Translational lung cancer research最新文献

{"title":"Spectral dual-layer detector CT-based radiomics-deep learning for predicting pathological aggressiveness of stage I lung adenocarcinoma: discrimination of precursor glandular lesions and invasive adenocarcinomas.","authors":"Tong Wang, Zheng Fan, Yong Yue, Xiaomei Lu, Xiaoxu Deng, Yang Hou","doi":"10.21037/tlcr-24-726","DOIUrl":"10.21037/tlcr-24-726","url":null,"abstract":"<p><strong>Background: </strong>Accurate diagnosis of early-stage lung adenocarcinoma (LA) subtypes is crucial for optimal patient management. Radiomics extract features from medical images reflect underlying biological information, while effective atomic number (Zeff) from new-generation spectral dual-layer detector computed tomography (SDCT) reflects tissue composition. This study evaluated the utility of SDCT-Zeff-based radiomics, deep learning (DL), and clinical features to differentiate between ground-glass nodule (GGN)-featured precursor glandular lesions (PGLs) and adenocarcinomas.</p><p><strong>Methods: </strong>Patients diagnosed with GGN who underwent preoperative contrast-enhanced SDCT at two medical centers were prospectively enrolled between January 2022 and April 2024. Center 1 (Shengjing Hospital of China Medical University; n=582) served as the training cohort, while Center 2 (Shengjing Hospital, Huaxiang Branch; n=210) served as the external validation cohort. SDCT-Zeff delineated the region of interest (ROI) for radiomics feature extraction. A pre-trained ResNet50 model was used for DL feature extraction. Features were fused, screened, and integrated with various machine learning algorithms and clinical features to construct a clinical-based DL radiomics (DLR) signature nomogram, which was externally validated. Model performance was assessed regarding identification, calibration, and clinical utility.</p><p><strong>Results: </strong>A total of 792 GGNs were analyzed, classified as glandular precursor lesions (n=296) and adenocarcinomas (n=496). Zeff was inversely correlated with invasiveness. Three features were obtained: clinical, radiomics, and DL. LightGBM was identified as the best-performing model. The area under the curves (AUCs) of DLR in the training and test sets were 0.974 [95% confidence interval (CI): 0.963-0.983] and 0.827 (95% CI: 0.770-0.884), outperforming radiomics (AUC =0.897 and 0.765), and DL (AUC =0.929 and 0.758). The nomogram coupling clinical features [Zeff_a, electron density (ED)_a, and tumor abnormal protein (TAP)] showed the best predictive ability, with AUCs of 0.983 (95% CI: 0.974-0.990) and 0.833 (95% CI: 0.779-0.885) in the training and test sets. The calibration curve indicated strong agreement between predicted and observed outcomes in both cohorts. Decision curve analysis (DCA) revealed that this nomogram offers significant clinical benefits, with a threshold probability range surpassing other models.</p><p><strong>Conclusions: </strong>The coupled nomogram integrating SDCT-Zeff DLR with clinical features demonstrated improved predictive performance and was particularly effective in detecting GGN-featured glandular precursor lesions and adenocarcinomas. It provides a foundation for managing GGNs and offers valuable insights for preoperative evaluation.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"431-448"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670858","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 of neoadjuvant immunochemotherapy in the treatment of stage III non-small-cell lung cancer with cancer driver gene mutations.","authors":"Yuhong Yang, Jiacong Liu, Linhai Zhu, Xuhua Huang, Jiayue Ye, Nagashree Seetharamu, Hiroyuki Adachi, Jinming Xu, Yiqing Wang, Pinghui Xia, Wang Lv, Chong Zhang, Jian Hu","doi":"10.21037/tlcr-2025-60","DOIUrl":"10.21037/tlcr-2025-60","url":null,"abstract":"<p><strong>Background: </strong>Patients with non-small-cell lung cancer (NSCLC) and cancer driver gene mutations are mainly treated with targeted therapy. Research into the application of neoadjuvant immunochemotherapy for these patients is active and ongoing. In this study, we assessed the feasibility and safety of immunochemotherapy as a neoadjuvant treatment in patients with stage III NSCLC with common cancer driver gene mutations.</p><p><strong>Methods: </strong>This retrospective study enrolled patients who had stage III NSCLC with the results of driver mutation testing [including epidermal growth factor receptor (<i>EGFR</i>), Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>), c-ros proto-oncogene 1, receptor tyrosine kinase (<i>ROS1</i>), rearranged during transfection (<i>RET</i>), anaplastic lymphoma kinase (<i>ALK</i>), human epidermal growth factor receptor 2 (<i>HER2</i>), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (<i>PIK3CA</i>)] and received neoadjuvant immunochemotherapy. The patients were followed for at least 1 year after the operation or until the day the treatment was discontinued. The primary endpoints were objective response rate (ORR) and adverse events (AEs), while the secondary endpoints were pathological response among patients who undergo surgery, disease-free survival (DFS) and overall survival (OS).</p><p><strong>Results: </strong>From 2020 to 2022, a total of 34 patients with stage III NSCLC were included in this study and were categorized into two groups according to the presence of cancer driver gene mutations: a mutation group (n=22) and a wild-type (WT) group (n=12). The rate of ORR in the WT group was 58.3%, and the rate of ORR in the mutation group was 68.2%. And no postoperative deaths or grade 3 or 4 AEs were observed in either of the groups. Among the patients who underwent surgery, the major pathological response (MPR) rate in the WT group and the mutation group was 75.0% and 47.0%, respectively (P=0.23). The pathological complete response (pCR) rate in the WT group and in the mutation group was 37.5% and 23.5%, respectively (P=0.64). The 1-year DFS rate in the WT group and the mutation group was 87.5% and 82.4%, respectively, while the 1-year OS rates in the WT group and the mutation group were both 100.0%.</p><p><strong>Conclusions: </strong>The potential of neoadjuvant immunochemotherapy for patients with stage III NSCLC with cancer driver gene mutations is promising.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"538-551"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671064","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":"Cerebrospinal fluid cytology for the diagnosis of lung cancer brain metastasis: a case report.","authors":"Lidan Xing, Jiajia Liu, Haiyang Yan, Jing Chen, Lingling Gao, Muhammad Zubair Afzal, Toyoaki Hida, Shuai Zhao, Jingna Sun","doi":"10.21037/tlcr-2025-37","DOIUrl":"10.21037/tlcr-2025-37","url":null,"abstract":"<p><strong>Background: </strong>The examination of cerebrospinal fluid (CSF) cytology holds significant value in the field of neuropathology, serving as a key diagnostic tool for clinical physicians in completing differential diagnosis and clinical assessment. Particularly in the context of infectious diseases affecting the central nervous system (CNS), cerebrovascular diseases, brain tumors, meningeal carcinoma, and immune-related disorders, this examination is critical to facilitating accurate diagnoses and distinguishing between various clinical conditions.</p><p><strong>Case description: </strong>A 57-year-old Han Chinese male was admitted to The First Hospital of Hebei Medical University for psychiatric symptoms. A series of diagnostic tests were sequentially conducted on the patient, including routine CSF examination, CSF biochemical analysis, test for autoimmune encephalitis antibodies and paraneoplastic syndrome autoantibodies, pathogen-targeted sequencing, cytokine analysis via flow cytometry, tumor marker tests, positron emission tomography-computed tomography, and cranial magnetic resonance imaging (MRI). The results showed an increase in CSF white blood cell count, CSF protein, and serum carcinoembryonic antigen. In conjunction with cranial MRI revealing multiple intracranial nodular abnormal signals, these can serve as effective evidence to aid in diagnosis. However, the definitive diagnosis of meningeal carcinomatosis (MC) ultimately depends on the cytological identification of atypical cells in the CSF. Given the patient's history of lung cancer, the final diagnosis was leptomeningeal metastasis from lung cancer, which belongs to the type of CNS metastatic carcinoma in MC.</p><p><strong>Conclusions: </strong>In this case, the cytological identification of atypical cells in the CSF confirmed the diagnosis of MC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"607-613"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670825","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":"Immunotherapy efficacy between exon 19 deletion and exon 21 L858R mutation in advanced EGFR mutant non-small-cell lung cancer: a direct and indirect meta-analysis.","authors":"Zihong Chen, Lanlan Pang, Yuwen Yang, Xinyi He, Jianhua Zhan, Lin Zhang, Kangqiao Xiong, Wenfeng Fang, Li Zhang, Yaxiong Zhang","doi":"10.21037/tlcr-24-884","DOIUrl":"10.21037/tlcr-24-884","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy (IO) exhibits poor therapeutic effect in epidermal growth factor receptor (EGFR) mutant advanced non-small-cell lung cancer (NSCLC). However, previous studies reveal different IO efficacy between exon 19 deletion (19 Del) and exon 21 L858R mutation (21 L858R). In this study, we aimed to evaluate the difference in IO efficacy between patients with EGFR 19 Del and EGFR 21 L858R.</p><p><strong>Methods: </strong>IO data of response rate, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) stratified by EGFR subtypes were extracted and synthesized on random-effect model using odds ratios (ORs) for dichotomous data and hazard ratios (HRs) for survival data with 95% confidence interval (CI). Efficacy comparisons between 19 Del and 21 L858R were estimated through direct and indirect methods respectively.</p><p><strong>Results: </strong>A total of 15 studies that involved 1,209 EGFR-mutant advanced NSCLC patients with IO treatment were included (19 Del, n=676; 21 L858R, n=533). Based on the data from 11 studies for direct meta-analysis, patients with 19 Del had shorter PFS (HR =1.55; 95% CI: 1.21-1.98; P=0.001) and OS (HR =1.36; 95% CI: 1.04-1.78; P=0.02) and poorer DCR (OR =0.51; 95% CI: 0.29-0.87; P=0.02) than those with 21 L858R significantly. Indirect meta-analysis from four trials showed the same result that patients with 19 Del had significantly shorter PFS (HR =1.50; 95% CI: 1.09-2.07; P=0.01) than those with 21 L858R. Subgroup analyses also showed similar tendency that 21 L858R had more clinical benefit compared to 19 Del no matter whether IO monotherapy or IO combination.</p><p><strong>Conclusions: </strong>For advanced EGFR mutant NSCLC patients, 21 L858R had superior IO efficacy compared with 19 Del.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"422-430"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671015","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":"Erratum: Tumor cavitation in patients with non-small-cell lung cancer receiving anti-angiogenic therapy with apatinib.","authors":"","doi":"10.21037/tlcr-2024-2","DOIUrl":"10.21037/tlcr-2024-2","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.21037/tlcr-24-465.].</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"652"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671066","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":"Dual-layer spectral detector computed tomography multiparameter machine learning model for prediction of invasive lung adenocarcinoma.","authors":"Jiayu Wan, Xue Lin, Zhaokai Wang, Peng Sun, Shen Gui, Tianhe Ye, Qianqian Fan, Weiwei Liu, Feng Pan, Bo Yang, Xiaotong Geng, Zhen Quan, Lian Yang","doi":"10.21037/tlcr-24-822","DOIUrl":"10.21037/tlcr-24-822","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths. High-resolution computed tomography (HRCT) has improved the detection of ground glass nodules (GGNs), which are early indicators of lung cancer. Accurate assessment of GGN invasiveness is crucial for determining the appropriate surgical approach. Dual-layer spectral detector computed tomography (DLCT) offers advanced imaging capabilities, including electron density and iodine density, which enhance the evaluation of GGN invasiveness. This study aims to develop a machine learning (ML) model that integrates DLCT parameters and clinical features to predict the invasiveness of GGNs in LUAD, aiding in surgical decision-making and prognosis improvement.</p><p><strong>Methods: </strong>The retrospective study encompassed 272 patients who were diagnosed with LUAD, comprising 154 cases of invasive adenocarcinomas (IA) and 118 cases of pre-invasive minimally invasive adenocarcinoma (MIA) which were then randomly allocated into a training set and a test set. Six ML models were developed based on five DLCT parameters (conventional, iodine density, virtual noncontrast, electron density, and effective atomic number). Subsequently, a nomogram was constructed using multi-factor logistic regression, incorporating radiomic characteristics and clinicopathological risk factors.</p><p><strong>Results: </strong>The ML model based on conventional plus electron density performed better than the models with other DLCT parameters, with the area under the curves (AUCs) of 0.945 and 0.964 in the training and test sets, respectively. The clinical model and radiomics score (Rad-score) were combined in the logistic regression to construct a joint model, of which the AUCs were 0.974 in the training sets and 0.949 in the test sets. The ML model effectively differentiated between IA and pre-invasive MIA, and further classified patients into high and medium risk categories for invasion using waterfall plots.</p><p><strong>Conclusions: </strong>The ML model based on DLCT parameters helps predict the invasiveness of GGNs and classifies the GGNs into different risk grades.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"385-397"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670864","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":"Alectinib impressively enters the adjuvant setting for early-stage <i>ALK</i>-rearranged non-small cell lung cancer and outperforms chemotherapy-let's define who benefits the most.","authors":"Eric Santoni-Rugiu, Jens Benn Sørensen, Edyta Maria Urbanska","doi":"10.21037/tlcr-24-961","DOIUrl":"10.21037/tlcr-24-961","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"310-313"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670807","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":"Aspirin impedes non-small cell lung cancer development via fine-tuning the CD36 localization regulated by GPIHBP1.","authors":"Wei Liu, Dujuan Qiao, Jia Chen, Ya Gao, Katsuhiro Okuda, Yoshihisa Shimada, Linong Yao","doi":"10.21037/tlcr-2024-1174","DOIUrl":"10.21037/tlcr-2024-1174","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer, a commonly diagnosed malignancy, is the leading cause of cancer-related death worldwide. Aspirin suppresses the progression and metastasis of various cancers. However, the effect of aspirin on non-small cell lung cancer (NSCLC) has not been fully understood. It has been established that glycosylphosphatidylinositol HDL-binding protein 1 (GPIHBP1) and CD36 play a vital role in lipid metabolism and transport. This study aimed to clarify the mechanism by which aspirin inhibits NSCLC cell proliferation and metastasis via GPIHBP1.</p><p><strong>Methods: </strong>The blood and tissues of 10 patients with NSCLC treated with aspirin and 10 patients without aspirin were collected and analyzed via RNA sequencing. GPIHBP1 expression was determined by immunohistochemistry (IHC), Western blotting, and quantitative real time polymerase chain reaction (qRT-PCR). A series of functional experiments were performed to evaluate the effects of aspirin on NSCLC progression in a GPIHBP1-dependent manner. The potential mechanism of GPIHBP1 was explored via coimmunoprecipitation and immunofluorescence staining. The effect of GPIHBP1 on tumor growth and metastasis was verified by constructing subcutaneous xenograft tumor model in nude mice.</p><p><strong>Results: </strong>GPIHBP1 was downregulated and was increased by treatment with aspirin in lung cancer tissues. Furthermore, GPIHBP1 overexpression inhibited the migration, cell proliferation, and epithelial-mesenchymal transition process in NSCLC cells while promoting their apoptosis, while in cells with GPIHBP1 knockdown, the opposite was observed. Mechanistically, GPIHBP1 directly interacted with CD36 while GPIHBP1 knockdown disrupted CD36 localization, thus promoting tumor progression and metastasis in NSCLC cells. In addition, through <i>in vivo</i> xenograft experiments, we found that GPIHBP1 overexpression inhibited tumor growth and metastasis.</p><p><strong>Conclusions: </strong>Our findings provide new insights into the mechanism by which aspirin suppresses lung cancer development in a GPIHBP1-dependent manner and may provide a promising target in NSCLC treatment.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"491-512"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670810","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":"Trastuzumab deruxtecan in HER2 overexpressing non-small cell lung cancer (NSCLC).","authors":"Omali Pitiyarachchi, Aaron C Tan","doi":"10.21037/tlcr-24-968","DOIUrl":"10.21037/tlcr-24-968","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"314-322"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670835","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":"Unravelling the complexity of <i>EGFR</i>-mutated lung adenocarcinoma: a unique case report with histological transformations and co-alteration acquisition.","authors":"Anissa Boutahir, Véronique Dalstein, Jean Baptiste Oudart, Gaëtan Deslee, Chistine Clavel, Maxime Dewolf, Anne Durlach, Julien Ancel","doi":"10.21037/tlcr-24-707","DOIUrl":"10.21037/tlcr-24-707","url":null,"abstract":"<p><strong>Background: </strong>Osimertinib, a third-generation tyrosine kinase inhibitor that targets epidermal growth factor receptor (EGFR), specifically inhibits both EGFR tyrosine kinase inhibitor-sensitive mutations and T790M resistance mutations. Despite initial positive responses to EGFR tyrosine kinase inhibitors, nearly all patients eventually experience disease progression. Mechanisms of resistance are classically divided into EGFR-dependent and EGFR-independent mechanisms, such as the activation of alternative pathways and histological changes. We report a case of histological transformation into large cell carcinoma associated with the subsequent acquisition of an anaplastic lymphoma kinase (ALK) rearrangement after osimertinib exposure.</p><p><strong>Case description: </strong>A 67-year-old female with no smoking history presented with supraclavicular lymphadenopathy and asthenia, which led to a diagnosis of stage IVB lung adenocarcinoma. Next generation sequencing (NGS) identified an <i>EGFR</i> Ex19del mutation, which suggested the use of afatinib, as it was prescribed prior to osimertinib and was covered by insurance. Initial treatment with afatinib resulted in partial remission, followed by pulmonary progression without the <i>EGFR</i>-T790M mutation. Moreover, ALK and ROS1 were identified through immunohistochemistry (IHC), with ROS1 expression subsequently confirmed by fluorescence in situ hybridization (FISH); this prompted a switch to crizotinib, which was discontinued owing to further disease progression. Osimertinib was then administered, which resulted in a significant positive response; however, after six months pulmonary progression was observed. A subsequent biopsy indicated a transformation to large cell neuroendocrine carcinoma, which led to treatment with platinum-etoposide chemotherapy and, later, paclitaxel and osimertinib, both of which are partially effective. Finally, a new biopsy confirmed ALK positivity in a large cell neuroendocrine carcinoma that was still harbouring an <i>EGFR</i> exon 19 deletion, so alectinib was introduced.</p><p><strong>Conclusions: </strong>To our knowledge, this case is the first reported incidence of transformation into large cell carcinoma coupled with a second acquisition of alterations in ALK. These findings underscore the necessity of monitoring patients with oncogenic addiction through both liquid biopsy for on-target mechanism detection and tissue sampling to detect histological transformations. These mechanisms can occasionally be combined, thereby providing comprehensive panels at each stage of tumour progression.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"639-648"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670837","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}