Translational lung cancer research最新文献

{"title":"Comprehensive management of MET tyrosine kinase inhibitor-induced peripheral edema in patients with <i>MET</i>-altered non-small-cell lung cancer: a narrative review.","authors":"Jia-Xin Lin, Hao Sun, Ying-Long Peng, Zhi Xie, Si-Yang Maggie Liu, Yi-Long Wu","doi":"10.21037/tlcr-24-866","DOIUrl":"10.21037/tlcr-24-866","url":null,"abstract":"<p><strong>Background and objective: </strong>The mesenchymal-epithelial transition factor (MET) proto-oncogene plays an important role in the development of non-small cell lung cancer (NSCLC). MET tyrosine kinase inhibitors (TKIs) have shown promising antitumor activity in patients with NSCLC harboring MET alterations. Peripheral edema (PE), the most common adverse event of MET TKIs, has received increasing attention from clinicians. The aim of this review is to describe the incidence, potential molecular mechanisms, diagnosis, and management of MET TKI-induced PE, to increase the recognition and standardize the management of PE.</p><p><strong>Methods: </strong>We conducted a comprehensive literature search across PubMed, Wanfang Med Online, China National Knowledge Infrastructure (CNKI), and the oncology conferences websites for related studies published between 2000 and 2023. Of the 491 titles screened, we identified 80 research articles fitting the inclusion criteria and a comprehensive literature review was conducted. The review incorporated patient conditions, comprehensive examinations, and clinical experiences to propose a standardized management framework.</p><p><strong>Key content and findings: </strong>The review focused on the incidence of MET TKI-induced PE, its potential molecular mechanisms, diagnostic criteria, and management strategies. The etiology of edema is complex in cancer patients; however, it may involve treatment-related increases in vascular permeability, impacts on renal function, and hypoalbuminemia. Based on the literature review, a diagnostic and comprehensive management approach for MET TKI-induced PE is proposed, which includes prevention strategies, non-pharmacological treatments, pharmacological interventions, and dosage adjustments related to MET TKIs.</p><p><strong>Conclusions: </strong>In this review, we propose a diagnostic and comprehensive management approach for MET TKI-induced PE. By standardizing management, clinicians can enhance patient care for those treated with MET TKIs, facilitating earlier detection of PE, reducing patient suffering, and improving treatment adherence and outcomes.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1482-1495"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of finotonlimab plus docetaxel <i>vs.</i> docetaxel in previously treated advanced squamous cell non-small-cell lung cancer: a randomized, double-blinded, phase III trial.","authors":"Baohui Han, Lin Wu, Runxiang Yang, Hongbo Wu, Wei Li, Yan Yu, Mingjuan Zhang, Hongmei Sun, Tianqing Chu, Fukuan Zhong, Yong Fang, Rong Wu, Tao Bian, Xiaoqing Guo, Meili Sun, Yanming Zhang, Lianke Liu, Xuewen Liu, Yueyin Pan, Ou Jiang, Zonghui Wei, Haifeng Lin, Wei Guo, Jian Fang, Jialei Wang, Cuimin Ding, Yanping Hu, Feng Ye, Wu Zhuang, Shucheng Ye, Lihong Wang, Zhe Huang, Chang Liu, Ling Yang, Jinling Wang, Liangzhi Xie","doi":"10.21037/tlcr-24-1042","DOIUrl":"10.21037/tlcr-24-1042","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the most common cancer in the world, and non-small cell lung cancer (NSCLC) constitutes about 80-85%. In this phase III trial, we evaluate the efficacy and safety of anti-programmed cell death-1 (PD-1) monoclonal antibody (SCT-I10A) plus docetaxel compared to docetaxel in patients with previously treated advanced squamous cell NSCLC (sqNSCLC).</p><p><strong>Methods: </strong>Patients were randomized 2:1 to finotonlimab plus docetaxel group (finotonlimab plus docetaxel) and docetaxel group (placebo plus docetaxel) for up to 6 cycles, followed by maintenance monotherapy with finotonlimab/placebo. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) as well as assessments of safety and immunogenicity.</p><p><strong>Results: </strong>There were 188 eligible patients enrolled (finotonlimab plus docetaxel group: n=126; docetaxel group: n=62). Median OS (mOS) was 17.1 months [95% confidence interval (CI): 11.2, 20.0] in the finotonlimab plus docetaxel group and 10.4 months (95% CI: 5.9, 14.0) in the control group. Hazard ratio (HR) was 0.66 (95% CI: 0.45, 0.96; P=0.03). Median PFS (mPFS) was 4.2 months (95% CI: 3.3, 6.9) and 2.9 months (95% CI: 1.5, 3.8) respectively in the finotonlimab plus docetaxel group and control group. Patients in the finotonlimab plus docetaxel group achieved an ORR of 27.0% (95% CI: 19.5%, 35.6%), which was significantly higher than the 3.2% (95% CI: 0.4%, 11.2%) in the control group. The DCR was 68.3% (95% CI: 59.4%, 76.3%) in the finotonlimab plus docetaxel group and 56.5% (95% CI: 43.3%, 69.0%) in the control group. Treatment-related adverse events (TRAEs) occurred in 91.3% (115/126) patients of finotonlimab plus docetaxel group and 87.1% (54/62) patients of control group.</p><p><strong>Conclusions: </strong>SCT-I10A combined with docetaxel significantly prolonged OS and improved clinical outcomes in patients with treated advanced sqNSCLC compared to docetaxel, without increasing safety risk.</p><p><strong>Trial registration: </strong>NCT04171284, ClinicalTrials.gov.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1231-1241"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uniportal video-assisted thoracoscopic surgery does not increase recurrence rates following pneumonectomy in non-small cell lung cancer: a retrospective study from the National Cancer Center of China.","authors":"Sikai Wu, Xiaowei Chen, Guangyu Bai, Yang Liu, Zhenlin Yang, Shugeng Gao","doi":"10.21037/tlcr-2025-41","DOIUrl":"10.21037/tlcr-2025-41","url":null,"abstract":"<p><strong>Background: </strong>The safety, feasibility, and potential benefits of uniportal video-assisted thoracoscopic surgery (U-VATS) pneumonectomy remain to be investigated. This study aimed to evaluate the postoperative outcomes, survival prognosis, and recurrence patterns in patients undergoing U-VATS versus those undergoing open pneumonectomy. The feasibility of U-VATS pneumonectomy in patients receiving neoadjuvant systemic therapy was also assessed.</p><p><strong>Methods: </strong>Patients with non-small cell lung cancer (NSCLC) underwent thoracic surgeries at the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from January 2017 to December 2022. Among these patients, those who underwent U-VATS or open pneumonectomy were included in our study. Propensity score matching (PSM) with a 3:1 ratio was conducted to balance the baseline characteristics between the groups. We compared perioperative outcomes and recurrence patterns between the two groups.</p><p><strong>Results: </strong>A total of 457 patients who underwent pneumonectomy were included in our study, with 348 in the open pneumonectomy group and 109 in the U-VATS group. After PSM, 334 patients (231 in the open group and 103 in the U-VATS group) were available for subsequent analyses. Patients who underwent U-VATS pneumonectomy experienced shorter postoperative hospital stays (P<0.001). No significant differences were observed in the 5-year overall survival (OS) rate (P=0.19) or the 5-year recurrence-free survival (RFS) rate (P=0.37) between the two groups. Additionally, subgroup analysis of patients receiving neoadjuvant systemic therapy indicated those in the U-VATS group did not exhibit significant differences in recurrence patterns between the two groups.</p><p><strong>Conclusions: </strong>Patients with NSCLC undergoing U-VATS pneumonectomy exhibit postoperative outcomes, survival rates, and recurrence patterns that are not inferior to those of patients undergoing open pneumonectomy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1274-1289"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A narrative review of preoperative CT for predicting spread through air spaces of lung cancer.","authors":"Qinling Jiang, Xiang Wang, Xin'ang Jiang, Hongbiao Sun, Qi Chen, Yuxin Cheng, Yunmeng Wang, Tianyi Xing, Xin Zhang, Yi Xiao","doi":"10.21037/tlcr-24-952","DOIUrl":"10.21037/tlcr-24-952","url":null,"abstract":"<p><strong>Background and objective: </strong>Spread through air space (STAS) is a recognized mechanism of lung cancer invasion and is associated with patient prognosis. However, current diagnostic accuracy of bronchial cytology and intraoperative frozen section for STAS remains insufficient to meet clinical needs. Therefore, accurate and non-invasive preoperative prediction of STAS is critical for clinical decision-making. In this paper, we review and summarize recent studies on the role of computed tomography (CT) in predicting STAS in lung cancer, and discuss the limitations and future directions of related research in this field.</p><p><strong>Methods: </strong>Relevant studies were identified through searches on the Web of Science, PubMed, Cochrane Library, and EMBASE. We included English-language articles published between July 2017 and June 2024, focusing on research related to STAS and CT.</p><p><strong>Key content and findings: </strong>This review aimed to assess the viability of preoperative CT imaging for predicting STAS. Current studies suggest that traditional imaging signs enable the assessment of STAS, and with the development of artificial intelligence, the efficacy of STAS prediction models has been greatly enhanced by radiomics and deep learning methods. However, risk stratification studies remain limited and require further refinement through more comprehensive pathological definitions of STAS.</p><p><strong>Conclusions: </strong>Preoperative CT imaging images demonstrated good predictive efficacy of STAS. However, further progress requires a more comprehensive definition of STAS and validation through large-sample, prospective, and multi-center studies to enhance its clinical applicability.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1471-1481"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracheobronchial resection and reconstruction: to wrap or not to wrap the anastomosis?","authors":"Chudong Wang, Zihao Liu, Rui Wang, Biao Hu, Binbin Xiang, Zijian Li, Jianxing He, Shuben Li","doi":"10.21037/tlcr-24-868","DOIUrl":"10.21037/tlcr-24-868","url":null,"abstract":"<p><strong>Background: </strong>Two opinions in tracheobronchial resection and reconstruction regarding the management of airway anastomosis remain controversial: whether to wrap the anastomosis with surrounding tissue or leave the anastomosis without additional embedding. This study aims to explore the relationship between the choice of anastomotic wrapping and anastomotic complications in tracheobronchial surgery.</p><p><strong>Methods: </strong>Patients who underwent tracheobronchial surgery between January 2019 and December 2021 were retrospectively analyzed. A total of 95 patients were enrolled, and their age and comorbidities were quantified using the age-adjusted Charlson comorbidity index. Based on the length of resection and neoadjuvant therapy, the cases were categorized into the complex surgery group and the standard surgery group. Each group was further divided into wrapped and non-wrapped subgroups.</p><p><strong>Results: </strong>The complex surgery group included 42 patients (wrapped subgroup: 32, non-wrapped subgroup: 10), and the standard surgery group comprised 53 patients (wrapped subgroup: 32, non-wrapped subgroup: 21). In the complex surgery group, the wrapped subgroup exhibited a significantly lower short-term postoperative anastomotic complication rate compared to the non-wrapped subgroup (P=0.004). This included lower rates of anastomotic mild necrosis or stenosis (18.8% <i>vs.</i> 20.0%) and anastomotic rupture or fistula (0% <i>vs.</i> 40.0%), as well as a lower 30-day mortality rate (0% <i>vs.</i> 30%, P=0.01). No statistically significant differences were observed in the standard surgery group.</p><p><strong>Conclusions: </strong>The wrapping procedure demonstrated a relatively positive effect in minimizing the risk of short-term anastomotic complications in complex tracheobronchial surgery without impacting long-term anastomotic complications. However, it did not play a significant role in standard tracheobronchial surgery.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1266-1273"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>LNCAROD</i> was stabilized through N⁶-methyladenosine methylation and exerted its anticancer effects in lung squamous cell carcinoma by inhibiting SIRT1 activity via CCAR2.","authors":"Qihang Yan, Wingshing Wong, Jinsong Lei, Dachuan Liang, Jie Yang, Li Gong, Rossana Berardi, Shuqin Dai, Junye Wang","doi":"10.21037/tlcr-2025-267","DOIUrl":"10.21037/tlcr-2025-267","url":null,"abstract":"<p><strong>Background: </strong>Lung squamous cell carcinoma (LUSC), a deadly malignant tumor, is highly prevalent worldwide. Accumulating evidence indicates that long-chain noncoding RNAs play crucial regulatory roles in the occurrence and progression of LUSC. <i>LNCAROD</i> regulates the proliferation, migration, and invasion of cells by upregulating SERPINE1 expression in lung adenocarcinoma (LUAD). However, the functional mechanism of <i>LNCAROD</i> action in LUSC remains unclear. The aim of this study was to investigate the regulatory function and mechanism of <i>LNCAROD</i> action in the development of LUSC.</p><p><strong>Methods: </strong>Using quantitative polymerase chain reaction (qPCR) detection, we determined the expression of <i>LNCAROD</i> in LUSC tissues and cell lines. Cell Counting Kit-8 (CCK-8), EdU (5-ethynyl-2'-deoxyuridine), JC-1 mitochondrial membrane potential, flow cytometry, colony formation, scratch healing, and Transwell assays were conducted, and cell proliferation, migration, and invasion, as well as physiological changes were assessed. The tumorigenicity of LUSC cells was analyzed by in vitro tumor formation in nude mice. Molecular interactions were verified via Western blotting, RNA-protein pull-down assay, RNA binding protein immunoprecipitation (RIP), N6-methyladenosine (m6A)-RIP, and coimmunoprecipitation (Co-IP) analyses.</p><p><strong>Results: </strong><i>LNCAROD</i> was specifically and highly expressed in LUSC cells and tissues. <i>LNCAROD</i> expression was mediated by IGF2BP2 m6A methylation, which, along with CCAR2, inhibited SIRTI1's acetylation activity. This further induced p53 protein acetylation and promoted the mitochondrial apoptosis of LUSC cells, thereby inhibiting cell proliferation, migration, and invasion.</p><p><strong>Conclusions: </strong><i>LNCAROD</i> is specifically highly expressed in LUSC cells and tissues and may be a tumor-suppressor gene. The findings contribute to a deeper understanding of the function of <i>LNCAROD</i> in LUSC, and it may serve as a potential prognostic marker for personalized medical diagnosis in clinical practice.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1351-1370"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of diagnostic alternative splicing events in tumor-educated platelets for non-small cell lung cancer in patients with ground-glass opacity: a multicenter study.","authors":"Mengqi Shao, Wanwen Li, Jieming Cao, Li Wang, Shenglong Xie, Yan Hu, Gang Feng, Feredun Azari, Luca Bertolaccini, Wenliang Liu, Bin He","doi":"10.21037/tlcr-2025-287","DOIUrl":"10.21037/tlcr-2025-287","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The diagnostic potential of tumor-educated platelets (TEPs) across various cancer types has gained increasing recognition; however, the relationship between alternative splicing (AS) events in TEPs and tumor development remains understudied. Early detection of non-small cell lung cancer (NSCLC) in ground-glass opacities (GGOs) is critical for improving patient outcomes, yet current methods lack sufficient accuracy. Our research identified diagnostic-related alternative splicing events (DASEs) in TEPs, revealing several promising biomarkers for NSCLC, specifically in patients presenting with GGOs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Patients with GGOs from two hospitals were prospectively enrolled [Hospital 1-Platelet (H1-P) and Hospital 2-Tissue (H2-T) in the validation cohort; Hospital 2-Platelet (H2-P) in the test cohort]. Benign/malignant diagnosis of GGOs was confirmed by pathological examination according to the World Health Organization (WHO) classification. TEPs from the H1-P cohort were collected for transcriptome sequencing and AS analysis. Chi-square tests, least absolute shrinkage and selection operator (LASSO) regression analysis, and protein-protein interaction (PPI) network were used for the preliminary screening of DASEs. Pathological tissue from the H2-T cohort was collected to validate the diagnostic efficacy of hub DASEs in NSCLC against the pathological gold standard. Moreover, TEPs from the H2-P cohort were used to assess the predictive performance of hub DASEs for GGOs using receiver operating characteristic (ROC) curves. Decision curve analysis (DCA) was used to determine whether diagnosing NSCLC in the GGOs population via hub DASEs could benefit patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 285 patients with GGOs were enrolled, including 151 NSCLC and 128 inflammatory nodules confirmed by pathological examination. Thirteen DASEs were screened with the chi-square test and LASSO regression analysis to identify diagnostic TEP AS markers for GGOs NSCLC. The PPI network identified four hub diagnostic-related alternative splice genes (DASGs) (&lt;i&gt;TMEM219&lt;/i&gt;, &lt;i&gt;MPV17&lt;/i&gt;, &lt;i&gt;FIBP&lt;/i&gt;, and &lt;i&gt;VPS28&lt;/i&gt;). Pathological tissues and platelets were collected to validate the four hub DASEs of these four hub DASGs. MXE-32112-&lt;i&gt;TMEM219&lt;/i&gt; yielded an area under the curve (AUC) of 0.82 [95% confidence interval (CI): 0.729-0.902], with a sensitivity of 83.33% and a specificity of 80.00%; RI-3259-&lt;i&gt;VPS28&lt;/i&gt; yielded an AUC of 0.77 (95% CI: 0.677-0.870) with a sensitivity of 93.33% and a specificity of 78.33%; and RI-3641-&lt;i&gt;MPV17&lt;/i&gt; yielded an AUC of 0.82 (95% CI: 0.728-0.901) with a sensitivity of 90.00% and a specificity of 80.00%. The DCA results suggested that using hub DASEs in diagnosing NSCLC in individuals with GGOs could provide benefits.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The specific diagnostic AS events (MXE-32112-&lt;i&gt;TMEM219&lt;/i&gt;, RI-3259-&lt;i&gt;VPS28&lt;/i&gt;, and RI-3641-&lt;i&gt;MPV17&lt;/i&gt;) identified in ","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1395-1407"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of machine learning models based on molecular features for estimating the probability of multiple primary lung carcinoma versus intrapulmonary metastasis in patients presenting multiple non-small cell lung cancers.","authors":"Ning Liu, Xue Li, Xu Luo, Bin Liu, Jie Tang, Fei Xiao, Weiya Wang, Yuan Tang, Pei Shu, Benxia Zhang, Yue Chen, Diyuan Qin, Qizhi Ma, Fuchun Guo, Xiaojun Tang, Daxing Zhu, Jiandong Mei, Weizhi Chen, Dan Li, Lili Jiang, Yongsheng Wang","doi":"10.21037/tlcr-24-875","DOIUrl":"10.21037/tlcr-24-875","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Discrimination of multiple non-small cell lung cancers (NSCLCs) as multiple primary lung cancers (MPLCs) or intrapulmonary metastases (IPMs) is critical but remains challenging. The aim of this study is to develop and validate the machine learning (ML) models based on the molecular features for estimating the probability of MPLC or IPM for patients presenting multiple NSCLCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 72 multiple NSCLCs patients with 157 surgical resection tumor lesions from January 2012 to January 2018 at two institutions were included for developing and testing models. Specifically, 46 patients with 103 tumors which were defined as definitive MPLC or IPM according to International Association for the Study of Lung Cancer (IASLC) criteria were used to develop models. They were spilt into training and validation sets using stratified random sampling and five-fold cross-validation. The developed models were tested in other 26 patients whose tumors were undetermined by traditional methods. Whole-exome sequencing (WES) was performed on all included tumor samples. Four molecular features were calculated to characterize tumors relatedness and served as model inputs, including genetic divergence, shared mutation number, Pearson correlation coefficient and early mutation number. Decision trees (DT), random forests (RF), and gradient boosting decision trees (GBDT) were employed, with performance assessed by areas under the curve (AUCs), accuracy, precision, recall, and F1 score in validation set. Disease-free survival (DFS) were used to evaluate model performance in test cohort. Clinical and genetic characteristics were then compared between MPLC and IPM populations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;All of the four molecular features showed significant differences between MPLC and IPM patients in development cohort. That is, MPLC exhibited higher genetic divergence, lower shared mutation number, Pearson correlation and early mutation number than IPM (P&lt;0.001). DT model, RF model and GBDT model were developed with these factors and achieved a mean AUC of 0.94 [standard deviation (SD) 0.09], 1.00 (SD 0.00) and 1.00 (SD 0.00) in validation set, respectively. DT model, RF model and GBDT model discriminated the undetermined multiple NSCLCs as MPLC (n=15) and IPM (n=11) consistently. MPLC identified by ML models had significantly prolonged DFS [hazard ratio =0.21; 95% confidence interval (CI): 0.04-1.0; P=0.04] than that of IPM. MPLC patients had a relative higher prevalence of family history of first-degree relatives with cancer, and more than half of these patients reported a family history of lung cancer. EGFR remains the most common mutated driver both in MPLC and IPM populations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;ML models based on the molecular features effectively distcriminate primary tumors from metastases in multiple NSCLCs, which improve the accuracy of multiple NSCLCs diagnosis and assist in clinica","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1118-1137"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of anlotinib plus EGFR tyrosine kinase inhibitors in slow- or locally progressing non-small cell lung cancer after adjuvant therapy.","authors":"Jiayue Ye, Jiacong Liu, Yucheng Ma, Wang Lv, Wenzhen Xu, Masaya Aoki, Yuhong Yang, Pinghui Xia, Luming Wang, Linhai Zhu, Jian Hu","doi":"10.21037/tlcr-2025-177","DOIUrl":"10.21037/tlcr-2025-177","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Anlotinib, a small-molecule tyrosine kinase inhibitor (TKI), suppresses angiogenesis and tumor progression. As the mechanisms underlying the resistance to epidermal growth factor receptor (EGFR)-TKIs are complex and diverse, further exploration of new treatment strategies is necessary. Combination therapy with EGFR-TKIs and anlotinib targets multiple signaling pathways, enhancing efficacy in patients with EGFR-positive non-small cell lung cancer (NSCLC). This study evaluated the efficacy and safety of anlotinib with EGFR-TKIs in patients with NSCLC who developed resistance to postoperative adjuvant therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;From January 2020 to December 2023, 48 patients at the Department of Thoracic Surgery, the First Affiliated Hospital of Zhejiang University, who developed resistance to adjuvant therapy were included in this retrospective study. All patients received anlotinib (10-12 mg, po, d1-14, q3w) alongside their original EGFR-TKI regimen. The primary endpoint was progression-free survival (PFS), while secondary endpoints included 6- and 12-month PFS rates, overall survival (OS), and safety. PFS was defined as the time from the initiation of anlotinib plus EGFR-TKI to disease progression or death, and OS was defined as the time from the start of anlotinib plus EGFR-TKI to death from any cause.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the 48 patients, 23 previously received first- or second-generation EGFR-TKIs, and 25 received third-generation EGFR-TKIs. As of March 25, 2024, the median follow-up duration was 33.3 months [95% confidence interval (CI): 23.2-43.3]. The median PFS was 9.5 months (95% CI: 4.8-14.3), and 6- and 12-month PFS rates were 70.8% and 47.9%, respectively. For patients previously treated with first-/second- and third-generation EGFR-TKIs, the median PFS was 10.3 months (95% CI: 6.1-14.4) and 7.7 months (95% CI: 4.8-10.6), with a 6-month PFS rate of 69.6% and 72.0%, respectively, and a 12-month PFS rate of 47.8% and 48.0%, respectively. The median OS was 31.0 months [95% CI: not reached (NR)-NR], with 6-month and 12-month rates of 91.7% and 85.4%, respectively. For patients previously treated with first-/second- and third-generation EGFR-TKIs, the median OS was NR and 20.3 months (95% CI: 10.7-30.0), respectively; meanwhile, the OS rates were 95.7% and 88.0% at 6 months, and 91.3% and 80.0% at 12 months, respectively. The incidence rates of any grade and grade ≥3 treatment-related adverse events (TRAEs) were 75.0% (36/48) and 10.4% (5/48), respectively. The most common TRAEs included hypertension (17/48, 35.4%), proteinuria (15/48, 31.3%), rash (11/48, 22.9%), fatigue (5/48, 10.4%), and diarrhea (4/48, 8.3%), and no new safety events were observed. Dose reduction and discontinuation of anlotinib were reported in four (8.3%) and five (10.4%) patients previously treated with first-/second- and third-generation EGFR-TKIs, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Patien","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1371-1383"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors predicting early recurrence in patients with unresectable stage III non-small cell lung cancer on durvalumab consolidation after chemoradiotherapy.","authors":"Ji Eun Park, Chanmi Kim, Sun Ha Choi, Jong Geol Jang, Kyung Soo Hong, Yong Shik Kwon, Keum-Ju Choi, Jung Seop Eom, Saerom Kim, Hee Yun Seol, Jehun Kim, Insu Kim, Jin Han Park, Tae Hoon Kim, June Hong Ahn","doi":"10.21037/tlcr-2024-1112","DOIUrl":"10.21037/tlcr-2024-1112","url":null,"abstract":"<p><strong>Background: </strong>Durvalumab consolidation after concurrent chemoradiotherapy (CCRT) is the present standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). However, some patients experience early recurrence. This study sought risk factors for early recurrence during durvalumab consolidation.</p><p><strong>Methods: </strong>This retrospective multicenter study was conducted between September 2017 and September 2022. We categorized patients into early and non-early recurrence groups. Early recurrence was defined as recurrence within 6 months after the first dose of durvalumab.</p><p><strong>Results: </strong>Of the 222 patients, 40 (18.0%) experienced early recurrence and 182 (82.0%) experienced non-early recurrence. The former group was younger than the latter group (P=0.02). Patients exhibiting lower-level programmed cell death-ligand 1 (PD-L1) expression were more likely to experience early recurrence (P=0.02). Stage IIIC patients tended to experience more early recurrence than stage IIIA/IIIB patients (P=0.055). Multivariate analyses revealed that older age [odds ratio (OR), 0.945; 95% confidence interval (CI): 0.902-0.991; P=0.02] and PD-L1 level ≥50% (OR, 0.303; 95% CI: 0.125-0.736; P=0.008) protected against early recurrence in NSCLC patients on durvalumab consolidation. Median overall survival was significantly longer in the non-early recurrence group than in the early recurrence group (non-evaluable <i>vs.</i> 11.0 months, respectively; P<0.001).</p><p><strong>Conclusions: </strong>Younger age and lower PD-L1 expression predicted early recurrence during durvalumab consolidation after CCRT. Careful follow-up of such patients is essential.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1149-1157"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}