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The Chinese Society of Clinical oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023

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Cancer Communications 2024年第1期44卷 127-172页

作者： Feng-Hua Wang Xiao-Tian Zhang Lei Tang Qi Wu Mu-Yan Cai Yuan-Fang Li Xiu-Juan Qu Hong Qiu Yu-Jing Zhang Jie-Er Ying Jun Zhang Ling-Yu Sun Rong-Bo Lin Chang Wang Hao Liu Miao-Zhen Qiu Wen-Long Guan Sheng-Xiang Rao Jia-Fu Ji Yan Xin Wei-Qi Sheng Hui-Mian Xu Zhi-Wei Zhou Ai-Ping Zhou Jing Jin Xiang-Lin Yuan Feng Bi Tian-Shu Liu Han Liang Yan-Qiao Zhang Guo-Xin Li Jun Liang Bao-Rui Liu Lin Shen Jin Li Rui-Hua Xu department of Medical oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China department of gastrointestinal oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer HospitalBeijingP.R.China department of Radiology Peking University Cancer HospitalBeijingP.R.China department of Endoscopy Center Peking University Cancer HospitalBeijingP.R.China department of Pathology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangzhouGuangdongP.R.China department of Gastric surgery Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China department of Medical oncology The First Hospital of China Medical UniversityShenyangLiaoningP.R.China department of Medical oncology Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and TechnologyWuhanHubeiP.R.China department of Radiotherapy Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China department of Medical oncology Zhejiang Cancer HospitalHangzhouZhejiangP.R.China department of Medical oncology Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiP.R.China department of surgical oncology The Fourth Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangP.R.China department of Medical oncology Fujian Cancer HospitalFuzhouFujianP.R.China Tumor Center The First Hospital of Jilin UniversityChangchunJilinP.R.China department of General surgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China department of Radiology Zhongshan HospitalFudan UniversityShanghaiP.R.China department of

The 2023 update of the Chinese Society of Clinical oncology(CSCO)Clini-cal Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China,reflecting the latest advancements in evidence-based medicine,healthcare resource availability,and precision *** updates address the differences in epidemiological characteristics,clinicopatho-logical features,tumor biology,treatment patterns,and drug selections between Eastern and Western gastric cancer *** revisions include a structured template for imaging diagnosis reports,updated standards for molecular marker testing in pathological diagnosis,and an elevated recommendation for neoadju-vant chemotherapy in stage III gastric *** advanced metastatic gastric cancer,the guidelines introduce new recommendations for immunotherapy,anti-angiogenic therapy and targeted drugs,along with updated management strategies for human epidermal growth factor receptor 2(HER2)-positive and deficient DNA mismatch repair(dMMR)/microsatellite instability-high(MSI-H)***,the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric *** 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice,particularly in the heterogeneous healthcare landscape of China,while maintaining a commitment to scientific rigor,impartiality,and timely revisions.

关键词： Chinese Society of Clinical oncology(CSCO) gastric cancer diagnosis surgery neoadjuvant adjuvant radiotherapy chemotherapy targeted therapy immunotherapy

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Mechanism of PARP inhibitor resistance and potential overcoming strategies

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Genes & Diseases 2024年第1期11卷 306-320页

作者： Xiaoyu Fu Ping Li Qi Zhou Ruyuan He Guannan Wang Shiya Zhu Amir Bagheri Gary Kupfer Huadong Pei Juanjuan Li department of oncology Georgetown Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonDC 20057USA department of Breast and Thyroid surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Cancer Center Renmin Hospital of Wuhan UniversityWuhanHubei 430060China department of Thoracic surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China

PARP inhibitors(PARPi)are a kind of cancer therapy that targets poly(ADP-ribose)*** is the first clinically approved drug to exert synthetic lethality by obstruct-ing the DNA single-strand break repair *** the significant therapeutic effect in pa-tients with homologous recombination(HR)repair deficiency,innate and acquired resistance to PARPi is a main challenge in the *** this review,we mainly discussed the underlying mechanisms of PARPi resistance and summarized the promising solutions to overcome PARPi resistance,aiming at extending PARPi application and improving patient outcomes.

关键词： Drug resistance Homologous recombination PARP PARP inhibitor Poly(ADP-ribose)polymerase

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Analysis of lymph node metastasis and survival prognosis in early gastric cancer patients: A retrospective study

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World Journal of gastrointestinal surgery 2024年第6期16卷 1637-1646页

作者： Dong-Yuan Liu Jin-Jin Hu Yong-Quan Zhou Ai-Rong Tan department of General surgery The 971st Hospital of Chinese People's Liberation ArmyQingdao 266071Shandong ProvinceChina department of Chest surgery Feicheng People's HospitalFeicheng 271600Shandong ProvinceChina department of gastrointestinal surgery Zhongshan Hospital of Fudan UniversityShanghai 200032China department of oncology Qingdao Municipal HospitalQingdao 266000Shandong ProvinceChina

BACKGROUND Early gastric cancer(EGC)is a common malignant tumor of the digestive system,and its lymph node metastasis and survival prognosis have been *** retrospectively analyzing the clinical data of EGC patients,we can better under-stand the status of lymph node metastasis and its impact on survival and *** To evaluate the prognosis of EGC patients and the factors that affect lymph node METHODS The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort *** were 561 males and 450 *** mean age was 58±11 *** patient underwent radical *** status of lymph node metastasis in each group was determined according to the pathological examination results of surgical *** outcomes were as follows:(1)Lymph node metastasis in EGC patients;(2)Analysis of influencing factors of lymph node metastasis in EGC;and(3)Analysis of prognostic factors in patients with *** distributed measurement data are expressed as mean±SD,and a t test was used for comparisons between *** data are expressed as absolute numbers or percentages,and the chi-square test was used for comparisons between *** data were compared using a nonparametric rank sum test.A log-rank test and a logistic regression model were used for univariate analysis.A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate *** Kaplan-Meier method was used to calculate the survival rate and construct survival curves.A log-rank test was used for survival *** Analysis of influencing factors of lymph node metastasis in *** results of the multifactor analysis showed that tumor length and diameter,tumor site,tumor invasion depth,vascular thrombus,and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC(odds ratios=1.80,1.49,2.6

关键词： Gastric neoplasms Lymph node metastasis Prognosis Influencing factor Retrospective study

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Frequency of and reasons behind non-listing in adult patients referred for liver transplantation: Results from a retrospective study

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World Journal of Transplantation 2024年第2期14卷 99-106页

作者： Marco Biolato Luca Miele Giuseppe Marrone Claudia Tarli Antonio Liguori Rosaria Calia Giovanni Addolorato Salvatore Agnes Antonio Gasbarrini Maurizio Pompili Antonio Grieco department of Medical and surgical Sciences CEMADFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy department of Translational Medicine and surgery Catholic University of Sacred HeartRome 00168Italy

BACKGROUND Few studies have evaluated the frequency of and the reasons behind the refusal of listing liver transplantation *** To assess the ineligibility rate for liver transplantation and its *** A single-center retrospective study was conducted on adult patients which entailed a formal multidisciplinary assessment for liver transplantation *** predictors for listing were evaluated using multivariable logistic *** In our center,314 patients underwent multidisciplinary work-up before liver transplantation enlisting over a three-year *** most frequent reasons for transplant evaluation were decompensated cirrhosis(51.6%)and hepatocellular carcinoma(35.7%).The non-listing rate was 53.8%and the transplant rate was 34.4%for the whole *** hundred and five motivations for ineligibility were *** most common contraindications were psychological(9.3%),cardiovascular(6.8%),and surgical(5.9%).Inappropriate or premature referral accounted for 76(37.1%)*** multivariable analysis,a referral from another hospital(OR:2.113;95%CI:1.259–3.548)served as an independent predictor of *** A non-listing decision occurred in half of our cohort and was based on an inappropriate or premature referral in one case out of *** referral from another hospital was taken as a strong predictor of non-listing.

关键词： Controindication Eligibility Evaluation Referral Personalized medicine

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Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis

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World Journal of gastrointestinal surgery 2024年第6期16卷 1845-1856页

作者： Ying Wang Yan Yang Qi-Qi Liu Shao-Zhao Wang department of Anus intestinal surgery Feicheng People’s HospitalFeicheng 271600Shandong ProvinceChina department of gastroenterology Qingdao Hospital of University of Health and Rehabilitation Sciences(Qingdao Municipal Hospital)Qingdao 266011Shandong ProvinceChina department of gastrointestinal surgery Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina department of Anorectal Words Central Hospital Affiliated Shandong First Medical UniversityJinan 250013Shandong ProvinceChina

BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy(TNT)and neoadjuvant chemoradiotherapy(nCRT)in the treatment of middle and low locally advanced rectal *** study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates,surgical resection rates,tumor-free survival,and severe adverse *** To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment *** A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese(CNKI,Wanfang,China Biomedical Literature Database)and English(PubMed,Embase)databases was *** system assessors independently screened the studies according to the inclusion and exclusion *** evaluation and RESULTS Finally,14 studies were included,six of which were randomized controlled studies.A total of 3797 patients were included,including 1865 in the TNT group and 1932 in the nCRT *** two sets of baseline data were *** results of the meta-analysis showed that the pCR rate[odds ratio(OR)=1.57,95%confidence interval(CI):1.30-1.90,P<0.00001],T stage degradation rate(OR=2.16,95%CI:1.63-2.57,P<0.00001),and R0 resection rate(OR=1.42,95%CI:1.09-1.85,P=0.009)were significantly greater in the nCRT group than in the nCRT *** was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two *** 5-year OS[hazard ratio(HR)=0.84,95%CI:0.69-1.02,P=0.08]and DFS(HR=0.94,95%CI:0.03-1.39,P=0.74)of the TNT group were similar to those of the nCRT *** TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.

关键词： Neoadjuvant therapy Neoadjuvant chemoradiotherapy Advanced rectal cancer Clinical efficacy Meta-analysis

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Traumatic lumbar hernia: A systematic review of the literature

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Chinese Journal of Traumatology 2024年第1期27卷 53-57页

作者： Ioannis Tsouknidas Nikolaos Tasis Maria Ioanna Antonopoulou Vasileios Acheimastos Dimitrios KManatakis department of surgery Stony Brook University HospitalStony BrookNew YorkUSA department of surgical oncology St Savvas Cancer HospitalAthensGreece nd department of surgery Athens Naval and Veterans HospitalAthensGreece department of surgery Naval Hospital of CreteChaniaGreece

Purpose:Traumatic lumbar hernia(TLH)constitutes a protrusion of content through a defect in the posterior abdominal wall,as a result of *** rare entity has been described in limited number of ***:A systematic review of the literature was performed according to the meta-analysis of observational studies in epidemiology *** English literature from 1990 until 2021 was reviewed,using PubMed,EMBASE and Google Scholar bibliographic databases,to identify case reports and case series with patients that were diagnosed with *** each eligible study,demographics,clinical presentation,hernia characteristics,preoperative imaging investigations,operation details,and postoperative data were extracted for *** analysis was performed on SPSS,version ***:A total of 62 studies were included for review,with 164 patients with *** age was(42.6±14.3)years(47.6%males,31.1%females,gender not specified in 35 cases).Mean diameter of hernia neck was(6.3±3.1)cm,while the triangles of Petit and Grynfeltt were affected in 74.5%and 14.6%,*** diagnosed in the emergency setting account for 54.2%,with CT scan establishing diagnosis in all but one case(97.7%).A delayed diagnosis was made in 45.8%,at a mean 1 year following *** bulging(82.8%)and chronic back pain(34.3%)were the most frequent *** both delayed and acute group,open surgery(63.6%and 92.3%,respectively)was the preferred surgical *** complications were reported in 11.4%of acute and 15.0%of delayed *** recurrence was 7%.Conclusions:TLH is uncommon with 164 cases described since *** scan is the gold standard in *** surgery is generally the preferred approach,particularly in the emergency *** TLH can be treated either by primary suture repair or mesh,depending on the local conditions,whereas delayed cases usually require a mesh.

关键词： Lumbar hernia Petit Grynfeltt Traumatic lumbar hernia Trauma

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Neoadjuvant camrelizumab(an anti-PD-1 antibody)plus chemotherapy or apatinib(a VEGFR-2 inhibitor)for initially unresectable stage II–III non-small-cell lung cancer:a multicentre,two-arm,phase 2 exploratory study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3015-3023页

作者： Haoran Xia Han Zhang Zheng Ruan Huibiao Zhang Liangdong Sun Hezhong Chen Yongxin Zhou Lele Zhang Dongliang Bian Xinsheng Zhu Jing Zhang Fenghuan Sun Huansha Yu Nan Song Xiaogang Liu Yuming Zhu Haiping Zhang Wenxin He Jian Chen Jie Yang Guohan Chen Shiliang Xie Dongfang Tang Xiaomiao Zhang Liang Duan Deping Zhao Qinchuan Li Peng Zhang Gening Jiang department of Thoracic surgery Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Thoracic surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of Thoracic surgery Huadong Hospital Affiliated to Fudan UniversityShanghaiChina department of Thoracic surgery Changhai HospitalNaval Medical UniversityShanghaiChina department of Thoracic-Cardiovascular surgery Tongji HospitalTongji University School of MedicineShanghaiChina Central Laboratory Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Experimental Animal Center Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Thoracic surgery Shanghai East HospitalTongji University School of MedicineShanghaiChina

This multicentre,two-arm,phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II–III non-small-cell lung cancer(NSCLC).Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks(arm A)or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily(arm B),for 2–4 cycles,followed by *** primary endpoint was major pathological response(MPR)*** patients in arm A and 21 in arm B were *** rates were 50.0%(15/30)in arm A and 42.9%(9/21)in arm B,with all patients achieving R0 *** these patients,the MPR and pathological complete response rates were both 20.0%(95%CI 4.3–48.1)in arm A and were 55.6%(95%CI 21.2–86.3)and 11.1%(95%CI 0.3–48.2)in arm B,*** corresponding objective response rates were 33.3%(95%CI 11.8–61.6)and 55.6%(95%CI 21.2–86.3).With a median follow-up of 22.4 months(95%CI 19.0–26.0),the median event-free survival was not reached(NR;95%CI 13.6-NR)in arm A and 16.8 months(95%CI 8.6-NR)in arm *** 3 or above treatment-related adverse events occurred in eight(26.7%)patients in arm A and three(14.3%)in arm *** analysis showed baseline TYROBP expression was predictive of treatment response in arm *** camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II–III NSCLC.

关键词： surgery chemotherapy treatment

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Comparing short-term outcomes of robot-assisted and conventional laparoscopic total mesorectal excision surgery for rectal cancer in elderly patients

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World Journal of gastrointestinal surgery 2024年第5期16卷 1271-1279页

作者： Hao Yang Gang Yang Wen-Ya Wu Fang Wang Xue-Quan Yao Xiao-Yu Wu The Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina department of surgical oncology The Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina

BACKGROUND Da Vinci Robotics-assisted total mesorectal excision(TME)surgery for rectal cancer is becoming more widely *** is no strong evidence that roboticassisted surgery and laparoscopic surgery have similar outcomes in elderly patients with TME for rectal *** To determine the improved oncological outcomes and short-term efficacy of robot-assisted surgery in elderly patients undergoing TME *** A retrospective study of the clinical pathology and follow-up of elderly patients who underwent TME surgery at the department of gastrointestinal oncology at the Affiliated Hospital of Nanjing University of Chinese Medicine was conducted from March 2020 through September *** patients were divided into a robotassisted group(the R-TME group)and a laparoscopic group(the L-TME group),and the short-term efficacy of the two groups was *** There were 45 elderly patients(≥60 years)in the R-TME group and 50 elderly patients(≥60 years)in the L-TME *** were no differences in demographics,conversion rates,or postoperative complication *** L-TME group had a longer surgical time than the R-TME group[145(125,187.5)vs 180(148.75,206.25)min,P=0.005),and the first postoperative meal time in the L-TME group was longer than that in the R-TME(4 vs 3 d,P=0.048).Among the sex and body mass index(BMI)subgroups,the R-TME group had better out-comes than did the L-TME group in terms of operation time(P=0.042)and intraoperative assessment of bleeding(P=0.042).In the high BMI group,catheter removal occurred earlier in the R-TME group than in the L-TME group(3 vs 4 d,P=0.001),and autonomous voiding function was *** The curative effect and short-term efficacy of robot-assisted TME surgery for elderly patients with rectal cancer are similar to those of laparoscopic TME surgery;however,robotic-assisted surgery has better short-term outcomes for individuals with risk factors such as obesity and pelvic *** the learning

关键词： Robotic surgery Laparoscopy Rectal cancer Total mesorectal excision Elderly

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Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis

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World Journal of gastroenterology 2024年第7期30卷 663-672页

作者： Xiao-Fei Cheng Feng Zhao Dong Chen Fan-Long Liu department of Colorectal surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina department of Radiation oncology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient *** resection,a key element in achieving prolonged survival,is often linked to a heightened risk of *** the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative ***,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing *** balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced *** article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable *** the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of *** the right balance between maximizing treatment efficacy and minimizing adverse effects is *** dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant ***,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of *** technical expertise and biological insights is crucial in refining neoadjuvant *** management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may *** conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable *** combining evidencebased insights with practical experiences,we aspire to contribute

关键词： Neoadjuvant therapy Colorectal cancer liver metastasis Multidisciplinary teams Chemotherapeutic regimens Resectability criteria

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The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua Liang department of Thoracic surgery and oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical department Genecast Biotechnology Co.LtdWuxiChina department of Radiation oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina department of Cardiothoracic surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina department of Thoracic surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina department of Medical oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains *** is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)*** primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and ***,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs *** total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over ***,the mIHC analysis showed more CD8^(+)T cells infiltrated in ***,responders’cytokine concentrations of EGF and CTLA-4 increased during *** exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among ***,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety *** effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

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