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Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated,EGFR-mutated,advanced non-small cell lung cancer:data froma randomized phase III trial(AENEAS)

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Cancer Communications 2024年第9期44卷 1005-1017页

作者： Shun Lu Xiaorong Dong Hong Jian Jianhua chen Gongyan chen Yuping Sun Yinghua Ji ZipingWang Jianhua Shi Junguo Lu shaoshui chen Dongqing Lv Guojun Zhang Chunling Liu Juan Li Xinmin Yu Zhong Lin Zhuang Yu ZhehaiWang Jiuwei Cui Xingxiang Xu Jian Fang Jifeng Feng Zhi Xu RuiMa Jie Hu Nong Yang Xiangdong Zhou XiaohongWu chengping Hu Zhihong Zhang You Lu Yanping Hu Liyan Jiang Qiming wang Renhua Guo Jianying Zhou Baolan Li Chunhong Hu Wancheng Tong Helong Zhang LinMa Yuan chen Zhijun Jie Yu Yao Longzhen Zhang JieWeng Weidong Li Jianping Xiong Xianwei Ye Jianchun Duan Haihua Yang Meili Sun HongyingWei JiaweiWei Zheyu Zhang QiongWu Department of Medical Oncology Shanghai Chest Hospital Shanghai JiaoTong UniversityShanghaiP.R.China Cancer Center Union Hospital Tongji Medical College Huazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Medical Oncology-Chest Hunan Cancer Hospital&The Affiliated Cancer Hospital of Central South University Xiangya School of MedicineChangshaHunanP.R.China Thoracic OncologyMedicine HarbinMedical University Cancer HospitalHarbinHeilongjiangP.R.China Department of Oncology Jinan Central HospitalJinanShandongP.R.China Department of Oncology First Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenanP.R.China Department of Chest Medicine Beijing Cancer HospitalBeijingP.R.China Department of Internal Medicine Linyi Cancer HospitalLinyiShandongP.R.China Department of Respiratory Medicine Nantong Tumor HospitalNantongJiangsuP.R.China Department of Oncology Binzhou Medical University HospitalBinzhouShandongP.R.China Breath Internal Medicine Taizhou Hospital of Zhejiang ProvinceLinhaiZhejiangP.R.China Department of Respiration The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China Department of Lung Internal Medicine Affiliated Tumor Hospital of Xinjiang Medical UniversityUrumqiXinjiangP.R.China Department of Thoracic Oncology Sichuan Cancer HospitalChengduSichuanP.R.China Thoracic Medical Oncology Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)HangzhouZhejiangP.R.China Department of Thoracic Oncology The Fifth Subsidiary Sun Yat-sen University HospitalZhuhaiGuangdongP.R.China Department of Oncology The Affiliated Hospital of QingdaoUniversityQingdaoShandongP.R.China Department of Oncology Shandong Cancer HospitalJinanShandongP.R.China Department of Oncology The First BethuneHospital of Jilin UniversityChangchunJilinP.R.China Department of Respiration Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityYangzhouJiangsuP.R.China Department of Internal

Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of *** study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS ***:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded *** with asymptomatic,stable CNS metastases were ***-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every *** responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,*** risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at *** new safety findings were ***:The

关键词： aumolertinib brain metastasis non-small cell lung cancer third-generation EGFR-TKI

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Concurrent chemoradiotherapyof different radiation doses and different irradiation fields for locally advanced thoracic esophageal squamous cell carcinoma:A randomized,multicenter,phase Ⅲ clinical trial

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Cancer Communications 2024年第10期44卷 1173-1188页

作者： Jian Zhang Minghao Li Kaixian Zhang Anping Zheng Guang Li Wei Huang shaoshui chen Xiangming chen Xiaomin Li Yanxing Sheng Xinchen Sun Liping Liu Xiaowei Liu Jie Li Jun Wang Hong Ge Shucheng Ye Qingsong Pang Xianwen Zhang Shengbin Dai Richard Yu Wendong Gu Mingming Dai Gaowa Siqin Yunwei Han Xiaolin Ge Xin Yuan Yongjing Yang Haiwen Zhu Juan Pu Lihua Dong Xiangdong Sun Jundong Zhou Weidong Mao Fei Gao Haiqun Lin Heyi Gong Tao Zhou Zhenjiang Li Hongsheng Li Zhongtang Wang Baosheng Li Department of Oncology Central Hospital Affiliated to Shandong First Medical UniversityJinanShandongP.R.China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongP.R.China Department of Oncology Tengzhou Central People’s HospitalTengzhouShandongP.R.China Department of Radiation Oncology Anyang Tumor HospitalAnyangHenanP.R.China Department of Radiation Oncology the First Hospital of China Medical UniversityShenyangLiaoningP.R.China Department of Oncology Binzhou Medical University HospitalBinzhouShandongP.R.China Department of Oncology Taian CentralHospitalTaianShandongP.R.China Department of Radiation Oncology Shanxi Province Cancer HospitalTaiyuanShanxiP.R.China Department of Oncology Liaocheng People’s HospitalLiaochengShandongP.R.China Department of Radiation Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China Department of Oncology Jining First People′s HospitalJiningShandongP.R.China Department of Oncology the Affiliated Hospital of Jining Medical UniversityJiningShandongP.R.China Department of Radiation Oncology the Fourth Hospital of Hebei Medical UniversityHebei Clinical Research Center for Radiation OncologyShijiazhuangHebeiP.R.China Department of Radiation Oncology the Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China Department of Radiation Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory ofCancer Prevention and TherapyTianjin’s ClinicalResearch Center for CancerTianjinP.R.China Department of Oncology Subei People’s Hospital of Jiangsu ProvinceYangzhouJiangsuP.R.China Department of Oncology Taizhou People’s Hospital of Jiangsu ProvinceTaizhouZhejiangP.R.China Department of Radiation Oncology the Affiliated Hospital of Inner Mongolia Medical UniversityHohhotInner MongoliaP.R.China Department of Radiation O

Background:Concurrent chemoradiotherapy(CCRT)is the standard treatment for locally advanced esophageal squamous cell carcinoma(ESCC).However,the optimal radiotherapy regimen,particularly in terms of total dose and planned range of irradiation field,remains *** phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target ***:This trial compared two aspects of radiation treatment,total dose and field,using a two-by-two factorial *** high-dose(HD)group received 59.4 Gy radiation,and the standard-dose(SD)group received 50.4 *** involved field irradiation(IFI)group and elective nodal irradiation(ENI)group adopted different irradiation *** participants were assigned to one of the four groups(HD+ENI,HD+IFI,SD+ENI and SD+IFI).The primary endpoint was overall survival(OS),and the secondary endpoints included progressionfree survival(PFS).The synergy indexwas used to measure the interaction effect between dose and ***:The interaction analysis did not reveal significant synergistic effects between the dose and irradiation *** comparison to the target field,patients in IFI or ENI showed similar OS(hazard ratio[HR]=0.99,95%CI:0.80-1.23,p=0.930)and PFS(HR=1.02,95%CI:0.82–1.25).TheHDtreatment did not show significantly prolonged OS compared with SD(HR=0.90,95%CI:0.72–1.11,p=0.318),but it suggested improved PFS(25.2 months to 18.0 months).Among the four groups,the HD+IFI group presented the best survival,while the SD+IFI group had the worst *** significant difference in the occurrence of severe adverse events was found in dose or field ***:IFI demonstrated similar treatment efficacy to ENI in CCRT of *** HD demonstrated improved PFS,but did not significantly improve *** dose escalation based on IFI(HD+IFI)showed better therapeutic efficacy than the current recommendation(SD+ENI)and is worth further validation.

关键词： clinical trial concurrent chemoradiotherapy elective nodal radiation esophageal squamous cell carcinoma high dose radiation involved field radiation overall survival standard dose radiation

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放射性脑损伤发病机制及防治的研究与进展

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中国医药科学 2020年第2期10卷 37-40,50页

作者：马龙陈绍水滨州医学院附属医院肿瘤科山东滨州256603

目前,颅脑放射治疗引起的放射性脑损伤(RBI)是影响颅脑放疗后患者生存质量的重要因素之一,晚期的放射性脑损伤往往是不可逆的。目前大量研究认为,血管与血脑屏障损伤、免疫炎症反应、氧化应激等多种机制可能参与了RBI的发病。近年来,随... 详细信息

目前,颅脑放射治疗引起的放射性脑损伤(RBI)是影响颅脑放疗后患者生存质量的重要因素之一,晚期的放射性脑损伤往往是不可逆的。目前大量研究认为,血管与血脑屏障损伤、免疫炎症反应、氧化应激等多种机制可能参与了RBI的发病。近年来,随着对RBI的研究及大量临床经验的积累,对RBI的治疗与预防有了进一步的认识。本文归纳了当前对RBI发病机制、临床诊断与治疗的相关研究,对其做一综述。

关键词：放射性脑损伤发病机制颅脑放疗预防

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体部伽马刀治疗早期周围型非小细胞肺癌的临床疗效观察

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滨州医学院学报 2015年第1期38卷 26-29,32页

作者：王兴陈绍水滨州医学院滨州256603 滨州医学院附属医院肿瘤科

目的：观察体部伽玛刀治疗42例早期（T1‐2aN0M0，Ⅰ期）周围型非小细胞肺癌（ NSCLC）患者的临床疗效和安全性。方法42例患者（90％的患者有病理学诊断）接受伽马刀治疗，其中ⅠA期者18例，ⅠB期者24例；放疗总剂量为48～60Gy（中位剂... 详细信息

目的：观察体部伽玛刀治疗42例早期（T1‐2aN0M0，Ⅰ期）周围型非小细胞肺癌（ NSCLC）患者的临床疗效和安全性。方法42例患者（90％的患者有病理学诊断）接受伽马刀治疗，其中ⅠA期者18例，ⅠB期者24例；放疗总剂量为48～60Gy（中位剂量为57Gy），50％以上的等剂量线必须包括100％以上的PTV ，60％的等剂量线覆盖90％ CTV ，70％等剂量线覆盖80％ GTV。完成治疗后评估近期和远期疗效以及不良反应。结果随访时间为3～42个月（中位随访时间为28个月），其中完全缓解者22例、部分缓解者17例、疾病稳定者1例、疾病进展者2例，有效率为92．9％，2年局部控制率为82．6％，1年总生存率为94．5％，2年总生存率为52.2％。结论体部伽玛刀作为立体定向放射治疗的主要设备之一，对于无法手术或拒绝手术的早期周围型非小细胞肺癌患者，疗效确切，毒副反应小，可明显改善病人的生存质量。

关键词：体部伽玛刀非小细胞肺癌疗效观察

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p53基因在非小细胞肺癌中的表达及临床意义

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国际肿瘤学杂志 2019年第2期46卷 102-104页

作者：温洁陈绍水滨州医学院附属医院肿瘤科 256600

非小细胞肺癌的发生、发展是多因素相互作用的复杂过程,在此过程中p53基因调控着细胞的正常生长,而突变后的p53基因可导致非小细胞肺癌的发生、促进肿瘤的转移、诱导化疗耐药、致使患者预后不良。恢复正常p53基因的表达对非小细胞肺癌... 详细信息

非小细胞肺癌的发生、发展是多因素相互作用的复杂过程,在此过程中p53基因调控着细胞的正常生长,而突变后的p53基因可导致非小细胞肺癌的发生、促进肿瘤的转移、诱导化疗耐药、致使患者预后不良。恢复正常p53基因的表达对非小细胞肺癌的治疗尤其重要,近年来p53基因治疗方面研究的飞速发展为非小细胞肺癌的治疗开辟了新的途径。

关键词：癌,非小细胞肺基因,p53 治疗应用

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SOX方案与XELOX方案治疗进展期胃癌的临床对比研究

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癌症进展 2017年第3期15卷 304-307页

作者：吕文瑜陈绍水滨州医学院附属医院肿瘤科山东滨州256603

目的比较奥沙利铂+替吉奥(SOX)方案与奥沙利铂+卡培他滨(XELOX)方案治疗进展期胃癌(AGCA)的临床疗效。方法选择接受化疗的AGCA患者88例,依据治疗方案分为SOX组(n=44)与XELOX组(n=44)。SOX组行SOX方案化疗,XELOX组行XELOX方案化疗。比较... 详细信息

目的比较奥沙利铂+替吉奥(SOX)方案与奥沙利铂+卡培他滨(XELOX)方案治疗进展期胃癌(AGCA)的临床疗效。方法选择接受化疗的AGCA患者88例,依据治疗方案分为SOX组(n=44)与XELOX组(n=44)。SOX组行SOX方案化疗,XELOX组行XELOX方案化疗。比较治疗前后两组C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)等炎性因子,CD3^+、CD4^+、CD8^+等T淋巴细胞因子。比较两组临床疗效、不良反应及1、2、3年生存情况。结果治疗前后,两组CRP、TNF-α、IL-6差值及CD3^+、CD4^+、CD8^+差值比较,差异无统计学意义(P﹥0.05)。SOX组PFS为(7.82±0.21)个月,XELOX组PFS为(7.69±0.18)个月,差异无统计学意义(P﹥0.05)。SOX组治疗有效率(70.45%)与XELOX组治疗有效率(68.18%)比较,差异无统计学意义(P﹥0.05)。SOX组1、2、3年生存率(84.09%、56.82%、40.91%)与XELOX组1、2、3年生存率(81.82%、59.09%、45.45%)比较,差异无统计学意义(P﹥0.05)。SOX组手足综合征发生率(13.64%)、外周神经症状发生率(27.27%)均低于XELOX组手足综合征发生率(31.82%)、外周神经症状发生率(61.36%),差异有统计学意义(P﹤0.05)。结论 SOX、XELOX两种方案治疗AGCA可有效杀灭肿瘤细胞,解除患者免疫抑制,促进免疫因子恢复,临床疗效均较为优异,但SOX方案不良反应发生率低,安全性更高。

关键词： SOX方案 XELOX方案进展期胃癌疗效不良反应

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放射性肺损伤的发生机制及防治进展

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国际医药卫生导报 2022年第24期28卷 3494-3499页

作者：张坤韩霞陈绍水滨州医学院附属医院肿瘤科滨州256600

胸部恶性肿瘤的发病率及病死率长期居高不下,最新发表的中国癌症数据显示,所有癌症患者中肺癌的发病率及病死率所占比例均超半数,仍占据着主导地位。放疗作为非小细胞肺癌、食管癌、乳腺癌等胸部恶性肿瘤的极其重要的一种治疗手段,其所... 详细信息

胸部恶性肿瘤的发病率及病死率长期居高不下,最新发表的中国癌症数据显示,所有癌症患者中肺癌的发病率及病死率所占比例均超半数,仍占据着主导地位。放疗作为非小细胞肺癌、食管癌、乳腺癌等胸部恶性肿瘤的极其重要的一种治疗手段,其所带来的严重不良反应之一便是放射性肺损伤(RILI)。RILI由于其后期进行性、不可逆地发展为肺纤维化的临床特点,吸引着越来越多的临床及科研工作者对其发生机制及相应治疗方案进行探索。本文就RILI的病理生理、发生发展过程中涉及的重要细胞、分子及预防治疗进展作一综述。

关键词：放射性肺损伤放射性肺纤维化发病机制治疗

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线粒体离子肽酶1的结构与功能及其在常见恶性肿瘤中的表达和作用

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中国医药科学 2021年第18期11卷 56-60,109页

作者：吴晓涵陈绍水滨州医学院附属医院肿瘤科山东滨州256600

线粒体离子肽酶1(LONP1)是由核脱氧核糖核酸(DNA)所编码的腺嘌呤核苷三磷酸(ATP)依赖蛋白,该蛋白位于线粒体基质中,参与线粒体稳态的维持,是保障线粒体功能和蛋白质稳定的主要蛋白酶之一。近年来,有研究证明,LONP1蛋白与多种肿瘤的发生... 详细信息

线粒体离子肽酶1(LONP1)是由核脱氧核糖核酸(DNA)所编码的腺嘌呤核苷三磷酸(ATP)依赖蛋白,该蛋白位于线粒体基质中,参与线粒体稳态的维持,是保障线粒体功能和蛋白质稳定的主要蛋白酶之一。近年来,有研究证明,LONP1蛋白与多种肿瘤的发生与发展密切相关,其上调与下调对肿瘤细胞的生存代谢产生影响,从而影响癌症患者的生存。本文就LONP1蛋白的结构、功能及其与结肠癌、膀胱癌、宫颈癌等常见恶性肿瘤的相关关系进行阐述。

关键词：线粒体离子酞酶1 线粒体稳态恶性肿瘤结肠癌膀胱癌宫颈癌

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血红蛋白氧载体增强肿瘤治疗效果研究进展

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国际医药卫生导报 2022年第18期28卷 2659-2663页

作者：杨晓倩陈绍水滨州医学院附属医院肿瘤科滨州256600

肿瘤细胞异常增殖所形成的缺氧微环境导致当前多种抗癌治疗效果不够理想,且加速恶性进展,增加转移。在实体瘤中,充足的氧气供应对于提高抗肿瘤治疗的敏感性是至关重要的。具有携氧功能的血红蛋白氧载体(HBOCs)能有效缓解肿瘤缺氧,并与... 详细信息

肿瘤细胞异常增殖所形成的缺氧微环境导致当前多种抗癌治疗效果不够理想,且加速恶性进展,增加转移。在实体瘤中,充足的氧气供应对于提高抗肿瘤治疗的敏感性是至关重要的。具有携氧功能的血红蛋白氧载体(HBOCs)能有效缓解肿瘤缺氧,并与当前多种肿瘤临床治疗手段联用,取得了良好的效果。本文通过对近5年来HBOCs研究进展及其在缓解肿瘤缺氧、增强肿瘤治疗效果方面的应用进行综述,为临床肿瘤治疗提供参考。

关键词：血红蛋白氧载体肿瘤缺氧肿瘤治疗

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Meridional deflection of global eddy propagation derived from tandem altimetry: Mechanism and implication

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Science China Earth Sciences 2024年第3期67卷 811-825页

作者： Ge chen Xiaoyan chen Frontiers Science Center for Deep Ocean Multispheres and Earth System School of Marine TechnologyOcean University of ChinaQindao 266100China Laboratory for Regional Oceanography and Numerical Modeling Laoshan LaboratoryQindao 266237China

A common view on meridional deflection of eddy propagation is poleward for cyclones and equatorward for anticyclones. This widely accepted polarity-sensitive pattern has been increasingly undermined given that it is systematically violated on both zonal and regional scales as recently reported. Here, we approach the problem by exploring these violations in terms of eddy effects of spatiotemporal geostrophy, thermal fading, and flow dragging, yielding the following main conclusions.(1) The polarity-dependent deflection discrepancy is a pseudo feature resulting from a biased fit to the normalized eddy tracks which are spatially asymmetric(though azimuthally symmetric) between the two signs;Instead, the primary pattern of eddy deflection appears to be geographically correlated and polarity independent.(2) Geostrophic adjustment plays a critical role in defining the meridional movement of an eddy. Specifically, a consistent poleward(equatorward) trajectory bending of spatially(temporally) ageostrophic eddies is observed irrespective of their polarity.(3) The mechanism of eddy deflection is also determined by its zonal propagation direction. Westward propagating eddies are substantially affected by thermal fading, while opposite ones by flow dragging. A realistic and comprehensive understanding of eddy deflection mechanisms serves as a significant contribution to the prediction of eddy trajectory, and the protection of ocean environment.

关键词： Mesoscale eddies Eddy propagation Eddy meridional deflection Satellite observation Geostrophic adjustment

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