Pub Date : 2024-09-09DOI: 10.1007/s12094-024-03704-0
Bo li, Yujia Gu, Weixing Zhao, Zirui Li, Wanjing Guo, Xinxin Lu, Jun Jiang
Background
Neoadjuvant immunochemotherapy (NICT) is a new treatment method for resectable non-small-cell lung cancer (NSCLC). Network meta-analysis assessed efficacy, safety, and optimal treatment.
Methods
We searched for randomized controlled trials (RCTs) comparing NICT with neoadjuvant chemotherapy (NCT) in PubMed, Embase, Web of Science, Cochrane Library, and international conferences. Outcomes were surgical resection rate, pathological complete response(pCR),event-free survival (EFS), and Grade 3–5 treatment-related adverse events (TRAEs).
Results
RCTs of 3,387 patients, six treatment combinations, and two modalities were included. Meta-analysis showed that NICT yielded higher pCR and EFS rates than NCT. The toripalimab-chemotherapy combination had the highest surgical resection rate (OR = 1.68, 95% CI: 1.05–2.73), pCR (OR = 38.84, 95% CI: 11.05–268.19) and EFS (HR = 0.40, 95% CI: 0.28–0.58).This regimen worked well for patients with low programmed death-ligand 1 (PD-L1) expression or squamous cell pathology. For high PD-L1 expression and patients with NSCLC, neoadjuvant nivolumab with chemotherapy had the most efficacy. The incidence of treatment-related adverse events increased with longer treatment cycles, with perioperative nivolumab combined with chemotherapy showing the worst safety profile (RR = 1.32, 95% CI: 1.00–1.76), while neoadjuvant nivolumab combined with chemotherapy alone had the best safety profile (RR = 0.91, 95% CI: 0.68–1.21). Indirect comparison showed no survival benefit for neoadjuvant-adjuvant immunotherapy (HR = 0.93, 95% CI: 0.65–1.35). In the indirect comparison between the two immune checkpoint inhibitors(ICIs), although there was no significant difference in EFS (HR = 0.81, 95% CI: 0.61–1.08), PD-1 inhibitors may still be the most effective treatment option.
Conclusions
NICT effectively and safely treats resectable NSCLC. The optimal treatment combination is typically toripalimab and chemotherapy. Treatment based on PD-L1 expression and pathological type is recommended.
{"title":"The efficacy and safety of neoadjuvant immunochemotherapy in resectable stage I-III non-small cell lung cancer: a systematic review and network meta-analysis","authors":"Bo li, Yujia Gu, Weixing Zhao, Zirui Li, Wanjing Guo, Xinxin Lu, Jun Jiang","doi":"10.1007/s12094-024-03704-0","DOIUrl":"https://doi.org/10.1007/s12094-024-03704-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Neoadjuvant immunochemotherapy (NICT) is a new treatment method for resectable non-small-cell lung cancer (NSCLC). Network meta-analysis assessed efficacy, safety, and optimal treatment.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We searched for randomized controlled trials (RCTs) comparing NICT with neoadjuvant chemotherapy (NCT) in PubMed, Embase, Web of Science, Cochrane Library, and international conferences. Outcomes were surgical resection rate, pathological complete response(pCR),event-free survival (EFS), and Grade 3–5 treatment-related adverse events (TRAEs).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>RCTs of 3,387 patients, six treatment combinations, and two modalities were included. Meta-analysis showed that NICT yielded higher pCR and EFS rates than NCT. The toripalimab-chemotherapy combination had the highest surgical resection rate (OR = 1.68, 95% CI: 1.05–2.73), pCR (OR = 38.84, 95% CI: 11.05–268.19) and EFS (HR = 0.40, 95% CI: 0.28–0.58).This regimen worked well for patients with low programmed death-ligand 1 (PD-L1) expression or squamous cell pathology. For high PD-L1 expression and patients with NSCLC, neoadjuvant nivolumab with chemotherapy had the most efficacy. The incidence of treatment-related adverse events increased with longer treatment cycles, with perioperative nivolumab combined with chemotherapy showing the worst safety profile (RR = 1.32, 95% CI: 1.00–1.76), while neoadjuvant nivolumab combined with chemotherapy alone had the best safety profile (RR = 0.91, 95% CI: 0.68–1.21). Indirect comparison showed no survival benefit for neoadjuvant-adjuvant immunotherapy (HR = 0.93, 95% CI: 0.65–1.35). In the indirect comparison between the two immune checkpoint inhibitors(ICIs), although there was no significant difference in EFS (HR = 0.81, 95% CI: 0.61–1.08), PD-1 inhibitors may still be the most effective treatment option.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>NICT effectively and safely treats resectable NSCLC. The optimal treatment combination is typically toripalimab and chemotherapy. Treatment based on PD-L1 expression and pathological type is recommended.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1007/s12094-024-03700-4
Zhicheng Li, Dan Wang, Xiaojun Zhu
Cancer is one of the most serious diseases that threaten human life and health. Among all kinds of diseases, the mortality rate of malignant tumors is the second highest, second only to cardio-cerebrovascular diseases. Cancer treatment typically involves imaging, surgery, and pathological analysis. When patients are identified as carcinoma by the above means, there are often problems of distant metastasis, delayed treatment, and drug tolerance, indicating that patients have some poor prognosis and overall survival. Hence, the development of novel molecular biomarkers is of great clinical importance. In recent years, as an important mediator of material and information exchange between cells in the tumor microenvironment, lncRNA have attracted widespread attention for their roles in tumor development. In this review, we comprehensively summarize the up-to-date knowledge of lncARSR on diverse cancer types which mainly focuses on tumor proliferation, drug tolerance, and lipid and cholesterol metabolism, highlighting the potential of lncARSR as a diagnostic and prognostic biomarker and even a therapeutic target. In our final analysis, we provide a synthesized overview of the directions for future inquiry into lncARSR, and we are eager to witness the advancement of research that will elucidate the multifaceted nature of this lncRNA.
{"title":"Roles of LncRNA ARSR in tumor proliferation, drug resistance, and lipid and cholesterol metabolism","authors":"Zhicheng Li, Dan Wang, Xiaojun Zhu","doi":"10.1007/s12094-024-03700-4","DOIUrl":"https://doi.org/10.1007/s12094-024-03700-4","url":null,"abstract":"<p>Cancer is one of the most serious diseases that threaten human life and health. Among all kinds of diseases, the mortality rate of malignant tumors is the second highest, second only to cardio-cerebrovascular diseases. Cancer treatment typically involves imaging, surgery, and pathological analysis. When patients are identified as carcinoma by the above means, there are often problems of distant metastasis, delayed treatment, and drug tolerance, indicating that patients have some poor prognosis and overall survival. Hence, the development of novel molecular biomarkers is of great clinical importance. In recent years, as an important mediator of material and information exchange between cells in the tumor microenvironment, lncRNA have attracted widespread attention for their roles in tumor development. In this review, we comprehensively summarize the up-to-date knowledge of lncARSR on diverse cancer types which mainly focuses on tumor proliferation, drug tolerance, and lipid and cholesterol metabolism, highlighting the potential of lncARSR as a diagnostic and prognostic biomarker and even a therapeutic target. In our final analysis, we provide a synthesized overview of the directions for future inquiry into lncARSR, and we are eager to witness the advancement of research that will elucidate the multifaceted nature of this lncRNA.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"157 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This retrospective study was undertaken to assess the predictive efficacy of 18F-FDG PET/CT -derived radiomic features concerning the co-mutation status of epidermal growth factor receptor (EGFR) and TP53 in LUAD.
Methods
A cohort of 150 LUAD patients underwent pretreatment 18F-FDG PET/CT scans with known mutation status of EGFR and TP53 were collected. The feature extraction based on their PET/CT images utilized the Pyradiomics package based on the 3D Slicer. The optimal radiomic features were selected through correlation analysis and the Gradient Boosting Decision Tree (GBDT) algorithm, followed by the construction of the radiomic model. The clinical model incorporated meaningful clinical variables, whereas the complex model integrated both the radiomic and clinical models. The area under the receiver operating characteristic curve (AUC) facilitated the comparison of prediction performance across the three models. The DCA gauged the clinical utility of these models.
Results
The patient cohort was randomly allocated into a training set (n = 105) and a validation set (n = 45) in a 7:3 ratio. Eleven PET and eleven CT optimal radiomic features were selected to construct the radiomic model. The model showed a good ability to discriminate the co-occurrence of EGFR and TP53, with AUC equal to 0.850 in the training set, and 0.748 in the validation set, compared with 0.750 and 0.626 for the clinical model. The complex model exhibited the highest AUC values, with 0.880 and 0.794 in both sets, but there were no significant differences compared to the radiomic model. The DCA revealed favorable clinical value.
{"title":"Prediction of EGFR-TP53 genes co-mutations in patients with lung adenocarcinoma (LUAD) by 18F-FDG PET/CT radiomics","authors":"Shuheng Li, Yujing Hu, Congna Tian, Jiusong Luan, Xinchao Zhang, Qiang Wei, Xiaodong Li, Yanzhu Bian","doi":"10.1007/s12094-024-03685-0","DOIUrl":"https://doi.org/10.1007/s12094-024-03685-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>This retrospective study was undertaken to assess the predictive efficacy of <sup>18</sup>F-FDG PET/CT -derived radiomic features concerning the co-mutation status of epidermal growth factor receptor (EGFR) and TP53 in LUAD.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A cohort of 150 LUAD patients underwent pretreatment <sup>18</sup>F-FDG PET/CT scans with known mutation status of EGFR and TP53 were collected. The feature extraction based on their PET/CT images utilized the Pyradiomics package based on the 3D Slicer. The optimal radiomic features were selected through correlation analysis and the Gradient Boosting Decision Tree (GBDT) algorithm, followed by the construction of the radiomic model. The clinical model incorporated meaningful clinical variables, whereas the complex model integrated both the radiomic and clinical models. The area under the receiver operating characteristic curve (AUC) facilitated the comparison of prediction performance across the three models. The DCA gauged the clinical utility of these models.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The patient cohort was randomly allocated into a training set (<i>n</i> = 105) and a validation set (<i>n</i> = 45) in a 7:3 ratio. Eleven PET and eleven CT optimal radiomic features were selected to construct the radiomic model. The model showed a good ability to discriminate the co-occurrence of EGFR and TP53, with AUC equal to 0.850 in the training set, and 0.748 in the validation set, compared with 0.750 and 0.626 for the clinical model. The complex model exhibited the highest AUC values, with 0.880 and 0.794 in both sets, but there were no significant differences compared to the radiomic model. The DCA revealed favorable clinical value.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-27DOI: 10.1007/s12094-024-03619-w
Zhicheng Li, Dan Wang, Xiaojun Zhu
Numerous studies over the past few decades have shown that RNAs are multifaceted, multifunctional regulators of most cellular processes, contrary to the initial belief that they only act as mediators for translating DNA into proteins. LncRNAs, which refer to transcripts longer than 200nt and lack the ability to code for proteins, have recently been identified as central regulators of a variety of biochemical and cellular processes, particularly cancer. When they are abnormally expressed, they are closely associated with tumor occurrence, metastasis, and tumor staging. Therefore, through searches on Google Scholar, PubMed, and CNKI, we identified five five recently characterized lncRNAs–Lnc-SLC2A12-10:1, LncRNA BCRT1, lncRNA IGFBP4-1, LncRNA PCNAP1, and LncRNA CDC6–that have been linked to the promotion of cancer cell proliferation, invasion, and metastasis. Consequently, this review encapsulates the existing research and molecular underpinnings of these five newly identified lncRNAs across various types of cancer. It suggests that these novel lncRNAs hold potential as independent biomarkers for clinical diagnosis and prognosis, as well as candidates for therapeutic intervention. In parallel, we discuss the challenges inherent in the research on these five newly discovered lncRNAs and look forward to the avenues for future exploration in this field.
{"title":"Unveiling the functions of five recently characterized lncRNAs in cancer progression","authors":"Zhicheng Li, Dan Wang, Xiaojun Zhu","doi":"10.1007/s12094-024-03619-w","DOIUrl":"https://doi.org/10.1007/s12094-024-03619-w","url":null,"abstract":"<p>Numerous studies over the past few decades have shown that RNAs are multifaceted, multifunctional regulators of most cellular processes, contrary to the initial belief that they only act as mediators for translating DNA into proteins. LncRNAs, which refer to transcripts longer than 200nt and lack the ability to code for proteins, have recently been identified as central regulators of a variety of biochemical and cellular processes, particularly cancer. When they are abnormally expressed, they are closely associated with tumor occurrence, metastasis, and tumor staging. Therefore, through searches on Google Scholar, PubMed, and CNKI, we identified five five recently characterized lncRNAs–Lnc-SLC2A12-10:1, LncRNA BCRT1, lncRNA IGFBP4-1, LncRNA PCNAP1, and LncRNA CDC6–that have been linked to the promotion of cancer cell proliferation, invasion, and metastasis. Consequently, this review encapsulates the existing research and molecular underpinnings of these five newly identified lncRNAs across various types of cancer. It suggests that these novel lncRNAs hold potential as independent biomarkers for clinical diagnosis and prognosis, as well as candidates for therapeutic intervention. In parallel, we discuss the challenges inherent in the research on these five newly discovered lncRNAs and look forward to the avenues for future exploration in this field.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141773827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Breast cancer (BRCA) is characterized by a unique metastatic pattern, often presenting with bone metastasis (BoM), posing significant clinical challenges. Through the study of the immune microenvironment in BRCA BoM offer perspectives for therapeutic interventions targeting this specific metastatic manifestation of BRCA.
Methods
This study employs single-cell RNA sequencing and TCGA data analysis to comprehensively compare primary tumors (PT), lymph node metastasis (LN), and BoM.
Results and Conclusions
Our investigation identifies a metastatic niche in BoM marked by an increased abundance of cancer-associated fibroblasts (CAFs) and reduced immune cell presence. A distinct subtype (State 1) of BRCA BoM cells associated with adverse prognosis is identified. State 1, displaying heightened stemness traits, may represent an initiation phase for BoM in BRCA. Complex cell communications involving tumor, stromal, and immune cells are revealed. Interactions of FN1, SPP1, and MDK correlate with elevated immune cells in BoM. CD46, MDK, and PTN interactions drive myofibroblast activation and proliferation, contributing to tissue remodeling. Additionally, MDK, PTN, and FN1 interactions influence FAP+ CAF activation, impacting cell adhesion and migration in BoM. These insights deepen our understanding of the metastatic niche in breast cancer BoM.
{"title":"Unraveling the metastatic niche in breast cancer bone metastasis through single-cell RNA sequencing","authors":"Xiangyu Li, Ziyu Gao, Meiling Yang, Ciqiu Yang, Dongyang Yang, Wenhui Cui, Dandan Wu, Jie Zhou","doi":"10.1007/s12094-024-03594-2","DOIUrl":"https://doi.org/10.1007/s12094-024-03594-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Breast cancer (BRCA) is characterized by a unique metastatic pattern, often presenting with bone metastasis (BoM), posing significant clinical challenges. Through the study of the immune microenvironment in BRCA BoM offer perspectives for therapeutic interventions targeting this specific metastatic manifestation of BRCA.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This study employs single-cell RNA sequencing and TCGA data analysis to comprehensively compare primary tumors (PT), lymph node metastasis (LN), and BoM.</p><h3 data-test=\"abstract-sub-heading\">Results and Conclusions</h3><p>Our investigation identifies a metastatic niche in BoM marked by an increased abundance of cancer-associated fibroblasts (CAFs) and reduced immune cell presence. A distinct subtype (State 1) of BRCA BoM cells associated with adverse prognosis is identified. State 1, displaying heightened stemness traits, may represent an initiation phase for BoM in BRCA. Complex cell communications involving tumor, stromal, and immune cells are revealed. Interactions of FN1, SPP1, and MDK correlate with elevated immune cells in BoM. CD46, MDK, and PTN interactions drive myofibroblast activation and proliferation, contributing to tissue remodeling. Additionally, MDK, PTN, and FN1 interactions influence FAP+ CAF activation, impacting cell adhesion and migration in BoM. These insights deepen our understanding of the metastatic niche in breast cancer BoM.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141773828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-18DOI: 10.1007/s12094-024-03468-7
Cristina Rius, Yiming Liu, Andrea Sixto-Costoya, Juan Carlos Valderrama-Zurián, Rut Lucas-Dominguez
Purpose
This study has been focused on assessing the Open Science scenario of cancer research during the period 2011–2021, in terms of the derived scientific publications and raw data dissemination.
Methods
A cancer search equation was executed in the Science Citation Index-Expanded, collecting the papers signed by at least one Spanish institution. The same search strategy was performed in the Data Citation Index to describe dataset diffusion.
Results
50,822 papers were recovered, 71% of which belong to first and second quartile journals. 59% of the articles were published in Open Access (OA) journals. The Open Access model and international collaboration positively conditioned the number of citations received. Among the most productive journals stood out Plos One, Cancers, and Clinical and Translational Oncology. 2693 genomics, proteomics and metabolomics datasets were retrieved, being Gene Expression Omnibus the favoured repository.
Conclusions
There has been an increase in oncology publications in Open Access. Most were published in first quartile journals and received higher citations than non-Open Access articles, as well as when oncological investigation was performed between international research teams, being relevant in the context of Open Science. Genetic repositories have been the preferred for sharing oncology datasets. Further investigation of research and data sharing in oncology is needed, supported by stronger Open Science policies, to achieve better data sharing practices among three scientific main pillars: researchers, publishers, and scientific organizations.
{"title":"State of open science in cancer research","authors":"Cristina Rius, Yiming Liu, Andrea Sixto-Costoya, Juan Carlos Valderrama-Zurián, Rut Lucas-Dominguez","doi":"10.1007/s12094-024-03468-7","DOIUrl":"https://doi.org/10.1007/s12094-024-03468-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>This study has been focused on assessing the Open Science scenario of cancer research during the period 2011–2021, in terms of the derived scientific publications and raw data dissemination.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A cancer search equation was executed in the Science Citation Index-Expanded, collecting the papers signed by at least one Spanish institution. The same search strategy was performed in the Data Citation Index to describe dataset diffusion.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>50,822 papers were recovered, 71% of which belong to first and second quartile journals. 59% of the articles were published in Open Access (OA) journals. The Open Access model and international collaboration positively conditioned the number of citations received. Among the most productive journals stood out <i>Plos One</i>, <i>Cancers</i>, and <i>Clinical and Translational Oncology</i>. 2693 genomics, proteomics and metabolomics datasets were retrieved, being Gene Expression Omnibus the favoured repository.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>There has been an increase in oncology publications in Open Access. Most were published in first quartile journals and received higher citations than non-Open Access articles, as well as when oncological investigation was performed between international research teams, being relevant in the context of Open Science. Genetic repositories have been the preferred for sharing oncology datasets. Further investigation of research and data sharing in oncology is needed, supported by stronger Open Science policies, to achieve better data sharing practices among three scientific main pillars: researchers, publishers, and scientific organizations.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"161 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.1007/s12094-024-03442-3
Yanqing Yang, Wei Chen, Lixian Dong, Lian Duan, Pengfei Gao
Background
The use of immune checkpoint inhibitors has led to an increase in randomized controlled trials exploring various first-line combination treatment regimens. With the introduction of new PD-1/PD-L1 inhibitors, there are now more clinical options available. For the first time, the AK105 monoclonal antibody Penpulimab, developed in China, was included. The AK105-302 Phase III trial studied the efficacy and safety of Penpulimab combined with chemotherapy in patients with advanced or metastatic squamous NSCLC. To determine the optimal treatment options, we conducted an updated network meta-analysis to compare the effectiveness and safety of these regimens.
Methods
The system retrieves data from Chinese and English electronic databases, Clinical Trials, and the gov Clinical Trial Registration website up to September 6, 2023. The study indirectly compared the efficacy and safety of PD-1/PD-L1 combination regimens, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), all-grade adverse events, and above-grade III adverse events. Subgroup analyses were conducted based on programmed death ligand 1 (PD-L1) level, histological type, ECOG score, sex, and smoking history.
Results
Nineteen RCTS were included, with a total of ten thousand eight hundred patients. Penpulimab plus chemotherapy (Pen + CT) provided the best OS (HR = 0.55, 95% CI 0.38–0.81) for PD-L1 patients with non-selective advanced NSCLC. Except Nivolumab plus Ipilimumab (Niv + Ipi), other PD-1/PD-L1 combination therapies significantly extended PFS compared with CT, and Nivolumab plus Bevacizumab combined with chemotherapy (Niv + Bev + CT) (HR = 0.43, 95% CI 0.26–0.74) provided the best PFS benefit and was comparable to Pen + CT (HR = 1.0) for PFS prolongation. For ORR, except Niv + Ipi, all the other regimens significantly improved ORR compared with CT. In terms of safety, except Tor + CT, the incidence of any-grade AEs or grade ≥ 3 adverse events may be higher than those of chemotherapy. The subgroup analysis revealed that for patients with PD-L1 levels below 1%, treatment with Tor + CT resulted in the best progression-free survival (HR = 0.47, 95% CI 0.25–0.86). For patients with PD-L1 levels of 1% or higher, Sintilimab plus chemotherapy (Sin + CT) (HR = 0.56, 95% CI 0.31–0.99) and Camrelizumab plus chemotherapy (Cam + CT) (HR = 0.43, 95% CI 0.28–0.64) were associated with the best overall survival and progression-free survival, respectively. For patients with SqNSCLC, combined immunotherapy may provide greater survival benefits. For patients with Non-sqNSCLC, Niv + Bev + CT and Tor + CT were associated with optimal PFS and OS, respectively. Cam + CT provided the best PFS in male patients with a history of smoking and an ECOG score of 0. In both female and non-smoking patient subgroups, Pem + CT was associ
{"title":"Comparison of efficacy and safety of PD-1/PD-L1 combination therapy in first-line treatment of advanced NSCLC: an updated systematic review and network meta-analysis","authors":"Yanqing Yang, Wei Chen, Lixian Dong, Lian Duan, Pengfei Gao","doi":"10.1007/s12094-024-03442-3","DOIUrl":"https://doi.org/10.1007/s12094-024-03442-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The use of immune checkpoint inhibitors has led to an increase in randomized controlled trials exploring various first-line combination treatment regimens. With the introduction of new PD-1/PD-L1 inhibitors, there are now more clinical options available. For the first time, the AK105 monoclonal antibody Penpulimab, developed in China, was included. The AK105-302 Phase III trial studied the efficacy and safety of Penpulimab combined with chemotherapy in patients with advanced or metastatic squamous NSCLC. To determine the optimal treatment options, we conducted an updated network meta-analysis to compare the effectiveness and safety of these regimens.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The system retrieves data from Chinese and English electronic databases, Clinical Trials, and the gov Clinical Trial Registration website up to September 6, 2023. The study indirectly compared the efficacy and safety of PD-1/PD-L1 combination regimens, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), all-grade adverse events, and above-grade III adverse events. Subgroup analyses were conducted based on programmed death ligand 1 (PD-L1) level, histological type, ECOG score, sex, and smoking history.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Nineteen RCTS were included, with a total of ten thousand eight hundred patients. Penpulimab plus chemotherapy (Pen + CT) provided the best OS (HR = 0.55, 95% CI 0.38–0.81) for PD-L1 patients with non-selective advanced NSCLC. Except Nivolumab plus Ipilimumab (Niv + Ipi), other PD-1/PD-L1 combination therapies significantly extended PFS compared with CT, and Nivolumab plus Bevacizumab combined with chemotherapy (Niv + Bev + CT) (HR = 0.43, 95% CI 0.26–0.74) provided the best PFS benefit and was comparable to Pen + CT (HR = 1.0) for PFS prolongation. For ORR, except Niv + Ipi, all the other regimens significantly improved ORR compared with CT. In terms of safety, except Tor + CT, the incidence of any-grade AEs or grade ≥ 3 adverse events may be higher than those of chemotherapy. The subgroup analysis revealed that for patients with PD-L1 levels below 1%, treatment with Tor + CT resulted in the best progression-free survival (HR = 0.47, 95% CI 0.25–0.86). For patients with PD-L1 levels of 1% or higher, Sintilimab plus chemotherapy (Sin + CT) (HR = 0.56, 95% CI 0.31–0.99) and Camrelizumab plus chemotherapy (Cam + CT) (HR = 0.43, 95% CI 0.28–0.64) were associated with the best overall survival and progression-free survival, respectively. For patients with SqNSCLC, combined immunotherapy may provide greater survival benefits. For patients with Non-sqNSCLC, Niv + Bev + CT and Tor + CT were associated with optimal PFS and OS, respectively. Cam + CT provided the best PFS in male patients with a history of smoking and an ECOG score of 0. In both female and non-smoking patient subgroups, Pem + CT was associ","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.1007/s12094-024-03455-y
Yanhua Wang, Jingwen Wei, Manyi Xu, Jing Xiang, Keda Shao, Yue Hao, Zhengbo Song
Background
Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations.
Methods
From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan–Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable.
Results
A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events.
Conclusion
NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.
{"title":"Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations","authors":"Yanhua Wang, Jingwen Wei, Manyi Xu, Jing Xiang, Keda Shao, Yue Hao, Zhengbo Song","doi":"10.1007/s12094-024-03455-y","DOIUrl":"https://doi.org/10.1007/s12094-024-03455-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan–Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, <i>p</i> = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.1007/s12094-024-03486-5
Xueyang Zhang, Wenbo Du, Xizhi Huang, Haoting Zhong, Ning Hu
Background
Cancer stem cells (CSCs) represent a potential mechanism contributing to tumorigenesis, metastasis, recurrence, and drug resistance. The objective of this study is to investigate the status quo and advancements in CSC research utilizing bibliometric analysis.
Methods
Publications related to CSCs from 2010 to 2022 were collected from the Web of Science Core Collection database. Various analytical tools including CiteSpace, VOSviewer, Scimago Graphica, and GraphPad Prism were used to visualize aspects such as co-authorship, co-occurrence, and co-citation within CSC research to provide an objective depiction of the contemporary status and developmental trajectory of the CSC field.
Results
A total of 22,116 publications were included from 1942 journals written by 95,992 authors. Notably, China emerged as the country with the highest number of publications, whereas the United States exerted the most significant influence within the field. MD Anderson Cancer Center emerged as the institution making the most comprehensive contributions. Wicha M.S. emerged as the most prolific and influential researcher. Among journals, Cancers emerged as a focal point for CSC research, consistently publishing a wealth of high-quality papers. Furthermore, it was observed that most journals tended to approach CSC research from molecular, biological, and immunological perspectives. The research into CSCs encompassed a broad array of topics, including isolation and enrichment techniques, biomarkers, biological characteristics, cancer therapy strategies, and underlying biological regulatory mechanisms. Notably, exploration of the tumor microenvironment and extracellular vesicles emerged as burgeoning research frontiers for CSCs.
Conclusion
The research on CSCs has garnered growing interest. A trend toward multidisciplinary homogeneity is emerging within the realm of CSCs. Further investigation could potentially center on the patients of extracellular vesicles and the tumor microenvironment in relation to CSCs.
背景癌症干细胞(CSCs)是导致肿瘤发生、转移、复发和耐药性的潜在机制。本研究的目的是利用文献计量学分析方法调查癌症干细胞研究的现状和进展。方法从科学网核心收藏数据库中收集了2010年至2022年与癌症干细胞有关的出版物。采用CiteSpace、VOSviewer、Scimago Graphica和GraphPad Prism等多种分析工具对CSC研究中的共同作者、共同出现和共同引用等方面进行可视化分析,以客观描述CSC领域的现状和发展轨迹。值得注意的是,中国是发表论文数量最多的国家,而美国在该领域的影响力最大。MD 安德森癌症中心(MD Anderson Cancer Center)是贡献最全面的机构。Wicha M.S.是发表论文最多、最有影响力的研究人员。在期刊中,《癌症》成为 CSC 研究的焦点,持续发表大量高质量论文。此外,据观察,大多数期刊都倾向于从分子、生物和免疫学的角度开展 CSC 研究。对 CSCs 的研究涵盖了广泛的主题,包括分离和富集技术、生物标志物、生物学特征、癌症治疗策略以及潜在的生物调控机制。值得注意的是,对肿瘤微环境和细胞外囊泡的探索已成为 CSCs 的新兴研究前沿。在 CSCs 领域正在出现多学科同质化的趋势。进一步的研究可能集中在细胞外囊泡和肿瘤微环境与 CSCs 的关系上。
{"title":"An overview of current research on cancer stem cells: a bibliometric analysis","authors":"Xueyang Zhang, Wenbo Du, Xizhi Huang, Haoting Zhong, Ning Hu","doi":"10.1007/s12094-024-03486-5","DOIUrl":"https://doi.org/10.1007/s12094-024-03486-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Cancer stem cells (CSCs) represent a potential mechanism contributing to tumorigenesis, metastasis, recurrence, and drug resistance. The objective of this study is to investigate the status quo and advancements in CSC research utilizing bibliometric analysis.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Publications related to CSCs from 2010 to 2022 were collected from the Web of Science Core Collection database. Various analytical tools including CiteSpace, VOSviewer, Scimago Graphica, and GraphPad Prism were used to visualize aspects such as co-authorship, co-occurrence, and co-citation within CSC research to provide an objective depiction of the contemporary status and developmental trajectory of the CSC field.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 22,116 publications were included from 1942 journals written by 95,992 authors. Notably, China emerged as the country with the highest number of publications, whereas the United States exerted the most significant influence within the field. MD Anderson Cancer Center emerged as the institution making the most comprehensive contributions. Wicha M.S. emerged as the most prolific and influential researcher. Among journals, Cancers emerged as a focal point for CSC research, consistently publishing a wealth of high-quality papers. Furthermore, it was observed that most journals tended to approach CSC research from molecular, biological, and immunological perspectives. The research into CSCs encompassed a broad array of topics, including isolation and enrichment techniques, biomarkers, biological characteristics, cancer therapy strategies, and underlying biological regulatory mechanisms. Notably, exploration of the tumor microenvironment and extracellular vesicles emerged as burgeoning research frontiers for CSCs.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The research on CSCs has garnered growing interest. A trend toward multidisciplinary homogeneity is emerging within the realm of CSCs. Further investigation could potentially center on the patients of extracellular vesicles and the tumor microenvironment in relation to CSCs.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.1007/s12094-024-03485-6
Ke Wang, Manyi Xu, Yanhua Wang, Chunwei Xu, Yue Hao, Zhengbo Song
Purpose
The treatment of the advanced non-small cell lung cancer (NSCLC) with KRAS mutation has been closely paid more attention. The aim of this study is to investigate the efficacy of different first-line regimens in advanced KRAS-mutated non-small cell lung cancer.
Methods
In our retrospective study, we collected patients with advanced NSCLC with KRAS mutation in Zhejiang Cancer Hospital between January 2015 and May 2023. We analyzed the benefit of different first-line therapy according to theraputic methods and the differential effect of the same treatment method among KRAS-mutated subtypes. We divided the patients into group A (A1, chemotherapy alone; A2, immunotherapy alone) and group B (B1, chemotherapy plus immunotherapy; B2, chemotherapy combined with antiangiogenic therapy; B3, chemotherapy combined with immunotherapy plus antiangiogenic therapy). The Kaplan–Meier survival curve was used to reflect the PFS and OS of different methods. The objective response rate (ORR) and the disease control rate (DCR) were used to evaluated the response.
Results
We enrolled 227 patients including eighty-two with KRAS G12C mutation. The ORR and DCR of first-line treatment in the overall population were 32.2% and 80.6% respectively. The median PFS was 6.7 months and the median OS was 17.4 months for the overall population. The PFS of the Group B was significantly better than that of the Group A (7.7 months vs 5.4 months, P = 0.003), while no significant difference in OS was observed (19.4 months vs 15.0 months, P = 0.077). In the Group B, chemotherapy combined immunotherapy with antiangiogenic therapy showed better PFS than chemotherapy plus immunotherapy (14.1 months vs 7.7 months, P = 0.049), and OS also showed that tendency of difference (31.9 months vs 19.3 months, P = 0.158). There was no statistically significant difference between KRAS G12C and non-G12C mutation according to first-line treatment methods, whereas patients with TP53 co-mutation showed a better survival benefit (OS, 23.7 vs 12.5 months, P = 0.023).
Conclusion
In the first-line treatment, combination regimen has advantages over single regimen. Among them, chemotherapy combined with immunotherapy plus antiangiogenic therapy can achieve significant efficacy benefits.
目的 KRAS突变晚期非小细胞肺癌(NSCLC)的治疗已受到越来越多的关注。方法在回顾性研究中,我们收集了浙江省肿瘤医院2015年1月至2023年5月期间KRAS突变的晚期非小细胞肺癌患者。我们根据治疗方法分析了不同一线治疗的获益情况,以及同一治疗方法在KRAS突变亚型中的不同效果。我们将患者分为A组(A1,单纯化疗;A2,单纯免疫治疗)和B组(B1,化疗加免疫治疗;B2,化疗联合抗血管生成治疗;B3,化疗联合免疫治疗加抗血管生成治疗)。Kaplan-Meier生存曲线用于反映不同方法的PFS和OS。客观反应率(ORR)和疾病控制率(DCR)用于评价反应。在所有患者中,一线治疗的ORR和DCR分别为32.2%和80.6%。全部患者的中位 PFS 为 6.7 个月,中位 OS 为 17.4 个月。B组的PFS明显优于A组(7.7个月 vs 5.4个月,P = 0.003),而OS无明显差异(19.4个月 vs 15.0个月,P = 0.077)。在B组中,化疗联合免疫治疗与抗血管生成治疗的PFS优于化疗联合免疫治疗(14.1个月 vs 7.7个月,P = 0.049),OS也显示出差异趋势(31.9个月 vs 19.3个月,P = 0.158)。根据一线治疗方法,KRAS G12C 突变与非 G12C 突变之间的差异无统计学意义,而 TP53 共突变患者的生存率更高(OS,23.7 个月 vs 12.5 个月,P = 0.023)。结论 在一线治疗中,联合方案比单一方案更具优势,其中化疗联合免疫治疗加抗血管生成治疗可取得显著疗效。
{"title":"Exploration of efficacy of different therapy regimens for advanced NSCLC patients with KRAS mutation in the first-line treatment","authors":"Ke Wang, Manyi Xu, Yanhua Wang, Chunwei Xu, Yue Hao, Zhengbo Song","doi":"10.1007/s12094-024-03485-6","DOIUrl":"https://doi.org/10.1007/s12094-024-03485-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>The treatment of the advanced non-small cell lung cancer (NSCLC) with KRAS mutation has been closely paid more attention. The aim of this study is to investigate the efficacy of different first-line regimens in advanced KRAS-mutated non-small cell lung cancer.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In our retrospective study, we collected patients with advanced NSCLC with KRAS mutation in Zhejiang Cancer Hospital between January 2015 and May 2023. We analyzed the benefit of different first-line therapy according to theraputic methods and the differential effect of the same treatment method among KRAS-mutated subtypes. We divided the patients into group A (A1, chemotherapy alone; A2, immunotherapy alone) and group B (B1, chemotherapy plus immunotherapy; B2, chemotherapy combined with antiangiogenic therapy; B3, chemotherapy combined with immunotherapy plus antiangiogenic therapy). The Kaplan–Meier survival curve was used to reflect the PFS and OS of different methods. The objective response rate (ORR) and the disease control rate (DCR) were used to evaluated the response.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We enrolled 227 patients including eighty-two with KRAS G12C mutation. The ORR and DCR of first-line treatment in the overall population were 32.2% and 80.6% respectively. The median PFS was 6.7 months and the median OS was 17.4 months for the overall population. The PFS of the Group B was significantly better than that of the Group A (7.7 months <i>vs</i> 5.4 months, <i>P</i> = 0.003), while no significant difference in OS was observed (19.4 months <i>vs</i> 15.0 months, <i>P</i> = 0.077). In the Group B, chemotherapy combined immunotherapy with antiangiogenic therapy showed better PFS than chemotherapy plus immunotherapy (14.1 months <i>vs</i> 7.7 months, <i>P</i> = 0.049), and OS also showed that tendency of difference (31.9 months <i>vs</i> 19.3 months, <i>P</i> = 0.158). There was no statistically significant difference between KRAS G12C and non-G12C mutation according to first-line treatment methods, whereas patients with TP53 co-mutation showed a better survival benefit (OS, 23.7 <i>vs</i> 12.5 months, <i>P</i> = 0.023).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In the first-line treatment, combination regimen has advantages over single regimen. Among them, chemotherapy combined with immunotherapy plus antiangiogenic therapy can achieve significant efficacy benefits.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"96 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}