Translational lung cancer research最新文献

{"title":"A preliminary analysis of integrating thymosin α1 into concurrent chemoradiotherapy and consolidative immunotherapy in unresectable locally advanced non-small cell lung cancer.","authors":"Hao-Ting Zhang, Fang-Jie Liu, Da-Quan Wang, Yi-Xin Xiong, Yuan-Yuan Zhao, Wen-Zhuo He, Peng-Xin Zhang, Shi-Yang Zheng, Biao Xia, Yu Situ, Meng-Ru Wang, Qian-Wen Liu, Yi Hu, Liang-Ping Xia, Bo Qiu, Hui Liu","doi":"10.21037/tlcr-2025-190","DOIUrl":"10.21037/tlcr-2025-190","url":null,"abstract":"<p><strong>Background: </strong>Concurrent chemoradiotherapy (CCRT) followed by consolidative immunotherapy represents the standard of care for unresectable locally advanced non-small cell lung cancer (LA-NSCLC), but critical challenges persist: a considerable number of patients discontinue consolidative immune checkpoint inhibitors (ICIs) due to treatment-related pneumonitis and lymphopenia, while \"cold\" tumor microenvironments further limit immunotherapy efficacy. Thymosin α1 (Tα1) is a pleiotropic immunomodulator that has been associated with infection prevention and the regulation of immune cells. Thus, we designed this retrospective study to investigate the therapeutic effect of integrating Tα1 into CCRT followed by consolidative immunotherapy in patients diagnosed with unresectable LA-NSCLC.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on a total of 196 patients with unresectable stage IIIA-IIIC LA-NSCLC treated from January 1, 2020, to May 31, 2023. All patients received CCRT (60-64 Gy total irradiation dose, weekly concurrent docetaxel and cisplatin) with or without consolidative nivolumab. According to the use of Tα1, patients were classified into 3 groups: non-Tα1 group, patients who did not receive Tα1; short-term Tα1 group, receipt of Tα1 (1.6 mg) once a week from the beginning of treatment until the end of CCRT; long-term Tα1 group, receipt of Tα1 (1.6 mg) once a week from the beginning of treatment until 12 months post-CCRT. The primary objective was progression-free survival (PFS). The secondary objectives included overall survival (OS), pneumonitis, circulating lymphocyte count and interleukin-6 (IL-6) levels. Pretreatment biopsy samples were collected to evaluate the potential influence of somatic mutations on treatment outcomes.</p><p><strong>Results: </strong>The non-Tα1, short-term Tα1, and long-term Tα1 groups included 48, 101, and 47 patients, respectively. Following CCRT, 77.1%, 75.2%, and 93.6% of patients in the respective groups were eligible for consolidative nivolumab (P=0.03). Median PFS was 14.6 months [95% confidence interval (CI): 11.9-17.3] for the non-Tα1 group, 16.0 months (95% CI: 13.2-18.8) for the short-term Tα1 group, and not reached for the long-term Tα1 group (P=0.03). Median OS was 20.0 months (95% CI: 16.1-23.9) for the non-Tα1 group, 27.6 months (95% CI: 13.8-41.3) for the short-term Tα1 group, and not reached in the long-term Tα1 group (P=0.01). The long-term Tα1 group experienced significantly lower rates of grade ≥2 pneumonitis (35.4% in non-Tα1, 14.5% in long-term Tα1 groups, P=0.02), and lower rates of lymphopenia at 6 months post-CCRT (55.8% in non-Tα1, 30.9% in short-term Tα1, and 22.5% in long-term Tα1 groups, P=0.01). At 2 months post-CCRT, the median IL-6 level in the non-Tα1 group (8.14 pg/mL) was significantly higher than that in the long-term Tα1 group (4.92 pg/mL, P=0.03).</p><p><strong>Conclusions: </strong>Integrating Tα1 into CCRT and consolidative immunotherap","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2710-2722"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837841","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":"Advances in immunotherapy for driver gene-positive non-small cell lung cancer: a narrative review.","authors":"Fangfei Qian, Runbo Zhong, Hua Zhong","doi":"10.21037/tlcr-2025-684","DOIUrl":"10.21037/tlcr-2025-684","url":null,"abstract":"<p><strong>Background and objective: </strong>Although immunotherapy has become the standard treatment for driver gene-negative advanced non-small cell lung cancer (NSCLC), its efficacy in driver gene-positive NSCLC patients remains conversational. This narrative review systematically and critically analyzes recently published literature, aiming to improve the current landscape of immunotherapy for driver gene-positive NSCLC.</p><p><strong>Methods: </strong>The databases of PubMed, Web of Science, Scopus, and Google Scholar were searched for relevant articles, including those published in leading journals and conference proceedings. Search queries were constructed using keywords (\"immunotherapy\", \"non-small cell lung cancer\", \"driver gene-positive\") and their combinations. Literature was included via dual independent screening and team meetings, followed by comprehensive interpretation, resulting in a high-quality literature corpus focused on advances in immunotherapy for driver gene-positive NSCLC.</p><p><strong>Key content and findings: </strong>This article reviews the recent advances and challenges in immunotherapy for driver gene-positive NSCLC, focusing on common driver gene mutations. Significant variations exist in how different driver genes regulate the tumor immune microenvironment, leading to disparate immunotherapy response rates. While targeted therapy is the first-line treatment for NSCLC with epidermal growth factor receptor (<i>EGFR</i>) mutations, immunotherapy combinations should be explored when drug resistance occurs. Immunotherapy plus chemotherapy is preferred in patients with Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>)-mutated NSCLC, whereas antibody-drug conjugates plus immunotherapy may be more appropriate for NSCLC with human epidermal growth factor receptor 2 (<i>HER2</i>) alterations. Despite the accumulation of studies of patients with common alterations, studies of patients with uncommon alterations are still lacking. Neoadjuvant immunotherapy combined with chemotherapy is currently being explored for driver gene-positive NSCLC.</p><p><strong>Conclusions: </strong>Many questions remain about the use of immunotherapy for the treatment of driver gene-positive NSCLC. With optimized biomarker and combination therapies, individualized strategies may be further developed for overcoming drug resistance.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2853-2868"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837842","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":"An online explainable ensemble machine learning model for predicting epidermal growth factor receptor mutation status in lung adenocarcinoma.","authors":"Qilong Song, Xiaohu Li, Biao Song, Tingting Zhang, Xiankuo Hu, Ao Li, Dongchun Ma, Xuhong Min, Yongqiang Yu","doi":"10.21037/tlcr-2025-237","DOIUrl":"10.21037/tlcr-2025-237","url":null,"abstract":"<p><strong>Background: </strong>Non-invasive determination of epidermal growth factor receptor (EGFR) mutation status is essential for selecting lung adenocarcinoma patients suitable for EGFR-tyrosine kinase inhibitors (EGFR-TKIs). This study aimed to develop and validate an online ensemble machine learning (EML) model that combines multiple machine learning (ML) models to predict the EGFR mutation status in lung adenocarcinoma.</p><p><strong>Methods: </strong>A total of 823 lung adenocarcinoma patients with known EGFR mutation status from three medical centers were divided into a training cohort (n=556) and a validation cohort (n=267) (ChiCTR2400083082 in the WHO International Clinical Trials Registry). Five ML models incorporating clinical and radiological characteristics-random forest (RF), logistic regression (LR), support vector machine (SVM), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost)-along with a CT-based deep learning (DL) model were constructed to predict EGFR mutation status. Subsequently, an EML model was created by combining these models. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), and the SHapley Additive exPlanation (SHAP) method was used to explain the EML model.</p><p><strong>Results: </strong>In the training cohort, the AUCs for the RF, LR, SVM, LightGBM, XGBoost, DL, and EML were 0.851, 0.790, 0.810, 0.835, 0.853, 0.884, and 0.928, respectively. In the validation cohort, the AUCs for the RF, LR, SVM, LightGBM, XGBoost, DL, and EML were 0.753, 0.744, 0.732, 0.749, 0.751, 0.754, and 0.813, respectively. The Delong test indicated that the AUC of the EML model showed outstanding performance compared to the single models in both the training and validation cohorts. Decision curve analysis indicated that the EML model provided a clinically useful net benefit, and calibration curves showed good agreement. SHAP analysis identified predictive characteristics ranked by their contribution to the EML model: DL score, long-axis diameter, smoking history, pleural retraction, texture, vascular convergence, sex, air bronchogram, and bubblelike lucency. These characteristics were further used to develop an online web tool.</p><p><strong>Conclusions: </strong>The EML model could serve as a non-invasive and accurate method for predicting EGFR mutation status in lung adenocarcinoma.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2670-2687"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837843","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":"Expert recommendations for biomarker evaluation of advanced non-small cell lung cancer in Thailand.","authors":"Shanop Shuangshoti, Naiyarat Prasongsook, Lucksamon Thamlikitkul, Thanyanan Reungwetwattana, Naravat Poungvarin, Artit Jinawath, Chinachote Teerapakpinyo, Songkhun Vinyuvat, Virote Sriuranpong","doi":"10.21037/tlcr-2025-201","DOIUrl":"10.21037/tlcr-2025-201","url":null,"abstract":"<p><strong>Background: </strong>Growing understanding of the heterogenous molecular profiles of non-small cell lung cancer (NSCLC) has led to changes in the treatment landscape of advanced NSCLC towards precision medicine to target actionable gene alterations. Practical barriers, such as lack of awareness/understanding of biomarkers, suboptimal quality or sample management, inappropriate use of biomarker testing results, limited patient access to biomarker tests and targeted treatments, and reimbursement/payment challenges, hinder the wider adoption of guideline-recommended biomarker testing. Limited reimbursement of targeted therapies is a key consideration for Thai oncologists when making a treatment choice for their patients with advanced NSCLC in Thailand. We aim to assess the current state of biomarker testing and treatment for advanced NSCLC in Thailand and provide recommendations to facilitate timely access to appropriate therapies, enhance patient quality of life, and optimize the use of Thailand's existing healthcare schemes.</p><p><strong>Methods: </strong>The expert panel comprising one clinical pathologist, three anatomic pathologists, one molecular geneticist, and four medical oncologists convened to review recent literature, discuss current clinical practice, and prioritize essential topics for biomarker assessment and management of advanced NSCLC in Thailand. Following the meeting, further discussions on these prioritized topics were conducted via email, and the recommendations were developed.</p><p><strong>Results: </strong>Our recommendations include adopting an exclusionary strategy for biomarker testing, emphasizing the role of a multidisciplinary team (MDT) in managing patients with advanced NSCLC, and underscoring the importance of laboratory accreditation and external quality assurance programs. Additionally, we highlight the need for high-quality data on the local impact of novel treatments to assist policymakers in making these therapies accessible to suitable patients.</p><p><strong>Conclusions: </strong>By proposing practical strategies tailored to our local healthcare setting, such as exclusionary biomarker testing approach, MDT involvement, and robust quality assurance measures, we provide a roadmap for improving the diagnosis and treatment of advanced NSCLC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2387-2402"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837858","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":"Overexpression of <i>PPM1G</i> promotes cell metabolism and activates the NOTCH signaling pathway in lung adenocarcinoma.","authors":"Guangmin Xi, Caibo Zhang, Cong Yu, Yiya Wang, Jinfeng Fu, Haining Qi, Kenichi Suda, Guoying Wu","doi":"10.21037/tlcr-2025-659","DOIUrl":"10.21037/tlcr-2025-659","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is one of the most malignant types of cancer with a high incidence. Protein phosphatase, Mg²⁺/Mn²⁺-dependent 1G (<i>PPM1G</i>) has recently been reported to promote cancer progression; however, its specific role in LUAD remains unknown. Therefore, in this study, we aimed to clarify the roles of <i>PPM1G</i> in LUAD and the related the regulatory mechanisms.</p><p><strong>Methods: </strong>We analyzed the expression profile of <i>PPM1G</i> in the LUAD dataset obtained from The Cancer Genome Atlas (TCGA) database using the Gene Expression Profiling Interactive Analysis (GEPIA) online tool and R software. The functions of <i>PPM1G</i> in LUAD were investigated by <i>in vivo</i> and <i>in vitro</i> assays. Gene set enrichment analysis (GSEA) was conducted to determine the signaling pathways that could be regulated by PPM1G.</p><p><strong>Results: </strong><i>PPM1G</i> was found to be highly expressed in LUAD tumor tissues than in non-tumor tissues and was correlated with the pathological and clinical stages of the disease and patient survival. PPM1G overexpression promoted cell proliferation, metastasis and glycolysis, while PPM1G knockdown conferred the opposite effects. Moreover, PPM1G knockdown promoted cell apoptosis and caused cell cycle arrest at the G1 phase. <i>In vivo</i>, PPM1G knockdown inhibited tumorigenesis. We found that NOTCH signaling as a key pathway associated with PPMIG overexpression.</p><p><strong>Conclusions: </strong>Our results revealed that high <i>PPM1G</i> expression acted as a prognostic factor in LUAD and promoted LUAD cell growth, metastasis, and glycolysis. Mechanistically, <i>PPM1G</i> activated the NOTCH pathway to promote these effects, indicating its potential as a novel therapeutic target for treating LUAD.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2771-2787"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837877","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":"Prognostic implications of MDM2 expression in surgically resected epidermal growth factor receptor mutant lung cancer with pathological lymph node metastasis.","authors":"Tetsuya Isaka, Yohei Miyagi, Rika Kasajima, Kota Washimi, Shuji Murakami, Haruhiro Saito, Yui Sueishi, Naoko Shigeta, Ikki Takada, Ryotaro Matsuyama, Chiaki Kanno, Takuya Nagashima, Hiroyuki Ito","doi":"10.21037/tlcr-2025-143","DOIUrl":"10.21037/tlcr-2025-143","url":null,"abstract":"<p><strong>Background: </strong>MDM2 protein regulates p53 protein activity; however, the prognostic impact of MDM2 expression in primary lung cancer on patient prognoses is unknown. This study investigated the prognostic implications of MDM2 protein expression among patients with epidermal growth factor receptor mutant (<i>EGFR</i>m) lung adenocarcinoma with pathologic lymph node metastases after surgery.</p><p><strong>Methods: </strong>Immunohistochemical analysis was conducted to determine the MDM2 expression of pN1-N2 <i>EGFR</i>m [exon 19 deletion mutation (Ex19) and exon 21 L858R mutation (Ex21)] lung cancer that were surgically resected between January 2010 and December 2020 (n=124). The postoperative prognosis and cumulative incidence of recurrence were retrospectively analyzed.</p><p><strong>Results: </strong>MDM2 protein expression was positive in 56 patients (45.2%) with <i>EGFR</i>m lung adenocarcinoma. The relapse-free survival (RFS) rate was significantly better among patients with MDM2⁺ <i>vs.</i> those with MDM2^- (5-year RFS: 35.5% <i>vs.</i> 14.8%, P=0.04). Multivariable analysis revealed MDM2⁺ as an independent favorable prognostic factor for RFS [hazard ratio (HR), 0.64; 95% confidence interval (CI): 0.42-0.98; P=0.04]. Among patients with Ex21 lung cancer (n=63), significantly better RFS and overall survival (OS) were seen in patients with MDM2⁺ than those with MDM2^- (5-year RFS: 36.4% <i>vs.</i> 9.2%, P=0.005; 5-year OS: 81.8% <i>vs.</i> 39.3%, P=0.002). Multivariable analysis revealed that among patients with Ex21 lung cancer, MDM2⁺ was an independent favorable prognostic factor for RFS (HR, 0.43; 95% CI: 0.23-0.80; P=0.008) and OS (HR, 0.32; 95% CI: 0.15-0.67; P=0.003), and it was also associated with a low cumulative incidence of overall distant recurrence (HR, 0.42; 95% CI: 0.20-0.87; P=0.02) and central nervous system recurrence (HR, 0.23; 95% CI: 0.07-0.80; P=0.02).</p><p><strong>Conclusions: </strong>MDM2 protein expression is a prognostic predictor of RFS and OS in patients with pN1-N2 Ex21 lung cancer after curative surgery. MDM2 can be a novel biomarker for predicting postoperative prognosis and distant metastasis, especially in the central nervous system.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2571-2583"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837881","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":"Prognostic significance of micropapillary pattern and risk factors in patients with resected stage I lung adenocarcinoma and possible benefit of adjuvant therapy: a real-world multicenter study.","authors":"Jianjie Li, Yujia Chi, Bo Jia, Qiwen Zheng, Minghan Yuan, Jianjun Zhang, Aishen Zhou, Wei Sun, Yue Yang, Jun Zhao, Tongtong An, Yuyan Wang, Minglei Zhuo, Xue Yang, Hanxiao Chen, Jingjing Wang, Xiaoyu Zhai, Yidi Tai, Yuling He, Lingdong Kong, Xumeng Ji, Yiliang Liu, Nan Wu, Ken Onodera, Paul Van Schil, Mathew Thomas, Fan Yang, Ziping Wang","doi":"10.21037/tlcr-2025-698","DOIUrl":"10.21037/tlcr-2025-698","url":null,"abstract":"<p><strong>Background: </strong>Micropapillary (MP) pattern has been identified as a negative prognostic factor in patients with lung adenocarcinoma, but it has not been recognized as a high-risk factor for patients with stage IB lung adenocarcinoma treated with adjuvant chemotherapy. This multicenter cohort study aimed to evaluate the prognostic value of histological subtypes for stage I lung adenocarcinoma and to determine the relative survival benefit of adjuvant chemotherapy for subgroups based on MP pattern.</p><p><strong>Methods: </strong>This retrospective study included 412 patients with stage I lung adenocarcinoma [according the eighth edition of the tumor-node-metastasis (TNM) classification] with MP pattern who underwent complete surgical resection between January 2010 and December 2019. Patients were classified into 3 groups based on the proportion of MP component (10% and 50% as the threshold): MP component >50% (n=8), 10-50% (n=273) and <10% (n=131).</p><p><strong>Results: </strong>Among the 412 patients, the median age was 63 years, and 73.4% (113/154) patients with MP component ≥10% and 63.8% (51/80) of those with MP component <10% had epidermal growth factor receptor (<i>EGFR</i>) mutations. Patients with MP component >50% had a shorter overall survival (OS) compared with those with MP components of 10-50% [10-50% <i>vs</i>. >50%: hazard ratio (HR) =0.293, 95% confidence interval (CI): 0.083-1.027; P=0.052] or <10% (<10% <i>vs</i>. >50%: HR =0.214, 95% CI: 0.056-0.816; P=0.02). Notably, in the univariate analysis, the factors associated with a worse recurrence-free survival (RFS) were spread-through-air-space (STAS) status (HR =2.131, 95% CI: 1.104-4.112; P=0.02), male sex (HR =1.693, 95% CI: 1.048-2.735; P=0.03), smoking history (HR =1.817, 95% CI: 1.126-2.931; P=0.01), and tumor size >2 cm (HR =1.832, 95% CI: 1.138-2.949; P=0.01).</p><p><strong>Conclusions: </strong>MP component and risk factors might be considered critical features for patients with stage I lung adenocarcinomas and may inform the selection of patients who may benefit from adjuvant chemotherapy although no randomized evidence is available.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2760-2770"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837883","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":"Radiomics-clinical integration guides prophylactic cranial irradiation decisions in limited-stage small cell lung cancer: a brain metastasis risk stratification model.","authors":"Yuntao Zhou, Li Xiao, Siyi Yang, Chengwen Yang, Jifeng Sun, Jiehan Wu, Zhiyong Cui, Lujun Zhao, Yunchuan Sun, Ningbo Liu","doi":"10.21037/tlcr-2025-326","DOIUrl":"10.21037/tlcr-2025-326","url":null,"abstract":"<p><strong>Background: </strong>Limited-stage small-cell lung cancer (LS-SCLC) is highly aggressive and prone to brain metastasis (BM). Early identification of BM risk is crucial for devising personalized prophylactic cranial irradiation (PCI) strategies. This study aimed to develop a multimodal model integrating radiomic and clinical features to stratify BM risk in LS-SCLC patients and guide personalized PCI strategies.</p><p><strong>Methods: </strong>This study analyzed 141 LS-SCLC patients (2013-2021) using computed tomography (CT) images and clinical records. Patients were randomly divided into training (n=98), internal validation (n=43), and external validation cohorts (n=24). Radiomic features were extracted and optimized using the minimum redundancy maximum relevance (mRMR) algorithm to form a radiomic score (RadScore). Clinical predictors were identified via univariate logistic regression (LR). Four machine learning models-LR, support vector machine, random forest, and eXtreme Gradient Boosting-were used to develop predictive models. Model performance was evaluated by the area under the receiver operating characteristic curve (AUC).</p><p><strong>Results: </strong>A total of 141 patients (mean age, 59.03 years; 109 men and 32 women) were evaluated. A total of 1,037 radiomic features were extracted from the simulated positioning CT images, with 10 optimal features selected to form the RadScore. By incorporating dynamic changes in platelet count, hemoglobin levels, and leukocyte indices before and after radiotherapy, along with the baseline lymphocyte-to-monocyte ratio (LMR), the LR combined model demonstrated superior predictive capability. The LR combined model showed superior performance with AUCs of 0.831 (training), 0.831 (internal validation), and 0.863 (external validation). Risk stratification indicated that PCI reduced BM risk in high-risk patients [hazard ratio (HR) =0.270, P<0.001] but not in low-risk patients (HR =0.225, P=0.13).</p><p><strong>Conclusions: </strong>The LR combined radiomic-clinical model demonstrated superior predictive performance. PCI significantly reduced the risk of BM in high-risk patients, whereas no statistically significant benefit was observed in low-risk patients.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2584-2597"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837893","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 new reality of molecular surveillance for resected lung cancer.","authors":"Shuo Shi, Petros Christopoulos","doi":"10.21037/tlcr-2025-523","DOIUrl":"10.21037/tlcr-2025-523","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2369-2373"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837840","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 first-generation epidermal growth factor receptor tyrosine kinase inhibitors in retreatment of patients without T790M.","authors":"Juwhan Choi, Jae Cheol Lee, In Ae Kim, Kye Young Lee, Jeong Eun Lee, Seung Hun Jang, Seong Hoon Yoon, In-Jae Oh, Sang Hoon Lee, Eun Young Kim, Sung Yong Lee","doi":"10.21037/tlcr-2025-36","DOIUrl":"10.21037/tlcr-2025-36","url":null,"abstract":"<p><strong>Background: </strong>Patients receiving first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) and undergoing second and/or third-line cytotoxic chemotherapy may experience regrowth of EGFR (+) clones. Retreatment with EGFR TKIs can provide antitumor effects and potentially induce T790M-positive conversion. This study evaluated the efficacy, safety, and T790M (+) conversion rates in patients without T790M mutation at the second biopsy retreated with first-generation EGFR TKIs as third-line or subsequent therapy.</p><p><strong>Methods: </strong>This open-label, multi-center, prospective phase II trial (NCT03382795) enrolled patients with non-small cell lung cancer (NSCLC) previously treated with first- or second-generation EGFR TKIs and cytotoxic chemotherapy They were retreated with gefitinib or erlotinib. Key endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Results: </strong>Among 63 patients (34 on gefitinib, 29 on erlotinib), ORR was 14.3%. Median PFS was 2.2 months, and median OS was 8.6 months. Adverse events occurred in 82.5% of patients, primarily grade ≤2. The T790M conversion rate was 31.7% and was significantly associated with prior EGFR TKI exposure duration (P=0.047). Patients with T790M conversion had a median OS of 29.3 months, significantly (P<0.001) longer than the median OS of 6.0 months for non-converters. Next-generation sequencing (NGS) of pre-retreatment blood samples identified additional T790M mutations (20.8%) undetected by conventional testing. Low TP53 expression showed a non-significant trend toward higher tendency T790M conversion (66.7% <i>vs.</i> 30.8%, P=0.32).</p><p><strong>Conclusions: </strong>EGFR retreatment induced T790M conversion in 32% of cases, enabling third-generation EGFR TKIs, leading to a substantial improvement in median OS. Blood-based NGS identified additional T790M mutations, undetected by routine polymerase chain reaction (PCR). EGFR TKI retreatment with blood-based NGS may enhance patient prognosis by identifying additional T790M positive mutations.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2483-2493"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837848","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}