Translational lung cancer research最新文献

{"title":"CT-derived abdominal organ volumetrics for predicting recurrence-free and disease-free survival in resected non-small cell lung cancer: a multicenter retrospective cohort study.","authors":"Huanli Huang, Bingxin Gong, Jie Lou, Dezhi Zhu, Yusheng Guo, Gang Xiang, Shu Peng, Wei Li, Hanxiao Li, Lian Yang","doi":"10.21037/tlcr-2026-0445","DOIUrl":"10.21037/tlcr-2026-0445","url":null,"abstract":"<p><strong>Background: </strong>Postoperative recurrence remains a major challenge after curative-intent resection for non-small cell lung cancer (NSCLC), and conventional clinicopathologic factors do not fully capture recurrence risk heterogeneity. Although computed tomography (CT)-derived body composition biomarkers have been associated with outcomes in NSCLC, the prognostic relevance of abdominal solid-organ volumetrics remains insufficiently characterized. We investigated whether preoperative CT-derived abdominal organ volumes and body surface area (BSA)-normalized organ indices were associated with recurrence-related outcomes in resected NSCLC.</p><p><strong>Methods: </strong>This multicenter retrospective cohort study included 1,762 patients with clinically and pathologically confirmed NSCLC who underwent curative-intent resection at five centers and had preoperative CT within 1 month before surgery. A healthy control cohort of 3,263 individuals was included for baseline organ-volumetric comparison. Clinical and laboratory variables were extracted from preoperative records, with laboratory tests generally obtained within 7 days before surgery. A deep learning-based automated segmentation pipeline quantified the spleen, liver, pancreas, bilateral kidneys, and bilateral adrenal glands, and organ indices were normalized to BSA. Propensity score matching (PSM) was restricted to patient-control organ-volumetric comparisons. Recurrence was ascertained from follow-up clinical and imaging records. Recurrence-free survival (RFS) and disease-free survival (DFS) were evaluated as recurrence-related outcomes. Multivariable Cox models were performed in the full NSCLC cohort and adjusted for age, sex, T stage, pathological types, diabetes, hypertension, smoking, drinking, body mass index (BMI), albumin, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR).</p><p><strong>Results: </strong>The NSCLC cohort had a median age of 60 years, and 934 patients (53.0%) were women. During median follow-up periods of 39.7 months for RFS and 39.4 months for DFS, 198 RFS events and 219 DFS events occurred. Compared with healthy controls after PSM, patients with NSCLC showed larger spleen, liver, kidney, and adrenal volumes and smaller pancreatic volume. In multivariable Cox analyses, lower pancreatic volume and pancreatic index were independently associated with shorter RFS [hazard ratio (HR) =0.735, P<0.001; HR =0.729, P<0.001, respectively] and DFS (HR =0.791, P=0.002; HR =0.787, P=0.001, respectively). Lower left adrenal gland index (LAGI) was also associated with shorter RFS (HR =0.845, P=0.030) and DFS (HR =0.833, P=0.01). Lower liver volume (LVV) index was associated with RFS only (HR =0.834, P=0.02), whereas lower left adrenal gland volume (LAGV) was associated with DFS only (HR =0.843, P=0.03).</p><p><strong>Conclusions: </strong>Preoperative CT-derived abdominal organ volumetrics, particularly pancreatic and left adrenal gland metrics, ","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 7","pages":"194"},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713677","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":"Intratumor immune heterogeneity across simulated core biopsy sizes in non-small cell lung cancer: an exploratory study.","authors":"Shaowen Lyu, Kobe Reynders, Iris E W G Laven, Christel Faes, Birgit Weynand, Lisa M Hillen, Paul De Leyn, Lizza E L Hendriks, Els Wauters, Maarten Lambrecht, Rianne D W Vaes, Dirk De Ruysscher","doi":"10.21037/tlcr-2026-1-0017","DOIUrl":"10.21037/tlcr-2026-1-0017","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint blockade (ICB) is widely used to treat patients with non-small cell lung cancer (NSCLC). However, intratumor (immune) heterogeneity may significantly impact the therapeutic efficacy of ICBs. It remains unknown whether larger core biopsies better represent the intratumor heterogeneity. This study aimed to explore the intra- and interpatient heterogeneity of selected immune-related parameters on varying simulated biopsy core sizes.</p><p><strong>Methods: </strong>In this exploratory prospective cohort study, patients with stage I-III NSCLC who had undergone curative-intent surgery, with or without neoadjuvant chemotherapy or chemoradiation, were enrolled. Intratumor immune heterogeneity was assessed using quadruple immunofluorescence stainings (CD31, Ki67, CD4, CD8, CD68, FOXP3, PD-L1, Pan-keratin, and DAPI) on resected tumor specimens. Digital images were used to simulate biopsy cores ranging from 1- to 4-mm in diameter. Heterogeneity was quantified using the quartile coefficient of dispersion (QCD) across 250 randomly selected subregions per core size.</p><p><strong>Results: </strong>Tumor specimens from 29 patients were analyzed, including 10 patients who had received neoadjuvant therapy. Intratumor QCD values decreased significantly with increasing simulated biopsy core diameter for all markers. Nonetheless, substantial spatial heterogeneity persisted for programmed death-ligand 1 (PD-L1), with 58.8% of patients showing heterogeneous distribution, even in 4-mm simulated biopsy cores.</p><p><strong>Conclusions: </strong>Larger biopsy core sizes were associated with reduced intratumor heterogeneity for most immune markers, suggesting a better reflection of the tumor immune landscape of the whole tumor. However, PD-L1 expression remained spatially heterogeneous even in larger cores. Further validation in larger prospective cohort studies will be essential to determine the translational relevance of heterogeneity metrics and to better inform biopsy sampling strategies in routine clinical practice.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 7","pages":"200"},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713850","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":"Tertiary lymphoid structures predict the neoadjuvant chemoimmunotherapy response of stage III non-small cell lung cancer.","authors":"Guibing Ren, Yajing Qu, Hainan Li, Zhihong Li, Yanyan Gao, Xiaoxiong Shi, Xiaoru Meng, Pengpeng Xu, Weihao Hu, Ningbo Liu, Lili Huo, Jing Luo","doi":"10.21037/tlcr-2026-0253","DOIUrl":"10.21037/tlcr-2026-0253","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant chemoimmunotherapy is standard for resectable stage III non-small cell lung cancer (NSCLC), yet reliable predictive biomarkers are lacking. Tertiary lymphoid structures (TLS) correlate with survival in NSCLC, but their role in predicting chemoimmunotherapy response remains unclear. This study aimed to characterize TLS comprehensively and develop a composite TLS score to predict pathological response and survival in stage III NSCLC.</p><p><strong>Methods: </strong>We retrospectively analyzed tumor tissues from patients with stage III (IIIA-IIIC) NSCLC who underwent neoadjuvant chemoimmunotherapy. TLS were characterized using hematoxylin and eosin (H&E) staining and multiplex immunohistochemistry (mIHC) for maturity, density, area, location, and spatial distribution. A composite TLS status score integrating these metrics was developed. Associations with pathological response, survival outcomes, and features of the tumor microenvironment (TME), including programmed death-ligand 1 (PD-L1) expression and immune cell composition were analyzed.</p><p><strong>Results: </strong>Greater TLS maturity was associated with earlier T-stage and clinical stages. Superior TLS characteristics-including advanced maturity, high density, large area, and stromal location-were significantly correlated with improved progression-free survival (PFS). Furthermore, patients who achieved a major pathological response (MPR) exhibited tumors characterized by more mature and denser TLS, and concomitant increase in tumor-infiltrating lymphocytes. A favorable TLS status, defined as a composite score =4, was a robust predictor of superior PFS [area under the curve (AUC) =0.82, P<0.001]. Furthermore, TLS maturity was inversely correlated with PD-L1 expression in the TME.</p><p><strong>Conclusions: </strong>TLS status, through its role in actively modulating the immune TME, serves as a predictive biomarker for neoadjuvant chemoimmunotherapy in resectable stage III NSCLC. This may offer a qualified advance for optimizing clinical therapeutics.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 7","pages":"197"},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713759","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":"Longevity-associated <i>FOXO3</i> genotype mitigates the risk of lung cancer after smoking cessation: a prospective cohort study.","authors":"Randi Chen, Timothy A Donlon, Vanessa L Cunanan, Kaon Fong, Keisuke Miyamoto, Bradley J Willcox, Kamal H Masaki","doi":"10.21037/tlcr-2026-0267","DOIUrl":"10.21037/tlcr-2026-0267","url":null,"abstract":"<p><strong>Background: </strong>Smoking cessation lowers lung cancer (LC) risk, but the magnitude of risk reduction varies across individuals. FOXO3, a key regulator of cellular stress-response and longevity pathways, may influence susceptibility to LC after smoking cessation. The aim of the present study was to investigate whether <i>FOXO3</i> genotype modifies the association between smoking cessation and incident LC.</p><p><strong>Methods: </strong>We examined 4,339 ever-smoking American men of Japanese ancestry who were free of LC at baseline in the Kuakini Japan-Hawaii Cancer Study (1971-1975; mean age, 60 years). Participants were genotyped for <i>FOXO3</i> rs2802292 and classified as <i>FOXO3</i>-G (TG/GG; longevity-associated G-allele carriers) or <i>FOXO3</i>-TT (TT, common allele homozygotes). Smoking status (former or current), cumulative exposure (pack-years), and duration of smoking cessation (years; current smokers assigned 0) were assessed. Incident LC cases through 1999 were identified. Cox proportional hazards models adjusted for potential confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and test interactions.</p><p><strong>Results: </strong>During 28 years of follow-up, 180 LC cases occurred, including 117 non-small cell lung cancer (NSCLC) cases. Significant interactions were observed between smoking status and <i>FOXO3</i> genotype for LC (P=0.02) and NSCLC (P=0.003). Among former smokers, <i>FOXO3</i>-G carriers had a lower risk than <i>FOXO3</i>-TT carriers (LC: HR, 0.42; 95% CI, 0.23-0.79; NSCLC: HR, 0.23; 95% CI, 0.09-0.60). In contrast, no genotype-related differences were observed among current smokers. Among <i>FOXO3</i>-G carriers, each additional year of smoking cessation was associated with a reduced risk of LC (HR, 0.87; 95% CI, 0.81-0.94) and NSCLC (HR, 0.72; 95% CI, 0.58-0.89), whereas only weaker associations were observed among <i>FOXO3</i>-TT carriers (LC: HR, 0.97; 95% CI, 0.94-1.00; NSCLC: HR, 0.98; 95% CI, 0.94-1.01).</p><p><strong>Conclusions: </strong><i>FOXO3</i> genotype may modify LC risk associated with smoking cessation. Compared with carriers of the longevity-associated <i>FOXO3</i> G allele, individuals with the <i>FOXO3</i>-TT genotype had a substantially elevated risk of LC after smoking cessation; this association was not observed among current smokers. These findings support the potential for genotype-informed precision prevention, pending replication in larger and more diverse cohorts.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 7","pages":"203"},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713788","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":"Role and clinical significance of VISTA (PD-1H) and PVR (CD155) expression in non-small cell lung carcinoma: a systematic review.","authors":"Maciej Baron, Piotr Lewandowski, Iwona Jabłońska, Andrzej Skrzypiec, Kamil Liberka, Marcin Fyrla, Bartosz Bula, Bogna Drozdzowska","doi":"10.21037/tlcr-2026-0402","DOIUrl":"10.21037/tlcr-2026-0402","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint blockade has improved outcomes in non-small cell lung carcinoma (NSCLC), yet primary and acquired resistance remain common. VISTA (PD-1H) and CD155 (poliovirus receptor, PVR) are emerging immune-regulatory pathways that may contribute to immune escape and represent potential therapeutic targets. Thus, this systematic review aimed to evaluate the expression patterns, molecular functions, and clinical significance of CD155 (PVR) and VISTA (PD-1H) in NSCLC.</p><p><strong>Methods: </strong>We performed a systematic review of studies assessing the expression, function, and clinical relevance of VISTA and/or CD155 in NSCLC. PubMed, Scopus, Embase, and Web of Science were searched through September 2025. Original human, <i>in vivo</i>, and <i>in vitro</i> studies were eligible. Risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS; human studies) and SYRCLE's tool (animal studies). The protocol was registered in PROSPERO.</p><p><strong>Results: </strong>Fifty-one studies met the inclusion criteria (22 VISTA; 29 CD155). VISTA was predominantly reported in stromal and immune-cell compartments and linked to immune-regulatory functions, but available evidence did not support a consistent association with survival. CD155 was mainly expressed on tumour cells, associated with an immunosuppressive microenvironment, and more consistently related to adverse prognosis in selected cohorts, particularly when co-expressed with programmed death-ligand 1 (PD-L1).</p><p><strong>Conclusions: </strong>Both pathways appear involved in immune modulation in NSCLC. Evidence for VISTA as a prognostic biomarker remains inconclusive, whereas CD155 shows a more reproducible association with unfavourable outcomes, supporting its further evaluation as a prognostic marker and therapeutic target.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 7","pages":"216"},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of machine learning diagnostic models integrating clinical, CT, and laboratory features to differentiate lung cancer from pulmonary tuberculosis in patients with solitary pulmonary nodules: a single-center retrospective study.","authors":"Yuhang Li, Weijun Wu, Huiling Xu, Jun Ma, Minwei Bao, Junjie Zhu, Shanhao Chen","doi":"10.21037/tlcr-2026-0559","DOIUrl":"10.21037/tlcr-2026-0559","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Differentiating lung cancer from pulmonary tuberculosis in patients with solitary pulmonary nodules (SPNs) remains clinically challenging, particularly in tuberculosis-endemic settings, because these two conditions may show overlapping computed tomography (CT) morphological features. This study aimed to develop and internally validate machine learning (ML) diagnostic models integrating these routinely available variables and to identify stable discriminative features using feature-importance analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This single-center retrospective diagnostic prediction model development and internal validation study included adult patients with CT-detected SPNs measuring ≤3 cm and a definitive diagnosis of primary lung cancer or pulmonary tuberculosis between May 2020 and June 2024. Candidate predictors were extracted from baseline clinical information, tuberculosis-related tests, manually assessed CT morphological features, circulating tumor cell indicators, routine laboratory tests, and blood gas analysis variables obtained within 7 days before surgery or biopsy. Variables with more than 5% missingness were excluded, and 72 variables were retained before least absolute shrinkage and selection operator (LASSO) feature selection. The dataset was randomly divided into training and validation sets in a stratified 7:3 ratio. Seven ML models were subsequently constructed, including logistic regression (LR), random forest (RF), extra trees (ET), radial basis function support vector machine (RBF-SVM), k-nearest neighbors (KNN), multilayer perceptron (MLP), and gradient boosting decision tree (GBDT). Model performance was evaluated using the area under the curve (AUC) for the receiver operating characteristic (ROC) curve, sensitivity, specificity, and balanced accuracy. Permutation importance and SHapley Additive exPlanations (SHAP) analyses were further performed to assess model interpretability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 431 patients were included, comprising 168 patients with pathologically confirmed lung cancer and 263 patients with pulmonary tuberculosis. The median age was 60.00 years (interquartile range, 53.00-67.00 years), 277 patients (64.3%) were male, 349 patients (81.0%) had solid nodules, and 277 patients (64.3%) had positive QuantiFERON-TB (QFT) results. After missingness filtering, 72 variables were retained, and 29 features were selected by LASSO for model development. Among the seven models, the RBF-SVM model achieved the highest validation AUC of 0.803, with a sensitivity of 0.686, specificity of 0.734, and balanced accuracy of 0.710. The ET model showed comparable validation performance, with an AUC of 0.791, whereas LR achieved the highest balanced accuracy of 0.711. Cross-model interpretability analyses identified nodule type and age as the most stable core features.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;ML models integrating routine clinical, manually assessed CT, an","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 7","pages":"209"},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713764","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":"Immune-preserving radiotherapy and perioperative immunotherapy in stage III NSCLC: a narrative review of current management and future directions for IIIA/IIIB NSCLC.","authors":"Zeta Chow, Charles B Simone, Haibo Lin, Jun Yang, Mark Bernard, Weisi Yan","doi":"10.21037/tlcr-2025-aw-1135","DOIUrl":"10.21037/tlcr-2025-aw-1135","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease with outcomes limited by distant failure, treatment-related toxicities, and loss of immune fitness during chemoradiation. Randomized trials support perioperative immunotherapy (IO) for resectable disease and consolidation durvalumab after concurrent chemoradiotherapy (cCRT) for unresectable disease. Immune-preserving radiotherapy (RT)-encompassing immune organ-at-risk (iOAR) and effective dose to immune cells (EDIC)-aware planning, judicious hypofractionation, and stereotactic body radiation therapy (SBRT) or spatially fractionated radiation therapy (SFRT)-is an emerging lever to optimize immune competence during treatment. This study aims to synthesize contemporary evidence for stage IIIA/IIIB management through a dual-track framework (resectable versus unresectable disease), outline practical algorithms integrating surgery, RT, and systemic therapy, and highlight translational strategies including SFRT and tumor-infiltrating lymphocyte (TIL)-based approaches, while clearly distinguishing established standards from investigational concepts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a narrative review of pivotal trials and practice-shaping studies, emphasizing perioperative IO (neoadjuvant chemo-IO ± adjuvant IO), the PACIFIC paradigm, RT dose/fractionation strategies, and approaches to mitigate RT-related lymphopenia. We propose an evidence-anchored clinical pathway and a checklist for immune-preserving RT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key content and findings: &lt;/strong&gt;Neoadjuvant nivolumab-chemotherapy improves pathological complete response (pCR), event-free survival (EFS), and overall survival (OS) in resectable disease (CheckMate 816). Perioperative pembrolizumab (KEYNOTE-671), durvalumab (AEGEAN), and nivolumab (CheckMate 77T) significantly prolong EFS. In unresectable stage III, durvalumab after cCRT confers durable OS benefit (5-year OS 42.9%), whereas uniform dose escalation to 74 Gy did not improve survival. RT-related lymphopenia is frequent and prognostic; reducing low-dose bath, minimizing exposure to iOARs, and optimizing target selection may preserve immune competence. SBRT/SFRT integrations and TIL-based cellular approaches warrant prospective testing but remain investigational.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;A dual-track algorithm-perioperative chemo-IO for operable IIIA and cCRT followed by durvalumab for unresectable IIIA/IIIB-remains the evidence-based standard. Refinements that prioritize immune preservation (iOAR-aware planning, limited-field and hypofractionated strategies) represent promising areas of investigation that should not compromise tumor control. In patients with oncogene-driven disease, targeted therapy should be considered. When surgical resection is performed, tissue acquisition for molecular profiling and, in the context of clinical trials, TIL expansion may support personalized treatment strategies","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 7","pages":"215"},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713868","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":"Neoadjuvant befotertinib plus vorolanib in resectable stage II-IIIB EGFR-mutant NSCLC: a study protocol for the prospective, single-arm phase I/II trial.","authors":"Leilei Wu, Lei Cai, Da Chen, Sheng Chen, Xiancong Huang, Qiqi Yang, Jinshi Liu, Qixun Chen, Xun Yang, Qiang Zhao, Taobo Luo, Jian Zeng","doi":"10.21037/tlcr-2026-0382","DOIUrl":"10.21037/tlcr-2026-0382","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant targeted therapy is a promising strategy for resectable non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, but pathological regression remains suboptimal with EGFR-tyrosine kinase inhibitor (TKI) monotherapy. Befotertinib is a third-generation EGFR-TKI, whereas vorolanib is a multi-target antiangiogenic TKI. Combined EGFR and vascular endothelial growth factor receptor (VEGFR) pathway inhibition may enhance tumor regression while preserving surgical feasibility.</p><p><strong>Methods: </strong>This is a prospective, open-label, single-arm phase I/II study enrolling NSCLC patients with clinically resectable stage II-IIIB harboring sensitizing EGFR exon 19 deletion and/or exon 21 L858R mutations. Phase I uses a 3+3 dose-escalation design to determine the maximum tolerated dose and recommended phase II dose of neoadjuvant befotertinib plus vorolanib. Phase II adopts a two-stage design and evaluates major pathological response after two 21-day neoadjuvant cycles. Patients undergo radiographic assessment after neoadjuvant therapy, followed by radical surgery 4-6 weeks after the last treatment dose. Secondary endpoints include pathological complete response, R0 resection rate, objective response rate, disease control rate, safety, disease-free survival, and overall survival.</p><p><strong>Discussion: </strong>This trial will prospectively explore the feasibility, safety, and preliminary activity of combined third-generation EGFR inhibition and antiangiogenic therapy in resectable stage II-IIIB EGFR-mutant NSCLC. The study may help define whether intensification of neoadjuvant targeted therapy can improve pathological regression in this molecularly selected population.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry (ChiCTR2500103324).</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 7","pages":"212"},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713775","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":"Best supportive care in stage I-III non-small cell lung cancer: survival by reason for curative treatment omission in a real-world study population.","authors":"Guus R M van den Heuvel, Bas L R Mandos, Hans J M Smit, Olga C J Schuurbiers, Francesco Ciompi, Erik H J G Aarntzen, Kaamar Azijli, Iris Walraven, Michel M van den Heuvel","doi":"10.21037/tlcr-2026-0327","DOIUrl":"10.21037/tlcr-2026-0327","url":null,"abstract":"<p><strong>Background: </strong>Despite advances in stage I-III non-small cell lung cancer (NSCLC) treatment, curative-intent therapy is withheld in patients deemed ineligible or preferring no treatment. Limited real-world data exist on overall and cancer-related survival outcomes in patients receiving primary best supportive care (BSC). The main aim of this study was to compare median overall survival (OS) by reason for BSC (patient preference versus other factors).</p><p><strong>Methods: </strong>We retrospectively analyzed overall and lung cancer-specific survival (LCSS) in patients with stage I-III NSCLC diagnosed between 2015 and 2019 in the Netherlands. Patients received primary BSC or curative treatment (surgery, radiotherapy or chemoradiation). The BSC cohort was categorized by main decisive factor: (I) patient preference; (II) insufficient performance status; or (III) relevant comorbidities. Survival data were compared using log-rank tests and Cox regression models.</p><p><strong>Results: </strong>Out of 1,895 patients, 234 (12%) received primary BSC, including 82 based on patient preference. Median OS was 5.9 months in the total BCS cohort and 9.6 months in the patient-preference cohort, compared to 54.1 months in the curative treatment cohort [hazard ratio (HR) 0.17; 95% confidence interval (CI): 0.13-0.22; P<0.001]. Median LCSS was 8.9 and 16.4 months in the total BSC and patient-preference cohort, respectively, versus not reached in the curative treatment cohort (HR 0.15; 95% CI: 0.11-0.21; P<0.001). These survival differences remained significant after adjusting for relevant confounders.</p><p><strong>Conclusions: </strong>In routine clinical practice, primary BSC was provided in a substantial proportion of patients with stage I-III NSCLC, due to medical reasons or patient preference. In either case, omission of curative treatment resulted in significantly reduced survival outcomes. Our data offer targeted evidence to guide treatment decisions in the outpatient oncology clinic.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 7","pages":"208"},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713740","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":"Association of symptoms at diagnosis with prognosis in patients with surgically treated stage I non-small cell lung cancer: a retrospective cohort analysis of a prospectively maintained registry.","authors":"Jiahan Cheng, Ruichen Cui, Xiaohu Hao, Xiangchao Kong, Wenjing Zhou, Shasha Li, Qiang Pu, Yunke Zhu","doi":"10.21037/tlcr-2026-0733","DOIUrl":"10.21037/tlcr-2026-0733","url":null,"abstract":"<p><strong>Background: </strong>Although most patients with stage I non-small cell lung cancer (NSCLC) are detected at an early and potentially curable stage, postoperative recurrence and mortality still occur after curative resection. Whether presenting symptoms at diagnosis provide additional prognostic information for risk stratification in surgically treated stage I NSCLC remains unclear. This study evaluated the association between symptoms at diagnosis and long-term outcomes in patients with pathologically confirmed stage I NSCLC.</p><p><strong>Methods: </strong>This retrospective cohort study used single-institution data from West China Hospital, Sichuan University, within the Western China Lung Cancer Database, a prospectively maintained institutional registry. Patients with pathologically confirmed stage IA-IB NSCLC who underwent curative-intent surgical resection between 2011 and 2021 were included. Patients receiving non-surgical primary treatment, undergoing non-curative resection, or lacking detailed survival or treatment information were excluded. Presenting symptoms were extracted from electronic medical records at diagnosis. Baseline demographic, clinical, surgical, and pathological covariates were collected. Follow-up was conducted through outpatient visits, hospital record review, and telephone interviews. Cox regression models were used to evaluate associations with overall survival (OS) and disease-free survival (DFS).</p><p><strong>Results: </strong>A total of 9,205 patients were included, of whom 2,657 (28.9%) were symptomatic at diagnosis. The most common symptoms were cough, chest pain, and blood-tinged sputum. Symptomatic patients were more likely to be older, male, smokers, and to have chronic obstructive pulmonary disease (COPD) or squamous cell carcinoma histology. Symptom presence was independently associated with poorer OS [adjusted hazard ratio (HR) =1.22, 95% confidence interval (CI): 1.01-1.47; P=0.03] and DFS (adjusted HR =1.27, 95% CI: 1.09-1.47; P=0.002). Among individual symptoms, blood-tinged sputum remained independently associated with worse OS (adjusted HR =1.71, 95% CI: 1.31-2.24; P<0.001) and DFS (adjusted HR =1.71, 95% CI: 1.36-2.14; P<0.001) after adjustment for demographic, clinical, surgical, and pathological covariates.</p><p><strong>Conclusions: </strong>Presenting symptoms at diagnosis, particularly blood-tinged sputum, was associated with poorer long-term outcomes in patients with surgically treated stage I NSCLC. Symptom status may provide a simple clinical cue for postoperative risk stratification and may help identify patients who require closer surveillance after curative resection.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 7","pages":"211"},"PeriodicalIF":3.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713671","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}