Lung Cancer最新文献

{"title":"KRAS G12C-associated immunotherapy benefit in NSCLC is substantially mediated by tobacco-induced tumor mutation burden, not allele-specific effects","authors":"Meng Liu ,&nbsp;Jeffrey P. Townsend","doi":"10.1016/j.lungcan.2025.108749","DOIUrl":"10.1016/j.lungcan.2025.108749","url":null,"abstract":"<div><h3>Background</h3><div>KRAS G12C mutations in non-small cell lung cancer (NSCLC) have been associated with improved immune-checkpoint inhibition (ICI) outcomes. However, it remains unclear whether this benefit reflects allele-intrinsic biology or shared dependence on tobacco-induced mutagenesis and elevated tumor mutation burden (TMB).</div></div><div><h3>Methods</h3><div>We analyzed 9,230 lung adenocarcinoma (LUAD) tumors to assess the mutational context and oncogenic potential of KRAS G12 variants. For each variant, we estimated cancer effect sizes, and assessed associations with tobacco-related mutational signature SBS4 exposure and TMB. We applied regression models to evaluate the linkage between SBS4 exposure, TMB, and ICI outcomes.</div></div><div><h3>Results</h3><div>KRAS G12C and G12D mutations exhibited comparable oncogenic effect sizes. However, G12C mutations were significantly enriched in tumors with higher tobacco-associated SBS4 exposure and higher TMB. SBS4 exposure and TMB were highly correlated. Models of ICI outcomes as functions of TMB as a consequence of SBS4 exposure recapitulated observed clinical trends: hazard ratios decreased and response rates increased as observed.</div></div><div><h3>Conclusions</h3><div>The improved ICI response observed in KRAS G12C-mutant tumors is more likely driven by tobacco-induced hypermutation and its immunogenic consequences than by G12C-specific biological properties. When available, smoking history and TMB remain more cogent biomarkers for ICI stratification than KRAS G12C-variant NSCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"209 ","pages":"Article 108749"},"PeriodicalIF":4.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving Trends in Surgically Managed Lung Cancer: A 16-Year Hospital-Based Epidemiological Analysis","authors":"Jieyu Wang ,&nbsp;Hang Cao ,&nbsp;Na He ,&nbsp;Xing Liu ,&nbsp;Fangqiu Fu ,&nbsp;Chaoqiang Deng ,&nbsp;Yuan Li ,&nbsp;Yang Zhang ,&nbsp;Haiquan Chen","doi":"10.1016/j.lungcan.2025.108754","DOIUrl":"10.1016/j.lungcan.2025.108754","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate longitudinal trends in clinical-epidemiological characteristics among surgically treated lung cancer patients and assess implications for prevention strategies.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on patients diagnosed with lung cancer and surgically treated at Fudan University Shanghai Cancer Center (2006–2021). Socio-demographics, clinical and pathological data were collected. Continuous and categorical data variables were analyzed using non-parametric tests and chi-square tests, respectively, with trend analysis conducted by linear regression.</div></div><div><h3>Results</h3><div>A total of 21,743 patients with a median age of 59 were included of whom 11,802 (54.3 %) were women. From 2006 to 2021, the female proportion surged from 29.9 % to 59.5 %, paralleled by an increase in patients aged &lt; 45 years (6.2 % to 15.4 %), with young females rising from 3.4 % to 19.2 %. Non-smokers predominated (72.0 % in 2021 vs. 42.3 % in 2006), particularly among women (97.5 % non-smokers), and the overall proportion of female non-smokers increased from 26.8 % to 58.5 %. Adenocarcinoma prevalence increased from 51.7 % to 82.9 % in females, while squamous carcinoma declined from 31.0 % to 4.1 %. Early-stage diagnoses (Stage 0-I) increased from 37.1 % to 85.0 %, coinciding with health checkup-driven detection rising from 44.0 % to 70.5 %. The EGFR mutation rate in adenocarcinoma was notably high in females (69.4 %) and non-smokers (68.9 %).</div></div><div><h3>Conclusions</h3><div>The rising percentage of non-smokers, growing incidence of lung cancer among young females, increase in early-stage lung cancer cases, and shift in major pathological subtypes present potential challenges and directions for lung cancer prevention and control in China. The emergence of lung cancer in young non-smoking females and its underlying factors warrant further research.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"208 ","pages":"Article 108754"},"PeriodicalIF":4.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of high-grade pre-invasive endobronchial lesions: To treat or not to treat?","authors":"Illaa Smesseim ,&nbsp;Adam Pennycuick ,&nbsp;Robert A. van Boerdonk ,&nbsp;Sam M. Janes ,&nbsp;Johannes M.A. Daniels","doi":"10.1016/j.lungcan.2025.108757","DOIUrl":"10.1016/j.lungcan.2025.108757","url":null,"abstract":"<div><h3>Background</h3><div>High-grade pre-invasive endobronchial lesions have the potential to progress to squamous cell carcinoma (SCC), but their natural history varies. The optimal management of these lesions is controversial, with treatment strategies varying across institutions. This study aims to compare the progression free and overall survival outcomes between patients with high-grade pre-invasive endobronchial lesions who received primary treatment versus patients who were treated on progression.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study across two oncology centers: University College London Hospitals (UCLH, United Kingdom) and Amsterdam University Medical Center (AUMC, The Netherlands). Patients with high-grade pre-invasive lesions underwent surveillance with repeat bronchoscopy and CT scans. At AUMC, patients routinely received endobronchial primary treatment, whereas at UCLH, treatment was reserved for cases that progressed to SCC. Primary outcome was progression-free survival (PFS), and the secondary outcome was overall survival (OS).</div></div><div><h3>Results</h3><div>Between 1998 and 2017, 85 patients were included in the study: 34 (40 %) received primary treatment, while 51 (60 %) received treatment on progression. The latter group had a higher proportion of carcinoma in situ (CIS) compared to the primary treatment group (78.4 % vs. 38.2 %, p = 0.001) and was significantly younger (median age: 67.0 vs. 77.0 years, p = 0.001). Median overall follow-up time was 46.2 months. Primary treatment was associated with a significantly reduced risk of disease progression (HR = 0.39, 95 % CI: 0.21–0.73, p = 0.002). Median PFS was 71.0 months in the primary treatment group versus 38.0 months in the treatment on progression group (p = 0.002). Multivariate Cox regression analysis identified both primary treatment (HR = 0.47, 95 % CI: 0.26–0.87, p = 0.015) and age (HR = 1.04, 95 % CI: 1.01–1.07, p = 0.013) as independent predictors of OS.</div></div><div><h3>Conclusion</h3><div>Our study showed that high-grade pre-invasive lesion patients who underwent primary treatment had a significantly improved PFS and OS.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"208 ","pages":"Article 108757"},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic implications of uncommon EGFR exon 19 deletion-insertion mutations in non-small cell lung cancer treated with third-generation EGFR-TKIs","authors":"Renzhi Zhang ,&nbsp;Huan Yan ,&nbsp;Fang Tian ,&nbsp;Yun Jiang ,&nbsp;Yangqian Chen ,&nbsp;Jiao Huang ,&nbsp;Zhaohui Ruan ,&nbsp;Shidong Xu ,&nbsp;Zhe Huang ,&nbsp;Qinqin Xu ,&nbsp;Liang Zeng ,&nbsp;Yongchang Zhang","doi":"10.1016/j.lungcan.2025.108755","DOIUrl":"10.1016/j.lungcan.2025.108755","url":null,"abstract":"<div><h3>Purpose</h3><div>The sensitivity of various epidermal growth factor receptor (EGFR) mutations to different EGFR tyrosine kinase inhibitors (EGFR-TKI) varies significantly. This study evaluated the survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) harboring <em>EGFR</em> exon 19 deletion-insertion (19delins) to third-generation EGFR-TKIs administered as first- or second-line therapy.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed clinical, molecular, and survival data from 215 patients detected with <em>EGFR</em> 19delins between March 2020 and July 2024. To evaluate progression-free survival, 57 patients with <em>EGFR</em> 19del who received first-line third-generation EGFR-TKIs (cohort A), and 48 patients who received the same treatment as second-line therapy (cohort B) were selected using 1:1 propensity score matching and served as control group.</div></div><div><h3>Results</h3><div>Thirty-nine unique <em>EGFR</em> 19delins genotypes were identified, with L747_P753delinsS (34.0 %), L747_A750delinsP (18.1 %), and E746_S752delinsV (9.8 %) being the top three variants. Patients with <em>EGFR</em> 19delins had significantly shorter median PFS compared with patients with common exon19del (first-line, 12.9 vs. 19.7 months, <em>p</em> = 0.0039; second-line, 7.9 vs. 10.5 months, <em>p</em> = 0.0387). Exploratory analyses indicated that L747_P753delinsS might be associated with poorer prognosis, while E746_S752delinsV appeared to show better outcomes with third-generation EGFR-TKIs, findings that require further validation.</div></div><div><h3>Conclusion</h3><div>These findings show real-world evidence that patients with <em>EGFR</em> 19delins derive limited clinical benefit from third-generation EGFR-TKI therapy compared to those with common <em>EGFR</em> 19del mutations, suggesting the need for optimal treatment regimen in this patient population.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"208 ","pages":"Article 108755"},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durvalumab in locally advanced unresectable non-small cell lung cancer – Benchmarking real-world outcomes in England against published trial data","authors":"Laura Webster ,&nbsp;Sarah Lawton ,&nbsp;Emma Kipps ,&nbsp;Katherine Thackray ,&nbsp;Nadza Tokaca","doi":"10.1016/j.lungcan.2025.108752","DOIUrl":"10.1016/j.lungcan.2025.108752","url":null,"abstract":"<div><h3>Background</h3><div>Durvalumab after chemoradiotherapy (CRT) is indicated for the treatment of locally advanced, unresectable non-small cell lung cancer based on the PACIFIC trial data. The National Institute for Health and Care Excellence recommended reimbursement via the Cancer Drugs Fund (CDF). Using the NHS England Systemic Anti-Cancer Therapy (SACT) dataset, we compared real-world outcomes against those of the PACIFIC trial.</div></div><div><h3>Methods</h3><div>Patients with a CDF application for durvalumab between 28 March 2019 and 1 February 2021 were identified from the NHS England Blueteq system and linked to SACT. Primary endpoints were overall survival (OS) and Time to First Subsequent Therapy (TFST). Comparisons between baseline characteristics including gender, age, performance status, stage of disease, histological subtype and PD-L1 expression were estimated using the log rank test.</div></div><div><h3>Results</h3><div>591 patients were included in this analysis (compared with PACIFIC n = 476). Median age was 67 years (PACIFIC 64y), 59 % were male (PACIFIC 70 %). Median OS was 50 months (PACIFIC 48 months). Median TFST was 38 months (PACIFIC 22 months).</div></div><div><h3>Conclusion</h3><div>Outcomes are comparable to the PACIFIC trial suggesting the trial data are generalisable to the real-world setting. This study demonstrates how population-based data can provide continued evaluation of clinical outcomes in routine care.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"209 ","pages":"Article 108752"},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of taxane versus gemcitabine for advanced stage lung squamous cell carcinoma in global EHR-based retrospective cohorts: A pairwise propensity score–matched comparison","authors":"Wen-Pin Cheng ,&nbsp;Chun-Yu Lai ,&nbsp;Hung-Chih Lai ,&nbsp;Ju-Fang Liu ,&nbsp;Shih-Sen Lin","doi":"10.1016/j.lungcan.2025.108751","DOIUrl":"10.1016/j.lungcan.2025.108751","url":null,"abstract":"<div><h3>Background</h3><div>Lung squamous cell carcinoma represents a significant global health challenge, with platinum-based chemotherapy regimens remaining a cornerstone of treatment. While both Taxanes and Gemcitabine are recommended as category 1 treatment options by the National Comprehensive Cancer Network (NCCN), their comparative effectiveness in real-world settings requires further investigation.</div></div><div><h3>Methods</h3><div>This retrospective cohort study utilized the TriNetX global collaborative network to analyze data between January 1, 1990, and October 31, 2024. Adults with stage IV lung squamous cell carcinoma were identified using ICD-10 code C34 and the TriNetX oncology disease classification system. Patients were categorized into Taxane and Gemcitabine groups. Propensity score matching was employed to minimize selection bias. Primary and secondary outcomes included overall survival, progression-free survival, and adverse events.</div></div><div><h3>Results</h3><div>A total of 992 patients were included, with 203 patients in each group after propensity score matching. The Taxane group demonstrated significantly improved overall survival compared to the Gemcitabine group (HR: 0.638, 95 % CI: 0.497-0.0821, p = 0.0004). Progression-free survival also showed statistically significant benefit over the Taxane group (HR: 0.686, 95 % CI: 0.532–0.885, p = 0.0035). Pairwise analysis revealed that Paclitaxel demonstrated superiority compared to both Docetaxel and Gemcitabine. The incidence of adverse events was comparable between groups.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that Taxane, particularly Paclitaxel, offers superiority compared to Gemcitabine in patients with advanced lung squamous cell carcinoma, with comparable safety profile. These results support the prioritization of Taxane-based regimens in clinical practice. Future research should focus on combination strategies with immunotherapy to enhance treatment outcomes.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"208 ","pages":"Article 108751"},"PeriodicalIF":4.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical factors and molecular co-alterations impact outcomes in patients receiving first-line osimertinib for EGFR-mutated non-small cell lung cancer","authors":"Fangdi Sun ,&nbsp;Mandeep K. Banwait ,&nbsp;Surbhi Singhal ,&nbsp;Amanda Herrmann ,&nbsp;Zofia Piotrowska ,&nbsp;Karen Yun ,&nbsp;Lyudmila Bazhenova ,&nbsp;Ayman T. Ullah ,&nbsp;Emily W. Guo ,&nbsp;Heather A. Wakelee ,&nbsp;Joel W. Neal ,&nbsp;Millie S. Das ,&nbsp;Kavitha J. Ramchandran ,&nbsp;Mohana Roy ,&nbsp;Maximilian Diehn ,&nbsp;Nathaniel J. Myall","doi":"10.1016/j.lungcan.2025.108747","DOIUrl":"10.1016/j.lungcan.2025.108747","url":null,"abstract":"<div><h3>Purpose</h3><div>Until recently, osimertinib was the preferred first-line therapy for nearly all patients with <em>EGFR</em>-mutated advanced NSCLC. However, with approval of the FLAURA2 and MARIPOSA regimens, identifying molecular or clinical factors that confer higher risk for inferior outcomes to first-line osimertinib may better inform upfront treatment selection for newly-diagnosed patients.</div></div><div><h3>Methods</h3><div>This real-world, multicenter retrospective study across 4 U.S. academic centers included adult patients with metastatic NSCLC and classic sensitizing <em>EGFR</em> mutations (exon 19 deletion, L858R mutation) receiving first-line osimertinib monotherapy who had tissue-based next-generation sequencing performed at diagnosis. Survival analyses for time-to-treatment discontinuation (TTD) on osimertinib and overall survival (OS) were conducted by number of co-alterations, individual gene alterations, previously defined molecular pathways, and clinical factors.</div></div><div><h3>Results</h3><div>A total of 219 patients were included (median age 68, 62 % female, 51 % with baseline CNS metastases). <em>TP53</em> was most frequently co-altered (58 %), followed by <em>EGFR</em> amplification (13 %), <em>CDKN2A</em> (10 %), <em>RB1</em> (9 %), and <em>PIK3CA</em> (8 %). Number of <em>de novo</em> co-alterations and presence of co-alterations by molecular pathway did not significantly predict TTD or OS. Co-alteration of both <em>TP53</em> and <em>PIK3CA</em>, but not <em>TP53</em> alone, demonstrated significantly shorter median OS compared to the <em>TP53</em> and <em>PIK3CA</em> wild-type population (21.9 vs 39.5 months, <em>p</em> = 0.046), with similar numerical trend for median TTD. On multivariate analysis, L858R mutation and CNS and bone metastases remained significant predictors for inferior clinical outcomes.</div></div><div><h3>Conclusion</h3><div>Co-alteration of <em>TP53</em> and <em>PIK3CA</em> may represent a high-risk molecular subgroup of <em>EGFR</em>-mutated NSCLC, however both clinical and molecular features should be considered in risk stratification.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"208 ","pages":"Article 108747"},"PeriodicalIF":4.4,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of primary tumor size on overall survival in patients with multifocal T3 non-small cell lung cancer","authors":"Ravi Rajaram ,&nbsp;Qing Huang ,&nbsp;Barbara H. Johnson ,&nbsp;Balaji Laxmanan ,&nbsp;Iftekhar Kalsekar ,&nbsp;Stephen Johnston ,&nbsp;Anil Vachani","doi":"10.1016/j.lungcan.2025.108746","DOIUrl":"10.1016/j.lungcan.2025.108746","url":null,"abstract":"<div><h3>Introduction</h3><div>In patients with non-small cell lung cancer (NSCLC) with T3 multifocal disease (within the same lobe), the prognostic significance of tumor size on overall survival (OS) is unclear. Here, we evaluate the implications of tumor size on OS in patients with multifocal T3 disease without/with limited nodal involvement (N0/N1) in surgical and non-surgical NSCLC.</div></div><div><h3>Methods</h3><div>Adults aged ≥ 66 years with newly diagnosed (2010–2015) early and locoregionally-advanced NSCLC (T1‒T3, N0/N1, M0 per the AJCC 8th/9th editions), without prior or concurrent primary cancer, were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. OS in patients with T3 multifocal disease stratified by primary tumor size (≤ 3 cm [T3-small] vs. &gt; 3 but ≤ 7 cm [T3-large]) was analyzed and compared with those without multifocal disease (T3-unicentric).</div></div><div><h3>Results</h3><div>Among N0 patients who were treated surgically, those with T3-small disease demonstrated improved median OS (months [95% confidence interval]: 86.1 [70.2, 95.9]) vs. those with T3-large and T3-unicentric disease (44.1 [36.4, 52.7] and 51.0 [44.6, 56.8], respectively). Similarly, among the non-surgical N0 patients, those with T3-small disease demonstrated improved median OS (26.7 [22.3, 30.7]) vs. those with T3-large and T3-unicentric disease (14.1 [12.3, 17.2] and 10.9 [10.0, 11.8], respectively). In both surgical and non-surgical cohorts, T3 with N1 disease had similar survival across the subgroups of interest.</div></div><div><h3>Conclusions</h3><div>In patients with T3 multifocal disease without nodal involvement, tumor size is an essential consideration and associated with OS. These findings may warrant reevaluation of the T3 stage classification and inform the evolution of future TNM classifications.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"208 ","pages":"Article 108746"},"PeriodicalIF":4.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of poor prognostic factors using circulating extracellular vesicles in durvalumab consolidation therapy for locally advanced non-small cell lung cancer","authors":"Hirofumi Utsumi ,&nbsp;Shigehiro Yagishita ,&nbsp;Kazuki Kawajiri ,&nbsp;Masahiro Torasawa ,&nbsp;Ayu Kiritani ,&nbsp;Kentaro Tamura ,&nbsp;Hiroshi Wakui ,&nbsp;Hidehito Horinouchi ,&nbsp;Jun Araya ,&nbsp;Yu Fujita","doi":"10.1016/j.lungcan.2025.108732","DOIUrl":"10.1016/j.lungcan.2025.108732","url":null,"abstract":"<div><h3>Background</h3><div>The risk factors associated with treatment resistance to consolidation durvalumab following chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC) have not been well established.</div></div><div><h3>Methods</h3><div>Extracellular vesicles (EVs) were isolated from the pretreatment serum of 73 patients treated with consolidation durvalumab. Isolation was performed using CD9/CD63 antibodies, and EV proteins were identified using liquid chromatography-tandem mass spectrometry (LC-MS). The relationship between the expression of these proteins and progression-free survival (PFS) after durvalumab initiation was analyzed.</div></div><div><h3>Results</h3><div>The median PFS was not reached<!--> <!-->(NR) (95 % confidence interval [CI], 17.2 months-NR), and<!--> <!-->the 24-month PFS rate was 54.7 % (95 % CI, 44.4–67.4). Proteomic analysis of circulating EVs identified RPS27A, SAA1, and S100A7 as the primary candidate biomarkers. Notably, patients with high RPS27A expression exhibited a significantly shorter PFS compared with those with low expression; hazard ratio (HR) 2.93 (95 % CI: 1.48–5.79),<!--> <em>P</em> = 0.002. Similarly, high SAA1 expression was associated with a shorter PFS; HR 2.94 (95 % CI: 1.37–6.30), <em>P</em> = 0.006. High S100A7 expression also correlated with poorer outcomes; HR 2.94 (95 % CI: 1.43–6.04), <em>P</em> = 0.003. In multivariate analysis, a high expression level of RPS27A was identified as an independent predictor of poor PFS; HR 2.29 (95 % CI: 1.01–5.17), <em>P</em> = 0.047. Multivariate receiver operating characteristic (ROC) analysis incorporating these three proteins yielded an area under the curve (AUC) of 0.71 (95 % CI: 0.59–0.83).</div></div><div><h3>Conclusion</h3><div>This study demonstrated<!--> <!-->favorable PFS outcomes in patients receiving durvalumab consolidation therapy. Circulating EV proteomic analysis identified RPS27A, SAA1, and S100A7, particularly RPS27A, as potential biomarkers for predicting resistance to durvalumab.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"208 ","pages":"Article 108732"},"PeriodicalIF":4.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical risk factors for developing brain metastases during first-line (chemo-)immunotherapy in patients with non-small cell lung cancer without known baseline brain metastases","authors":"Jarno W.J. Huijs ,&nbsp;Anna M. Sadowska ,&nbsp;Juliette H.R.J. Degens ,&nbsp;Christi M.J. Steendam ,&nbsp;Frederike Bensch ,&nbsp;Lucie B.M. Hijmering-Kappelle ,&nbsp;Tom M.T. de Schrevel ,&nbsp;Wouter H. van Geffen ,&nbsp;Magdolen Youssef-El Soud ,&nbsp;Michelle M.H. Steens ,&nbsp;Cordula Pitz ,&nbsp;Dirk K.M. De Ruysscher ,&nbsp;Lizza E.L. Hendriks","doi":"10.1016/j.lungcan.2025.108745","DOIUrl":"10.1016/j.lungcan.2025.108745","url":null,"abstract":"<div><h3>Background</h3><div>Brain metastases (BM) are common in non-small cell lung cancer (NSCLC). Although guidelines recommend baseline BM screening in asymptomatic patients, its benefit remains unproven. Routine imaging burdens healthcare systems and patients. Immune checkpoint inhibitors (ICI) show similar intra-and extracranial response percentages, supporting deferral of local BM treatment and possibly screening. However, dissociated responses occur. Therefore, patients newly diagnosed with BM during first-line ICI probably would have benefited most from baseline (and follow-up) screening. Identifying high-risk patients for BM progression or development during first-line ICI-based therapy is crucial to optimize screening.</div></div><div><h3>Methods</h3><div>Retrospective multicenter cohort study of patients with stage IV NSCLC without known baseline BM, treated with first-line (chemo-)ICI between 2018–2021. Incidence, timing, and symptom burden of newly diagnosed BM were analyzed. Cox regression identified predictive factors, and a nomogram was developed.</div></div><div><h3>Results</h3><div>Among 589 patients, BM were diagnosed during therapy in 9.0 %, 88.7 % occurred within the first year. Most cases (90.6 %) were symptomatic. Four factors predicted higher BM risk: age &lt; 65 years (HR 2.66; 95 % CI: 1.49–4.74), T4 stage (HR 2.08; 95 % CI: 1.18–3.65), M1c stage (HR 2.19; 95 % CI: 1.22–3.94) and PD-L1 &lt; 50 % (HR 2.03; 95 % CI: 1.16–3.54). The nomogram showed good performance (C-index 0.70). Twelve-month cumulative incidence was 11.7 % (95 % CI: 8.5–14.9 %).</div></div><div><h3>Conclusion</h3><div>BM detection during first-line (chemo-)ICI is relatively low in patients with stage IV NSCLC without known baseline BM, but the burden (symptoms) is high. Upon validation, the identified risk factors may support selective brain imaging in high-risk patients, avoiding routine screening in low-risk patients.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"208 ","pages":"Article 108745"},"PeriodicalIF":4.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}