JTO Clinical and Research Reports最新文献

{"title":"Machine Learning Models Using General and Tissue-Specific Feature Extractors for Accurate Subtyping of Biopsy Samples: Advancing Lung Cancer Diagnosis in Latin America","authors":"Viviane Teixeira Loiola de Alencar MD, PhD candidate ,&nbsp;Felipe Navarro Balbino Alves BSc, MSc ,&nbsp;Guilherme de Souza Velozo BSc, MSc ,&nbsp;Luiz Edmundo Lopes Mizutani BSc, MSc ,&nbsp;Iusta Caminha MD, MSc, PhD candidate ,&nbsp;Gabriel Barbosa Silva BSc in Biomedical Science ,&nbsp;Vladmir Cláudio Cordeiro de Lima MD, PhD ,&nbsp;Fábio Rocha Fernandes Távora MD, PhD","doi":"10.1016/j.jtocrr.2025.100906","DOIUrl":"10.1016/j.jtocrr.2025.100906","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung cancer is the leading cause of cancer-related deaths worldwide, with accurate histologic subtype classification critical for diagnosis and treatment planning. Diagnostic variability and resource disparities, particularly in underrepresented regions such as Latin America, pose substantial challenges. This study developed and evaluated novel artificial intelligence models trained on both global and Latin American pathology samples for subtype classification of hematoxylin and eosin (HE)–stained whole-slide images (WSIs).</div></div><div><h3>Methods</h3><div>Two DinoV2-based feature extractors, LungDino and OncoDino, trained on large data sets for task-specific and general pathology applications, were developed. The training data set consisted of 1308 HE-stained WSIs, including 412 adenocarcinomas, 323 squamous cell carcinomas, 41 small cell carcinomas, and 532 benign tissue samples, sourced from The Cancer Genome Atlas and an in-house Latin American data set. A ResNet model trained on ImageNet served as the baseline. Models were evaluated on 79 Latin American WSIs using receiver operating characteristic curves, and heatmaps were generated for tumor localization.</div></div><div><h3>Results</h3><div>The DinoV2-based models outperformed the ResNet baseline. LungDino achieved the highest overall performance, with area under the curves of 0.97 for adenocarcinoma and 0.96 for squamous cell carcinoma. OncoDino excelled in underrepresented categories, achieving an area under the curve of 0.99 for small cell carcinoma, demonstrating its generalizability. Both models generated interpretable heatmaps, with LungDino demonstrating precise tumor localization. In the subset of samples classified as poorly differentiated or undifferentiated in HE pathology reports, the DinoV2 models also maintained high classification performance.</div></div><div><h3>Conclusion</h3><div>These findings underscore the effectiveness of task-specific and general feature extractors in delivering accurate, explainable results and address a gap in artificial intelligence–driven histopathology advancements, paving the way for future clinical applications.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100906"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing Global Disparities in Lung Cancer Screening: Lessons From Puerto Rico and Beyond","authors":"Patrick Goodley MBBChir ,&nbsp;Matthew Evison MD","doi":"10.1016/j.jtocrr.2025.100919","DOIUrl":"10.1016/j.jtocrr.2025.100919","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100919"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145576880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Characteristics of Disease Flare After Lenvatinib Discontinuation in Patients With Thymic Carcinoma: A Brief Report","authors":"Tomoaki Nakamura MD ,&nbsp;Tatsuya Yoshida MD, PhD ,&nbsp;Ken Masuda MD ,&nbsp;Jun Sato MD, PhD ,&nbsp;Yuki Shinno MD, PhD ,&nbsp;Yuji Matsumoto MD, PhD ,&nbsp;Yusuke Okuma MD, PhD ,&nbsp;Yasushi Goto MD, PhD ,&nbsp;Hidehito Horinouchi MD, PhD ,&nbsp;Noboru Yamamoto MD, PhD ,&nbsp;Yuichiro Ohe MD, PhD","doi":"10.1016/j.jtocrr.2025.100872","DOIUrl":"10.1016/j.jtocrr.2025.100872","url":null,"abstract":"<div><h3>Introduction</h3><div>Lenvatinib, an orally administered multitargeted kinase inhibitor, has exhibited antitumor activity against several cancer types, including thymic carcinomas. Although “disease flare” (a rapid worsening of the tumor on the discontinuation of lenvatinib) has been reported, such cases are rare in thymic carcinoma. Understanding this phenomenon is clinically significant, as it may cause rapid deterioration requiring urgent therapeutic intervention and patient death. This retrospective study aimed to determine the frequency and characteristics of disease flares in patients with thymic carcinoma.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed the records of patients with thymic carcinoma who received lenvatinib between January 2018 and March 2024 at the National Cancer Center Hospital in Tokyo, Japan. Patients were categorized into flare and nonflare groups, with their characteristics, clinical outcomes, and genetic profiles compared.</div></div><div><h3>Results</h3><div>Of the 52 patients, four patients (8%) experienced disease flares after lenvatinib failure. Baseline characteristics according to the presence of disease flares after discontinuation revealed no significant differences. All four patients experienced increased pleural effusions within 1 week of lenvatinib discontinuation. Progression-free survival (<em>p</em> = 0.307) or objective response rates (<em>p</em> = 0.257) did not differ significantly between the flare and nonflare groups regarding lenvatinib treatment efficacy. Similarly, 24 of the 52 patients underwent comprehensive genomic profiling using next-generation sequencing platforms and RNA sequencing. In the flare group, <em>KIT</em> mutations occurred in 50% of patients, with <em>KMT2C</em> mutations being significantly more common (<em>p</em> = 0.022).</div></div><div><h3>Conclusions</h3><div>The discontinuation of lenvatinib in patients with thymic carcinoma caused disease flare in 8% of cases, with <em>KMT2C</em> and <em>KIT</em> mutations emerging as potential contributing factors. These findings suggest that molecular profiling helps in identifying patients at high risk of disease flare and informs future treatment sequencing strategies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100872"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145469060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Report: Relationship Between Tumor Volume and Clinical Outcomes in Relapsed SCLC","authors":"Matthew Lu MD ,&nbsp;Hayden Byrd MD ,&nbsp;Heidi Chen PhD ,&nbsp;Wade Iams MD","doi":"10.1016/j.jtocrr.2025.100904","DOIUrl":"10.1016/j.jtocrr.2025.100904","url":null,"abstract":"<div><h3>Introduction</h3><div>For patients with limited-stage SCLC (LS-SCLC), tumor burden is a predictor of clinical outcomes, but there are no known data exploring whether tumor burden is a predictor of clinical outcomes in relapsed SCLC.</div></div><div><h3>Methods</h3><div>In this retrospective correlative study analyzing a cohort of 93 patients with relapsed SCLC, total body tumor volume at time of relapse (TV), progression-free survival (PFS), and overall survival (OS) were calculated and a Cox proportional hazards model was used to evaluate the relationship between TV and PFS and OS.</div></div><div><h3>Results</h3><div>A total of 93 patients with relapsed SCLC were analyzed, of whom 70% initially had extensive-stage SCLC (ES-SCLC) and 30% initially had LS-SCLC. Eastern Cooperative Oncology Group performance status and receipt of second-line therapy were significantly associated with OS in a linear fashion (<em>p</em> = 0.002 and <em>p</em> = 0.0457, respectively). TV was significantly associated with OS in a nonlinear fashion, even when controlling for Eastern Cooperative Oncology Group performance status, response to initial therapy, chemotherapy-free interval, and receipt of second-line therapy (<em>p</em> = 0.0031).</div></div><div><h3>Conclusions</h3><div>TV was observed to be a predictor of OS in patients with relapsed SCLC. Further studies are needed to evaluate whether initiation of standard systemic therapy at lower TV is able to consistently improve PFS and OS in relapsed SCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100904"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145420052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central Nervous System Progression in Patients Receiving ALK-Targeted Central Nervous System–Penetrable Tyrosine Kinase Inhibitors: Treatment Patterns and Outcomes","authors":"Surbhi Singhal MD ,&nbsp;Caressa Hui MD ,&nbsp;Joel W. Neal MD, PhD ,&nbsp;Seema Nagpal MD ,&nbsp;Mohana Roy MD ,&nbsp;Millie Das MD ,&nbsp;Kavitha Ramchandran MD ,&nbsp;Erqi Pollom MD ,&nbsp;Giovanni Selvaggi MD ,&nbsp;Heather A. Wakelee MD ,&nbsp;Nathaniel J. Myall MD","doi":"10.1016/j.jtocrr.2025.100914","DOIUrl":"10.1016/j.jtocrr.2025.100914","url":null,"abstract":"<div><h3>Introduction</h3><div>Central nervous system (CNS) metastases are common in <em>ALK</em>-rearranged NSCLC. The optimal treatment strategy for patients who develop CNS progression during treatment with CNS-penetrable <em>ALK</em> tyrosine kinase inhibitors (TKIs) is unknown. Here, we characterized practice patterns and outcomes for patients who developed CNS progression during treatment with CNS-penetrable TKI.</div></div><div><h3>Methods</h3><div>This retrospective study included patients who developed CNS progression (time 0, [T0]) on alectinib, lorlatinib, brigatinib, or ensartinib. Patients were characterized according to TKI management (i.e., TKI unaltered, TKI-altered [switched TKI or increased TKI dose], TKI discontinued) at T0. Intracranial progression-free survival was evaluated using Kaplan-Meier and compared using the log-rank test.</div></div><div><h3>Results</h3><div>Among 98 patients treated with a CNS-penetrable TKI, 36 (37%) experienced CNS progression. Overall, 33 (92%) developed parenchymal and seven (19%) developed leptomeningeal progression, respectively. At T0, 16 (44%) had TKI unaltered, 14 (39%) had TKI altered (eight switched TKI, six increased TKI dose), and six (17%) discontinued TKI. Patients with TKI-altered tended to have more frequent leptomeningeal disease or concurrent systemic progression at T0. Intracranial radiation was given at T0 in 14 (88%) of TKI-unaltered and three (21%) of TKI-altered patients. The median intracranial progression-free survival from T0 was not significantly different between the TKI-altered versus unaltered groups (<em>p</em> = 0.21).</div></div><div><h3>Conclusions</h3><div>For patients with <em>ALK-</em>rearranged NSCLC with leptomeningeal progression or concurrent systemic progression, TKI change or dose increase was a feasible salvage strategy for CNS progression during treatment with CNS-penetrable TKI.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100914"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145420517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiologic and Survival Analyses of Lung Cancer in Nagano Prefecture: Impact of Serial Low-Dose Computed Tomography Screening","authors":"Tomonobu Koizumi MD, PhD ,&nbsp;Kengo Otsuki ,&nbsp;Yuichiro Maruyama MD","doi":"10.1016/j.jtocrr.2025.100893","DOIUrl":"10.1016/j.jtocrr.2025.100893","url":null,"abstract":"<div><h3>Introduction</h3><div>Low-dose computed tomography (LDCT) screening for lung cancer has been implemented in many municipalities in Nagano prefecture. We analyzed epidemiologic and survival data of patients with lung cancer among municipalities in Nagano prefecture to evaluate the impact of LDCT.</div></div><div><h3>Methods</h3><div>This was a retrospective cohort study. Data regarding the number of LDCT screenings, population, and lung cancer deaths in each municipality in 2011 to 2020 were collected and collated with information from the population-based cancer registry. These data were compared between municipalities that had continuously implemented LDCT (LDCT [+], n = 26) and those that had not (LDCT [−], n = 11).</div></div><div><h3>Results</h3><div>The mean lung cancer crude mortality rate and standardized mortality ratio were significantly lower in LDCT (+) (82.2 ± 14.1 per 100,000 (<em>p</em> &lt; 0.02) and 69.7 ± 11.9 (<em>p</em> &lt; 0.005), respectively) than LDCT (−) (92.0 ± 10.1 per 100,000 and 81.6 ± 11.5, respectively). In addition, the mortality rate in each municipality was significantly negative correlated with the numbers of LDCT implementation in each municipality (<em>r</em> = 0.39). With regard to the extent of lung cancer at diagnosis, the proportion of localized lung cancer was significantly higher in LDCT (+) (39.4 ± 7.4%) than in LDCT (−) (34.6 ± 7.4%), and the proportion of localized lung cancer in each municipality was positively correlated with the number of LDCT implementation.</div></div><div><h3>Conclusion</h3><div>This retrospective analysis in Nagano prefecture indicated that serial LDCT could contribute to a decrease in lung cancer mortality in the general population.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100893"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145469064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to ‘Recent Survival Gains in Stage IV NSCLC by Sociodemographic Strata’ [JTO Clinical and Research Reports Volume 6 Issue 4 (2025) 100798]","authors":"Oluwaseun F. Ayoade MD, MSHA ,&nbsp;Maureen E. Canavan PhD, MPH ,&nbsp;Emily J. Zolfaghari MD, MS ,&nbsp;Giorgio Caturegli MD ,&nbsp;So Yeon Kim MD ,&nbsp;Daniel J. Boffa MD, MBA","doi":"10.1016/j.jtocrr.2025.100850","DOIUrl":"10.1016/j.jtocrr.2025.100850","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100850"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Added Value of Genome-Wide Copy Numbers to Objectively Resolve Clonality of Multiple Tumors With Pulmonary Involvement and Ambiguous or Inconclusive Mutational Diagnosis","authors":"Jurriaan Janssen MSc ,&nbsp;Bárbara Andrade Barbosa MSc ,&nbsp;Tim R. Mocking MSc ,&nbsp;Hendrik F. van Essen MA ,&nbsp;Paul P. Eijk BSc ,&nbsp;Jacqueline Egthuijsen BSc ,&nbsp;Anabela Ferro PhD ,&nbsp;Jose-Pedro Parracha de Matos MSc ,&nbsp;Swip Draijer PhD ,&nbsp;Albrecht Stenzinger Dr. (Prof.) ,&nbsp;Anke van den Berg Dr. (Prof.) ,&nbsp;José Carlos Machado Dr. (Prof.) ,&nbsp;Erik Thunnissen PhD ,&nbsp;Yongsoo Kim PhD ,&nbsp;Teodora Radonic PhD ,&nbsp;Bauke Ylstra Dr. (Prof.)","doi":"10.1016/j.jtocrr.2025.100921","DOIUrl":"10.1016/j.jtocrr.2025.100921","url":null,"abstract":"<div><h3>Introduction</h3><div>The incidence of patients presenting with multiple cancers (MCs) and pulmonary involvement is increasing. Although next-generation sequencing mutation panels can discern metastases (clonal) from separate primary cancers (nonclonal), it does not warrant a reliable diagnosis for all patients despite significant therapeutic implications. We evaluated the added value of genome-wide copy number aberrations (CNAs) for clonality diagnosis.</div></div><div><h3>Methods</h3><div>Two cohorts were assembled: 41 clonal and 41 nonclonal pairs from the TRACERx cohort and 21 MC pairs that had sufficient DNA for whole-exome sequencing (WES) from 120 patients diagnosed using CNA analysis in our routine pathology practice between 2016 and 2022. Clonality was determined by comparing tumor pairs using (1) WES mutations as a definitive standard, (2) a conventional mutation panel with an adapted 2024 International Association for the Study of Lung Cancer algorithm, and (3) CNAs with log-likelihood ratio and Pearson correlation metrics.</div></div><div><h3>Results</h3><div>All tumor pairs classified as definite “clonal” or “nonclonal” by mutation analysis (TRACERx: 35 of 82 [43%], MC cohort: 6 of 21 [29%]) were in concordance with WES and CNAs. Of the tumor pairs classified as “probable nonclonal” or “inconclusive” by mutation analysis (TRACERx: 47 of 82 [57%], MC cohort: 15 of 21 [71%]), most could be correctly reclassified by CNAs (TRACERx: 46 of 47 [98%], MC cohort: 15 of 16 [94%]). For each cohort, one tumor pair remained inconclusive. Furthermore, we present a CNA clonality workflow for implementation in molecular diagnostics.</div></div><div><h3>Conclusion</h3><div>Genome-wide CNA analysis provides complementary information to resolve clonality of MCs with ambiguous mutational clonality status, enhancing clinical decision-making.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100921"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145576878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DESTINY of Immunotherapy in Patients With HER2 Mutant Lung Cancer: Case Report","authors":"Lorenza Landi MD ,&nbsp;Francesca Fusco MD ,&nbsp;Enrico Melis MD ,&nbsp;Simonetta Buglioni PhD ,&nbsp;Paolo Visca MD ,&nbsp;Gabriele Minuti MD ,&nbsp;Federico Cappuzzo MD","doi":"10.1016/j.jtocrr.2025.100818","DOIUrl":"10.1016/j.jtocrr.2025.100818","url":null,"abstract":"<div><div>Immunotherapy has significantly transformed the landscape of non–oncogene-driven NSCLC. Multiple trials have reported that immunotherapy, either alone or in combination with chemotherapy, can induce pathologic complete responses—essentially tumor eradication—in non–oncogene-driven patients, at least in resectable stages. In contrast, tumors with specific molecular alterations, such as <em>EGFR</em> mutations or <em>ALK</em> rearrangements, are generally considered refractory to immune checkpoint inhibitors. Data on other lung cancer drivers, including <em>HER2</em> mutations, are scarce and limited to retrospective series, raising the question of whether immunotherapy should be avoided in all oncogene-addicted lung cancers. Here, we present the case of a patient with advanced <em>HER2</em> mutant NSCLC who achieved complete pathologic response to chemoimmunotherapy. Our observation suggests that not all driver mutations equally drive resistance to immunotherapy, and some molecular events, such as <em>HER2</em> mutations, need additional investigations.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100818"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145576881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Factors Associated With Incidence of Lung Cancer in Never-Smokers: A Systematic Review and Meta-Analysis","authors":"Sindhu Bhaarrati Naidu M.B.B.S. ,&nbsp;Allegra Wisking BSc ,&nbsp;Akul Karoshi BSc ,&nbsp;Sarah Burdett MSc ,&nbsp;Peter J. Godolphin PhD ,&nbsp;Sanjay Popat PhD ,&nbsp;OLIVE PPI Group,&nbsp;Sam M. Janes PhD ,&nbsp;Neal Navani PhD","doi":"10.1016/j.jtocrr.2025.100910","DOIUrl":"10.1016/j.jtocrr.2025.100910","url":null,"abstract":"<div><h3>Objectives</h3><div>Lung cancer is the leading cause of cancer mortality globally. Although often associated with smoking, up to 25% of cases worldwide and 50% in East Asia occur in “never-smokers.” There are currently no robust tools for predicting lung cancer in individuals who have never smoked (LCINS) for populations outside East Asia.</div><div>Together with a group of patient representatives, the authors of this study aimed to summarise risk factors for LCINS and quantify risk in different geographical regions.</div></div><div><h3>Methods</h3><div>This study was prospectively registered (PROSPERO-CRD42022379253). The systematic review and meta-analysis included studies published from 2017 and aimed to comprehensively investigate risk factors associated with LCINS incidence. Risk of bias was assessed using Newcastle-Ottawa Scale.</div></div><div><h3>Results</h3><div>A total of 6725 reports were identified and 54 studies were included, with multivariable analysis of 192 factors in 16 million never-smokers. No studies were assessed as having high risk of bias. Of the participants, 8,241,269 (51.0%) were from Western countries.</div><div>The meta-analysis found that female sex (adjusted hazard ratio [aHR] 1.28 [95% confidence interval or CI 1.12–1.47]), previous cancer (aHR 2.04 [1.95–2.13]), rheumatoid arthritis (aHR 1.41 [1.15–1.73]), passive smoking (aHR 1.30 [1.22–1.40]), PM10 (aHR 1.10 [1.09–1.11]), and PM2.5 (aHR 1.16 [1.03–1.30]) pollution were associated with LCINS. In planned subgroup analyses by region, LCINS was associated with family history of lung cancer in East Asian (aHR 1.56 [1.23–1.98]) but not Western countries (aHR 0.86 [0.35–2.11]).</div></div><div><h3>Conclusion</h3><div>We found key factors linked with LCINS, including female sex, rheumatoid arthritis, and pollution and, for the first time, quantified their association through meta-analyses of studies globally. This may be used to develop tools to detect LCINS earlier.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100910"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145469062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}