Lung Cancer最新文献

{"title":"Patient and oncologist preferences for ALK+ advanced non-small cell lung cancer tyrosine kinase inhibitor treatments: a discrete choice experiment in the United States","authors":"Hannah Le ,&nbsp;Josh Coulter ,&nbsp;Ken Culver ,&nbsp;Joseph C. Cappelleri ,&nbsp;Nada Rifi ,&nbsp;Hui Lu ,&nbsp;Matthew Quaife ,&nbsp;Keila Meginnis ,&nbsp;Gabriela S. Fernandez ,&nbsp;Shailja Vaghela ,&nbsp;Brett Hauber ,&nbsp;Thomas E. Stinchcombe","doi":"10.1016/j.lungcan.2025.108850","DOIUrl":"10.1016/j.lungcan.2025.108850","url":null,"abstract":"<div><h3>Purpose</h3><div>Next-generation anaplastic lymphoma kinase (ALK)-targeting tyrosine kinase inhibitors (TKIs) are standard first-line (1L) treatments for ALK+ advanced non-small cell lung cancer (aNSCLC). Treatments differ in systemic and central nervous system (CNS) efficacy and adverse event (AE) profiles. There is a need for understanding treatment preferences of patients and oncologists in this setting.</div></div><div><h3>Patients and methods</h3><div>Patients receiving TKIs for ALK<em>+</em> aNSCLC and oncologists were recruited from patient databases, patient advocacy groups and an online panel to complete a discrete choice experiment, which included progression-free survival (PFS), brain metastases (BM) development, BM progression, metabolic events, weight gain, CNS AEs, fatigue/asthenia, and muscle/bone pain. Responses were analyzed using a mixed logit model. Relative attribute importance (RAI), minimum acceptable benefit, and maximal acceptable risk were calculated.</div></div><div><h3>Results</h3><div>Of the 151 patients, 23.2 % had BM and 50.3 % were on 1L treatment. Treatment benefits outweighed AEs and contributed to 73.6 % of patients’ and 67.0 % of oncologists’ total RAI. Stopping BM progression was most important to patients (27.2 %), whereas PFS was most important to oncologists (31.1 %). Oncologists placed two and four times as much importance on avoiding CNS AEs and metabolic events, respectively, than patients. Patients placed more importance on avoiding fatigue/asthenia than oncologists.</div></div><div><h3>Conclusions</h3><div>To our knowledge, this was the first study to quantify preferences regarding 1L treatments for ALK+ aNSCLC in the US. As patients and oncologists were shown to have different priorities, understanding the differing trade-offs between treatment benefits and AEs can facilitate shared decision-making and personalized 1L treatment for ALK+ aNSCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108850"},"PeriodicalIF":4.4,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623072","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":"Entrectinib in Asian patients with ROS1 fusion-positive non-small cell lung cancer: updated efficacy and safety analysis","authors":"Shun Lu ,&nbsp;Yun Fan ,&nbsp;Xiaorong Dong ,&nbsp;Yan Yu ,&nbsp;Juan Li ,&nbsp;Jun Zhao ,&nbsp;Chia-Chi Lin ,&nbsp;Pengcheng Zhang ,&nbsp;Yanjun Shi ,&nbsp;Rui Luo ,&nbsp;Xichun Hu","doi":"10.1016/j.lungcan.2025.108851","DOIUrl":"10.1016/j.lungcan.2025.108851","url":null,"abstract":"<div><h3>Background</h3><div>In an integrated analysis of phase I/II trials (STARTRK-2, STARTRK-1, ALKA-372–001), entrectinib induced responses in global populations with advanced <em>ROS1</em>-fusion positive (<em>ROS1</em>-fp) non-small cell lung cancer (NSCLC). This study reports updated efficacy and safety data in Asian patients from the integrated analysis (cutoff: 16 July 2023).</div></div><div><h3>Methods</h3><div>Asian patients with ROS1 tyrosine kinase inhibitor-naïve locally advanced/metastatic <em>ROS1</em>-fp NSCLC, with/without central nervous system (CNS) metastasis were included. The primary endpoints were overall response rate (ORR) and duration of response (DoR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR, IC-DoR, and safety. An exploratory subgroup analysis of patients naïve to systemic therapy in the metastatic setting (1L) was also investigated.</div></div><div><h3>Results</h3><div>The efficacy-evaluable population included 99 patients. Median (range) age was 53 (20, 86) years; 32.3 % of patients had baseline CNS metastases. Confirmed ORR was 68.7 % (95 % confidence interval [CI] 58.6 %–77.6 %); median DoR was 18.6 months (95 % CI 11.1–38.5). Confirmed IC-ORR was 34.8 % (95 % CI 16.4 %–57.3 %); median IC-DoR was 9.4 months (95 % CI 6.8–not evaluable). Median time to CNS progression was 28.9 months (95 % CI 15.7–41.4). In the 1L population (n = 40), confirmed ORR was 67.5 % (95 % CI 50.9 %–81.4 %); median DoR was 38.5 months (95 % CI 11.1–not evaluable). The most frequent treatment-related adverse events were weight increased (45.9 %), constipation (40.4 %), and dysgeusia (39.4 %).</div></div><div><h3>Conclusion</h3><div>This analysis demonstrates continued efficacy of entrectinib in Asian patients with advanced <em>ROS1</em>-fp NSCLC, both overall and in the 1L setting. No new safety signals emerged.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108851"},"PeriodicalIF":4.4,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668976","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":"KRASG12D/G13D-USP15 axis promotes TGF-β/SMAD signaling and glycolytic flux to accelerate NSCLC pathogenesis","authors":"Ikhlas A. Sindi ,&nbsp;Abdelghafar M. Abu-Elsaoud ,&nbsp;Amany I. Almars ,&nbsp;Nahlah M. Ghouth ,&nbsp;Sameerah Shaheen ,&nbsp;Ahmed M. Basri ,&nbsp;Zaki H Hakami ,&nbsp;Tawfiq N. Jurayb ,&nbsp;Abdullah A. Alqasem ,&nbsp;Iman S. Abumansour ,&nbsp;Hind M. Naffadi ,&nbsp;Nasser A. Elhawary ,&nbsp;Hassan Rudayni ,&nbsp;Mohammed Al-zharani ,&nbsp;Lina M. Alneghery ,&nbsp;Mohamed M.I. Ghoneim","doi":"10.1016/j.lungcan.2025.108848","DOIUrl":"10.1016/j.lungcan.2025.108848","url":null,"abstract":"<div><h3>Background</h3><div>Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality worldwide, with activating <em>KRAS</em> mutations representing a key oncogenic driver. These mutations profoundly reprogram cellular metabolism, especially glycolysis, thereby sustaining uncontrolled tumor proliferation. We identified ubiquitin-specific peptidase 15 (USP15) as a pivotal regulator in KRAS-driven metabolic remodeling and tumor progression. This study aims to elucidate the biological functions and molecular mechanisms of USP15 in <em>KRAS^G12D</em>^/G13D-mutant NSCLC.</div></div><div><h3>Methods</h3><div>Comprehensive bioinformatics analyses were performed to identify key metabolic genes significantly associated with NSCLC prognosis. The expression of USP15 was examined in <em>KRAS</em>-mutant NSCLC tissues and cell lines. Functional assays, including CCK-8, EdU incorporation, wound-healing, and subcutaneous xenograft tumor models, were employed to evaluate the oncogenic role of USP15 <em>in vitro</em> and <em>in vivo</em>. In addition, qPCR, Western blotting, ELISA, immunofluorescence, and Seahorse metabolic flux assays were integrated with transcriptomic and metabolomic profiling to comprehensively delineate the mechanisms by which USP15 regulates tumor metabolism and growth in <em>KRAS^G12D</em>^/G13D-mutant NSCLC.</div></div><div><h3>Results</h3><div><em>USP15</em> expression was elevated in <em>KRAS</em>-mutant NSCLC and was transcriptionally regulated by the MEK/ERK signaling pathway. Silencing <em>USP15</em> significantly inhibited NSCLC cell proliferation, migration, and tumorigenicity, while inducing apoptosis and enhancing chemosensitivity. Multi-omics analyses revealed that USP15 exerts its oncogenic function primarily through modulation of the TGF-β/SMAD signaling axis. Mechanistically, USP15 stabilized SMAD4 by deubiquitination and promoted the phosphorylation of SMAD2/3, thereby sustaining TGF-β/SMAD pathway activation. Moreover, USP15 enhanced glycolytic flux, evidenced by increased extracellular acidification rates and upregulated glycolytic genes expression, ultimately facilitating metabolic adaptation and tumor progression in <em>KRAS^G12D</em>^/G13D-mutant NSCLC.</div></div><div><h3>Conclusion</h3><div>USP15 acts as a critical mediator of oncogenic KRAS-driven metabolic reprogramming in NSCLC by promoting glycolysis via the TGF-β/SMAD signaling cascade. These findings uncover a previously unrecognized role of USP15 in linking metabolic regulation to tumorigenic signaling in <em>KRAS</em>-mutant NSCLC and suggest that targeting USP15 may represent a promising therapeutic strategy for this aggressive cancer subtype.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108848"},"PeriodicalIF":4.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623071","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":"First-line treatment in EGFR-mutated non-small cell lung cancer: brief report of an individual patient data comparison of phase 3 clinical trials","authors":"Andrea Torchia ,&nbsp;Arianna Sabatini ,&nbsp;Elisabetta Bengala ,&nbsp;Mattia Alberto Di Civita ,&nbsp;Fabio Ciurluini ,&nbsp;Daniele Marinelli ,&nbsp;Maristella Giammaruco ,&nbsp;Anastasia Laudisi ,&nbsp;Alain Gelibter ,&nbsp;Gabriele Minuti ,&nbsp;Lorenza Landi ,&nbsp;Daniele Santini ,&nbsp;Federico Cappuzzo","doi":"10.1016/j.lungcan.2025.108845","DOIUrl":"10.1016/j.lungcan.2025.108845","url":null,"abstract":"<div><h3>Introduction</h3><div>Clinical trials evaluated the efficacy and safety of novel first-line treatment strategies for advanced epidermal growth factor receptor (<em>EGFR</em>)-mutated non-small cell lung cancer (NSCLC), relative to osimertinib monotherapy.</div></div><div><h3>Methods</h3><div>After review of the literature, we performed an individual patient data comparison of efficacy and safety of investigational regimens from phase 3 randomized controlled trials in untreated <em>EGFR</em>-mutated NSCLC.</div></div><div><h3>Results</h3><div>Two studies were included in the analysis: FLAURA2 and MARIPOSA, evaluating the osimertinib-chemotherapy and amivantamab-lazertinib combinations, respectively. In progression free survival (PFS), there was a statistically significant difference favoring the FLAURA2 in the intent-to-treat (ITT) population [Hazard ratio (HR) 0.79], not confirmed in the overall survival (OS) analysis where we did not find any significant difference. FLAURA2 PFS was longer in patients with central nervous system (CNS) metastases (HR 0.63), without liver metastases (HR 0.73), and with <em>EGFR</em> L858R (HR 0.68). In intracranial PFS (icPFS), there was a statistically significant difference favoring the FLAURA2 (HR 0.52). We found no differences in PFS in patients without CNS metastases, and with exon 19 deletions. No new safety signals resulted from the safety analysis. In FLAURA2, anemia, diarrhea, and neutropenia were more frequent, while in MARIPOSA rash and paronychia.</div></div><div><h3>Conclusion</h3><div>In the ITT population, we found no differences in OS between amivantamab-lazertinib and osimertinib-chemotherapy, despite a slightly higher PFS of the latter. Osimertinib-chemotherapy could be more effective in patients with CNS metastases, without liver metastases, and <em>EGFR</em> L858R mutation, however we could not compare OS in these subgroups. Due to the indirect nature of the comparison and the limitation of the methods our results are not definitive, but rather hypothesis-generating. Other factors must be considered in the choice of the treatment, including patient’s characteristics, the safety profile of the combinations, and center’s facilities and expertise.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108845"},"PeriodicalIF":4.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569612","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":"Long-term outcomes of Extensive-Stage small cell lung cancer treated with chemotherapy or Chemo-immunotherapy: A propensity score adjusted cohort study","authors":"Heya Batah ,&nbsp;Emily C. Zabor ,&nbsp;Bridget Adcock ,&nbsp;Monica Lee ,&nbsp;Preeyal Patel ,&nbsp;Meera Patel ,&nbsp;Hadil Zureigat ,&nbsp;Ahmed Nabil Mohamed ,&nbsp;Daniel Paul Nurse ,&nbsp;Yohanna B. Bedelu ,&nbsp;Jacqulyn Tomer ,&nbsp;Lukas Delasos ,&nbsp;Khaled A. Hassan ,&nbsp;Nathan A. Pennell ,&nbsp;Marc A. Shapiro ,&nbsp;James Stevenson ,&nbsp;Alex A. Adjei ,&nbsp;Moaath Khader Mustafa Ali","doi":"10.1016/j.lungcan.2025.108847","DOIUrl":"10.1016/j.lungcan.2025.108847","url":null,"abstract":"<div><h3>Background</h3><div>Combining atezolizumab with carboplatin plus etoposide (Carbo-E) improved overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). However, there is a paucity of real-world outcomes. We present the largest and longest follow-up retrospective study evaluating treatment outcomes in ES-SCLC.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study to compare response rate, OS, and progression-free survival (PFS) in patients with ES-SCLC who received Carbo-E, Carbo-E and atezolizumab (Carbo-E-Atezo), and cisplatin and etoposide (Cis-E). We included all adult patients (≥ 18 years) treated at Cleveland Clinic between 1/2010–12/2022. Propensity score (PS) weighting and multivariable Cox proportional hazards regression adjusted for confounders.</div></div><div><h3>Results</h3><div>Among 602 ES-SCLC patients, 375 (62 %) received Carbo-E, 160 (27 %) received Carbo-E-Atezo, and 67 (11 %) received Cis-E. The median age was 67, 65, and 59 years, respectively. The median follow-up among survivors was 23.9 months (IQR: 13.3–––57.3). Five-year unadjusted OS was 4.5 % (Carbo-E), 7 % (Carbo-E-Atezo), and 5.2 % (Cis-E). Carbo-E-Atezo was associated with a longer PS-adjusted median OS than Carbo-E (9.1 vs. 8.2 months, P = 0.039), but no difference was seen in PFS (5.5 vs. 5.5, P = 0.09) or response rate (P &gt; 0.9). Compared to Carbo-E, Cis-E showed higher response rates (OR: 1.67, P = 0.03) but no improvement in OS (11 vs 8.3 months, P = 0.067) or PFS (7.7 vs. 5.5 months, P = 0.058). Cis-E did not differ significantly from Carbo-E-Atezo in response rate, OS, or PFS.</div></div><div><h3>Conclusion</h3><div>Long-term outcomes in ES-SCLC remain poor. Atezolizumab added to Carbo-E modestly improved OS but not PFS. Cisplatin-based regimens increased response rates but did not improve survival.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108847"},"PeriodicalIF":4.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564323","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":"Reappraising preoperative ctDNA in EGFR-mutant NSCLC: from detection to responsible clinical integration","authors":"Man Sun ,&nbsp;Dan Zang ,&nbsp;Jun Chen","doi":"10.1016/j.lungcan.2025.108846","DOIUrl":"10.1016/j.lungcan.2025.108846","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108846"},"PeriodicalIF":4.4,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569680","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":"Tarlatamab population survival kinetics in extensive-stage small cell lung cancer: brief report","authors":"David J. Stewart ,&nbsp;Bingnan Zhang ,&nbsp;Razelle Kurzrock","doi":"10.1016/j.lungcan.2025.108844","DOIUrl":"10.1016/j.lungcan.2025.108844","url":null,"abstract":"<div><h3>Purpose</h3><div>Immune checkpoint inhibitors (ICIs) prolong progression-free survival (PFS) and overall survival (OS) in extensive-stage small cell lung cancer (ES-SCLC). ES-SCLC PFS curve exponential decay nonlinear regression analyses (EDNLRAs) suggests that only 10% of patients benefit. Here we report ES-SCLC EDNLRAs for the bispecific T-cell engager tarlatamab.</div></div><div><h3>Experimental design</h3><div>We digitized tarlatamab ES-SCLC PFS and OS curves from published studies and performed EDNLRAs of curve data.</div></div><div><h3>Results</h3><div>All four PFS curves fit 2-phase decay models, suggesting the presence of two distinct subpopulations- one with a short PFS half-life (median 3.2 months, similar to the tarlatamab DeLLphi-304 study chemotherapy arm) and the other with a very long PFS half-life). EDNLRAs indicated that 88 % of the patients belonged to the rapidly progressing subpopulation. The proportion of patients in the subpopulation with long PFS was lower than the study response rates. However, log-linear plots of response-duration curves also suggested 2-phase decay, with one subpopulation having very long responses and the other having very short responses. Two of four OS curves assessed fit 2-phase decay models. Longer follow-up will be required to assess the other two curves. For curves fitting 2-phase decay models, OS half-life for the subpopulation with shorter OS was modestly longer than the OS for the Dellphi-304 chemotherapy arm.</div></div><div><h3>Conclusions</h3><div>In ES-SCLC, EDNLRA of tarlatamab PFS curves and log-linear plots of response duration curves suggest two distinct subpopulations- one deriving marked benefit from tarlatamab and the other deriving much less benefit. Individual patient data might provide insight into underlying driving factors.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108844"},"PeriodicalIF":4.4,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557126","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":"Prevalence and molecular landscape of NRG1 fusions in Japanese solid tumors: a nationwide data analysis using the C-CAT database","authors":"Masaki Ishida ,&nbsp;Tadaaki Yamada ,&nbsp;Ryo Tsunashima ,&nbsp;Midori Morita ,&nbsp;Nobutaka Kataoka ,&nbsp;Yusuke Kunimatsu ,&nbsp;Ryo Sawada ,&nbsp;Tae Hata ,&nbsp;Hayato Kawachi ,&nbsp;Masahiro Iwasaku ,&nbsp;Yasuto Naoi ,&nbsp;Koichi Takayama","doi":"10.1016/j.lungcan.2025.108843","DOIUrl":"10.1016/j.lungcan.2025.108843","url":null,"abstract":"<div><h3>Introduction</h3><div>Neuregulin 1 (<em>NRG1</em>) gene fusions are critical oncogenic drivers that activate the ERBB signaling pathway across various solid tumors. Although targeted therapies for <em>NRG1</em> fusion-positive cancers are advancing rapidly in clinical settings, their epidemiological and clinicogenomic characteristics remain poorly understood, warranting large-scale investigations.</div></div><div><h3>Methods</h3><div>We performed a retrospective analysis of patients with advanced solid tumors who were registered in the Center for Cancer Genomics and Advanced Therapeutics database of Japan between June 2019 and February 2025. Our evaluation focused on the prevalence of <em>NRG1</em> fusions, identities of fusion partners, co-occurring genomic alterations, tumor mutational burden, microsatellite instability status, and relevant clinical characteristics.</div></div><div><h3>Results</h3><div>Our study included 95,149 patients with advanced solid tumors who underwent comprehensive genomic profiling. Among them, 29 (0.03 %) harbored <em>NRG1</em> fusions, most frequently in lung cancer (17 of 5,670 cases, 0.30 %). CD74 emerged as the predominant fusion partner, constituting 82.4 % of lung cancers, whereas other solid tumors exhibited a more diverse range of partners. Co-occurring genomic alterations were detected in 20 of 29 patients (69.0 %), with the most frequent alterations found in <em>CDKN2A</em>, <em>CDKN2B</em>, and <em>MTAP</em>. Additionally, pathological examination revealed mucinous adenocarcinoma in 17.6 % of lung cancers associated with <em>NRG1</em> fusions.</div></div><div><h3>Conclusion</h3><div>This study confirms that <em>NRG1</em> fusions are rare but significantly associated with lung cancer and the CD74 fusion partner. Our nationwide analysis represents the most comprehensive assessment of <em>NRG1</em> fusions in Japanese patients with advanced solid tumors.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108843"},"PeriodicalIF":4.4,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534535","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":"Treatment and outcomes of limited stage small cell lung cancer in the Canadian small cell lung cancer database (CASCADE)","authors":"William J. Phillips ,&nbsp;Luna Jia Zhan ,&nbsp;Deepro Chowdhury ,&nbsp;Jeniszka Gill ,&nbsp;Alexander Sun ,&nbsp;Rebekah Rittberg ,&nbsp;Victor Cohen ,&nbsp;Amanda J.W. Gibson ,&nbsp;Michael Yan ,&nbsp;Daniel Liwski ,&nbsp;Saritha Surapaneni ,&nbsp;Marie Frederique D’Amours ,&nbsp;Fabian P.S. Yu ,&nbsp;YongJin Kim ,&nbsp;Rana A. Qadeer ,&nbsp;David E. Dawe ,&nbsp;Jason Agulnik ,&nbsp;Vishal Navani ,&nbsp;Andrea S. Fung ,&nbsp;Stephanie Snow ,&nbsp;Sara Moore","doi":"10.1016/j.lungcan.2025.108840","DOIUrl":"10.1016/j.lungcan.2025.108840","url":null,"abstract":"<div><h3>Introduction</h3><div>There have been minimal advances in the systemic treatment of limited stage small cell lung cancer (LS-SCLC) for decades. With the publication of the ADRIATIC trial, consolidation durvalumab is a new standard of care. This study evaluated real-world treatments and clinical outcomes prior to the era of immunotherapy for LS-SCLC.</div></div><div><h3>Methods</h3><div>The Canadian Small Cell Lung Cancer Database (CASCADE) is a Canadian multi-institutional federated database that includes patients with SCLC from 9 academic institutions. This analysis included patients with pathologically confirmed LS-SCLC treated curatively between January 2001 and December 2022. Baseline characteristics and treatment patterns were obtained from medical records and assessed descriptively. The primary outcome was overall survival (OS) assessed using Kaplan Meier (KM) methods. OS was also assessed among patients who received treatment eligible for participation in the ADRIATIC trial.</div></div><div><h3>Results</h3><div>A total of 1,024 patients were included. Median age was 66 years old and 52 % of patients were female. Concurrent chemoradiation therapy (cCRT) was the most common treatment modality (76 %), followed by surgery (11 %) and sequential CRT (10 %). Median OS was 24.9 months (95 % confidence interval [CI] = 23.4–27.4). Only 36 % of patients treated with cCRT received treatment meeting eligibility criteria for the ADRIATIC trial. The most common reason for ineligibility was due to the radiation therapy (RT) dose/schedule used. Median OS of eligible and ineligible patients was 30.3 months (95 % CI = 26.4–36.4) versus 21.7 months (95 % CI = 19.7–24.9).</div></div><div><h3>Conclusions</h3><div>Survival outcomes for LS-SCLC remain poor despite curative-intent multimodality treatment. Immunotherapy represents a promising advance but a high proportion of patients in the real-world receive treatment that was not represented in the ADRIATIC trial. Future work evaluating the outcomes of patients treated with immunotherapy is critical to assess its real-world impact.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108840"},"PeriodicalIF":4.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569681","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":"Genetic composition and evolutionary trajectories of brain metastasis in non-small-cell lung cancer","authors":"Marcin Nicoś ,&nbsp;Natalia Galant ,&nbsp;Anna Kowalczyk ,&nbsp;Rafał Pęksa ,&nbsp;Bożena Jarosz ,&nbsp;Monika Żuk ,&nbsp;Bartosz Wasąg ,&nbsp;Renata Duchnowska ,&nbsp;Paweł Krawczyk ,&nbsp;Jacek Jassem ,&nbsp;Nicola Crosetto","doi":"10.1016/j.lungcan.2025.108842","DOIUrl":"10.1016/j.lungcan.2025.108842","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-small cell lung cancer (NSCLC) is an aggressive solid malignancy that commonly disseminates to the central nervous system (CNS). Comparative analysis of primary NSCLC and brain metastases (BM) by next-generation sequencing may reveal somatic genetic alterations that drive or favor NSCLC-derived BM.</div></div><div><h3>Methods</h3><div>We performed whole-exome sequencing (WES) in 62 archival samples from 31 paired-matched primary NSCLC sites and corresponding BM. The median age of patients was 66 years; 22 had adenocarcinoma, and 9 had squamous cell carcinoma, 6 patients presented synchronous BM at lung cancer diagnosis, and 22 developed BM after 1–78 months (median 13 months).</div></div><div><h3>Results</h3><div>Mutations in the <em>RTK-RAS</em>, WNT, NOTCH, and <em>PIK</em> pathways were enriched across all samples. The <em>KMT2D</em> and <em>TP53</em> genes were the most frequently mutated in the primary tumor and corresponding BM. <em>FAT1</em>, <em>NSD1</em>, and <em>NF1</em> mutations were among the most frequent alterations newly detected in BM. Non-druggable hotspot alterations in actionable genes, including <em>EGFR</em>, <em>KRAS</em>, <em>ALK</em>, and <em>ROS1</em>, showed various patterns between the two tumor sites.</div></div><div><h3>Conclusions</h3><div>Our study provides a comprehensive overview of genetic alterations specific to primary NSCLC, unique to BM, and shared between both sites, which may contribute to BM formation affecting various evolutionary trajectories.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108842"},"PeriodicalIF":4.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541179","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}