Clinical lung cancer最新文献

{"title":"Brief Report: Real-World Clinical Utility of Next-Generation Sequencing of Circulating Tumor DNA for Patients With Advanced Lung Squamous Cell Carcinoma (SQUIN).","authors":"Miguel García-Pardo, Marta García de Herreros, Juan Carlos Laguna, Teresa Gorría, Yolanda Lage, Ana Gómez, Mª Eugenia Olmedo, Pilar Garrido, Víctor Manuel Albarran-Artahona, Ainara Arcocha, Cristina Teixido, Noemí Reguart, Alejandro Navarro, Edouard Auclin, Mike S Nahorski, Karen Howarth, David Planchard, Benjamin Besse, Natasha B Leighl, Laura Mezquita","doi":"10.1016/j.cllc.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.02.007","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Racial Diversity and Co-Mutational Analysis of Biologically Relevant Alterations in EGFR Mutant Lung Cancers.","authors":"Radhika Gutta, Emily Teslow, Ellen Jaeger, Melissa C Stoppler, Calvin Chao, Fawzi Abu Rous, Bindu Potguari, Shirish Gadgeel","doi":"10.1016/j.cllc.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.02.008","url":null,"abstract":"<p><strong>Background: </strong>EGFR alterations have significant therapeutic implications in lung cancer (LCa), yet their prevalence and co-mutational patterns in African American populations remain understudied. This study analyzes EGFR-mutant LCa across races using the Tempus database.</p><p><strong>Methods: </strong>De-identified records sequenced via Tempus xT assay, (595 to 648 gene DNA panel) were included if they had ≥ 1 pathogenic EGFR mutation (short variants (SVs), copy number amplifications (CNAs), or fusions). Race was determined based on recorded clinical records. Co-mutations were restricted to genes with ≥ 5% frequency in at least 1 race. Statistical analyses were performed using chi-squared tests with Bonferroni or false discovery rate adjustments for multiple testing.</p><p><strong>Results: </strong>Among 17,482 LCa samples, EGFR alterations occurred in 8.9% of CA, 7.6% of BAA, 39% of API, 15% of other races, and 12% of unknown races. Exon 19 deletions (P = .017) and L858R mutations (P < .001) varied by race, with higher L858R frequency in CA compared to BAA (P = .034) and in API compared to CA (P = .006). EGFR copy number variants (CNVs) were highest in BAA (P < .001). TP53 alterations occurred at a higher frequency in patients with a history of smoking, those with high tumor mutational burden (TMB), and high PD-L1. KMT2C co-mutations were significantly more common in BAA (13%) compared to CA (3%) and API (4%) (q = 0.003). Similarly, GLI1 co-mutations were most frequent in BAA (5.8%) compared to 1.5% in CA and 0% in API patients (q = 0.025).</p><p><strong>Conclusions: </strong>EGFR mutation subtypes and co-mutations differ by race. KMT2C may influence TMB and immunotherapy response, while GLI1 is linked to TKI resistance. TP53 alterations were more commen in smokers, and patients with high PDL-1 and TMB, highlighting additional factors that drive tumors with these alterations.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PESGA Trial: A Prospective, Open-Label, Single-Arm, Phase II Study to Evaluate First Line Therapy for Extensive-Stage Small Cell Lung Cancer (ES-SCLC) Patients, Treated by Induction Carboplatin/Etoposide/Pembrolizumab Followed by Maintenance of Pembrolizumab/ Sacituzumab Govitecan.","authors":"Laila C Roisman, Shir Mann, Afifi Basel, Ranin Marei, Belal Krayim, Gleb Kornev, Noam Asna, Nir Peled","doi":"10.1016/j.cllc.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.02.002","url":null,"abstract":"<p><strong>Introduction: </strong>Despite recent advances in immunotherapy combinations for extensive-stage small cell lung cancer (ES-SCLC), rapid disease progression following chemotherapy discontinuation remains a significant challenge. While the addition of pembrolizumab to platinum-etoposide has demonstrated a modest improvement in progression-free survival (PFS), there is an urgent need for more effective maintenance strategies. Sacituzumab govitecan (SG), an antibody-drug conjugate targeting Trop-2, has shown promising activity in pretreated ES-SCLC. This phase II study evaluates the efficacy and safety of adding SG to pembrolizumab maintenance therapy following chemoimmunotherapy induction in treatment-naïve ES-SCLC patients.</p><p><strong>Methods: </strong>In the PESGA trial, a prospective, open-label, single-arm phase II trial, patients with previously untreated ES-SCLC will receive induction therapy consisting of pembrolizumab (200 mg Q3 W) plus carboplatin (AUC 5) and etoposide (100 mg/m² Days 1-3) for 4 cycles. This will be followed by maintenance therapy combining pembrolizumab (200 mg Q3 W) with SG (10 mg/kg on Days 1 and 8 of 21-day cycles) for up to 31 cycles. The primary endpoint is PFS from the start of induction treatment. Secondary endpoints include overall survival, duration of response, and safety. Exploratory analyses will investigate molecular resistance mechanisms through sequential liquid and tissue biopsies and evaluate correlations between tumor Trop-2 expression and clinical outcomes. The study plans to enroll 21 patients over 18 months, with an estimated total study duration of 54 months. Results will be analyzed after 50% of patients have achieved PFS.</p><p><strong>Conclusions: </strong>The PESGA study design builds upon the KEYNOTE-604 regimen by incorporating SG into the maintenance phase, potentially addressing the challenge of early progression in ES-SCLC. The study may provide valuable insights into novel maintenance strategies and molecular mechanisms of treatment resistance in ES-SCLC.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Radiation Dose to Immune Cells in Stage IV Non-Small Cell Lung Cancer in the Era of Immunotherapy","authors":"Junyi He ,&nbsp;Yingxin Liu ,&nbsp;Xiaoqing Wang ,&nbsp;Ruiting Song ,&nbsp;Jingze Zhang ,&nbsp;Butuo Li ,&nbsp;Haohua Wang ,&nbsp;Jinming Yu ,&nbsp;Linlin Wang","doi":"10.1016/j.cllc.2025.02.006","DOIUrl":"10.1016/j.cllc.2025.02.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Thoracic radiotherapy (RT) is now widely used in the treatment of advanced non-small cell lung cancer (NSCLC) as palliative, consolidative or radical therapy. However, RT adversely impacts the immune system, which can be evaluated by calculating the estimated dose of radiation to immune cells (EDRIC). We evaluated the prognostic impact of the EDRIC in patients with advanced NSCLC who received immunotherapy and thoracic RT.</div></div><div><h3>Methods</h3><div>We retrospectively enrolled 152 stage IV NSCLC patients who had received first-line immunotherapy and thoracic RT. EDRIC was a model developed by Jin et al., calculated using the number of radiotherapy fractions, mean lung dose, mean heart dose, and mean body dose. Spearman's rank correlation was used to assess the correlations between variables. The relationships of EDRIC (≥5.7 Gy vs. &lt;5.7 Gy) with survival were assessed using Kaplan-Meier and Cox proportional hazard models.</div></div><div><h3>Results</h3><div>The median PFS and OS were shorter in the EDRIC ≥ 5.7 Gy group (PFS: 10.2 months vs. 18.6 months, <em>P</em> &lt; .0001; OS: 19.8 months vs. 30.2 months, <em>P</em> = .024). In the multivariate model, higher EDRIC was associated with worse PFS (HR = 2.791, P &lt; .0001) and OS (HR = 1.823, P = .028). Additionally, bone metastasis was associated with worse OS (HR = 1.751, P = .022).</div></div><div><h3>Conclusion</h3><div>EDRIC was an independent predictor for PFS and OS in advanced NSCLC patients receiving immunotherapy and RT. These observations necessitate further exploration into techniques to optimize radiation exposure to the immune system in cancer treatment.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 3","pages":"Pages 221-227.e1"},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonbacterial Thrombotic Endocarditis (NBTE) Treated With Crizotinib in Lung Adenocarcinoma Harboring ROS-1 Rearrangement: Two Case Report and Review of Literature.","authors":"Jesús Chamorro-Pérez, Yolanda Lage, Víctor Albarrán-Fernández, Diana Isabel Rosero-Rodríguez, Pilar Agudo, Pablo Martínez-Vives, María Eugenia Olmedo, Ana Gómez-Rueda, Miguel García-Pardo, Pilar Garrido-López","doi":"10.1016/j.cllc.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.02.005","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Profiling of Driver Gene Alterations in Patients With Non-Small Cell Lung Cancer, Patterns of Treatment and Impact on Survival Outcomes: A Single Center Experience of More Than 1200 Patients.","authors":"Minit Shah, Vanita Noronha, Vijay Patil, Ajay Kumar Singh, Nandini Menon, Supriya Goud, Srushti Shah, Sucheta More, Akhil Kapoor, Bal Krishna Mishra, Pratik Chandrani, Anuradha Chougule, Vinod Gupta, Priyanka Pange, Omshree Shetty, Trupti Pai, Rajiv Kaushal, Subhash Yadav, Moitrri Basu, Deep Vora, Arvind Vaidyanathan, Prashant Kumar, Rohan Jacob, Anjali Shah, Rashmi Ranjan Pradhan, Debdeep Samaddar, Vallish Shenoy, Bhanupratap Singh, Raveendranath Puviarasan, Saurabh Bagra, Rachit Desai, Elveera Saldanha, Disha Poojary, Akash Pathak, Shivangi Ray, Himanshu Bhardwaj, Ujwal Shetty, Ramya Iyer, Richa Das, Neha Mer, Hetakshi Shah, Yuvraj Kaushal, Ananya Singh, Hrutika Panmand, Ganesh Gosavi, Ahmad Ubharay, Anusha Iyer, Ushaan Turel, Ankush Shetake, Kamesh Maske, Amit Janu, Nilendu Purandare, Akash Pawar, Madhvi Mandhania, Kumar Prabhash","doi":"10.1016/j.cllc.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.02.001","url":null,"abstract":"<p><strong>Background: </strong>The utility of Next-Generation-Sequencing (NGS) in patients of non-small-cell-lung-cancer (NSCLC) has led to an exponential increase in the identification of driver-gene alterations, however, Indian NGS data was lacking.</p><p><strong>Materials and methods: </strong>This retrospective study conducted between May'2019 and Dec'2023 included histologically confirmed NSCLC cases with NGS testing done on tissue and/or liquid biopsy samples prior to treatment initiation. We reported the frequency of driver-gene alterations, clinicopathological profile, treatment patterns, and outcomes [Overall-Survival (OS)].</p><p><strong>Results: </strong>Data of 1230 patients was analyzed. Median age was 59 years (IQR,51-66), 65.3% (n = 803) were males, 34.6% (n = 426) had a history of smoking, and 78.1% (n = 961) had an adenocarcinoma histology. NCCN-recommended driver-gene alterations were seen in 64.8% (n = 797) cases. EGFR, ALK, ROS1, ERBB2, MET, RET, NTRK, BRAF and KRAS gene alterations were seen in 33.7% (n = 414), 7.6% (n = 94), 2.4% (n = 29), 6.1% (n = 75), 1.9% (n = 23), 2.2% (n = 22), 0.7% (n = 8), 3.3% (n = 40), and 9.6% (n = 118) cases respectively. 62.1% (n = 495/797) driver-positive patients could receive targeted therapy, and 21.7% (n = 94/433) driver-negative patients could receive immunotherapy. With the receipt of targeted therapy, median-OS of driver-positive patients was 26.7 months (95%CI, 23.3-32.7) versus 9.3 months (95%CI, 7.3-12.2, P < .001) without. Similarly, in driver-negative patients, median OS with the receipt of immunotherapy was 16.4months (95%CI, 14.7-24.4) versus 11.5 months (95%CI, 9.0-13.4, P = .006) without.</p><p><strong>Conclusion: </strong>All eligible NSCLC patients must undergo molecular testing by appropriately chosen and cost-effective methods at diagnosis. Wherever possible, this should be done by NGS. Efforts should focus on improving access to targeted agents in India, and developing cost-effective alternatives.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supraclavicular Lymph Node Metastases in Advanced Lung Cancer: Prevalence and Analysis of Demographic, Clinical and Molecular Characteristics.","authors":"Rocco Trisolini, Valeria Cetoretta, Giovanni Sotgiu, Alessandra Cancellieri, Mariangela Puci, Marta Viscuso, Vanina Livi, Massimiliano Cani, Giovanni Scambia, Federico Cappuzzo, Emilio Bria, Silvia Novello","doi":"10.1016/j.cllc.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.02.003","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of supraclavicular lymph nodes metastases (SNM) in advanced lung cancer has not been systematically evaluated, nor has then been a comparison of demographic, clinical, or molecular characteristics between patients with and without SNM.</p><p><strong>Methods: </strong>In this prospective cohort study, the presence of SNM was evaluated using imaging studies (CT, PET, neck ultrasonography) in patients with suspected advanced lung cancer referred for biopsy aimed at diagnosis and molecular profiling. Ultrasound-guided biopsy confirmed or excluded metastatic involvement when suspicious supraclavicular nodes were identified. We assessed the prevalence of SNM and compared the demographic, clinicopathologic and molecular characteristics of patients with and without SNM.</p><p><strong>Results: </strong>Among the 348 patients with advanced lung cancer, 94 (27%) had SMN. SMN was more common in small cell lung cancer (24/48, 50%) and adenocarcinoma (61/248, 24.6%) than in squamous cell carcinoma (4/35, 11.4%). Compared to patients without SMN, those with SMN were more likely to have small-cell lung cancer, N2/3 disease (97.9 vs. 83.9%, P < .0001), liver metastases (29.8% vs. 16.1% P = .006), and metastases to less common sites (33.7% vs. 14.1%, P < .0001). The prevalence of genomic alterations and PD-L1 expression did not differ between biopsy samples obtained from SNM and those from the primary tumor or other metastatic sites.</p><p><strong>Conclusion: </strong>SNM is common in patients with advanced small-cell lung cancer and adenocarcinoma. Ultrasound-guided biopsy of SNM is a simple and relatively inexpensive method for obtaining adequate tissue samples for diagnosis and comprehensive molecular profiling.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of Segmentectomy With or Without Preoperative Biopsy in Non-Small Cell Lung Cancer (NSCLC).","authors":"Sneha S Alaparthi, Annie Ho, Hamza Rshaidat, Gregory Whitehorn, Isheeta Madeka, Anurag Ishwar, Tyler Grenda, John D Jacob, Nathaniel R Evans, Olugbenga T Okusanya","doi":"10.1016/j.cllc.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.02.004","url":null,"abstract":"<p><strong>Background: </strong>There is a discussion amongst oncologic societies regarding the necessity of preoperative biopsy prior to resection in lung cancer. We aim to examine outcomes of segmentectomy with or without preoperative biopsy in non-small cell lung cancer (NSCLC) patients.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted utilizing the National Cancer Database. Adult patients diagnosed with clinical stage I (N0 M0, tumor size ≤ 2 cm) NSCLC between 2010 and 2019 who underwent segmentectomy were included. Patients with carcinoid tumors or who received neoadjuvant systemic or radiation therapy were excluded. Demographic and clinical variables were analyzed. Propensity score matching (PSM) was performed to adjust for confounders between patients who underwent segmentectomy with versus without preoperative biopsy. Short term outcomes (readmission, 30-day and 90-day survival) and long-term overall survival (OS) were compared between groups.</p><p><strong>Results: </strong>In total, 6891 patients met inclusion criteria, of which 2287 (33.2%) underwent preoperative biopsy and 4604 (66.8%) did not. There was no significant difference in 30-day readmission (P = .13), 30-day survival (P = .26), and 90-day survival (P = .31). Patients who did not receive preoperative biopsy was associated with a higher 5-year OS (P = .02); however, post-PSM, there was no significant difference between the 2 groups (P = .20).</p><p><strong>Conclusions: </strong>After PSM, no significant difference was found in margin positivity, nodal upstaging, 30-day readmission, 30- and 90-day survival, and 5-year OS between cohorts. This demonstrates that segmentectomy without preoperative biopsy remains a safe option for those with early stage, ≤ 2 cm NSCLC.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Immunophenotypic Correlates in Patients Aged 80 Years or Older With Non-Small Cell Lung Cancer and Outcomes to First-Line Pembrolizumab in PD-L1 High (≥50%) Patients.","authors":"Adriana P C Barrichello, Arielle Elkrief, Biagio Ricciuti, Teja Ganta, Thomas U Marron, Xinan Wang, William Lotter, James Lindsay, Valentina Santo, Alessio Cortellini, Bijaya Sharma, Kristen Felt, Kathleen Pfaff, Giuseppe Lamberti, Federica Pecci, Alessandro Di Federico, Maisam Makarem, Malini M Gandhi, Tom Nguyen, Danielle Haradon, Victor R Vaz, Bruce E Johnson, Neha Debnath, Yinghong Wang, Andrew G Kuang, Anwaar Saeed, Maluki Radford, Christine M Lovly, Caroline A Nebhan, David J Pinato, Scott J Rodig, Adam J Schoenfeld, Mark M Awad, Joao V Alessi, Abdul Rafeh Naqash","doi":"10.1016/j.cllc.2025.01.014","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.01.014","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) patients aged ≥80 years [y] are underrepresented in clinical trials. We evaluated whether age correlates with a distinct immunophenotype or impacts outcomes to first-line pembrolizumab in patients with advanced NSCLC, PD-L1 Tumor Proportion Score (TPS) of ≥50%, and aged ≥80y.</p><p><strong>Methods: </strong>Three NSCLC cohorts were retrospectively analyzed to assess the impact of age (<80y versus ≥80y) on pembrolizumab efficacy and the tumor microenvironment (TME). Cohort A encompassed patients receiving first-line pembrolizumab for advanced NSCLC with PD-L1 ≥50%. Cohort B comprised patients with tumor profiling using multiplexed immunofluorescence (ImmunoPROFILE). Cohort C included The Cancer Genome Atlas (TCGA) and Stand Up to Cancer (SU2C) databases for gene expression analysis.</p><p><strong>Results: </strong>In Cohort A (N = 669), patients ≥80y (N = 111) showed no significant differences in objective response rate or median progression-free survival compared to younger patients (N = 558), but had shorter median overall survival and were less likely to receive second-line therapy after progression on pembrolizumab. In Cohort B (N = 567), tumors from patients ≥80y (N = 45) exhibited higher intratumoral FOXP3+ T cells and closer vicinity of PD-1+ immune cells to tumor cells compared to <80y (N = 522). Cohort C revealed a distinct immunophenotype in samples from patients ≥ 80y, with elevated specific immune cell subsets and up-regulated immune checkpoint proteins.</p><p><strong>Conclusion: </strong>Patients ≥80y with PD-L1-high NSCLC displayed a distinct immunophenotype in the TME but achieved similar ORR and mPFS with first-line pembrolizumab compared to younger patients. OS was shorter in older patients, who were less likely to receive second-line therapy.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients With Advanced Non-small Cell Lung Cancer Harboring MET Alterations: A Descriptive Cohort Study.","authors":"Dina Oksen, Emmanuelle Boutmy, Yuexi Wang, Christopher Stroh, Andreas Johne, Alnecia R Nisbett, Alex Ryder","doi":"10.1016/j.cllc.2025.01.013","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.01.013","url":null,"abstract":"<p><strong>Purpose: </strong>Mesenchymal-epithelial transition factor (MET) alterations are rare oncogenic drivers in patients with non-small cell lung cancer (NSCLC). This study characterized patients with advanced NSCLC harboring MET exon 14 (METex14) skipping and MET amplification (METamp) in routine clinical practice in the United States.</p><p><strong>Patients and methods: </strong>Using electronic medical record data from the ConcertAI Oncology Dataset (2004-2022), 2 patient cohorts were identified: 1 with METex14 skipping with or without METamp, and 1 with METamp without METex14 skipping. A subgroup with METamp and concomitant epidermal growth factor receptor (EGFR) mutations who had received EGFR-tyrosine kinase inhibitors (TKIs) was also analyzed. Patient characteristics, treatment patterns and outcomes were described.</p><p><strong>Results: </strong>93 patients with advanced NSCLC harboring METex14 skipping and 164 with advanced NSCLC harboring METamp were identified. Established oncogenic drivers other than MET were less frequent in the METex14 skipping cohort than the METamp cohort. In both cohorts, first-line chemotherapy use decreased over time while immune checkpoint inhibitor (ICI) and MET inhibitor use increased. Treatment patterns were heterogeneous, with patients receiving multiple drug classes across therapy lines. Outcomes were better for patients with METex14 skipping NSCLC who received targeted therapies or ICIs versus chemotherapy. Subgroup analyses of EGFR-TKI-treated patients with METamp indicated poor outcomes.</p><p><strong>Conclusion: </strong>Patients with METex14 skipping and/or METamp NSCLC require targeted and personalized treatment approaches to optimize treatment effect and have an unmet medical need. With targeted therapies recently available and others under exploration, treatment outcomes could significantly improve for patients with NSCLC harboring these rare drivers.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}