Lung Cancer最新文献

{"title":"Beyond environmental risk: Genetic insights into lung cancer susceptibility through whole exome analysis","authors":"C. Lintas ,&nbsp;R. Petti ,&nbsp;G. Colella ,&nbsp;I. Cassano ,&nbsp;A. Azzarà ,&nbsp;A. Cortellini ,&nbsp;F. Longo ,&nbsp;L. Frasca ,&nbsp;F. Gurrieri ,&nbsp;P. Crucitti","doi":"10.1016/j.lungcan.2025.108560","DOIUrl":"10.1016/j.lungcan.2025.108560","url":null,"abstract":"<div><h3>Background</h3><div>unlike familial non polyposis colorectal cancer (Lynch syndrome) and familial breast cancer, no genes have been confidently associated with familial lung cancer with the exception of the EGFR and the TP53 genes. Germinal Pathogenetic Variants (GPV) in these two genes account for 0.34–0.9% and 0.8 % lung adenocarcinoma, respectively.</div></div><div><h3>Objective</h3><div>the aim of this study was to identify rare genetic variants associated with higher risk of developing lung cancer.</div></div><div><h3>Methods</h3><div>we performed exome sequencing in the germinal DNA of 16 patients who had a positive familial history of lung cancer: 14 patients had lung cancer at enrollment whereas 2 patients developed cancer during the course of the study.. Two families had two affected relatives (mother and daughter and two sisters).</div></div><div><h3>Results</h3><div>we identified rare clinically significant variants and VUS (Variant of Unknown Significance) in five well known cancer genes (POLE, PDGFRA, RTEL1, HNF1A and MITF) in five patients. One patient carried three variants and was exposed to environmental risk factors as smoking and asbestos. Common suscetibility variants in known cancer genes were also identified.</div><div>We also identified additional potentially clinically relevant rare variants in other genes not previously associated to lung cancer. These genes include HGS, NME4, HAPLN1, ATMIN, CEACAM, MPEG1, USP4, TP53BP2, ERAP1, TNFAIP8L3, CASP1, MCC, SERPINA3, VIRMA, FOXK2, DNAH8, RASA2, GLI3.</div></div><div><h3>Conclusions</h3><div>several lines of evidence suggest that these genes are of potential clinical impact in lung cancer even though they have not been correlated with lung cancer in the OMIM database or other genetic databases. Therefore, these genes deserve further investigations: segregation analysis, enlarged cohorts and in vitro/in vivo studies could help to clarify their role in lung cancer.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108560"},"PeriodicalIF":4.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891648","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":"Antibody-drug conjugate components in association with the incidence of ADC-related interstitial lung disease: A systematic review and meta‐analysis","authors":"Tianyu Shao ,&nbsp;Jiayao Yang ,&nbsp;Jialu Chen ,&nbsp;Yao Zhang ,&nbsp;Liumei Shou","doi":"10.1016/j.lungcan.2025.108559","DOIUrl":"10.1016/j.lungcan.2025.108559","url":null,"abstract":"<div><h3>Background</h3><div>Antibody-drug conjugates (ADCs) have emerged as an innovative approach in cancer therapy. Although the incidence of ADC-related interstitial lung disease (ILD) is low, it remains a clinically significant and potentially fatal adverse event. This study focuses on evaluating the incidence of ADC-related ILD and examining how specific ADC components contribute to the risk of ILD.</div></div><div><h3>Methods</h3><div>Five databases were conducted to identify clinical studies on ADC-related ILD published up to September 2024. The incidence of treatment-related adverse events was calculated by a random effects (RE) model.</div></div><div><h3>Results</h3><div>A total of 120 clinical studies involving 20,119 patients were included. The overall incidence of ADC-related ILD was 4.40 % (1215/20119) for all-grade and 2.35 % (603/20119) for grade ≥ 3 ILD. Among these, 2287 patients had hematologic tumors and 17,832 patients had solid tumors. Particularly, gastrointestinal cancers (12.81 %, 107/835), followed by lung cancer (9.70 %, 290/2991) were observed with a high incidence of ILD. A detailed subgroup analysis was performed, stratified by payload, drug-to-antibody ratio (DAR) value, linker type, and target. ADCs with cleavable linkers exhibited a higher incidence, notably, ADCs with glutathione (GSH) linkers were the highest. Furthermore, ADCs with high DAR had a higher incidence of ILD. Interestingly, payload type alone did not significantly affect the incidence, while a marked increase in ILD risk was observed when specific payloads (such as topoisomerase I inhibitors) were combined with high DAR values or cleavable linkers.</div></div><div><h3>Conclusion</h3><div>This study reveals variability of ADC-related ILD incidence, largely driven by the specific components of the ADCs, offer valuable insights into potential ILD occurrence patterns and guide for optimizing ADC design.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108559"},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888185","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":"It is premature to close the door on hippocampal avoidance in prophylactic cranial irradiation?","authors":"Eric J. Lehrer,&nbsp;William G. Breen,&nbsp;Paul D. Brown","doi":"10.1016/j.lungcan.2025.108558","DOIUrl":"10.1016/j.lungcan.2025.108558","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108558"},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935977","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":"Epidemiology and clinical course of large cell neuroendocrine carcinoma of the lung: The Japanese lung cancer registry study","authors":"Yukina Shirai ,&nbsp;Takehito Shukuya ,&nbsp;Tetsuhiko Asao ,&nbsp;Kazuhisa Takahashi ,&nbsp;Yasushi Shintani ,&nbsp;Ikuo Sekine ,&nbsp;Koichi Takayama ,&nbsp;Akira Inoue ,&nbsp;Isamu Okamoto ,&nbsp;Tomoya Kawaguchi ,&nbsp;Nobuyuki Yamamoto ,&nbsp;Etsuo Miyaoka ,&nbsp;Ichiro Yoshino ,&nbsp;Hiroshi Date","doi":"10.1016/j.lungcan.2025.108557","DOIUrl":"10.1016/j.lungcan.2025.108557","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to investigate the characteristics and clinical courses of patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) and compare the differences across lung cancer types.</div></div><div><h3>Methods</h3><div>This prospective study included 11,310 patients with LCNEC, small cell lung cancer (SCLC), squamous cell carcinoma, and adenocarcinoma from the Japanese Joint Committee of Lung Cancer Registry (JJCLCR) database. The registry was opened in January 2012, and the follow-up was completed in April 2016.</div></div><div><h3>Results</h3><div>In total, 80 patients (0.7 %) were diagnosed with LCNEC. LCNEC shared similar patient characteristics with SCLC, characterized by a median age of 68 years and a high prevalence of men (93.8 %) and smokers (97.5 %). In stage IV patients, the best overall response and disease control rates for first-line cisplatin-based chemotherapy were 34.8 % and 43.5 % for LCNEC but 60.6 % and 69.7 % for SCLC. Similarly, the overall response and disease control rates for first-line carboplatin-based chemotherapy in stage IV patients were 29.4 % and 41.2 % for LCNEC, but 56.1 % and 68.4 % for SCLC. The 3-year survival rates for LCNEC, SCLC, squamous cell carcinoma, and adenocarcinoma were 14.2 %, 15.9 %, 17.8 %, and 27.1 %, respectively. Kaplan–Meier curves of overall survival showed similarity between LCNEC and SCLC, with no statistical significance in the Cox hazard analysis (hazard ratio 0.818, 95 % confidence interval 0.611–1.096, <em>p</em> = 0.178).</div></div><div><h3>Conclusions</h3><div>Although patient characteristics and survival curves were similar in LCNEC and SCLC, our data demonstrate that LCNEC had inferior overall response and disease control rates in response to first-line chemotherapy compared to SCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108557"},"PeriodicalIF":4.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899242","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":"Midazolam with fentanyl for endobronchial ultrasound-guided transbronchial needle aspiration: a randomized, double-blind, phase III study","authors":"Jun Yamada,&nbsp;Daisuke Hazama,&nbsp;Takafumi Fukui,&nbsp;Atsuhiko Yatani,&nbsp;Mariko Okamoto,&nbsp;Shodai Fujimoto,&nbsp;Ryosuke Yoshimura,&nbsp;Mizuki Takayasu,&nbsp;Naoya Takata,&nbsp;Hiroki Sato,&nbsp;Chihiro Mimura,&nbsp;Koichi Furukawa,&nbsp;Naoko Katsurada,&nbsp;Masatsugu Yamamoto,&nbsp;Motoko Tachihara","doi":"10.1016/j.lungcan.2025.108556","DOIUrl":"10.1016/j.lungcan.2025.108556","url":null,"abstract":"<div><h3>Background</h3><div>Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a common technique for sampling mediastinal and hilar lymph nodes. However, the optimal sedation for EBUS-TBNA remains unclear. We aimed to evaluate the efficacy of adding fentanyl to midazolam.</div></div><div><h3>Materials and methods</h3><div>We conducted a single-center, randomized, double-blind, phase III study. Patients who received midazolam with fentanyl (fentanyl group) were compared with those who received midazolam with placebo (placebo group) during EBUS-TBNA. The primary outcome was the proportion of patients meeting all three criteria: 1) adequate sedation (Modified Observer’s Assessment of Alertness and Sedation scale ≤4 or bispectral index values ≤80), 2) minimal additional sedation requirement (no more than two additional sedative administrations within the first 30 min), and 3) successful procedure completion (at least three EBUS-TBNA punctures).</div></div><div><h3>Results</h3><div>A total of 84 patients (fentanyl group, 41; placebo group, 43) were enrolled. There were no significant differences in patient characteristics between the two groups. The primary outcome was significantly better in the fentanyl group than in the placebo group (46.3 % vs. 23.3 %, p = 0.038). A significantly lower rate of sedative-induced delirium, a lower number of additional sedative administrations, and a higher rate of ≥3 punctures were observed in the fentanyl group. There were no significant differences in complications. The operator visual analog scale questionnaire on cough, sputum, cooperation, and sedative effects was significantly better in the fentanyl group.</div></div><div><h3>Conclusion</h3><div>Adding fentanyl to midazolam provided better sedation. Midazolam combined with fentanyl should be considered during EBUS-TBNA.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108556"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924799","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":"Comprehensive molecular profiling of advanced NSCLC using NGS: Prevalence of druggable mutations and clinical trial opportunities in the ATLAS study","authors":"Roberto Serna-Blasco ,&nbsp;Pilar Mediavilla-Medel ,&nbsp;Karla Medina ,&nbsp;María Ángeles Sala ,&nbsp;David Aguiar ,&nbsp;Asunción Díaz-Serrano ,&nbsp;Mónica Antoñanzas ,&nbsp;Julio Ocaña ,&nbsp;Xabier Mielgo ,&nbsp;Inmaculada Fernández ,&nbsp;Rafael López-Castro ,&nbsp;Manuel Cobo ,&nbsp;Mireia Martínez ,&nbsp;José Carlos Villa ,&nbsp;Petra Rosado ,&nbsp;Ana López ,&nbsp;María Guirado ,&nbsp;Santiago Viteri ,&nbsp;Delvys Rodríguez ,&nbsp;Florencia García ,&nbsp;Mariano Provencio","doi":"10.1016/j.lungcan.2025.108550","DOIUrl":"10.1016/j.lungcan.2025.108550","url":null,"abstract":"<div><h3>Background</h3><div>In Spain, next-generation sequencing (NGS) is currently available in a limited number of specialized centers and remains inaccessible to a significant proportion of patients. The ATLAS study aims to explore the tumor molecular profile beyond known <em>EGFR</em> mutations and <em>ALK</em> translocations using NGS on tumor biopsy samples.</div></div><div><h3>Methods</h3><div>Patients with <em>EGFR</em>-sensitizing mutations or <em>ALK</em> translocations were excluded. A total of 455 patients with advanced non-small cell lung cancer (NSCLC) were enrolled from 22 Spanish hospitals. DNA and RNA were extracted from formalin-fixed paraffin-embedded samples, and libraries were prepared using the Oncomine Focus Assay. The Trialing app was used to identify active clinical trials in Spain.</div></div><div><h3>Results</h3><div>Mutations were detected in 65.7 % of the cases. Local pathology assessments detected druggable mutations in only 7.9 % of cases, while centralized NGS testing increased this detection rate to 25.9 %. The most prevalent druggable alteration was KRAS G12C (53.6 %), followed by <em>MET</em> amplification (8.1 %) and <em>MET</em> exon 14 skipping (7.3 %). Additionally, 34.5 % of patients had molecular alterations matching clinical trials, offering potential treatment opportunities. Women had a significantly higher probability of harbouring druggable mutations (36 % vs. 20.3 %, p &lt; 0.001), including the KRAS G12C which was significantly more frequent in females (22.6 % vs. 10 %). <em>KRAS</em> mutations were more common in adenocarcinomas and increased with tumor differentiation grade (p &lt; 0.001 and p = 0.049, respectively). Likewise, <em>ALK</em> translocations, <em>EGFR</em> mutations, BRAF V600E, <em>MET</em> exon 14 skipping, and <em>RET</em>/<em>ROS1</em> fusions were mainly found in adenocarcinomas whereas copy number variations were more frequent in squamous carcinomas (28.6 % vs. 15.1 %; p = 0.003) and in men (22 % vs. 11.6 %; p = 0.008).</div></div><div><h3>Conclusion</h3><div>The ATLAS study demonstrates the utility of comprehensive NGS testing, which detects clinically relevant mutations in more than one-third of patients and may extend therapy options.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108550"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878642","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":"Impact of immune-related adverse event severity on overall survival in patients with advanced NSCLC receiving immune checkpoint inhibitors therapy, with a focus on combination regimens","authors":"Mayu Sugai,&nbsp;Yoshiaki Amino,&nbsp;Shunsuke Fujishima,&nbsp;Kyujiro Nibuya,&nbsp;Hirokazu Iso,&nbsp;Masahiro Ito,&nbsp;Ryosuke Tsugitomi,&nbsp;Ryo Ariyasu,&nbsp;Ken Uchibori,&nbsp;Noriko Yanagitani,&nbsp;Makoto Nishio","doi":"10.1016/j.lungcan.2025.108555","DOIUrl":"10.1016/j.lungcan.2025.108555","url":null,"abstract":"<div><h3>Background</h3><div>Immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) may serve as prognostic markers in non-small cell lung cancer (NSCLC). While prior studies suggest differences in overall survival (OS) based on irAE, their prognostic impact across various ICI regimens remains underexplored.</div></div><div><h3>Methods</h3><div>This retrospective study analyzed data from patients with advanced or recurrent NSCLC treated with ICIs between January 2018 and December 2022. Patients were categorized into three groups: severe irAEs (Grade 3–5), mild irAEs (Grade 1–2), and no-irAEs. OS was assessed across three regimens: anti-programmed cell death protein 1 (anti-PD-1) monotherapy, anti-PD-1/anti-programmed death-ligand 1 (anti-PD-L1) with chemotherapy (CT), and anti-PD-1 with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) ± CT.</div></div><div><h3>Results</h3><div>Among the 256 patients included, 55 received anti-PD-1 monotherapy, 116 received anti-PD-1/L1 with CT, and 85 received anti-PD-1 with anti-CTLA-4 ± CT. For anti-PD-1 monotherapy, median OS (95 % confidence interval) was 38.3 (17.0–42.5) months in the mild irAE group, 16.1 (5.2–28.6) months in the severe irAE group, and 9.6 (12.3–37.1) months in the no-irAE group. In the anti-PD-1/L1 with CT group, median OS were 33.6 (14.2–40.3), 16.0 (1.84–not reached [NR]), and 17.7 (3.8–23.4) months, respectively. For anti-PD-1 with anti-CTLA-4 ± CT, median OS were 28.0 (21.8–NR), 10.9 (7.0–19.6), and 16.3 (8.7–23.4) months, respectively.</div></div><div><h3>Conclusions</h3><div>The relationship between irAE severity and OS was consistent across all ICI regimens, with patients experiencing mild irAEs demonstrating better OS across all ICI regimens.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108555"},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888186","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":"Multimodality treatment in synchronous oligometastatic NSCLC: Analysis of the ETOP CHESS trial","authors":"Matthias Guckenberger ,&nbsp;Isabelle Opitz ,&nbsp;Tereza Dellaporta ,&nbsp;Alessandra Curioni-Fontecedro ,&nbsp;Thomas Frauenfelder ,&nbsp;Karin Ribi ,&nbsp;Ferdinando Cerciello ,&nbsp;Ivana Sullivan ,&nbsp;Lizza Hendriks ,&nbsp;Miriam Dorta ,&nbsp;Ana Callejo ,&nbsp;Joachim Aerts ,&nbsp;Alfredo Addeo ,&nbsp;Anne-Marie C. Dingemans ,&nbsp;Giulia Pasello ,&nbsp;Mariano Provencio ,&nbsp;Filippo de Marinis ,&nbsp;Nuria Mederos-Alfonso ,&nbsp;Heidi Roschitzki-Voser ,&nbsp;Barbara Ruepp ,&nbsp;Rolf Stahel","doi":"10.1016/j.lungcan.2025.108553","DOIUrl":"10.1016/j.lungcan.2025.108553","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the addition of immunotherapy and metastasis-directed stereotactic body radiotherapy (SBRT) to induction chemotherapy followed by definitive local therapy of the locoregional primary tumour in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC).</div></div><div><h3>Methods</h3><div>CHESS is a prospective, international, multicentre, single-arm, phase II trial evaluating the efficacy and safety of combined chemotherapy (carboplatin plus paclitaxel), immune checkpoint inhibition (durvalumab) and metastasis-directed SBRT, followed by definitive radiotherapy or surgery of the primary tumour (if no disease progression at the 3-month restaging) and maintenance durvalumab for maximum one year in patients with synchronous oligometastatic NSCLC. The primary endpoint was one-year progression-free survival, aiming to an improvement from 25% to 50%.</div></div><div><h3>Results</h3><div>A total of 49 patients were enrolled from 11/2019 to 07/2022. Up to 05/2023, the median follow-up was 22 months. Of 47 patients starting treatment, 10 progressed and 2 died before restaging, while 35 proceeded to definitive therapy of the locoregional primary (11<!--> <!-->surgery, 24 radiotherapy). Among the first 42 evaluable patients, 14 (33%; ≥17 required) reached one year without progression, and the null hypothesis could not be rejected. The one-year overall survival rate for all patients was 74.9% (95% CI: 60.0%–84.9%). Treatment-related grade ≥ 3 adverse events were reported in 34% of patients, with no grade 5 event.</div></div><div><h3>Conclusion</h3><div>The CHESS trial did not meet its primary endpoint. However, the favourable safety profile and promising overall survival provided the basis for further intensification of induction systemic therapy (addition of tremelimumab in a subsequent study cohort; CHESS–Cohort 2).</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108553"},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888239","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":"Whole slide image-level classification of malignant effusion cytology using clustering-constrained attention multiple instance learning","authors":"Dongwoo Kim ,&nbsp;Jongwon Lee ,&nbsp;Minsoo Jung ,&nbsp;Kwangil Yim ,&nbsp;Gisu Hwang ,&nbsp;Hongjun Yoon ,&nbsp;Daeky Jeong ,&nbsp;Won June Cho ,&nbsp;Mohammad Rizwan Alam ,&nbsp;Gyungyub Gong ,&nbsp;Nam Hoon Cho ,&nbsp;Chong Woo Yoo ,&nbsp;Yosep Chong ,&nbsp;Kyung Jin Seo","doi":"10.1016/j.lungcan.2025.108552","DOIUrl":"10.1016/j.lungcan.2025.108552","url":null,"abstract":"<div><h3>Background</h3><div>Cytological diagnosis of pleural effusion plays an important role in the early detection and diagnosis of lung cancers. Recently, attempts have been made to overcome low diagnostic accuracy and interobserver variability using artificial intelligence-based image analysis. However, such analysis is primarily performed at the image-patch level and not at the whole-slide image (WSI) level. This study aims to develop a WSI-level classification of malignant effusions in metastatic lung cancer based on pleural fluid cytology using a quality-controlled, nationwide dataset.</div></div><div><h3>Methods</h3><div>The dataset was collected by a consortium research group that included three major university hospitals and the Quality Assurance Program Committee of the Korean Society of Cytopathology. It contains 576 normal and 309 cancer WSIs from pleural fluids. A clustering-constrained attention multiple-instance learning (CLAM) model was used for WSI-level classification.</div></div><div><h3>Results</h3><div>The CLAM model achieved a high accuracy of 97%, with an area under the curve of 0.97, representing a 13% improvement over the image patch classification model-based WSI classification. It also significantly reduced the analysis time and computing resources compared to those required during image patch-level classification and heat map generation on the WSIs.</div></div><div><h3>Conclusion</h3><div>The CLAM model successfully demonstrated high performance in differentiating malignant effusion at the WSI level using a large, quality-controlled, nationwide dataset. Further external validation is required to ensure generalizability.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108552"},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888184","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":"Real-world frontline treatments in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor exon 20 insertions and adjusted comparisons versus amivantamab plus chemotherapy from the PAPILLON study","authors":"Christos Chouaid ,&nbsp;Lise Bosquet ,&nbsp;Craig Knott ,&nbsp;Ziming Li ,&nbsp;Marcy Schaeffer ,&nbsp;Xiwu Lin ,&nbsp;Claudio A. Schioppa ,&nbsp;Nolen Joy Perualila ,&nbsp;Joris Diels ,&nbsp;Eduardo Quintero Caparros ,&nbsp;Francesca Galea ,&nbsp;Annika Hultén ,&nbsp;Alastair Greystoke","doi":"10.1016/j.lungcan.2025.108548","DOIUrl":"10.1016/j.lungcan.2025.108548","url":null,"abstract":"<div><h3>Introduction</h3><div>In PAPILLON, frontline amivantamab + carboplatin + pemetrexed (ACP) demonstrated superior efficacy over carboplatin + pemetrexed in patients with advanced or metastatic non-small-cell lung cancer (aNSCLC) harboring mutations in epidermal growth factor receptor (<em>EGFR</em>) exon 20 insertions (<em>exon20ins</em>). Real-world (RW) treatment patterns and comparative effectiveness of ACP versus RW treatments are unknown.</div></div><div><h3>Materials and methods</h3><div>The present study (NECTAR) retrospectively analyzed frontline treatments prescribed 2012–2023 for patients with aNSCLC and confirmed <em>EGFR exon20ins</em> from English (ENG-NCRD), French (FR-ESME), and US (US-COTA and US-ConcertAI) datasets. Overall survival (OS), time to next treatment (TTNT), and progression-free survival (PFS) were assessed in RW pooled and individual treatment classes and in indirect treatment comparisons (ITC) between ACP from PAPILLON and RW treatments using Cox proportional hazards model adjusted for prognostic factors.</div></div><div><h3>Results</h3><div>NECTAR assessed 208 RW patients: ENG-NCRD, n = 23; FR-ESME, n = 91; US-COTA, n = 39, and US-ConcertAI, n = 55. Common frontline treatment classes were platinum-based chemotherapy (33.7 %), platinum + immunotherapy (23.1 %), EGFR tyrosine kinase inhibitors (TKIs) alone (15.4 %), platinum + VEGF inhibitors (VEGFi) (11.1 %), and immunotherapy alone (7.7 %). Compared with platinum-based chemotherapy, none of the evaluated treatment classes demonstrated improved OS, TTNT, and PFS. Exceptions were platinum + VEGFi in TTNT and PFS and platinum + immunotherapy in TTNT.</div><div>In ITCs, ACP significantly improved OS over pooled RW treatments (HR = 0.48 [95 % CI, 0.32–0.71]; <em>P</em> &lt; 0.001), platinum-based chemotherapy (HR = 0.48 [0.30–0.77]; <em>P</em> = 0.003), platinum + immunotherapy (HR = 0.41 [0.23–0.73]; <em>P</em> = 0.003), and EGFR TKI alone (HR = 0.48 [0.23–1.02]; <em>P</em> = 0.055). TTNT and PFS results were similar to OS.</div></div><div><h3>Conclusions</h3><div>In patients with <em>EGFR exon20ins</em> aNSCLC, frontline ACP was superior to common RW treatments, highlighting the need for practice change.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"203 ","pages":"Article 108548"},"PeriodicalIF":4.5,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855776","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}