Translational lung cancer research最新文献

{"title":"Invasive mucinous adenocarcinoma of the lung: integrating molecular landscape, imaging phenotypes, and translational therapeutic strategies.","authors":"Zihan Wang, Jiashuo Wang, Shiqi Liu, Shi Zong, Xiwen Wang","doi":"10.21037/tlcr-2026-0430","DOIUrl":"10.21037/tlcr-2026-0430","url":null,"abstract":"<p><p>Invasive mucinous adenocarcinoma (IMA) of the lung is an uncommon but clinically important subtype of lung adenocarcinoma with distinctive radiologic, histopathologic, and molecular features. Its indolent symptoms, mucin-rich growth pattern, and frequent pneumonia-like or multifocal presentation can obscure early diagnosis and complicate distinction from infection, synchronous primary tumors, and intrapulmonary spread. This review integrates current evidence on the clinical course, imaging phenotypes, diagnostic workflow, histopathologic features, molecular alterations, tumor immune microenvironment, and treatment response patterns of IMA. Emphasis is placed on the relationship between radiologic appearance and underlying mucinous pathology, the clinical significance of spread through air spaces (STAS), and the need for adequate tissue sampling and comprehensive molecular profiling. Compared with non-mucinous lung adenocarcinoma, IMA is enriched for KRAS mutations and selected fusion or receptor alterations, whereas canonical EGFR mutations are less frequent. These biological differences help explain why treatment strategies extrapolated from broader non-small cell lung cancer (NSCLC) populations may be insufficient, particularly for multifocal, pneumonic-type, or advanced disease. Although surgery can provide favorable outcomes in localized disease, systemic therapy remains challenging, and the role of immunotherapy requires further clarification. Future progress will depend on integrated imaging-pathology-genomic models, prospective IMA-specific cohorts, and translational studies aimed at refining classification and developing individualized therapeutic strategies.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 8","pages":"260"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931048","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 an interpretable medical deep foundation model for predicting occult lymph node metastasis in early-stage small cell lung cancer: a multicenter retrospective diagnostic study.","authors":"Xu Jiang, Qin Peng, Jing Zhang, Alex Zwanenburg, Xin Peng, Chao Luo, Jialiang Ren, Lin Yang, Yajia Gu, Steffen Löck, Kunfeng Liu, Meng Li, Jianwei Wang","doi":"10.21037/tlcr-2026-0714","DOIUrl":"10.21037/tlcr-2026-0714","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Occult lymph node metastasis (OLM) is common in patients with clinical stage T1-2N0M0 small cell lung cancer (SCLC) and is strongly associated with inferior survival. Accurate preoperative identification of OLM remains challenging using conventional imaging, yet is critical for nodal staging, surgical planning, and individualized treatment decision-making. This study aimed to develop and externally validate an interpretable deep foundation model-based approach using preoperative contrast-enhanced computed tomography (CECT) to predict OLM in early-stage SCLC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this multicenter retrospective diagnostic study, 416 surgically treated patients with postoperative pathologically confirmed SCLC and preoperative cT1-2N0M0 status were included. Patients from the largest center were randomly divided into training (n=201) and internal validation (n=86) cohorts, while patients from four additional centers constituted an external test cohort (n=129). Deep imaging features were extracted from preoperative CECT using a cancer-specific pretrained foundation model, and predictive models were constructed using machine-learning classifiers. Model performance was compared with handcrafted radiomics, conventional convolutional neural network (CNN)-based models, and a clinical model. Discrimination, calibration, and clinical utility were assessed using the area under the receiver operating characteristic curve (AUC), calibration analysis, and decision curve analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The overall incidence of OLM was 33.9% (141/416). Among the evaluated imaging approaches, the foundation model-derived DFM50N achieved an external test AUC of 0.787 [95% confidence interval (CI): 0.703-0.871]. In unadjusted pairwise DeLong comparisons, its AUC was higher than those of RadN and the clinical model (P=0.02 and P=0.02, respectively), whereas no significant difference was observed compared with the combined model (AUC, 0.790; 95% CI: 0.705-0.874; P=0.90). The DFM50N model demonstrated relatively preserved external calibration and provided greater net benefit than strategies of additional staging for all or no patients across a clinically relevant range of threshold probabilities. Model interpretability analysis using SHapley Additive exPlanations (SHAP) revealed similar feature-ranking patterns associated with OLM risk across cohorts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;An interpretable deep foundation model based on preoperative CECT achieved favorable and stable external performance for the noninvasive prediction of OLM in early-stage SCLC. The model showed favorable discrimination compared with handcrafted radiomics, conventional CNN-based approaches, and clinical assessment alone, and its integration with clinical predictors enabled individualized risk estimation. This approach may facilitate the identification of patients requiring more comprehensive mediastinal evaluation and support more inf","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 8","pages":"224"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931107","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":"Comparison of diagnostic yield between electromagnetic navigation bronchoscopy-guided forceps biopsy and target-fixing technique-assisted RP-EBUS-guided transbronchial cryobiopsy with a guide sheath for peripheral lung lesions.","authors":"Taehun Kim, Jae Woon Song, Jung Hee Hong, Seong Hwan Youn, Hyun Jung Kim, Jae Seok Park, Sun Hyo Park","doi":"10.21037/tlcr-2026-0743","DOIUrl":"10.21037/tlcr-2026-0743","url":null,"abstract":"<p><strong>Background: </strong>Accurate diagnosis of peripheral lung lesions remains challenging, particularly for small nodules. Electromagnetic navigation bronchoscopy (ENB) improves access to peripheral airways but shows variable diagnostic yield. Radial probe endobronchial ultrasound-guided transbronchial cryobiopsy with a guide sheath (RP-EBUS-guided TBC with GS) allows semi-real-time lesion confirmation and acquisition of larger tissue samples. This study compared the diagnostic yield and safety of ENB-guided biopsy and RP-EBUS-guided TBC.</p><p><strong>Methods: </strong>This retrospective observational study included patients who underwent ENB-guided transbronchial biopsy or RP-EBUS-guided TBC with a GS for lung lesions suspected to be malignant on computed tomography between May 2021 and December 2025 in South Korea. Propensity score matching was applied using logistic regression with a caliper width of 0.2 standard deviation (SD) of the logit of the propensity score, adjusting for lesion size, axial distribution, lobe location, nodule characteristics, and bronchus sign.</p><p><strong>Results: </strong>Matching resulted in 201 pairs, although some baseline imbalances remained. The overall diagnostic yield was significantly higher for RP-EBUS-guided TBC than for ENB (91.1% <i>vs</i>. 73.4%, P<0.001). Sensitivity for malignancy was also higher with RP-EBUS-guided TBC (88.4% <i>vs</i>. 73.3%, P<0.001). In the matched cohort, RP-EBUS-guided TBC was significantly associated with higher diagnostic yield [odds ratio (OR) 2.715, P<0.001] and sensitivity (OR 3.897, P<0.001). Pneumothorax occurred more frequently in the RP-EBUS-guided TBC group; however, the difference was not statistically significant (OR 2.054, P=0.20).</p><p><strong>Conclusions: </strong>RP-EBUS-guided TBC with a GS was associated with a higher diagnostic yield than ENB-guided forceps biopsy, without a statistically significant increase in major complications in patients with peripheral lung lesions.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 8","pages":"220"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931148","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":"Predictive modeling of peripheral blood EGFR positivity in patients with advanced primary non-small cell lung cancer.","authors":"Ying-Bo Xie, Yi-Ke Wang, Xuan Yao, Kelan Ke, Pei Ma, Feng-Nan Wang, Qin Liu, Xiao-Hong Xie, Ming Liu, Xin-Qing Lin, Cheng-Zhi Zhou, Zhan-Hong Xie","doi":"10.21037/tlcr-2026-0625","DOIUrl":"10.21037/tlcr-2026-0625","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Epidermal growth factor receptor (&lt;i&gt;EGFR&lt;/i&gt;) mutations are the most prevalent driver alterations in NSCLC, and tyrosine kinase inhibitors (TKIs) have markedly improved survival outcomes. Accurate molecular testing is essential for guiding targeted therapy. However, tissue biopsy, the current gold standard, is often limited by insufficient samples, invasive procedure risks, or tumor heterogeneity, some patients experiencing sampling failure. Liquid biopsy based on circulating tumor DNA (ctDNA) offers a minimally invasive alternative and can shorten the detection cycle by 2 to 3 weeks, but its sensitivity depends on ctDNA shedding, and patient selection for blood-based testing remains challenging in clinical practice. This study aimed to develop a peripheral blood &lt;i&gt;EGFR&lt;/i&gt; positivity prediction model and a simple scoring system to identify high probability candidates for liquid biopsy and prioritize blood-based &lt;i&gt;EGFR&lt;/i&gt; testing when tissue samples are inadequate.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective case-control study design was employed. Data were collected from 384 patients with NSCLC who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University between June 2018 and September 2024 and met the study's inclusion criteria. The patients were categorized into two groups: the peripheral blood &lt;i&gt;EGFR&lt;/i&gt;-positive group (191 cases) and peripheral blood EGFR-negative group (193 cases). Univariate and binary logistic regression analyses were conducted to establish a predictive model for &lt;i&gt;EGFR&lt;/i&gt; in peripheral blood, which was subsequently converted into a scoring system.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The results of multi-factor analysis showed that gender, smoking status, pulmonary lymphangitic carcinomatosis, non-vertebral bone metastasis, brain metastasis, and liver metastasis were independent factors for the prediction of EGFR positivity in peripheral blood (P&lt;0.05). The receiver operating characteristic (ROC) curve analysis of predicted peripheral blood &lt;i&gt;EGFR&lt;/i&gt; positivity showed that the area under the curve (AUC) was 0.884. A score of ≥3 was considered a high-probability population with positive &lt;i&gt;EGFR&lt;/i&gt; in peripheral blood. The sensitivity for diagnosing positive &lt;i&gt;EGFR&lt;/i&gt; in peripheral blood was 84.8%, and the specificity was 73.1%. Taking the next-generation sequencing (NGS) detection results as the reference standard, the sensitivity of amplification refractory mutation system polymerase chain reaction (ARMS-PCR) detection was 94.96%, the specificity was 100%, and the overall compliance rate was 96.2% [Kappa (Cohen's kappa coefficient) =0.903, P&lt;0.001].&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The Gspnbl score demonstrates good predictive performance in identifying patients with a high probability of periphera","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 8","pages":"229"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931261","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":"Increasing incidence and improved survival of leptomeningeal metastasis in advanced lung cancer: a 10-year real-world cohort study.","authors":"Jing Sun, Qian Zhang, Yehao Yang, Haicheng Wu, Wanchen Zhai, Yuwei Li, Linjing Zhou, Mengqi Bao, Yi Chen, Xiheng Yu, Yun Fan","doi":"10.21037/tlcr-2026-0531","DOIUrl":"10.21037/tlcr-2026-0531","url":null,"abstract":"<p><strong>Background: </strong>In advanced lung cancer, leptomeningeal metastasis (LM) is a severe complication associated with an exceptionally poor prognosis. This study investigates the incidence, histopathological features, and genetic characteristics of LM, while also examining treatment outcomes and prognostic determinants in affected patients.</p><p><strong>Methods: </strong>From January 2014 through December 2023, 8,213 patients with advanced lung cancer were evaluated, among whom 234 developed LM. The primary endpoint was overall survival (OS) in patients with advanced lung cancer complicated by LM.</p><p><strong>Results: </strong>By the data cutoff on December 28, 2023, the median follow-up was 39.5 (range: 0.2-45.0) months. The incidence of LM at initial presentation was 0.44%, with an overall incidence of 2.85%. A significant upward trend was observed, rising from 1.25% during 2014-2018 to 3.79% during 2019-2023 (P<0.05). Among patients with LM, adenocarcinoma comprised 96.6% of cases, and epidermal growth factor receptor (<i>EGFR</i>) mutations were predominant, detected in 82.5% of patients. The median OS (mOS) following LM diagnosis was 10.2 months [95% confidence interval (CI): 6.2-11.1]. Patients treated with targeted therapies achieved significantly longer survival than those receiving chemotherapy or best supportive care (11.4 <i>vs.</i> 7.9 <i>vs.</i> 3.3 months, P<0.001). High-dose tyrosine kinase inhibitor (TKI) therapy provided a superior benefit over standard dosing (12.6 <i>vs.</i> 10.8 months, P=0.001). Patients who received intrathecal chemotherapy (ITC) also showed a significantly longer OS than those who did not receive ITC (11.7 <i>vs.</i> 7.6 months, P=0.04). In multivariate analysis, lower Eastern Cooperative Oncology Group performance status (ECOG PS) and synchronous LM were independent predictors of favorable prognosis (all P<0.05).</p><p><strong>Conclusions: </strong>Over the past decade, the incidence of LM in patients with advanced lung cancer has increased significantly. Targeted therapies (including dose-intensified TKIs) and ITC were strongly associated with meaningful survival improvements. While these active treatments offer substantial clinical benefits, their optimal outcomes are closely linked to favorable baseline patient characteristics, emphasizing the need for personalized multidisciplinary management.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 8","pages":"236"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930970","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":"Lepidic pattern as a favorable prognostic factor in pathologically high-risk stage I invasive lung adenocarcinoma.","authors":"Zhaokang Huang, Jie Cao, Nan Chen, Zhiyu Peng, Zetao Liu, Xizhou Liao, Xiaorong Zong, Peidi Li, Chenglin Guo, Lunxu Liu, Jiandong Mei","doi":"10.21037/tlcr-2026-0770","DOIUrl":"10.21037/tlcr-2026-0770","url":null,"abstract":"<p><strong>Background: </strong>The prognostic value of lepidic pattern in small stage I lung adenocarcinoma (LUAD) with pathological high-risk features remains unclear. This study evaluated whether lepidic pattern was associated with improved survival outcomes in this pathologically high-risk population.</p><p><strong>Methods: </strong>Consecutive patients with surgically resected stage I invasive LUAD measuring ≤3 cm at West China Hospital, Sichuan University, between January 2018 and April 2025 were retrospectively reviewed. Patients with at least one pathological high-risk feature were included and stratified according to the presence or absence of lepidic pattern. Recurrence-free survival (RFS) and overall survival (OS) were compared before and after propensity score matching. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>A total of 1,233 patients were included, including 412 without lepidic pattern and 821 with lepidic pattern. After 1:1 propensity score matching, 315 matched pairs were generated. The median follow-up duration was 44 months. In the overall cohort, patients with lepidic pattern had better RFS than those without lepidic pattern, with 3-year RFS rates of 96.8% and 87.0%, respectively, and estimated 5-year RFS rates of 94.0% and 81.9%, respectively (HR, 0.42; 95% CI: 0.25-0.70; P<0.001). This association persisted after matching, with 3-year RFS rates of 96.3% and 86.6%, respectively, and estimated 5-year RFS rates of 92.2% and 81.2%, respectively (HR, 0.37; 95% CI: 0.20-0.69; P=0.001). In multivariable analysis, lepidic pattern remained independently associated with improved RFS (adjusted HR, 0.42; 95% CI: 0.25-0.70; P=0.001). OS was not significantly associated with lepidic pattern after matching or multivariable adjustment.</p><p><strong>Conclusions: </strong>Lepidic pattern was independently associated with improved RFS, but not OS, in patients with pathologically high-risk small stage I LUAD. Lepidic pattern may serve as a complementary histologic marker for postoperative recurrence risk stratification.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 8","pages":"248"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931019","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":"Osimertinib <i>vs.</i> erlotinib combined with an angiogenesis inhibitor in <i>EGFR</i>-mutated non-small cell lung cancer with malignant pleural effusion: a retrospective cohort study.","authors":"Tae Hata, Tadaaki Yamada, Koji Mikami, Toshihide Yokoyama, Tomohiro Oba, Yasuhiro Goto, Naoki Furuya, Shun Futamura, Hirokazu Taniguchi, Tamio Okimoto, Soichi Hirai, Sayaka Uda, Asuka Okada, Rie Watanabe, Naoko Ishizaki, Hayato Kawachi, Takashi Kijima, Koichi Takayama","doi":"10.21037/tlcr-2026-0343","DOIUrl":"10.21037/tlcr-2026-0343","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Osimertinib is the standard first-line treatment for non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (&lt;i&gt;EGFR&lt;/i&gt;) mutation. Erlotinib plus an angiogenesis inhibitor (erlotinib+A) has demonstrated efficacy in controlling malignant pleural effusion (MPE) through reduction of vascular permeability; however, no clinical trials have directly compared its MPE control efficacy with that of osimertinib. This study aimed to compare the efficacy of osimertinib &lt;i&gt;vs.&lt;/i&gt; erlotinib+A in controlling MPE in patients with &lt;i&gt;EGFR&lt;/i&gt;-mutant NSCLC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This multicenter retrospective cohort study analyzed longitudinal medical records of patients with advanced or recurrent &lt;i&gt;EGFR&lt;/i&gt;-mutant NSCLC presenting with MPE at treatment initiation who received osimertinib or erlotinib+A at 14 institutions in Japan between November 2009 and October 2023. Patients with squamous cell carcinoma were excluded. The primary endpoint was time to MPE recurrence [MPE-progression-free survival (PFS)]. Secondary endpoints included PFS, overall survival (OS), and adverse events (AEs) graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Multivariable Cox proportional hazards regression served as the primary analysis, with propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) utilized for sensitivity analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 421 patients (median age, 73 years; 65% female; 66% never-smokers; 99% adenocarcinoma), 373 received osimertinib and 48 received erlotinib+A. In the multivariable Cox regression analysis, no significant differences were observed between the osimertinib and erlotinib+A groups in MPE-PFS [adjusted hazard ratio (HR): 0.79; 95% confidence interval (CI): 0.54-1.15; P=0.22], PFS (adjusted HR: 0.87; 95% CI: 0.60-1.25; P=0.45), or OS (adjusted HR: 0.95; 95% CI: 0.63-1.44; P=0.83). However, a significant interaction between the treatment regimen and &lt;i&gt;EGFR&lt;/i&gt; mutation type was identified (P=0.004 for MPE-PFS). Subgroup analysis demonstrated that osimertinib was significantly superior to erlotinib+A in patients with &lt;i&gt;EGFR&lt;/i&gt; exon 19 deletions (MPE-PFS: adjusted HR: 0.38; 95% CI: 0.21-0.67; P&lt;0.001), whereas no difference was observed in those with L858R mutations. Grade ≥3 AEs were more frequent in the erlotinib+A group (38% &lt;i&gt;vs.&lt;/i&gt; 21%, P=0.02), whereas osimertinib was associated with a higher incidence of all-grade interstitial pneumonia (21% &lt;i&gt;vs.&lt;/i&gt; 6%, P=0.01).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Osimertinib showed comparable efficacy to erlotinib+A in MPE control with a more favorable safety profile. Subgroup analysis suggested a particular benefit in patients harboring &lt;i&gt;EGFR&lt;/i&gt; exon 19 deletions, highlighting the potential importance of mutation subtype-based treatment selection. Given the retrospective design and potential for residual confounding, prospective validation is warran","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 8","pages":"228"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931187","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":"Using an artificial intelligence tool to improve the recognition of pseudoprogression in pleural mesothelioma patients treated with immunotherapy: a case series.","authors":"Illaa Smesseim, Kalina Chupetlovska, Valerio Pugliese, Jacobus A Burgers, Kevin B W Groot Lipman","doi":"10.21037/tlcr-2026-1-0207","DOIUrl":"10.21037/tlcr-2026-1-0207","url":null,"abstract":"<p><strong>Background: </strong>Pseudoprogression, defined as initial radiological tumor growth followed by treatment response, can complicate treatment response assessment in patients receiving immunotherapy. In pleural mesothelioma (PM) patients treated with immunotherapy reliable identification of pseudoprogression remains challenging with the modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1 criteria. Automated volumetric assessment using an artificial intelligence (AI) tool (ARTIMES) may provide additional insight into tumor response patterns. We aim to describe cases of pseudoprogression identified using the ARTIMES criteria in PM patients treated with immunotherapy.</p><p><strong>Case description: </strong>We performed a retrospective observational study of adult PM patients treated with immunotherapy at a tertiary center between January 1, 2013 and July 1, 2022. Tumor volumes were automatically segmented and quantified using the ARTIMES model. Patients demonstrating disease progression according to ARTIMES criteria followed by subsequent tumor volume decrease were evaluated for pseudoprogression. The results were presented in graphs depicting tumor volume, treatment duration, and the start and stop dates of immunotherapy. Among 368 PM patients treated with immunotherapy, 8 patients met inclusion criteria for confirmed pseudoprogression. All patients were male, with a median age of 67.5 years. Most patients had epithelioid histology (75.0%). All patients showed initial volumetric progression on early follow-up imaging, followed by objective tumor volume reduction either during continued immunotherapy or after treatment discontinuation. Volumetric tumor tracking enabled visualization of delayed responses that would have been difficult to interpret using standard imaging comparisons alone.</p><p><strong>Conclusions: </strong>Pseudoprogression occurs in a subset of PM patients treated with immunotherapy. Automated volumetric tumor assessment can help identify pseudoprogression patterns. Integrating volumetric analysis with clinical evaluation may reduce premature discontinuation of potentially effective immunotherapy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 8","pages":"254"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931200","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":"Lipid metabolic reprogramming of tumor-associated macrophages drives resistance to immune checkpoint blockade in lung cancer: a narrative review of mechanisms and therapeutic strategies.","authors":"Tong Wu, Yun Jiang","doi":"10.21037/tlcr-2026-0871","DOIUrl":"10.21037/tlcr-2026-0871","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Immune checkpoint inhibitors (ICIs), represented by programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), have shown remarkable efficacy in non-small cell lung cancer (NSCLC); however, many patients still develop resistance to immunotherapy. Although small cell lung cancer (SCLC) is also an important histological type of lung cancer, NSCLC accounts for the majority of lung cancer cases. Current research on ICI development, first-line treatment efficacy, and the mechanisms of lipid metabolism in tumor-associated macrophages (TAMs) is predominantly focused on NSCLC. In patients with advanced NSCLC, objective response rates (ORRs) with PD-1/PD-L1 inhibitor monotherapy remain limited. Only in patients with high PD-L1 expression [tumor proportion score (TPS) ≥50%] and without sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements does the ORR increase to approximately 40-45%. TAMs are a key component of the immunosuppressive tumor microenvironment (TME). Lipid metabolic reprogramming profoundly influences the functional and transcriptional features of TAMs. This review aims to integrate relevant evidence, elucidate how TAM lipid metabolism promotes immunosuppression and resistance to ICIs, and outline potential therapeutic strategies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We searched PubMed/MEDLINE, Web of Science, and Scopus for publications up to June 2026 using terms combining lung cancer, TAMs, lipid metabolism, and immune checkpoint blockade/resistance. Mechanistic, translational, and clinically relevant studies were selected by author consensus.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key content and findings: &lt;/strong&gt;Lipid uptake, de novo lipogenesis, fatty acid oxidation (FAO), cholesterol remodeling, and eicosanoid metabolism are not independent processes in TAMs. Lipid metabolic reprogramming in TAMs ultimately suppresses type I interferon (IFN-I) signaling, upregulates PD-L1 expression, and impairs the function of CD8&lt;sup&gt;+&lt;/sup&gt; T cells with stem-like features, thereby establishing an immunosuppressive TME and leading to resistance to ICIs. In lung cancer, hypoxia, high lactate levels, and tobacco exposure further shape the lipid phenotype of TAMs, such as lipid raft enrichment and lipid-laden macrophage subsets like SPP1&lt;sup&gt;+&lt;/sup&gt; macrophages. Different driver genomic backgrounds differentially impact tumor cell-intrinsic metabolism and the lipid metabolic programs of myeloid cells. In preclinical models, interventions targeting these metabolic axes, including TAM-directed delivery systems, have demonstrated potential therapeutic benefit when combined with anti-PD-1/PD-L1 therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Targeting TAM lipid metabolism to convert immunologically cold tumors into more inflamed, ICI-responsive tumors is a promising strategy to overcome resistance in NSCLC. Identification of predictive biomarkers of therapeutic response ","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 8","pages":"262"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931081","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 of candidate variants in plasma associated with early versus late disease progression under anti-PD-1 therapy in metastatic NSCLC.","authors":"Aitor Rodriguez-Casanova, Patricia Mondelo-Macía, Luis Leon-Mateos, Jorge García-González, Nicolás Costa-Fraga, Jaime Dubbelman, María Ángeles Gómez-García, Irene Lorenzo-Gómez, Alicia Abalo, Laura Muinelo-Romay, Rafael López-López, Angel Díaz-Lagares","doi":"10.21037/tlcr-2026-0463","DOIUrl":"10.21037/tlcr-2026-0463","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 (anti-PD-1) antibodies, have significantly improved outcomes in patients with metastatic non-small cell lung cancer (mNSCLC). However, substantial heterogeneity exists in clinical benefit, with some patients exhibiting early progression (EP) and others late progression (LP). To date, no biomarkers of EP versus LP disease have been implemented in clinical practice. Circulating tumor DNA (ctDNA) analysis represents a minimally invasive strategy for identifying such biomarkers. In this proof-of-concept study, we evaluated the performance of the TruSight Oncology 500 ctDNA (TSO500 ctDNA) panel and explored its feasibility to identify candidate variants associated with early and late disease progression under anti-PD-1 therapy.</p><p><strong>Methods: </strong>Baseline ctDNA from eight mNSCLC patients treated with pembrolizumab was extracted and sequenced using the TSO500 ctDNA assay, a 523-gene targeted next-generation sequencing panel. Patients were classified according to their response as LP or EP. Variant calling was performed using the DRAGEN Bio-IT platform, and variants were annotated and clinically interpreted using the Clinical Genomics Workspace (CGW; PierianDx) according to Association for Molecular Pathology (AMP)/American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Survival outcomes were assessed using Kaplan-Meier and log-rank tests. Performance of ctDNA variants was evaluated using receiver operating characteristic (ROC) curve analysis, and multi-gene models were assessed using leave-one-out cross-validation with penalized logistic regression.</p><p><strong>Results: </strong>All patients harbored detectable variants, including SNVs (100%), MNVs (87.5%), deletions (75%), and insertions (62.5%). Tier I variants were identified in 37.5% of patients, while all cases showed tier II and multiple tier III alterations. <i>TP53</i> variants were associated with poorer outcomes under anti-PD-1 therapy. Individual gene alterations in <i>TP53</i>, <i>ERBB3</i>, <i>SMC1A</i> or <i>LATS1</i> showed moderate discriminatory performance between LP and EP patients; however, combination of mutated genes improved apparent discrimination. Notably, specific two-gene combinations (<i>SMC1A</i> + <i>LATS1</i> or <i>ERBB3</i> + <i>LATS1</i>) showed the highest discriminatory performance between LP and EP patients in this exploratory cohort.</p><p><strong>Conclusions: </strong>This study demonstrates the feasibility and analytical performance of the TSO500 ctDNA panel and provides hypothesis-generating evidence that plasma gene variants may be useful to evaluate early versus late disease progression in patients with mNSCLC receiving immunotherapy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 8","pages":"223"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930755","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}