Translational lung cancer research最新文献

{"title":"Natural course of lung adenocarcinoma manifesting as ground-glass nodules: invasiveness assessment based on growth evaluation.","authors":"Yuanhui Wei, Zhen Yang, Zirui Wang, Jiabo Ren, Yue Yin, Shangshu Liu, Xiaoyan Su, Sara Ricciardi, Takehiro Izumo, Wei Zhao, Liang-An Chen","doi":"10.21037/tlcr-2025-395","DOIUrl":"10.21037/tlcr-2025-395","url":null,"abstract":"<p><strong>Background: </strong>Investigating the growth characteristics of lung adenocarcinoma manifesting as ground-glass nodules (gLUAD) and assessing its invasiveness based on these features are crucial for optimizing follow-up and intervention strategies. This study aimed to systematically analyze the growth dynamics of gLUAD and compare the value of different growth evaluation methods in predicting gLUAD invasiveness.</p><p><strong>Methods: </strong>A total of 564 participants with 625 gLUAD were retrospectively enrolled from the First and Fourth Medical Centers of the Chinese PLA General Hospital between January 2018 and December 2022. gLUAD was pathologically classified into two categories: adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC). Growth evaluation was conducted using four definitions (size growth, volume growth, mass growth, and stage shift) and two growth models (linear and exponential models). These methods were further evaluated in terms of their effectiveness in assessing gLUAD invasiveness.</p><p><strong>Results: </strong>The median follow-up period of gLUAD in this study was 1,050 days. The median doubling times for total/solid size, volume, and mass of gLUAD were >3,650/3,042 days, 1,460/1,014 days, and 1,521/1,014 days, respectively. For AIS/MIA, all doubling times exceeded 3,650 days, whereas for IAC, they were 3,318/2,147 days, 1,141/777 days, and 1,074/760 days, respectively. The R<sup>2</sup> and root mean squared error (RMSE) values for the linear and exponential growth models in fitting total/solid size, volume, and mass were 0.98/0.95 <i>vs.</i> 0.98/0.95, 0.98/0.90 <i>vs.</i> 0.98/0.93, and 0.95/0.90 <i>vs.</i> 0.98/0.92 for R<sup>2</sup>, while they were 0.53/0.92 <i>vs.</i> 0.51/0.94, 169.80/100.00 <i>vs.</i> 143.87/106.81, and 116.12/101.24 <i>vs.</i> 72.81/108.99 for RMSE, respectively. The median growth times for size growth, volume growth, mass growth, and stage shift of gLUAD were 1,273, 750, 792, and 1,672 days, respectively. Compared to AIS/MIA, IAC exhibited significantly higher growth rates (all P values <0.001). For invasiveness assessment, the linear growth rates (LGRs) outperformed the exponential growth rates (EGRs) in discriminative value (all P values <0.05). Among the growth evaluation methods, the LGR of total mass demonstrated the highest discriminative ability for pathological subtypes of gLUAD, with an area under the curve (AUC) of 0.83. At an optimal cutoff of 16.80 mg/year, the accuracy, sensitivity, and specificity for distinguishing gLUAD with different invasiveness were 0.78, 0.77, and 0.79, respectively.</p><p><strong>Conclusions: </strong>gLUAD exhibited an indolent growth pattern, with significant differences in growth trends between AIS/MIA and IAC. Both the linear and exponential growth models showed similar fitting performance for gLUAD growth, while the linear growth model provided a more reliable assessment of invasiveness. T","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2180-2196"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650668","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 immunotherapy in advanced <i>ALK</i>-rearranged non-small cell lung cancer patients with disease progression on ALK-TKIs.","authors":"Danni Wang, Yujing Li, Beibei Liu, Yuqing Lou, Lele Zhang, Yueran Sun, Fangfei Qian, Jun Lu, Fusheng Li, Edyta M Urbanska, Diego Kauffmann-Guerrero, Xinwei Wu, Baohui Han, Yanwei Zhang, Wei Zhang","doi":"10.21037/tlcr-2025-505","DOIUrl":"10.21037/tlcr-2025-505","url":null,"abstract":"<p><strong>Background: </strong>Treatment of tyrosine kinase inhibitor (TKI)-resistant anaplastic lymphoma kinase (<i>ALK</i>) rearranged non-small cell lung cancer (NSCLC) remains an unmet need. Among these patients, the efficacy of immunotherapy has not been thoroughly investigated. The purpose of our study was to evaluate the efficacy of immunotherapy in patients with ALK-TKI-resistant NSCLC, stratified by programmed cell death ligand-1 (PD-L1) expression.</p><p><strong>Methods: </strong>We retrospectively collected the data of advanced NSCLC patients with <i>ALK</i>-rearrangement, who were treated with immunotherapy or chemotherapy after the development of ALK-TKI resistance at the Shanghai Chest Hospital. Progression-free survival (PFS) was used to evaluate the outcomes.</p><p><strong>Results: </strong>The final analysis included 89 patients between June 1, 2018, and December 31, 2022, who met the selection criteria. The entire cohort had a median follow-up time of 33.4 months. The patients who received immunotherapy had better PFS than those who received non-immunotherapy (median PFS: 5.3 <i>vs.</i> 2.5 months; P=0.009). The PD-L1-positive patients who received immunotherapy had a median PFS of 7.1 months, while those who received non-immunotherapy had a median PFS of 2.5 months (P=0.02). No such statistically significant difference was observed in the PD-L1-negative patients (median PFS for with immunotherapy <i>vs.</i> without immunotherapy: 1.5 <i>vs.</i> 2.9 months; P=0.68). The PD-L1-positive patients who underwent re-biopsy after the development of TKI resistance and who received immunotherapy had a PFS of 7.8 months, while those who received non-immunotherapy had a PFS of 2.7 months (P=0.002).</p><p><strong>Conclusions: </strong>This was the first real-world retrospective study to show that some patients with positive PD-L1 expression may benefit from immune-based therapy after the development of ALK-TKI resistance. However, we still recommend biopsy for patients who develop ALK-TKI resistance to provide further treatment guidance.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2197-2209"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650640","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 growth prediction models for multiple pulmonary ground-glass nodules based on CT features, radiomics, and deep learning.","authors":"Shulei Cui, Linlin Qi, Weixiong Tan, Yujian Wang, Fenglan Li, Jianing Liu, Jiaqi Chen, Sainan Cheng, Zhen Zhou, Jianwei Wang","doi":"10.21037/tlcr-24-1039","DOIUrl":"10.21037/tlcr-24-1039","url":null,"abstract":"<p><strong>Background: </strong>The development of growth prediction models for multiple pulmonary ground-glass nodules (GGNs) could help predict their growth patterns and facilitate more precise identification of nodules that require close monitoring or early intervention. Previous studies have demonstrated the indolent growth pattern of GGNs and developed growth prediction models; however, these investigations predominantly focused on solitary GGN. This study aimed to investigate the natural history of multiple pulmonary GGNs and develop and validate growth prediction models based on computed tomography (CT) features, radiomics, and deep learning (DL) as well as compare their predictive performances.</p><p><strong>Methods: </strong>Patients with two or more persistent GGNs who underwent CT scans between October 2010 and November 2023 and had at least 3 years of follow-up without radiotherapy, chemotherapy, or surgery were retrospectively reviewed. The growth of GGN is defined as an increase in mean diameter by at least 2 mm, an increase in volume by at least 30%, or the emergence or enlargement of a solid component by at least 2 mm. Based on the interval changes during follow-up, the enrolled patients and GGNs were categorized into growth and non-growth groups. The data were randomly divided into a training set and a validation set at a ratio of 7:3. Clinical model, Radiomics model, DL model, Clinical-Radiomics model, and Clinical-DL model were constructed. Model performance was assessed using the area under the receiver operating characteristic curve (AUC).</p><p><strong>Results: </strong>A total of 732 GGNs [mean diameter (interquartile range, IQR), 5.5 (4.5-6.5) mm] from 231 patients (mean age 54.1±9.9 years; 26.4% male, 73.6% female) were included. Of the 156 (156/231, 67.5%) patients with GGN growth, the fastest-growing GGN had a volume doubling time (VDT) and mass doubling time (MDT) of 2,285 (IQR, 1,369-3,545) and 2,438 (IQR, 1,361-4,140) days, respectively. Among the growing 272 (272/732, 37.2%) GGNs, the median VDT and MDT were 2,934 (IQR, 1,648-4,491) and 2,875 (IQR, 1,619-5,148) days, respectively. Lobulation (P=0.049), vacuole (P=0.009), initial volume (P=0.01), and mass (P=0.01) were risk factors of GGN growth. The sensitivity and specificity of the Clinical model 1, Clinical model 2, Radiomics, DL, Clinical-Radiomics, and Clinical-DL models were 77.2% and 80.0%, 77.2% and 79.3%, 75.9% and 77.8%, 59.5% and 75.6%, 82.3% and 86.7%, 78.5% and 80.7%, respectively. The AUC for Clinical model 1, Clinical model 2, Radiomics, DL, Clinical-Radiomics, and Clinical-DL models were 0.876, 0.869, 0.845, 0.735, 0.908, and 0.887, respectively.</p><p><strong>Conclusions: </strong>Multiple pulmonary GGNs exhibit indolent biological behaviour. The Clinical-Radiomics model demonstrated superior accuracy in predicting the growth of multiple GGNs compared to Clinical, Radiomics, DL, Clinical-DL models.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"1929-1944"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650638","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":"Long-term efficacy and improved overall survival of lorlatinib in anaplastic lymphoma kinase-rearranged lung cancer: is cure a dream or a reality?","authors":"Yoshitsugu Horio, Hiroaki Kuroda, Eiichi Sasaki, Katsuhiro Masago","doi":"10.21037/tlcr-2025-694","DOIUrl":"10.21037/tlcr-2025-694","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2353-2358"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650660","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":"Radiographic ground-glass nodules predict less aggressive features and favorable immune landscapes in early lung adenocarcinoma and its precursors.","authors":"Runzhe Chen, Mingdian Wang, Qi Quan, Dijian Shen, Qiong Li, Xiujiao Shen, Xuan Li, Ming Chen","doi":"10.21037/tlcr-2025-231","DOIUrl":"10.21037/tlcr-2025-231","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) remains the leading cause of cancer-related deaths globally, often due to late-stage diagnosis. Advancements in computed tomography (CT) have revolutionized the detection of indeterminate pulmonary nodules (IPNs), spanning benign lesions to early-stage LUAD. We aimed to understand early lung carcinogenesis and identify clinicopathological and immune features that may influence patient prognosis.</p><p><strong>Methods: </strong>This study retrospectively integrates clinical, radiographic, pathological, and immune data from 174 patients with resected pulmonary nodules, including atypical adenomatous hyperplasia (AAH, n=19), adenocarcinoma in situ (AIS, n=50), minimally invasive adenocarcinoma (MIA, n=40), and stage I invasive adenocarcinoma (ADC, n=65).</p><p><strong>Results: </strong>Among 174 resected nodules, ground-glass nodules (GGNs) were observed in 54.6% of all cases. Early-stage ADCs exhibited the lowest proportion of GGNs compared to AAH, AIS, and MIA, respectively (AAH: 52.6%; AIS: 86.0%; MIA: 72.5%; ADC: 20.0%; P<0.001). Well differentiated ADCs were significantly associated with lower rates of pleural traction (6.7%) and lymphovascular invasion (0%) compared to poorly differentiated ADCs (pleural traction: 36.4%, lymphovascular invasion: 18.2%). Immune profiling showed a progressive decline in CD8⁺ T cells and an increased CD4/CD8 ratio from AAH to ADC. GGNs exhibited lower intratumoral CD4⁺ and CD8⁺ T cell densities than non-GGNs, consistent with their indolent histology and less invasive behavior. Radiographic appearance was strongly correlated with tumor differentiation and aggressiveness.</p><p><strong>Conclusions: </strong>These insights deepen our understanding of early lung carcinogenesis and offer potential pathways for prognostic stratification and personalized care for patients presenting with IPNs during CT screening.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2089-2099"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650672","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":"Utility of serum CYFRA 21-1 as a prognostic biomarker in ALK-positive non-small cell lung cancer treated with ALK-TKIs: a retrospective cohort study.","authors":"Ryo Sawada, Tadaaki Yamada, Yasuhiro Goto, Yoshiki Negi, Akira Nakao, Akihiro Yoshimura, Naoki Furuya, Tomohiro Oba, Makoto Hibino, Haruka Nakatani, Hirokazu Taniguchi, Aya Ohtsubo, Satoshi Watanabe, Takahiro Yamada, Yusuke Chihara, Takashi Kijima, Koichi Takayama","doi":"10.21037/tlcr-2024-1180","DOIUrl":"10.21037/tlcr-2024-1180","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Anaplastic lymphoma kinase (ALK) fusion gene-positive non-small cell lung cancer (NSCLC) represents 3-7% of all cases and causes oncogene addiction. Although ALK tyrosine kinase inhibitors (ALK-TKIs) are effective for treating ALK-positive NSCLC, some patients still show suboptimal responses and poor outcomes. Clinically simple and detectable biomarkers for this group are limited. Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1 and CYFRA) are widely used tumor markers in NSCLC. Elevated CEA levels are linked to tumor progression and resistance to cell death, while CYFRA is widely expressed in poorly differentiated squamous cell carcinomas. CYFRA has been identified as a prognostic factor in epidermal growth factor receptor (EGFR)-positive NSCLC, but its role in ALK-positive NSCLC remains unclear. Therefore, we retrospectively assessed the value of CEA and CYFRA as predictive biomarkers in patients with ALK-positive NSCLC treated with ALK-TKIs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This retrospective study analyzed 197 patients with advanced or recurrent ALK-positive NSCLC, who were diagnosed across 13 institutions in Japan and received their first ALK-TKI between July 1, 2014 and December 31, 2022. Eligible patients had measurable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients were stratified based on normal (≤5.0 and ≤3.5 ng/mL) or high (&gt;5.0 and &gt;3.5 ng/mL) baseline serum CEA and CYFRA levels. Serum CYFRA and CEA levels, which were measured using commercially available immunoassays per standard institutional protocols. The primary endpoint was progression-free survival (PFS) with initial ALK-TKI therapy, and secondary endpoints included overall survival (OS) and objective response rate (ORR). Multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 152 patients with available CYFRA data, 91 (59.9%) had normal CYFRA levels and 61 (40.1%) had elevated levels. In this analysis, patients in the high CYFRA group had significantly shorter median PFS and OS (9.27 and 28.8 months, respectively) than those in the normal CYFRA group (42.0 and 143.3 months, respectively). Multivariate analysis confirmed that high CYFRA levels were independent predictors of poor PFS (HR: 2.35, 95% CI: 1.50-3.68, P&lt;0.001) and OS (HR: 3.28, 95% CI: 1.89-5.70, P&lt;0.001). Furthermore, the high CYFRA group had lower ORR and complete response (CR) rates, compared with the normal CYFRA group. In contrast, no significant differences in PFS or OS were observed between patients with normal and elevated CEA levels.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Elevated CYFRA levels correlate with reduced PFS and OS in ALK-positive NSCLC, indicating potential as a prognostic biomarker. Given CYFRA's association with tumor heterogeneity, which reduces ALK-TKI efficacy, its assessment could aid in risk strat","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"1986-2000"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650683","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":"Good responses to first-line immunotherapy-included treatment in lung squamous carcinoma with rare driver gene mutations: a report of three cases.","authors":"Li Tu, Yanyang Liu, Xiaoming Qiu, Jiewei Liu","doi":"10.21037/tlcr-2025-469","DOIUrl":"10.21037/tlcr-2025-469","url":null,"abstract":"<p><strong>Background: </strong>In terms of treatment, non-small cell lung cancer (NSCLC) can be classified into driver gene mutation-positive or -negative lung cancer. Compared with adenocarcinoma, lung squamous carcinoma (LUSC) patients with rare driver gene mutations are a small proportion of NSCLC, who experience significantly less benefit from targeted therapies and have limited second-line treatment options and poor prognosis. Immunotherapy is an important treatment strategy for patients with NSCLC. In clinical practice, LUSC patients could receive immunotherapy regardless of the patient's gene mutation status and gene mutation detection is not recommended for LUSC patients for first-line treatment decision. Therefore, there is little data on the efficacy of first-line immunotherapy-included treatments in LUSC with rare driver gene mutations, which deserves to be collected and reported.</p><p><strong>Case description: </strong>In this study, we report three female patients, aged from 28 to 65 years with stage IIIA-IVB LUSC and rare driver gene mutations, including epidermal growth factor receptor (EGFR) exon 18 point mutation G719X/S768I, EGFR exon 20 insertion, and echinoderm microtubule associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion, respectively. All three patients received first-line immunotherapy in combination with chemotherapy and achieved notable treatment outcomes. Case 1 achieved pathologic complete response (CR) after two cycles of immunochemotherapy, followed by a disease-free survival (DFS) of at least 30 months. Case 2 underwent four cycles of immunochemotherapy and rapidly achieved partial response (PR), followed by 2 years of monoimmunotherapy, with a progression-free survival (PFS) of at least 68 months. In case 3, except the primary lesion, there were CR for all metastatic lesions after 2 cycles of immunochemotherapy. These lesions remained absent in the subsequent 8 months until salvage surgery was performed and the DFS was at least 24 months.</p><p><strong>Conclusions: </strong>These findings suggested that first-line immunotherapy-included treatment may provide promising survival benefits for LUSC patients with rare driver gene mutations.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2337-2346"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650655","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":"Needle tract seeding after endobronchial ultrasound-guided intranodal forceps biopsy and cryobiopsy: a case report.","authors":"Kohei Yamamoto, Tatsuya Imabayashi, Yukari Kano, Toshiyuki Tanaka, Kazuki Jinno, Shunya Tanaka, Sayaka Uda, Tatsuya Yuba, Chieko Takumi","doi":"10.21037/tlcr-2025-218","DOIUrl":"10.21037/tlcr-2025-218","url":null,"abstract":"<p><strong>Background: </strong>Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure for diagnosing intrathoracic lymphadenopathy; however, it has limitations in diagnostic yield and sampling adequacy for certain conditions. To address this issue, EBUS-guided intranodal forceps biopsy (EBUS-IFB) and cryobiopsy (EBUS-CRYO) have been performed. Both techniques require the creation of a tract for the insertion of forceps or cryoprobes into the lymph nodes. However, potential adverse events associated with this tract remain unclear. Needle tract seeding (NTS), which is defined as the implantation of tumor cells along the puncture tract, is a rare but clinically significant complication of gastrointestinal procedures. However, its occurrence after bronchoscopy has rarely been reported. This report describes a rare case of NTS following EBUS-IFB and EBUS-CRYO.</p><p><strong>Case description: </strong>An 83-year-old woman with lung adenocarcinoma harboring <i>MET</i> exon 14 skipping mutation presented with right upper lobe nodules and bilateral mediastinal lymphadenopathy. The initial EBUS-TBNA yielded insufficient specimens for molecular testing. Subsequent EBUS-IFB and mediastinal cryobiopsy provided sufficient specimens for definitive diagnosis. Twenty-nine days after the procedure, computed tomography revealed rapid growth of the right upper lobe nodules and a tracheal mass at the biopsy site, consistent with NTS. Despite this complication, the patient demonstrated a marked response to tepotinib therapy, with significant regression of both the lung and tracheal lesions.</p><p><strong>Conclusions: </strong>This case highlights the need for increased awareness of NTS following advanced biopsy techniques. Tumor-related factors such as high malignancy and necrosis, combined with procedural elements, likely contribute to its occurrence. Bronchoscopists should carefully evaluate the procedural approaches and follow-up protocols to mitigate this risk and ensure early detection.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2317-2323"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650669","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":"Utility of CK8/18 in identifying circulating tumor cells derived from lesions in patients with non-small cell lung cancer.","authors":"Tetsuya Sakai, Mami Onishi, Yoshitaka Zenke, Eri Morita Yamamoto, Yuichi Ijiri, Kana Kawasaki, Fumie Kato, Tomoko Sugano, Bishnu Devi Maharjan, Ali Asgar S Bhagat, Tomokazu Yoshida, Shigeki Iwanaga, Masatoshi Yanagida, Koichi Goto","doi":"10.21037/tlcr-2025-155","DOIUrl":"10.21037/tlcr-2025-155","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumor cells (CTCs) are identified by the absence of pan-leukocyte markers and positive staining for cytokeratin (CK). Anti-panCK antibody (AE1/AE3) is a widely used marker for CK. However, epithelial-mesenchymal transition reduces the expression of panCK markers, leading to low detection rates of CTCs, especially in non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy of a novel CTC detection system using CK8/18 as an epithelial cell marker in patients with NSCLC.</p><p><strong>Methods: </strong>A total of 20 patients with NSCLC (10 <i>EGFR</i> mutant and 10 <i>EGFR</i> wild-type) were included in this study. Blood samples were examined using the novel CTC detection system. Both anti-panCK and anti-CK8/18 antibodies were used to identify CK and detect CTCs. Additionally, CTCs isolated from patients with <i>EGFR</i> mutations underwent single-cell sorting, whole genome amplification, and gene analysis to verify their lung cancer origin.</p><p><strong>Results: </strong>CTCs were detected in 17 patients (8 <i>EGFR</i> mutant and 9 <i>EGFR</i> wild-type) using CK8/18 and in only 8 patients (5 <i>EGFR</i> mutant and 3 <i>EGFR</i> wild-type) using panCK. The sensitivity of CTC detection based on CK8/18 was significantly higher than that based on panCK (85% <i>vs.</i> 40%, P<0.01). Among the 10 patients with <i>EGFR</i> mutations, <i>EGFR</i> mutations were confirmed in CTCs obtained from six patients in the gene analysis through single-cell sorting, aligning with mutations identified in tissue samples.</p><p><strong>Conclusions: </strong>This study demonstrated the effectiveness of CK8/18 over panCK in detecting CTCs. Adopting CK8/18 in the novel system improved the detection rate of CTCs, highlighting its potential in clinical applications.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2100-2112"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650682","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":"Cytokine-driven modulation of WT1 and IL-10 in lung cancer progression.","authors":"Juan Manuel Izaguirre-Alvarez, Pablo Zapata-Benavides, Mariela Arellano-Rodríguez, Norma Cesilia Arellano-Rodríguez, Felipe-de-Jesús Torres-Del-Muro, Moisés Armides Franco-Molina, María Cristina Rodríguez-Padilla","doi":"10.21037/tlcr-2024-1242","DOIUrl":"10.21037/tlcr-2024-1242","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is driven by complex interactions between oncogenes and the inflammatory microenvironment. In particular, the cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), and their modulation of key regulators like Wilms' tumor 1 (WT1) and interleukin-10 (IL-10) remain underexplored. This study aims to investigate the role of these cytokines in WT1 and IL-10 regulation during lung cancer progression.</p><p><strong>Methods: </strong>A total of 982 lung cancer patient samples from The Human Protein Atlas were analyzed. <i>In vitro</i>, RAW264.7 macrophages were transfected with a WT1 plasmid (pWT1) and treated with TNF-α, IL-1β, and lipopolysaccharide (LPS). WT1 and IL-10 expression was evaluated in A549, B16-F10, and J774.2 cell lines using reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was employed to assess WT1 localization and phosphorylation, while immunohistochemistry was used to evaluate the correlation between WT1 and IL-10 in patient samples.</p><p><strong>Results: </strong>WT1 expression progressively increased from stage I to IV lung cancer and positively correlated with IL-10 in stages II and IV. WT1 overexpression in RAW264.7 cells treated with LPS led to a 12.9-fold increase in IL-10 expression. Proinflammatory cytokines decreased WT1 in A549 and B16-F10 cells but increased it in J774.2 macrophages, leading to cytoplasmic localization and phosphorylation. Patient sample analysis revealed a positive correlation between WT1 and IL-10 in advanced stages.</p><p><strong>Conclusions: </strong>These findings suggest that WT1 and IL-10 are modulated by inflammatory cytokines in a stage-dependent manner in lung cancer. WT1 upregulation is associated with increased IL-10 expression, particularly in advanced stages, highlighting potential therapeutic targets for modulating the immune response in lung cancer.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"1896-1913"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650637","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}