease(TTPD),duration of response(DoR),quality of life(QoL)and safety.The patients are randomized in a 1:1 ratio to receive gefitinib(250 mg,p.o.q.d.)plus apatinib(500 mg,p.o.q.d.)or gefitinib plus placebo,given until disease progression or intolerable adverse events.Exploratory biomarker analysis will be performed.This study is being conducted across China and comprises of 30 participating centers.Enrollment commenced in August 2017 and finished in December 2018,most of the patients are in the follow-up period.Anticipated outcomes and significance:The present study will be the first to evaluate the efficacy and safety profile of the combination of apatinib plus gefitinib as a first-line therapy for patients with EGFR-positive advanced non-squamous NSCLC.Importantly,this trial will provide comprehensive evidence on the treatment of EGFR-TKIs combined with antiangiogenic therapy. 展开更多

关键词 NSCLC EGFR VEGFR Tyrosine kinase inhibitors Apatinib Gefitinib Randomized Double-blind Placebo Phase III

Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma 认领 引用 被引量：7

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作者 Jiajun Xie Zifeng Wang +22 位作者 Wenjun Fan Youping Liu Fang Liu Xiangbo Wan Meiling Liu Xuan Wang Deshun Zeng Van Wang Bin He Min Yan Zijian Zhang Mengjuan Zhang Zhijie Hou Chunli Wang Zhijie Kang Wenfeng Fang Li Zhang Eric W-F Lam Xiang Guo Jinsong Yan Yixin Zeng Mingyuan Chen Quentin Liu 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2021年第10期3045-3061,共17页

Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been lagging.Nasopharyngeal carci noma(NPC)is a distinctive cancer with poor differe ntiatio n and high ... Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been lagging.Nasopharyngeal carci noma(NPC)is a distinctive cancer with poor differe ntiatio n and high prevalenee of Epstein-Barr virus(EBV)infection.Here,we show that the expressi on of EBV latent protein LMP1 in duces dediffere ntiated and stem-like status with high plasticity through the transcriptional inhibition of CEBPA.Mechanistically,LMP1 upregulates STAT5A and recruits HDAC 1/2 to the CEBPA locus to reduce its histone acetylation.HDAC inhibition restored CEBPA expression,reversing cellular dedifferentiation and stem-like status in mouse xeno graft models.These fin dings provide a novel mecha nistic epigenetic-based in sight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity. 展开更多

关键词 LMP1 cancer plasticity

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Surufatinib plus toripalimab combined with etoposide and cisplatin as first-line treatment in advanced small-cell lung cancer patients: a phase Ib/Ⅱ trial 认领 引用 被引量：5

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作者 Yaxiong Zhang Yan Huang +10 位作者 Yunpeng Yang Yuanyuan Zhao Ting Zhou Gang Chen Shen Zhao Huaqiang Zhou Yuxiang Ma Shaodong Hong Hongyun Zhao Li Zhang Wenfeng Fang 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2024年第10期4700-4707,共8页

There is still room for improvement in first-line treatment of advanced small cell lung cancer(SCLC).This trial firstly investigated efficacy and safety of antiangiogenic therapy(surufatinib)(200 mg,qd,po)plus anti-PD... There is still room for improvement in first-line treatment of advanced small cell lung cancer(SCLC).This trial firstly investigated efficacy and safety of antiangiogenic therapy(surufatinib)(200 mg,qd,po)plus anti-PD-1 treatment(toripalimab)(240 mg,d1,ivdrip)combined with etoposide(100 mg/m²,d1-d3,iv,drip)and cisplatin(25 mg/m²,d1-d3,ivdrip)for advanced SCLC as first-line treatment,which has been registered on ClinicalTrials.gov under the identifier NCT04996771.The four-drug regimen was conducted q3w for 4 cycles with maintenance therapy of surufatinib and toripalimab.The primary endpoint was progression-free survival(PFS).The secondary end points included objective response rate(ORR),disease control rate(DCR),overall survival(OS)and safety.All of the 38 patients were enrolled for safety analysis,while only 35 patients were enrolled for efficacy analysis since loss of efficacy evaluation in 3 cases after treatment.After a median follow-up of 21.3 months,the ORR was 97.1%(34/35),and the DCR and the tumor shrinkage rate were both 100%(35/35).The median PFS was 6.9 months(95%CI:4.6 m–9.2 m)and the median OS was 21.1 months(95%CI:12.1 m–30.1 m).The 12-month,18-month,and 24-month OS rates were 66.94%,51.39%and 38.54%.The occurrence rate of grade≥3 treatment-emergent adverse events(TEAEs)was 63.2%(24/38),including neutrophil count decreased(31.6%,12/38),white blood cell count decreased(23.7%,9/38)and platelet count decreased(10.5%,4/38).No unexpected adverse events occurred.This novel four-drug regimen(surufatinib,toripalimab,etoposide plus cisplatin)revealed impressive therapeutic efficacy and tolerable toxicities. 展开更多

关键词 cisplatin patients etoposide

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Expert consensus on the diagnosis and treatment of solid tumors with BRAF mutations 认领 引用 被引量：6

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作者 Wenxian Wang Bin Lian +133 位作者 Chunwei Xu Qian Wang Ziming Li Nan Zheng Aijun Liu Jinpu Yu Wenzhao Zhong Zhijie Wang Yongchang Zhang Jingjing Liu Shirong Zhang Xiuyu Cai Anwen Liu Wen Li Lili Mao Ping Zhan Hongbing Liu Tangfeng Lv Liyun Miao Lingfeng Min Yu Chen Jingping Yuan Feng Wang Zhansheng Jiang Gen Lin Long Huang Xingxiang Pu Rongbo Lin Weifeng Liu Chuangzhou Rao Dongqing Lv Zongyang Yu Xiaoyan Li Chuanhao Tang Chengzhi Zhou Junping Zhang Junli Xue Hui Guo Qian Chu Rui Meng Xuewen Liu Jingxun Wu Rui Zhang Jin Zhou Zhengfei Zhu Yongheng Li Hong Qiu Fan Xia Yuanyuan Lu Xiaofeng Chen Jian Feng Rui Ge Enyong Dai Yu Han Weiwei Pan Fei Pang Xin Huang Meizhen Hu Qing Hao Kai Wang Fan Wu Binbin Song Bingwei Xu Liping Wang Youcai Zhu Li Lin Yanru Xie Xinqing Lin Jing Cai Ling Xu Jisheng Li Xiaodong Jiao Kainan Li Jia Wei Huijing Feng Lin Wang Yingying Du Wang Yao Xuefei Shi Xiaomin Niu Dongmei Yuan Yanwen Yao Jianhui Huang Yue Feng Yinbin Zhang Pingli Sun Hong Wang Mingxiang Ye Dong Wang Zhaofeng Wang Yue Hao Zhen Wang Bin Wan Donglai Lv Shengjie Yang Jin Kang Jiatao Zhang Chao Zhang Wenfeng Li Jianfei Fu Lizhi Wu Shijie Lan Juanjuan Ou Lin Shi Zhanqiang Zhai Yina Wang Bihui Li Zhang Zhang Ke Wang Xuelei Ma Zhongwu Li Zhefeng Liu Nong Yang Lin Wu Huijuan Wang Gu Jin Guansong Wang Jiandong Wang Hubing Shi Meiyu Fang Yong Fang Yuan Li Xiaojia Wang Jing Chen Yiping Zhang Xixu Zhu Yi Shen Shenglin Ma Biyun Wang Yong Song Zhengbo Song Wenfeng Fang Yuanzhi Lu Lu Si 《The Innovation》 EI 2024年第6期100-116,共17页

The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signa... The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signaling pathway,which promotes cell proliferation,inhibits cell apoptosis,and ultimately contributes to the occurrence and development of cancer.BRAF mutations are widely present in various cancers,including malignant melanoma,thyroid cancer,colorectal cancer,non-small cell lung cancer,and hairy cell leukemia,among others.BRAF is an important target for the treatment of various solid tumors,and targeted combination therapies,represented by BRAF inhibitors,have become one of the main treatment modalities for a variety of BRAF-mutation-positive solid tumors. 展开更多

关键词 BRAF diagnosis treatment

FOXO3 mutation predicting gefitinib-induced hepatotoxicity in NSCLC patients through regulation of autophagy 认领 引用 被引量：2

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作者 Shaoxing Guan Xi Chen +15 位作者 Youhao Chen Guohui Wan Qibiao Su Heng Liang Yunpeng Yang Wenfeng Fang Yan Huang Hongyun Zhao Wei Zhuang Shu Liu Fei Wang Wei Feng Xiaoxu Zhang Min Huang Xueding Wang Li Zhang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2022年第9期3639-3649,共11页

Hepatotoxicity is a common side effect for patients treated with gefitinib,but the related pathogenesis is unclear and lacks effective predictor and management strategies.A multi-omics approach integrating pharmacomet... Hepatotoxicity is a common side effect for patients treated with gefitinib,but the related pathogenesis is unclear and lacks effective predictor and management strategies.A multi-omics approach integrating pharmacometabolomics,pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution.Here,we found that patients with rs4946935 AA,located in Forkhead Box O3(FOXO3)which is a well-known autophagic regulator,had a higher risk of hepatotoxicity than those with the GA or GG variant(OR=18.020,95%CI=2.473 to 459.1784,P=0.018)in a gefitinib-concentration dependent pattern.Furthermore,functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity,increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury.In contrast,erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3.This study reveals that FOXO3 mutation,leading to autophagic imbalance,plays important role in gefitinib-induced hepatotoxicity,especially for patients with high concentration of gefitinib.In conclusion,FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA. 展开更多

关键词 Gefitinib Hepatotoxicity Pharmacometabolomic Pharmacokinetics Pharmacogenomics FOXO3 Autophagy

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Chinese expert consensus on the diagnosis and treatment of bone metastasis in lung cancer(2022 edition) 认领 引用 被引量：4

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作者 Jianchun Duan Wenfeng Fang +32 位作者 Hairong Xu Jinliang Wang Yuan Chen Yi Ding Xiaorong Dong Yun Fan Beili Gao Jie Hu Yan Huang Cheng Huang Dingzhi Huang Wenhua Liang Lizhu Lin Hui Liu Zhiyong Ma Meiqi Shi Yong Song Chuanhao Tang Jialei Wang Lifeng Wang Yongfeng Wang Zhehai Wang Nong Yang Yu Yao Yan Yu Qitao Yu Hongmei Zhang Jun Zhao Mingfang Zhao Zhengfei Zhu Xiaohui Niu Li Zhang Jie Wang 《Journal of the National Cancer Center》 2023年第4期256-265,共10页

Lung cancer is the leading cause of cancer-related deaths worldwide.Bone is a common metastatic site of lung cancer,about 50%of bone metastatic patients will experience skeletal related events(SREs).SREs not only seri... Lung cancer is the leading cause of cancer-related deaths worldwide.Bone is a common metastatic site of lung cancer,about 50%of bone metastatic patients will experience skeletal related events(SREs).SREs not only seriously impact the quality of life of patients,but also shorten their survival time.The treatment of bone metastasis requires multi-disciplinary therapy(MDT)and development of individualized treatment plan.In order to standardize the diagnosis and treatment of bone metastasis in lung cancer,the expert group of the MDT Committee of the Chinese Medical Doctor Association has developed the expert consensus on the diagnosis and treatment of lung cancer bone metastasis. 展开更多

关键词 Lung cancer Bone metastasis Multi-disciplinary therapy Bone-modifying drugs

Phase I study of camrelizumab in patients with advanced solid tumors 认领 引用 被引量：2

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作者 Yuxiang Ma Jiaxin Cao +7 位作者 Yang Zhang Qianwen Liu Wenfeng Fang Yunpeng Yang Yuanyuan Zhao Qing Yang Hongyun Zhao Li Zhang 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2023年第3期885-887,共3页

Dear Editor,Camrelizumab(SHR-1210)is a humanized monoclonal antibody(mAb)that binds to programmed cell death protein 1(PD-1).1 Since May 2019,camrelizumab has been successfully approved for the therapy of patients wit... Dear Editor,Camrelizumab(SHR-1210)is a humanized monoclonal antibody(mAb)that binds to programmed cell death protein 1(PD-1).1 Since May 2019,camrelizumab has been successfully approved for the therapy of patients with various malignancies.2 However,only a few studies have focused on the pharmacokinetics(PK). 展开更多

关键词 patients monoclonal death

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Preferable background filtering for next-generation sequencing analysis in non-small cell lung cancer:pericarcinomatous tissues or peripheral blood lymphocytes? 认领 引用

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作者 Yaxiong Zhang Lianpeng Chang +7 位作者 Wenfeng Fang Yunpeng Yang Lanjun Zhang Shaodong Hong Huaqiang Zhou Yanfang Guan Xin Yi Li Zhang 《Cancer Communications》 SCIE 2019年第1期314-317,共4页

Dear editor,Lung cancer is the leading cause of cancer-related death worldwide,with the predominant pathological type being non-small cell lung cancer(NSCLC)[1,2].Next-gener-ation sequencing(NGS)analysis is increasing... Dear editor,Lung cancer is the leading cause of cancer-related death worldwide,with the predominant pathological type being non-small cell lung cancer(NSCLC)[1,2].Next-gener-ation sequencing(NGS)analysis is increasingly used to help clinicians select appropriate target therapies,such as epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)for EGFR-mutant patients[3].Both pericarcinomatous tissues and peripheral blood lymphocytes are widely used as normal control for NGS analysis.However,whether pericarcinomatous tissue is suitable for background filtering in mutation analysis remains controversial.According to the whole-genome sequencing data from The Cancer Genome Atlas(TCGA)database,there were some genomic variations in peri-carcinomatous tissue from NSCLC patients,but no driver gene mutation was detected[4,5].Therefore,deep sequencing of pericarcinomatous and tumor tissues is necessary to confirm whether pericarcinomatous tissue harbors low-frequency mutations. 展开更多

关键词 lymphocytes lung filtering