Journal of Thoracic Oncology最新文献

{"title":"PP01.12 Extracellular Matrix Remodeling and Immune Evasion Drive Lung Adenocarcinoma Brain Metastasis","authors":"Manlu Liu , Albert Wang , Jared Brown , Darya Buehler , Saniya Khullar , Christina Kendziorski , Andrew M. Baschnagel , Gopal Iyer","doi":"10.1016/j.jtho.2025.03.019","DOIUrl":"10.1016/j.jtho.2025.03.019","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 4","pages":"Page S7"},"PeriodicalIF":21.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759393","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}

{"title":"PP01.05 Targeting MUC16-Mediated KRASi Resistance in NSCLC","authors":"Ashu Shah , Shamema Salam , Sanjib Chaudhary , Iniyan A. Muthamil , Imayavaramban Lakshmanan , Surinder K. Batra , Apar K. Ganti","doi":"10.1016/j.jtho.2025.03.013","DOIUrl":"10.1016/j.jtho.2025.03.013","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 4","pages":"Pages S4-S5"},"PeriodicalIF":21.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759519","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}

{"title":"PP01.02 Potentiating ERK Hyperactivation by Targeting the Proteostasis Network","authors":"Dylan A. Farnsworth , Lok In Josephine Ma , Elise Macdougall , Daniel Lu , Farhana Naznin , Rocky Shi , Katherine Sew , Asha Subramanian , Romel Somwar , Arun M. Unni , William W. Lockwood","doi":"10.1016/j.jtho.2025.03.010","DOIUrl":"10.1016/j.jtho.2025.03.010","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 4","pages":"Page S3"},"PeriodicalIF":21.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759343","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}

{"title":"PP01.07 Alterations in Tumor Suppressor Genes are Associated With Aggressive Disease Phenotypes in EGFR-Mutant NSCLC","authors":"Paul Stockhammer , Kieran Sweeney , Stephen V. Liu , Balazs Halmos , Dipesh Uprety , Andrew Elliott , Ari VanderWalde , Katerina Politi , Sarah B. Goldberg , Michael Grant","doi":"10.1016/j.jtho.2025.03.015","DOIUrl":"10.1016/j.jtho.2025.03.015","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 4","pages":"Page S5"},"PeriodicalIF":21.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759520","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}

{"title":"PP01.20 Predictive Utility of Circulating Tumor DNA in First- Line Osimertinib Therapy for EGFR-Mutant Metastatic Lung Adenocarcinoma","authors":"Rodrigo Paredes , Toshiro Goto , Shira Litchman , Jorge Gomez , Deborah Doroshow , Fred R. Hirsch , Rajwanth Veluswamy , Thomas Marron , Cardinale Smith , Nicholas Rohs , Christian Rolfo","doi":"10.1016/j.jtho.2025.03.025","DOIUrl":"10.1016/j.jtho.2025.03.025","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 4","pages":"Pages S9-S10"},"PeriodicalIF":21.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759187","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}

{"title":"Identification of Defined Molecular Subgroups on the Basis of Immunohistochemical Analyses and Potential Therapeutic Vulnerabilities of Pulmonary Carcinoids","authors":"Daphne J.G. Leunissen MSc ,&nbsp;Laura Moonen PhD ,&nbsp;Jan H. von der Thüsen MD, PhD ,&nbsp;Michael A. den Bakker MD, PhD ,&nbsp;Lisa M. Hillen MD, PhD ,&nbsp;Tijmen J.J. van Weert MSc ,&nbsp;Axel zur Hausen MD, PhD ,&nbsp;Thierry P.P. van den Bosch PhD ,&nbsp;Lisa M.V. Lap ,&nbsp;Ronald A. Damhuis MD, PhD ,&nbsp;Niki L. Reynaert PhD ,&nbsp;Esther C. van den Broek PhD ,&nbsp;PALGA group ,&nbsp;Lynnette Fernandez-Cuesta PhD ,&nbsp;Matthieu Foll PhD ,&nbsp;Nicolas Alcala PhD ,&nbsp;Alexandra Sexton-Oates PhD ,&nbsp;Anne-Marie C. Dingemans MD, PhD ,&nbsp;Ernst-Jan M. Speel PhD ,&nbsp;Jules L. Derks MD, PhD","doi":"10.1016/j.jtho.2024.11.018","DOIUrl":"10.1016/j.jtho.2024.11.018","url":null,"abstract":"<div><h3>Introduction</h3><div>Multi-omic studies have identified three molecular separated pulmonary carcinoid (PC) subgroups (A1, A2, B) with distinctive mRNA expression profiles (e.g., orthopedia homeobox protein [<em>OTP</em>], achaete-scute homolog [<em>ASCL1</em>], and hepatocyte nuclear factor 1 homeobox A [<em>HNF1A</em>]). We aimed to establish an immunohistochemical (IHC) biomarker panel that enables subgroup identification, and assessment of its potential clinical relevance.</div></div><div><h3>Methods</h3><div>All patients with resected pulmonary carcinoids (2003–2012) were identified from the Dutch Cancer/Pathology Registry, and tumors were revised. The IHC expression of OTP, ASCL1, and HNF1A was scored in a blinded fashion in a mRNA-profiled (n = 5 per subgroup) and national carcinoid cohort (N = 478). The expression of potential therapeutic targets (somatostatin receptor type 2a [SSTR2A] and delta-like canonical Notch ligand 3 [DLL3]) was assessed. Immunohistochemistry was assessed using H-scoring.</div></div><div><h3>Results</h3><div>OTP, ASCL1, and HNF1A reported similar IHC and mRNA expression patterns in the matched primary samples. In the national cohort, IHC separated PCs into subgroups A1 (n = 224 [53%], OTP^high-ASCL1^high-HNF1A^low), A2 (n = 161 [38%], OTP^high-ASCL1^low-HNF1A^high), and B (n = 37 [9%], OTP^low-ASCL1^low-HNF1A^high). In 12% of PCs, no distinct classification could be provided. Patients with A1 were enriched for older age (83% &gt; 50 y), female individuals (83%), and peripheral location (55%) with low SSTR2A (median = 10) and high DLL3 (median = 52) expression. A2 included younger patients (34% &lt; 40 y) and endobronchial/central (87%) tumors with high SSTR2A (median = 160), but low DLL3 (median 0) expression. Group B included more male individuals (59%) and recurrence was more frequent (19%) than in groups A1 (8%) and A2 (6%). Neuroendocrine cell hyperplasia was enriched in A1 (25%) compared with A2 (3%) and B (0%).</div></div><div><h3>Conclusions</h3><div>An OTP, ASCL1, and HNF1A IHC panel enables the identification of molecular-defined pulmonary carcinoid subgroups with distinct clinical phenotypes and diverging therapeutic vulnerabilities that require further prospective evaluation.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 4","pages":"Pages 451-464"},"PeriodicalIF":21.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptor Tyrosine Kinase Fusion-Mediated Resistance to EGFR TKI in EGFR-Mutant NSCLC: A Multi-Center Analysis and Literature Review","authors":"Yang Xia MD ,&nbsp;Kaiwen Wang PharmD ,&nbsp;Jing Zhao MD ,&nbsp;Zhaohui Arter MD ,&nbsp;Yongchang Zhang MD ,&nbsp;Jiaqi Zhou MD ,&nbsp;Yuefei Lu MD ,&nbsp;Liang Zeng MD ,&nbsp;Robyn Du MS ,&nbsp;Jennifer A. Owens MS ,&nbsp;Yasir Y. Elamin MD ,&nbsp;Carl M. Gay MD, PhD ,&nbsp;Ferdinandos Skoulidis MD, PhD ,&nbsp;Anne S. Tsao MD ,&nbsp;Charles Lu MD ,&nbsp;Tina Cascone MD, PhD ,&nbsp;Don L. Gibbons MD, PhD ,&nbsp;Jianjun Zhang MD, PhD ,&nbsp;Olivia Chen MD ,&nbsp;Kevin K.S. Mok MD ,&nbsp;Xiuning Le MD, PhD","doi":"10.1016/j.jtho.2024.11.027","DOIUrl":"10.1016/j.jtho.2024.11.027","url":null,"abstract":"<div><h3>Introduction</h3><div>Drug resistance remains a major clinical challenge in <em>EGFR</em>-mutant NSCLC tumors owing to pathway reactivation, pathway bypass, and pathway indifference resistance mechanisms to evade tyrosine kinase inhibitor (TKI) suppression. Fusion of receptor tyrosine kinases (RTKs), such as <em>RET</em>, <em>ALK</em>, and <em>FGFR3</em>, has been reported to mediate <em>EGFR</em> TKI resistance. Given the rarity of these fusions and the heterogeneous nature of the condition, no prospective clinical trials evaluated the incidence, safety, and therapeutic benefit of dual <em>EGFR-RTK</em> inhibition.</div></div><div><h3>Methods</h3><div>We queried clinical databases from multiple institutions to identify patients who had <em>RTK</em> fusions detected on next-generation sequencing testing results from tissue or blood at five institutions: the Second Affiliated Hospital Zhejiang University School of Medicine, Hunan Cancer Hospital, Prince of Wales Hospital Chinese University of Hong Kong, Chao Family Cancer Center, and the University of Texas MD Anderson Cancer Center from March 1, 2016, to September 30, 2023. The data analyzed included objective response rate (ORR) to treatment post RTK fusion detection, duration of treatment, and safety. A comprehensive literature search was conducted to identify patients with <em>RTK</em> fusion as the primary resistance mechanism in <em>EGFR-</em>mutated NSCLC patients.</div></div><div><h3>Results</h3><div>Twenty-seven patients were identified to be eligible in the analysis. <em>ALK</em> fusions were most reported (42.9%), followed by <em>RET</em> fusions (35.7%). Fifteen patients received dual TKI after fusion detection and nine received fusion targeting single TKIs. The median time on treatment was 169 days or 5.8 months (35–1050 d). ORR by the Response Evaluation Criteria in Solid Tumors in the evaluable 25 patients was 24% and the disease control rate was 80%. In 14 evaluable patients who received dual TKI therapy, ORR by the Response Evaluation Criteria in Solid Tumors was 21.4%, and the disease control rate was 78.6%. No new toxicities were observed with dual <em>EGFR-RTK</em> inhibition. In the literature review, after pooling 291 patients from 59 studies, <em>RET</em> fusions were the most common (50.0%), followed by <em>BRAF</em> (13.3%), <em>ALK</em> (13.3%), <em>FGFR</em> (10%), <em>NTRK</em> (5.3%), <em>EGFR</em> (1.7%), <em>ROS1</em> (1.3%), <em>MET</em> (1%), and <em>ERBB</em> (0.7%).</div></div><div><h3>Conclusion</h3><div>The emergence of <em>RTK</em> fusions is one of the mechanisms of bypass resistance of <em>EGFR</em> TKI. Dual inhibition of <em>EGFR-RTK</em> was safe and efficacious in patients with targetable <em>RTK</em> fusion after progression to <em>EGFR</em> TKIs.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 4","pages":"Pages 465-474"},"PeriodicalIF":21.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meeting Announcements","authors":"","doi":"10.1016/S1556-0864(25)00113-3","DOIUrl":"10.1016/S1556-0864(25)00113-3","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 4","pages":"Page A4"},"PeriodicalIF":21.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited Predictive Value of Incidental Pulmonary Nodules for NSCLC Cancer Mortality","authors":"Jia Yang PhD,&nbsp;Zuoyun Wang PhD","doi":"10.1016/j.jtho.2024.12.008","DOIUrl":"10.1016/j.jtho.2024.12.008","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 4","pages":"Pages e56-e57"},"PeriodicalIF":21.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785173","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}

{"title":"PP01.24 Diarylpentanoid Inhibits Selected Metabolic Pathways in EGFR-Mutated Lung Adenocarcinoma","authors":"Sareshma Sudhesh Dev ,&nbsp;Syafiq Asnawi Zainal Abidin ,&nbsp;Iekhsan Othman ,&nbsp;Rakesh Naidu","doi":"10.1016/j.jtho.2025.03.027","DOIUrl":"10.1016/j.jtho.2025.03.027","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 4","pages":"Page S10"},"PeriodicalIF":21.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759352","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}