Pub Date : 2026-02-01Epub Date: 2025-09-04DOI: 10.1016/j.jtho.2025.08.024
Hyungjin Kim MD, PhD , Eunseo Jo BA , Jinseob Kim MD , Seung Hun Jang MD, PhD , Joo Sung Sun MD , Gong Yong Jin MD, PhD , Hyae Young Kim MD, PhD , Yeol Kim MD, PhD , Jin Mo Goo MD, PhD
Introduction
Interval lung cancers (ILCs) are key indicators of lung cancer screening (LCS) performance. However, data on the proportion, characteristics, and mortality of ILCs under biennial screening in Asian populations remain limited.
Methods
We analyzed participants from the baseline biennial Korean national LCS program between 2019 and 2020. Screening-detected lung cancers (SLCs) were defined as those diagnosed within 1 year of a positive screening result. ILCs were defined as cancers diagnosed more than 1 year after a negative screening result but within 2 years or before the next screening. Risk factors for ILC were assessed using multivariable logistic regression among participants with a negative screening result. All-cause mortality was compared between SLCs and ILCs using multivariable Cox regression analysis.
Results
Among 124,595 participants, SLCs and ILCs occurred in 0.56% and 0.17%, respectively. ILCs accounted for 18.5% of all lung cancers within 2 years; 65.4% were in Lung-RADS category 1. Risk factors for ILC included older age (adjusted odds ratio [OR], 1.14; 95% confidence interval [CI]: 1.11–1.17; p < 0.001), greater smoking exposure (adjusted OR, 1.010; 95% CI: 1.004–1.016; p = 0.002), a history of malignancy (adjusted OR, 2.22; 95% CI: 1.41–3.51; p < 0.001), emphysema (adjusted OR, 2.88; 95% CI: 2.15–3.85; p < 0.001), and interstitial lung abnormalities (adjusted OR, 4.16; 95% CI: 2.88–6.01; p < 0.001). ILCs had higher all-cause mortality than SLCs (adjusted hazard ratio, 1.43; 95% CI: 1.13–1.80; p = 0.002).
Conclusions
ILCs are common under biennial LCS, making them potentially suboptimal for Asian heavy smokers.
{"title":"Screening-Detected Versus Interval Lung Cancer in the Biennial Korean National Lung Cancer Screening Program: Proportion, Characteristics, and Mortality","authors":"Hyungjin Kim MD, PhD , Eunseo Jo BA , Jinseob Kim MD , Seung Hun Jang MD, PhD , Joo Sung Sun MD , Gong Yong Jin MD, PhD , Hyae Young Kim MD, PhD , Yeol Kim MD, PhD , Jin Mo Goo MD, PhD","doi":"10.1016/j.jtho.2025.08.024","DOIUrl":"10.1016/j.jtho.2025.08.024","url":null,"abstract":"<div><h3>Introduction</h3><div>Interval lung cancers (ILCs) are key indicators of lung cancer screening (LCS) performance. However, data on the proportion, characteristics, and mortality of ILCs under biennial screening in Asian populations remain limited.</div></div><div><h3>Methods</h3><div>We analyzed participants from the baseline biennial Korean national LCS program between 2019 and 2020. Screening-detected lung cancers (SLCs) were defined as those diagnosed within 1 year of a positive screening result. ILCs were defined as cancers diagnosed more than 1 year after a negative screening result but within 2 years or before the next screening. Risk factors for ILC were assessed using multivariable logistic regression among participants with a negative screening result. All-cause mortality was compared between SLCs and ILCs using multivariable Cox regression analysis.</div></div><div><h3>Results</h3><div>Among 124,595 participants, SLCs and ILCs occurred in 0.56% and 0.17%, respectively. ILCs accounted for 18.5% of all lung cancers within 2 years; 65.4% were in Lung-RADS category 1. Risk factors for ILC included older age (adjusted odds ratio [OR], 1.14; 95% confidence interval [CI]: 1.11–1.17; <em>p</em> < 0.001), greater smoking exposure (adjusted OR, 1.010; 95% CI: 1.004–1.016; <em>p</em> = 0.002), a history of malignancy (adjusted OR, 2.22; 95% CI: 1.41–3.51; <em>p</em> < 0.001), emphysema (adjusted OR, 2.88; 95% CI: 2.15–3.85; <em>p</em> < 0.001), and interstitial lung abnormalities (adjusted OR, 4.16; 95% CI: 2.88–6.01; <em>p</em> < 0.001). ILCs had higher all-cause mortality than SLCs (adjusted hazard ratio, 1.43; 95% CI: 1.13–1.80; <em>p</em> = 0.002).</div></div><div><h3>Conclusions</h3><div>ILCs are common under biennial LCS, making them potentially suboptimal for Asian heavy smokers.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 283-293"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-02-04DOI: 10.1016/j.jtho.2025.11.015
Wei-Chin Chang MD, PhD , Teh-Ying Chou MD, PhD
{"title":"Resolving the Staging Dilemma in Multiple Lung Cancers: A Prevalence-Weighted Bioinformatic Approach to the 2024 IASLC Recommendations","authors":"Wei-Chin Chang MD, PhD , Teh-Ying Chou MD, PhD","doi":"10.1016/j.jtho.2025.11.015","DOIUrl":"10.1016/j.jtho.2025.11.015","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 221-223"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-22DOI: 10.1016/j.jtho.2025.10.010
Michael Allgäuer PhD , Klaus Kluck MS , Petros Christopoulos MD , Markus Ball PhD , Anna-Lena Volckmar PhD , Teodora Radonic MD, PhD , Lukas Bubendorf MD , Paul Hofman MD, PhD , Claus Peter Heußel MD , Hauke Winter MD , Felix Herth MD , Michael Thomas MD , Bauke Ylstra PhD , Solange Peters MD, PhD , Peter Schirmacher MD , Daniel Kazdal PhD , Jan Budczies PhD , Albrecht Stenzinger MD , Martina Kirchner PhD
Introduction
Accurate distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is essential for staging and treatment of multifocal NSCLC. Next-generation sequencing (NGS) enables assessment of clonal relatedness. The proposed International Association for the Study of Lung Cancer (IASLC) algorithm integrates histologic and molecular data, though its clinical utility is yet to be validated.
Methods
We focused on the molecular component of the algorithm and assessed 240 tumor pairs from 120 patients with formalin-fixed, paraffin-embedded tumor samples that underwent small-scale gene-panel NGS testing (31–54 genes) within routine clinical care. Most tumors were adenocarcinomas (n = 222), with 18 tumors other NSCLC subtypes. Inconclusive pairs by molecular classification were subjected to large-scale panel analyses (531 genes). In addition, we developed a bioinformatic method to complement and refine the IASLC method.
Results
In total, 22 tumor pairs (18%) remained inconclusive and 16 (13%) were classified ambiguous (probable SPLCs) using the molecular IASLC method. Resequencing classified nine of 22 inconclusive pairs as IPMs. Using a newly developed bioinformatic method for clonality classification incorporating likelihood ratios of mutational prevalence and small-scale sequencing, only three pairs remained inconclusive (2%). Tumors classified as SPLCs had a significantly longer overall survival than IPMs.
Conclusions
Small-scale panel sequencing of biopsy material allows unambiguous clonality determination in three of four cases. Large-scale sequencing resolves approximately half of inconclusive cases. Our bioinformatic method reduces inconclusive pairs to 2% even with small-scale NGS. It is made publicly available as a Shiny App. Clonality is reflected in survival data and therefore pivotal in daily clinical practice.
{"title":"Advancing Lung Cancer Staging: Integrating IASLC Recommendations and Bioinformatics to Delineate Tumor Origins","authors":"Michael Allgäuer PhD , Klaus Kluck MS , Petros Christopoulos MD , Markus Ball PhD , Anna-Lena Volckmar PhD , Teodora Radonic MD, PhD , Lukas Bubendorf MD , Paul Hofman MD, PhD , Claus Peter Heußel MD , Hauke Winter MD , Felix Herth MD , Michael Thomas MD , Bauke Ylstra PhD , Solange Peters MD, PhD , Peter Schirmacher MD , Daniel Kazdal PhD , Jan Budczies PhD , Albrecht Stenzinger MD , Martina Kirchner PhD","doi":"10.1016/j.jtho.2025.10.010","DOIUrl":"10.1016/j.jtho.2025.10.010","url":null,"abstract":"<div><h3>Introduction</h3><div>Accurate distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is essential for staging and treatment of multifocal NSCLC. Next-generation sequencing (NGS) enables assessment of clonal relatedness. The proposed International Association for the Study of Lung Cancer (IASLC) algorithm integrates histologic and molecular data, though its clinical utility is yet to be validated.</div></div><div><h3>Methods</h3><div>We focused on the molecular component of the algorithm and assessed 240 tumor pairs from 120 patients with formalin-fixed, paraffin-embedded tumor samples that underwent small-scale gene-panel NGS testing (31–54 genes) within routine clinical care. Most tumors were adenocarcinomas (n = 222), with 18 tumors other NSCLC subtypes. Inconclusive pairs by molecular classification were subjected to large-scale panel analyses (531 genes). In addition, we developed a bioinformatic method to complement and refine the IASLC method.</div></div><div><h3>Results</h3><div>In total, 22 tumor pairs (18%) remained inconclusive and 16 (13%) were classified ambiguous (probable SPLCs) using the molecular IASLC method. Resequencing classified nine of 22 inconclusive pairs as IPMs. Using a newly developed bioinformatic method for clonality classification incorporating likelihood ratios of mutational prevalence and small-scale sequencing, only three pairs remained inconclusive (2%). Tumors classified as SPLCs had a significantly longer overall survival than IPMs.</div></div><div><h3>Conclusions</h3><div>Small-scale panel sequencing of biopsy material allows unambiguous clonality determination in three of four cases. Large-scale sequencing resolves approximately half of inconclusive cases. Our bioinformatic method reduces inconclusive pairs to 2% even with small-scale NGS. It is made publicly available as a Shiny App. Clonality is reflected in survival data and therefore pivotal in daily clinical practice.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 267-282"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-09-20DOI: 10.1016/j.jtho.2025.09.010
Federica Pecci MD , Prashasti Agrawal MD , Jessica S. Ross MD , Biagio Ricciuti MD, PhD , Seshiru Nakazawa MD, PhD , Alessandro Di Federico MD , Mihaela Aldea MD, PhD , Edoardo Garbo MD , Valentina Santo MD , Eleonora Gariazzo MD , Maisam Makarem MD, PhD , Danielle Haradon MS , Igor Odintsov MD , Marina Baine MD, PhD , William Travis MD , Soo-Ryum Yang MD , Paula A. Ugalde Figueroa MD , Katherine D. Gray MD , Mizuki Nishino MD, PhD , Maria Mayoral Penalva MD , Jamie E. Chaft MD
Introduction
MET exon 14 (METex14) skipping mutations are found in 3% to 4% of NSCLC and can be detected through DNA- or RNA-based sequencing assays. Although RNA sequencing simply reports skipping of exon 14, DNA sequencing assays indicate the precise DNA nucleotide changes that result in METex14 skipping. Here, we reveal the importance of DNA-based sequencing assays for identifying patients with multiple, distinct, METex14-mutant lung cancers.
Methods
NSCLC cases with available targeted exome next-generation sequencing through OncoPanel or Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assays were evaluated. Patients with METex14 mutations in ≥2 NSCLC tumor samples at any stage were reviewed to assess tumor relatedness based on clinicopathologic and genomic criteria.
Results
Among 589 patients with METex14-mutant NSCLC and available in-house next-generation sequencing, 112 had ≥2 NSCLC tumor samples sequenced with METex14 mutations; among these, seven patients had two distinct METex14-mutant primary lung cancers, and one patient had three primary METex14-mutant lung cancers. Four cases were synchronous primary cancers, occurring within 12 months of the initial diagnosis, whereas the other four were metachronous, occurring after 12 months. Comprehensive DNA genomic analysis confirmed the distinct clonality of the tumors, with each case showing different METex14 alterations and other distinct genomic events, supporting the diagnosis of independent primary lung cancers.
Conclusions
DNA-based sequencing of the MET gene improves staging accuracy to guide appropriate management for patients with multiple primary METex14-mutant NSCLCs.
{"title":"Brief Report: Critical Role for DNA-Based Sequencing in Discriminating Distinct Primary Lung Cancers With Different MET Exon 14 Skipping Mutations","authors":"Federica Pecci MD , Prashasti Agrawal MD , Jessica S. Ross MD , Biagio Ricciuti MD, PhD , Seshiru Nakazawa MD, PhD , Alessandro Di Federico MD , Mihaela Aldea MD, PhD , Edoardo Garbo MD , Valentina Santo MD , Eleonora Gariazzo MD , Maisam Makarem MD, PhD , Danielle Haradon MS , Igor Odintsov MD , Marina Baine MD, PhD , William Travis MD , Soo-Ryum Yang MD , Paula A. Ugalde Figueroa MD , Katherine D. Gray MD , Mizuki Nishino MD, PhD , Maria Mayoral Penalva MD , Jamie E. Chaft MD","doi":"10.1016/j.jtho.2025.09.010","DOIUrl":"10.1016/j.jtho.2025.09.010","url":null,"abstract":"<div><h3>Introduction</h3><div><em>MET</em> exon 14 (<em>MET</em>ex14) skipping mutations are found in 3% to 4% of NSCLC and can be detected through DNA- or RNA-based sequencing assays. Although RNA sequencing simply reports skipping of exon 14, DNA sequencing assays indicate the precise DNA nucleotide changes that result in <em>MET</em>ex14 skipping. Here, we reveal the importance of DNA-based sequencing assays for identifying patients with multiple, distinct, <em>MET</em>ex14-mutant lung cancers.</div></div><div><h3>Methods</h3><div>NSCLC cases with available targeted exome next-generation sequencing through OncoPanel or Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assays were evaluated. Patients with <em>MET</em>ex14 mutations in ≥2 NSCLC tumor samples at any stage were reviewed to assess tumor relatedness based on clinicopathologic and genomic criteria.</div></div><div><h3>Results</h3><div>Among 589 patients with <em>MET</em>ex14-mutant NSCLC and available in-house next-generation sequencing, 112 had ≥2 NSCLC tumor samples sequenced with <em>MET</em>ex14 mutations; among these, seven patients had two distinct <em>MET</em>ex14-mutant primary lung cancers, and one patient had three primary <em>MET</em>ex14-mutant lung cancers. Four cases were synchronous primary cancers, occurring within 12 months of the initial diagnosis, whereas the other four were metachronous, occurring after 12 months. Comprehensive DNA genomic analysis confirmed the distinct clonality of the tumors, with each case showing different <em>MET</em>ex14 alterations and other distinct genomic events, supporting the diagnosis of independent primary lung cancers.</div></div><div><h3>Conclusions</h3><div>DNA-based sequencing of the <em>MET</em> gene improves staging accuracy to guide appropriate management for patients with multiple primary <em>MET</em>ex14-mutant NSCLCs.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 310-317"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-02-04DOI: 10.1016/j.jtho.2025.11.007
Jan P. Van Meerbeeck MD, PhD , Jelle E. Bousema MD, PhD , Wen Wen MD , Paul E.Y. Van Schil MD, PhD
Accurate staging is pivotal in lung cancer management, yet standardized key performance indicators (KPIs) for staging practices are lacking. We identified a number of critical areas in the staging process and outlined a starter set of SMART KPIs for patients with early stage NSCLC. We propose clear definitions (numerators/denominators, timing anchors) and risk-adjusted benchmarks. These KPIs should be used to monitor and improve clinical practice; they are not intended to dictate the structure of the TNM classification, which must remain an objective, globally applicable anatomic language. Implementing staging KPIs can enhance diagnostic accuracy and treatment outcomes in lung cancer care.
{"title":"Staging of Lung Cancer: A Call for Developing Uniform and Universal Key Performance Indicators and Benchmarks to Elevate Clinical Standards","authors":"Jan P. Van Meerbeeck MD, PhD , Jelle E. Bousema MD, PhD , Wen Wen MD , Paul E.Y. Van Schil MD, PhD","doi":"10.1016/j.jtho.2025.11.007","DOIUrl":"10.1016/j.jtho.2025.11.007","url":null,"abstract":"<div><div>Accurate staging is pivotal in lung cancer management, yet standardized key performance indicators (KPIs) for staging practices are lacking. We identified a number of critical areas in the staging process and outlined a starter set of SMART KPIs for patients with early stage NSCLC. We propose clear definitions (numerators/denominators, timing anchors) and risk-adjusted benchmarks. These KPIs should be used to monitor and improve clinical practice; they are not intended to dictate the structure of the TNM classification, which must remain an objective, globally applicable anatomic language. Implementing staging KPIs can enhance diagnostic accuracy and treatment outcomes in lung cancer care.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 253-257"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-21DOI: 10.1016/j.jtho.2025.10.007
Madeleine Di Frisco MD , Miguel F. Sanmamed MD , José María Ferrández MD , Anna Vilalta MD , Miguel Sogbe MD , Marta García-Goñi MD , Ángela Martin-Palmero MD , Samantha Aso-González MD , Ernest Nadal MD , Jaime Signes-Costa MD , Valentina Gambardella MD , Víctor Seguí Manzaneque MD , Paloma Martin MD , Amelia Insa MD , José Franco MD , Carmen Lores MD , Juan P. de Torres MD
Introduction
Chronic obstructive pulmonary disease (COPD) and emphysema are independent risk factors for lung cancer development and have been independently associated with longer overall survival (OS) in patients with NSCLC treated with immune checkpoint inhibitors (ICIs). However, their combined impact on prognosis remains unclear. This study evaluates emphysema as a prognostic factor in patients with COPD with advanced NSCLC (aNSCLC) undergoing immunotherapy.
Methods
This study included patients with aNSCLC with COPD (defined by spirometry) treated with single-agent ICI as first- or second-line treatment, from 2013 to 2024. Patients were classified based on visually detected emphysema on chest computed tomography.
Results
The study included 111 patients with COPD, of whom 77 had coexisting emphysema. Patients with COPD and emphysema had significantly longer OS compared with those without emphysema (17.3 versus 8.5 mo, p = 0.008), with a nonsignificant trend toward improved progression-free survival (3.3 versus 2.4 mo, p = 0.641). Emphysema remained an independent factor of better OS in multivariate analysis (hazard ratio: 0.49; 95% confidence interval: 0.30–0.81). Adverse event rates were similar regardless of emphysema status (p = 0.455).
Conclusions
This study suggests that visually detected emphysema on chest computed tomography could be a potential prognostic marker in patients with aNSCLC with COPD receiving ICIs. Further studies are guaranteed to confirm these findings.
{"title":"Brief Report: Emphysema as a Prognostic Factor in Patients With Advanced NSCLC With COPD Receiving Immune Checkpoint Inhibitors","authors":"Madeleine Di Frisco MD , Miguel F. Sanmamed MD , José María Ferrández MD , Anna Vilalta MD , Miguel Sogbe MD , Marta García-Goñi MD , Ángela Martin-Palmero MD , Samantha Aso-González MD , Ernest Nadal MD , Jaime Signes-Costa MD , Valentina Gambardella MD , Víctor Seguí Manzaneque MD , Paloma Martin MD , Amelia Insa MD , José Franco MD , Carmen Lores MD , Juan P. de Torres MD","doi":"10.1016/j.jtho.2025.10.007","DOIUrl":"10.1016/j.jtho.2025.10.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic obstructive pulmonary disease (COPD) and emphysema are independent risk factors for lung cancer development and have been independently associated with longer overall survival (OS) in patients with NSCLC treated with immune checkpoint inhibitors (ICIs). However, their combined impact on prognosis remains unclear. This study evaluates emphysema as a prognostic factor in patients with COPD with advanced NSCLC (aNSCLC) undergoing immunotherapy.</div></div><div><h3>Methods</h3><div>This study included patients with aNSCLC with COPD (defined by spirometry) treated with single-agent ICI as first- or second-line treatment, from 2013 to 2024. Patients were classified based on visually detected emphysema on chest computed tomography.</div></div><div><h3>Results</h3><div>The study included 111 patients with COPD, of whom 77 had coexisting emphysema. Patients with COPD and emphysema had significantly longer OS compared with those without emphysema (17.3 versus 8.5 mo, <em>p</em> = 0.008), with a nonsignificant trend toward improved progression-free survival (3.3 versus 2.4 mo, <em>p</em> = 0.641). Emphysema remained an independent factor of better OS in multivariate analysis (hazard ratio: 0.49; 95% confidence interval: 0.30–0.81). Adverse event rates were similar regardless of emphysema status (<em>p</em> = 0.455).</div></div><div><h3>Conclusions</h3><div>This study suggests that visually detected emphysema on chest computed tomography could be a potential prognostic marker in patients with aNSCLC with COPD receiving ICIs. Further studies are guaranteed to confirm these findings.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 328-333"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-09-30DOI: 10.1016/j.jtho.2025.09.1761
Mari Mino-Kenudson MD , Sabina Berezowska MD , Yuko Minami MD, PhD , Shuyan Chen PhD , Meredith A. Ray PhD , Vilasinee Rerkpichaisuth MD , Mikiko Hashisako MD, PhD , Tereza Losmanova MD , Takuo Hayashi MD, PhD , Hyo-Sup Shim MD, PhD , Luisella Righi MD, PhD , Andréanne Gagné MD, PhD , Tae-Jung Kim MD, PhD , Lukas Bubendorf MD , Fernando Lopez-Rios MD, PhD , Daiske Matsubara MD, PhD , Jan von der Thüsen MD, PhD , Sylvie Lantuejoul MD, PhD , Anja C. Roden MD, PhD , Andrew Nicholson DM, FRCPath. , Mauro G. Papotti MD
Introduction
Tumor grading informs therapy and patient management across many organs, yet no consensus exists for grading invasive squamous cell carcinoma of the lung (LUSC). This study aimed to develop a globally applicable grading system using international cohorts.
Methods
Histologic features, including tumor budding, smallest tumor nest size, nuclear size, and tumor spread through air spaces (STAS), were evaluated in two training sets comprising 262 and 427 LUSCs resected without neoadjuvant therapy from three institutions. Kaplan-Meier and Cox proportional hazards models were used to identify features associated with recurrence-free survival (RFS) and overall survival (OS). Features significant in both training sets were used to construct a grading system, which was then validated in a test set (n = 827, five institutions). Interobserver agreement was assessed among 10 pathologists on 25 cases.
Results
Tumor budding (two-tier: cutoff at 10 buds per 0.785 mm2) was the only histologic feature significantly associated with both RFS and OS in multivariable analyses across both training sets. The proposed two-tier grading system—low-grade (0–9 buds), high-grade (≥10 buds)—was validated in the test set, demonstrating median RFS of 4.8 versus 1.6 years for low- versus high-grade tumors in the entire cohort and 7.2 versus 3.4 years within stage I patients. Interobserver agreement was moderate (Fleiss’ kappa = 0.524).
Conclusions
The authors propose a simple, prognostically relevant grading system for resected invasive LUSC based on tumor budding. It is reproducible across international data sets and practical for routine pathology, offering a unified framework for clinical and research use.
{"title":"A Grading System for Resected Invasive Squamous Cell Carcinoma of the Lung: A Multi-Institutional Study by the IASLC Pathology Committee","authors":"Mari Mino-Kenudson MD , Sabina Berezowska MD , Yuko Minami MD, PhD , Shuyan Chen PhD , Meredith A. Ray PhD , Vilasinee Rerkpichaisuth MD , Mikiko Hashisako MD, PhD , Tereza Losmanova MD , Takuo Hayashi MD, PhD , Hyo-Sup Shim MD, PhD , Luisella Righi MD, PhD , Andréanne Gagné MD, PhD , Tae-Jung Kim MD, PhD , Lukas Bubendorf MD , Fernando Lopez-Rios MD, PhD , Daiske Matsubara MD, PhD , Jan von der Thüsen MD, PhD , Sylvie Lantuejoul MD, PhD , Anja C. Roden MD, PhD , Andrew Nicholson DM, FRCPath. , Mauro G. Papotti MD","doi":"10.1016/j.jtho.2025.09.1761","DOIUrl":"10.1016/j.jtho.2025.09.1761","url":null,"abstract":"<div><h3>Introduction</h3><div>Tumor grading informs therapy and patient management across many organs, yet no consensus exists for grading invasive squamous cell carcinoma of the lung (LUSC). This study aimed to develop a globally applicable grading system using international cohorts.</div></div><div><h3>Methods</h3><div>Histologic features, including tumor budding, smallest tumor nest size, nuclear size, and tumor spread through air spaces (STAS), were evaluated in two training sets comprising 262 and 427 LUSCs resected without neoadjuvant therapy from three institutions. Kaplan-Meier and Cox proportional hazards models were used to identify features associated with recurrence-free survival (RFS) and overall survival (OS). Features significant in both training sets were used to construct a grading system, which was then validated in a test set (n = 827, five institutions). Interobserver agreement was assessed among 10 pathologists on 25 cases.</div></div><div><h3>Results</h3><div>Tumor budding (two-tier: cutoff at 10 buds per 0.785 mm<sup>2</sup>) was the only histologic feature significantly associated with both RFS and OS in multivariable analyses across both training sets. The proposed two-tier grading system—low-grade (0–9 buds), high-grade (<u>≥</u>10 buds)—was validated in the test set, demonstrating median RFS of 4.8 versus 1.6 years for low- versus high-grade tumors in the entire cohort and 7.2 versus 3.4 years within stage I patients. Interobserver agreement was moderate (Fleiss’ kappa = 0.524).</div></div><div><h3>Conclusions</h3><div>The authors propose a simple, prognostically relevant grading system for resected invasive LUSC based on tumor budding. It is reproducible across international data sets and practical for routine pathology, offering a unified framework for clinical and research use.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 294-309"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-01DOI: 10.1016/j.jtho.2025.10.006
David P. Carbone , Fred R. Hirsch , Raymond Uyiosa Osarogiagbon , Katherine K. Nishimura , Ming Sound Tsao , William D. Travis , Dawei Yang , Soo-Ryum Yang , Yasushi Yatabe , Luiz Henrique Araujo , Frank Detterbeck , Kendra J. Lechtenberg , Eric Lim , Philip C. Mack , José-María Matilla , Luis M. Montuenga , Andrew G. Nicholson , Kenichi Suda , Ricardo M. Terra , Ramón Rami-Porta , Murry W. Wynes
{"title":"Corrigendum to “The International Association for the Study of Lung Cancer Staging Project: The Impact of Common Molecular Alterations on Overall Survival in NSCLC in Initial Analyses of the IASLC Ninth Edition Staging Database. [Journal of Thoracic Oncology Vol. 20 No. 10: 1423–1440]”","authors":"David P. Carbone , Fred R. Hirsch , Raymond Uyiosa Osarogiagbon , Katherine K. Nishimura , Ming Sound Tsao , William D. Travis , Dawei Yang , Soo-Ryum Yang , Yasushi Yatabe , Luiz Henrique Araujo , Frank Detterbeck , Kendra J. Lechtenberg , Eric Lim , Philip C. Mack , José-María Matilla , Luis M. Montuenga , Andrew G. Nicholson , Kenichi Suda , Ricardo M. Terra , Ramón Rami-Porta , Murry W. Wynes","doi":"10.1016/j.jtho.2025.10.006","DOIUrl":"10.1016/j.jtho.2025.10.006","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Page 342"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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