Pub Date : 2025-11-14DOI: 10.1016/j.lungcan.2025.108840
William J. Phillips , Luna Jia Zhan , Deepro Chowdhury , Jeniszka Gill , Alexander Sun , Rebekah Rittberg , Victor Cohen , Amanda J.W. Gibson , Michael Yan , Daniel Liwski , Saritha Surapaneni , Marie Frederique D’Amours , Fabian P.S. Yu , YongJin Kim , Rana A. Qadeer , David E. Dawe , Jason Agulnik , Vishal Navani , Andrea S. Fung , Stephanie Snow , Sara Moore
Introduction
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.
Methods
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.
Results
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).
Conclusions
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.
几十年来，有限期小细胞肺癌（LS-SCLC）的全身治疗进展甚微。随着ADRIATIC试验的发表，巩固durvalumab成为一种新的治疗标准。本研究评估了免疫治疗时代之前LS-SCLC的实际治疗和临床结果。方法加拿大小细胞肺癌数据库（CASCADE）是一个加拿大多机构联合数据库，包括来自9个学术机构的SCLC患者。该分析包括2001年1月至2022年12月期间病理证实的LS-SCLC治愈患者。从医疗记录中获得基线特征和治疗模式，并进行描述性评估。主要终点是使用Kaplan Meier （KM）方法评估的总生存期（OS）。接受治疗的有资格参加亚得里亚海试验的患者也进行了OS评估。结果共纳入1024例患者。中位年龄66岁，52%的患者为女性。同步放化疗（cCRT）是最常见的治疗方式（76%），其次是手术（11%）和序贯CRT（10%）。中位OS为24.9个月（95%置信区间[CI] = 23.4-27.4）。在接受cCRT治疗的患者中，只有36%的患者接受了符合亚得里亚海试验资格标准的治疗。最常见的不合格原因是由于使用的放射治疗（RT）剂量/时间表。合格和不合格患者的中位OS分别为30.3个月（95% CI = 26.4-36.4）和21.7个月（95% CI = 19.7-24.9）。结论：尽管采用了多模式治疗，但LS-SCLC的生存结果仍然很差。免疫疗法代表了一个有希望的进步，但在现实世界中，有很大比例的患者接受了亚得里亚海试验中没有出现的治疗。未来评估患者免疫治疗结果的工作对于评估其实际影响至关重要。
{"title":"Treatment and outcomes of limited stage small cell lung cancer in the Canadian small cell lung cancer database (CASCADE)","authors":"William J. Phillips , Luna Jia Zhan , Deepro Chowdhury , Jeniszka Gill , Alexander Sun , Rebekah Rittberg , Victor Cohen , Amanda J.W. Gibson , Michael Yan , Daniel Liwski , Saritha Surapaneni , Marie Frederique D’Amours , Fabian P.S. Yu , YongJin Kim , Rana A. Qadeer , David E. Dawe , Jason Agulnik , Vishal Navani , Andrea S. Fung , Stephanie Snow , 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}
Pub Date : 2025-11-14DOI: 10.1016/j.lungcan.2025.108842
Marcin Nicoś , Natalia Galant , Anna Kowalczyk , Rafał Pęksa , Bożena Jarosz , Monika Żuk , Bartosz Wasąg , Renata Duchnowska , Paweł Krawczyk , Jacek Jassem , Nicola Crosetto
Introduction
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.
Methods
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).
Results
Mutations in the RTK-RAS, WNT, NOTCH, and PIK pathways were enriched across all samples. The KMT2D and TP53 genes were the most frequently mutated in the primary tumor and corresponding BM. FAT1, NSD1, and NF1 mutations were among the most frequent alterations newly detected in BM. Non-druggable hotspot alterations in actionable genes, including EGFR, KRAS, ALK, and ROS1, showed various patterns between the two tumor sites.
Conclusions
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.
{"title":"Genetic composition and evolutionary trajectories of brain metastasis in non-small-cell lung cancer","authors":"Marcin Nicoś , Natalia Galant , Anna Kowalczyk , Rafał Pęksa , Bożena Jarosz , Monika Żuk , Bartosz Wasąg , Renata Duchnowska , Paweł Krawczyk , Jacek Jassem , 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}
Pub Date : 2025-11-13DOI: 10.1016/j.lungcan.2025.108839
Bin Luo , Shenhua Liang , Leqi Zhong , Wuyou Gao, Mingyue Zeng, Youfang Chen, Zhesheng Wen
Objectives
This study aimed to evaluate the prognostic value of quantitative N1 nodal burden metrics—including positive node count, positive station count, lymph node ratio (LNR), and lymph node station ratio (LNsR)—in patients with non-skip pN2 non-small cell lung cancer (NSCLC).
Methods
This retrospective study included 477 non-skip pN2 NSCLC patients who underwent complete surgical resection at our center from December 2008 to December 2020. N1 metrics were dichotomized based on optimal cutoffs determined by overall survival (OS). Kaplan-Meier analysis and Cox regression models were utilized to assess disease-free survival (DFS) and OS and to identify independent prognostic factors.
Results
In multivariable analysis, a high N1 LNR emerged as the sole N1 metric that independently predicted worse DFS (HR = 1.47, 95 % CI: 1.05–2.04, p = 0.023). In contrast, its prognostic significance for OS was attenuated (p = 0.162). However, an advanced pT4 stage (p = 0.044) was an independent predictor of worse OS, while adjuvant therapy (p = 0.016) was associated with improved OS. Notably, subgroup analysis revealed that an elevated N1 LNR independently predicted worse DFS in the pN2a subgroup (p = 0.009). Building on this, we developed a novel three-tiered stratification (pN2a-low LNR, pN2a-high LNR, and pN2b) that effectively discriminated patient outcomes for both DFS (p < 0.001) and OS (p < 0.01).
Conclusions
N1 LNR is a powerful and independent predictor of disease recurrence in non-skip pN2 NSCLC, outperforming other N1 metrics for predicting DFS. Incorporating N1 LNR into clinical assessments, particularly for pN2a patients, can enhance prognostic accuracy and potentially guide more personalized surveillance and treatment strategies.
{"title":"Impact of N1 lymph node burden on survival outcomes in non-skip pN2 non-small-cell lung cancer","authors":"Bin Luo , Shenhua Liang , Leqi Zhong , Wuyou Gao, Mingyue Zeng, Youfang Chen, Zhesheng Wen","doi":"10.1016/j.lungcan.2025.108839","DOIUrl":"10.1016/j.lungcan.2025.108839","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to evaluate the prognostic value of quantitative N1 nodal burden metrics—including positive node count, positive station count, lymph node ratio (LNR), and lymph node station ratio (LNsR)—in patients with non-skip pN2 non-small cell lung cancer (NSCLC).</div></div><div><h3>Methods</h3><div>This retrospective study included 477 non-skip pN2 NSCLC patients who underwent complete surgical resection at our center from December 2008 to December 2020. N1 metrics were dichotomized based on optimal cutoffs determined by overall survival (OS). Kaplan-Meier analysis and Cox regression models were utilized to assess disease-free survival (DFS) and OS and to identify independent prognostic factors.</div></div><div><h3>Results</h3><div>In multivariable analysis, a high N1 LNR emerged as the sole N1 metric that independently predicted worse DFS (HR = 1.47, 95 % CI: 1.05–2.04, p = 0.023). In contrast, its prognostic significance for OS was attenuated (p = 0.162). However, an advanced pT4 stage (p = 0.044) was an independent predictor of worse OS, while adjuvant therapy (p = 0.016) was associated with improved OS. Notably, subgroup analysis revealed that an elevated N1 LNR independently predicted worse DFS in the pN2a subgroup (p = 0.009). Building on this, we developed a novel three-tiered stratification (pN2a-low LNR, pN2a-high LNR, and pN2b) that effectively discriminated patient outcomes for both DFS (p < 0.001) and OS (p < 0.01).</div></div><div><h3>Conclusions</h3><div>N1 LNR is a powerful and independent predictor of disease recurrence in non-skip pN2 NSCLC, outperforming other N1 metrics for predicting DFS. Incorporating N1 LNR into clinical assessments, particularly for pN2a patients, can enhance prognostic accuracy and potentially guide<!--> <!-->more personalized surveillance and treatment strategies.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108839"},"PeriodicalIF":4.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518090","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}
Pub Date : 2025-11-12DOI: 10.1016/j.lungcan.2025.108838
Hanbo Pan , Hui Yin , Wanyu Li , Weicheng Kong , Jiaqi Zhang , Hang Chen , Zhen Ge , Yu Tian , Junwei Ning , Zhizhuo Dai , Weiyang Huang , Liang Fang , Min Zheng , Guomo Ruan , Zhongjie Chen , Ming Zhang , Xiaomin Niu , Jia Huang , Chengwei Zhou , Guodong Xu , Qingquan Luo
Objectives
Sub-lobar resection (SR) is an established treatment for peripheral clinical stage IA1-2 (cIA1-2) non-small cell lung cancer (NSCLC). However, it may fail to achieve complete resection and is associated with worse survival than lobar resection (LR) in spread through air spaces (STAS)+ populations. This study aims to define the threshold of an adequate SR margin that may yield survival outcomes comparable to LR in peripheral cIA1-2 STAS+ NSCLC.
Methods
Consecutive patients with peripheral cIA1-2 (consolidation-to-tumor ratio > 0.5) NSCLC who underwent surgery between 2010 and 2020 across seven high-volume institutions were retrospectively reviewed. Stabilized inverse probability of treatment weighting (IPTW) was applied to mitigate selection bias. The primary endpoint was overall survival (OS), and the secondary endpoint was recurrence-free survival (RFS).
Results
A total of 6,027 STAS+ and 15,994 STAS− patients were included. IPTW analyses demonstrated that SR was associated with improved long-term outcomes in STAS− populations, whereas LR provided superior outcomes in STAS+ populations. Greater resection margin length and higher margin-to-tumor ratio (MTR) were independently associated with improved OS and RFS in STAS+ but not in STAS− patients undergoing SR. Among STAS+ patients undergoing SR, cut-point analysis identified threshold values of 2.5 cm for resection margin length and 1.7 for MTR, which were validated in an external multi-center cohort. These cutoff values remained effective in patients with pathological visceral pleural invasion, lymphovascular invasion, or nodal involvement, and in those undergoing either segmentectomy or wedge resection.
Conclusions
In peripheral cIA1-2 NSCLC, STAS status may modify the prognostic impact of both resection extent and margin. For STAS+ patients, an SR margin length of ≥2.5 cm or an MTR of ≥1.7 may be recommended to achieve oncologic outcomes comparable to LR.
{"title":"Threshold of adequate resection margin for sub-lobar resection in peripheral clinical stage IA1-2 non-small cell lung cancer with tumor spread through air spaces","authors":"Hanbo Pan , Hui Yin , Wanyu Li , Weicheng Kong , Jiaqi Zhang , Hang Chen , Zhen Ge , Yu Tian , Junwei Ning , Zhizhuo Dai , Weiyang Huang , Liang Fang , Min Zheng , Guomo Ruan , Zhongjie Chen , Ming Zhang , Xiaomin Niu , Jia Huang , Chengwei Zhou , Guodong Xu , Qingquan Luo","doi":"10.1016/j.lungcan.2025.108838","DOIUrl":"10.1016/j.lungcan.2025.108838","url":null,"abstract":"<div><h3>Objectives</h3><div>Sub-lobar resection (SR) is an established treatment for peripheral clinical stage IA1-2 (cIA1-2) non-small cell lung cancer (NSCLC). However, it may fail to achieve complete resection and is associated with worse survival than lobar resection (LR) in spread through air spaces (STAS)<sup>+</sup> populations. This study aims to define the threshold of an adequate SR margin that may yield survival outcomes comparable to LR in peripheral cIA1-2 STAS<sup>+</sup> NSCLC.</div></div><div><h3>Methods</h3><div>Consecutive patients with peripheral cIA1-2 (consolidation-to-tumor ratio > 0.5) NSCLC who underwent surgery between 2010 and 2020 across seven high-volume institutions were retrospectively reviewed. Stabilized inverse probability of treatment weighting (IPTW) was applied to mitigate selection bias. The primary endpoint was overall survival (OS), and the secondary endpoint was recurrence-free survival (RFS).</div></div><div><h3>Results</h3><div>A total of 6,027 STAS<sup>+</sup> and 15,994 STAS<sup>−</sup> patients were included. IPTW analyses demonstrated that SR was associated with improved long-term outcomes in STAS<sup>−</sup> populations, whereas LR provided superior outcomes in STAS<sup>+</sup> populations. Greater resection margin length and higher margin-to-tumor ratio (MTR) were independently associated with improved OS and RFS in STAS<sup>+</sup> but not in STAS<sup>−</sup> patients undergoing SR. Among STAS<sup>+</sup> patients undergoing SR, cut-point analysis identified threshold values of 2.5 cm for resection margin length and 1.7 for MTR, which were validated in an external multi-center cohort. These cutoff values remained effective in patients with pathological visceral pleural invasion, lymphovascular invasion, or nodal involvement, and in those undergoing either segmentectomy or wedge resection.</div></div><div><h3>Conclusions</h3><div>In peripheral cIA1-2 NSCLC, STAS status may modify the prognostic impact of both resection extent and margin. For STAS<sup>+</sup> patients, an SR margin length of ≥2.5 cm or an MTR of ≥1.7 may be recommended to achieve oncologic outcomes comparable to LR.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108838"},"PeriodicalIF":4.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518053","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}
Pub Date : 2025-11-12DOI: 10.1016/j.lungcan.2025.108837
Arif Hakan Önder
{"title":"Letter to the Editor: On the clinical irrelevance of SUCRA rankings in relapsed small-cell lung cancer","authors":"Arif Hakan Önder","doi":"10.1016/j.lungcan.2025.108837","DOIUrl":"10.1016/j.lungcan.2025.108837","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108837"},"PeriodicalIF":4.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518091","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}
Pub Date : 2025-11-12DOI: 10.1016/j.lungcan.2025.108841
Linrui Ma , Xiangyu Zhang , Shidong Xu , Jiacheng Dai , Zhe Huang , Zhaohui Ruan , Yuda Zhang , Xuexue Zhou , Yuanze Sun , Yahui Chen , Huan Yan , Chun Zou , Si Qi Xiang , Jingyi Li , Yangqian Chen , Tian Xu , Renzhi Zhang , Dan Yang , Fang Tian , Nachuan Zou , Yongchang Zhang
Background
Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. The lack of effective targeted therapies for SCLC is a major limitation of this field. Bromodomain and Extra-Terminal (BET) inhibitors have emerged as a promising class of anticancer agents. This study aimed to evaluate the preclinical efficacy and mechanism of action of NHWD-870, a novel BET inhibitor targeting BRD4, in SCLC.
Method
The therapeutic effects of NHWD-870 on SCLC have been validated through compassionate use. The anti-tumor effects of NHWD-870 were explored using in vitro and in vivo models. CCK-8 assays and flow cytometry were utilized to examine cell viability, apoptosis, and mechanisms of cell cycle arrest. The in vivo effectiveness of NHWD-870 was evaluated using cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of SCLC. Mechanistic studies involving RNA sequencing, Western blotting, qPCR, and transfection were conducted to investigate and confirm the underlying mechanisms of NHWD-870.
Result
Our study observed the efficacy of NHWD-870 in a patient with SCLC. NHWD-870 demonstrated robust anti-tumor activity against SCLC in both in vitro and in vivo models, effectively halting tumor growth, inducing apoptosis, and disrupting the cell cycle. RNA sequencing confirmed that the cell cycle is its primary pathway of action, with BRD4, STRADA, and CCND1 identified as key targets.
Conclusion
NHWD-870 exhibits anti-tumor activity both in vitro and in vivo against SCLC, primarily by regulating the BRD4/STRADA/CCND1 axis and inhibiting the transition of the cell cycle from the G1 phase to the S phase. These findings highlight the therapeutic potential of NHWD-870 as a novel BET inhibitor for SCLC treatment and provide a molecular basis for further clinical development.
{"title":"NHWD-870 suppresses tumor proliferation via the BRD4/STRADA/CCND1 axis in small cell lung cancer","authors":"Linrui Ma , Xiangyu Zhang , Shidong Xu , Jiacheng Dai , Zhe Huang , Zhaohui Ruan , Yuda Zhang , Xuexue Zhou , Yuanze Sun , Yahui Chen , Huan Yan , Chun Zou , Si Qi Xiang , Jingyi Li , Yangqian Chen , Tian Xu , Renzhi Zhang , Dan Yang , Fang Tian , Nachuan Zou , Yongchang Zhang","doi":"10.1016/j.lungcan.2025.108841","DOIUrl":"10.1016/j.lungcan.2025.108841","url":null,"abstract":"<div><h3>Background</h3><div>Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. The lack of effective targeted therapies for SCLC is a major limitation of this field. Bromodomain and Extra-Terminal (BET) inhibitors have emerged as a promising class of anticancer agents. This study aimed to evaluate the preclinical efficacy and mechanism of action of NHWD-870, a novel BET inhibitor targeting BRD4, in SCLC.</div></div><div><h3>Method</h3><div>The therapeutic effects of NHWD-870 on SCLC have been validated through compassionate use. The anti-tumor effects of NHWD-870 were explored using in vitro and in vivo models. CCK-8 assays and flow cytometry were utilized to examine cell viability, apoptosis, and mechanisms of cell cycle arrest. The in vivo effectiveness of NHWD-870 was evaluated using cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of SCLC. Mechanistic studies involving RNA sequencing, Western blotting, qPCR, and transfection were conducted to investigate and confirm the underlying mechanisms of NHWD-870.</div></div><div><h3>Result</h3><div>Our study observed the efficacy of NHWD-870 in a patient with SCLC. NHWD-870 demonstrated robust anti-tumor activity against SCLC in both in vitro and in vivo models, effectively halting tumor growth, inducing apoptosis, and disrupting the cell cycle. RNA sequencing confirmed that the cell cycle is its primary pathway of action, with BRD4, STRADA, and CCND1 identified as key targets.</div></div><div><h3>Conclusion</h3><div>NHWD-870 exhibits anti-tumor activity both in vitro and in vivo against SCLC, primarily by regulating the BRD4/STRADA/CCND1 axis and inhibiting the transition of the cell cycle from the G1 phase to the S phase. These findings highlight the therapeutic potential of NHWD-870 as a novel BET inhibitor for SCLC treatment and provide a molecular basis for further clinical development.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108841"},"PeriodicalIF":4.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518092","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}
Pub Date : 2025-11-08DOI: 10.1016/j.lungcan.2025.108836
Hui Cai , Xiao-Ou Shu , Shenghui Wu , Yu-Tang Gao , Qing Lan , Nathaniel Rothman , Wei Zheng , Gong Yang
Background
Whether female being more susceptible to lung cancer among never smokers (LCNS) than males has been a long-standing debate.
Method
A total of 26,339 married heterosexual couples included in this cohort study. Truncated (40–89) age-standardized incidence rates and incidence rate ratio (IRR) of lung cancer were calculated and compared between the two sexes. Cox regression models were used to estimate hazard ratio (HR) for evaluating sex differences in lung cancer risk.
Results
In this large couples cohort study the prevalence of ever smoking was 2.1 % in wives and 65.4 % in husbands. Over a median follow-up of 12.5 years, incident lung cancer was documented in 293 wives and 500 husbands. The truncated age-standardized incidence rate per 100,000 person-years in all couples was significantly lower in wives (56.1) than their husbands (117.4), with an IRR of 0.48 for wives vs husbands. A similar pattern was observed among dual-smoker couples. However, the sex difference diminished when further adjusting for the duration and intensity of cigarette smoking. In contrast, among dual-nonsmoker couples, the corresponding age-standardized rate was significantly higher in wives (52.6) than their husbands (33.4), with an IRR of 1.57. Multivariable adjustment did not alter the result, with an HR for wives vs husbands of 1.54 (95 % CI, 1.05–2.27).
Conclusions
This study, for the first time, using a large cohort of married couples, demonstrates that females are more susceptible to LCNS than males.
{"title":"Higher lung cancer risk among female never-smokers than males in a large married couple study","authors":"Hui Cai , Xiao-Ou Shu , Shenghui Wu , Yu-Tang Gao , Qing Lan , Nathaniel Rothman , Wei Zheng , Gong Yang","doi":"10.1016/j.lungcan.2025.108836","DOIUrl":"10.1016/j.lungcan.2025.108836","url":null,"abstract":"<div><h3>Background</h3><div>Whether female being more susceptible to lung cancer among never smokers (LCNS) than males has been a long-standing debate.</div></div><div><h3>Method</h3><div>A total of 26,339 married heterosexual couples included in this cohort study. Truncated (40–89) age-standardized incidence rates and incidence rate ratio (IRR) of lung cancer were calculated and compared between the two sexes. Cox regression models were used to estimate hazard ratio (HR) for evaluating sex differences in lung cancer risk.</div></div><div><h3>Results</h3><div>In this large couples cohort study the prevalence of ever smoking was 2.1 % in wives and 65.4 % in husbands. Over a median follow-up of 12.5 years, incident lung cancer was documented in 293 wives and 500 husbands. The truncated age-standardized incidence rate per 100,000 person-years in all couples was significantly lower in wives (56.1) than their husbands (117.4), with an IRR of 0.48 for wives vs husbands. A similar pattern was observed among dual-smoker couples. However, the sex difference diminished when further adjusting for the duration and intensity of cigarette smoking. In contrast, among dual-nonsmoker couples, the corresponding age-standardized rate was significantly higher in wives (52.6) than their husbands (33.4), with an IRR of 1.57. Multivariable adjustment did not alter the result, with an HR for wives vs husbands of 1.54 (95 % CI, 1.05–2.27).</div></div><div><h3>Conclusions</h3><div>This study, for the first time, using a large cohort of married couples, demonstrates that females are more susceptible to LCNS than males.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108836"},"PeriodicalIF":4.4,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518089","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}
EGFR tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the outcomes of EGFR-mutant non-small cell lung cancer (NSCLC); however, resistance commonly develops. While secondary EGFR mutations (e.g., C797S) and histological transformations are known mechanisms, their coexistence at distinct sites is rarely documented.
Methods
We established patient-derived cell lines from pleural effusion and mediastinal lymph node metastasis before and after osimertinib resistance in a patient with EGFR L858R–mutated NSCLC. Resistance mechanisms were characterized using cell viability assays, Western blotting, Sanger sequencing, RNA sequencing, and whole-exome sequencing.
Results
Pleural effusion–derived cells (JFCR-330-4 and -7) retained adenocarcinoma morphology and harbored an acquired EGFR L718V mutation, causing resistance to first-, third- and next-generation TKIs but sensitivity to second-generation TKI afatinib. Conversely, mediastinal lymph node–derived cells (JFCR-330-5) exhibited small cell lung cancer (SCLC)-like morphology, low EGFR expression, high neuroendocrine marker expression, and maintained EGFR L858R. RNA sequencing revealed SCLC-associated transcriptional signatures, while whole-exome and Sanger sequencing identified a small deletion in RB1 gene around exon 19 and a concurrent TP53 mutation, collectively suggesting transformation into SCLC.
Conclusion
Spatially distinct and simultaneous resistance mechanisms, namely, EGFR L718V mutation and SCLC transformation, contributed to osimertinib resistance. The detection of RB1 2.4 kb small deletion in RB1 gene highlights the importance of deep genomic profiling. Multi-site biopsy and molecular diagnostics are necessary to guide treatment decisions in EGFR-TKI–resistant NSCLC.
{"title":"Tumor heterogeneity involving SCLC with a single exon deletion in RB1 and adenocarcinoma with EGFR-L718V mutation in EGFR-TKI–resistant lung cancer","authors":"Sho Kakuto , Ken Uchibori , Yuri Yamamoto , Eisaku Miyauchi , Makoto Nishio , Hisatoshi Sugiura , Ryohei Katayama","doi":"10.1016/j.lungcan.2025.108833","DOIUrl":"10.1016/j.lungcan.2025.108833","url":null,"abstract":"<div><h3>Introduction</h3><div>EGFR tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the outcomes of EGFR-mutant non-small cell lung cancer (NSCLC); however, resistance commonly develops. While secondary EGFR mutations (e.g., C797S) and histological transformations are known mechanisms, their coexistence at distinct sites is rarely documented.</div></div><div><h3>Methods</h3><div>We established patient-derived cell lines from pleural effusion and mediastinal lymph node metastasis before and after osimertinib resistance in a patient with EGFR L858R–mutated NSCLC. Resistance mechanisms were characterized using cell viability assays, Western blotting, Sanger sequencing, RNA sequencing, and whole-exome sequencing.</div></div><div><h3>Results</h3><div>Pleural effusion–derived cells (JFCR-330-4 and -7) retained adenocarcinoma morphology and harbored an acquired EGFR L718V mutation, causing resistance to first-, third- and next-generation TKIs but sensitivity to second-generation TKI afatinib. Conversely, mediastinal lymph node–derived cells (JFCR-330-5) exhibited small cell lung cancer (SCLC)-like morphology, low EGFR expression, high neuroendocrine marker expression, and maintained EGFR L858R. RNA sequencing revealed SCLC-associated transcriptional signatures, while whole-exome and Sanger sequencing identified a small deletion in <em>RB1</em> gene around exon 19 and a concurrent <em>TP53</em> mutation, collectively suggesting transformation into SCLC.</div></div><div><h3>Conclusion</h3><div>Spatially distinct and simultaneous resistance mechanisms, namely, EGFR L718V mutation and SCLC transformation, contributed to osimertinib resistance. The detection of RB1 2.4 kb small deletion in <em>RB1</em> gene highlights the importance of deep genomic profiling. Multi-site biopsy and molecular diagnostics are necessary to guide treatment decisions in EGFR-TKI–resistant NSCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108833"},"PeriodicalIF":4.4,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564309","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}
Pub Date : 2025-11-07DOI: 10.1016/j.lungcan.2025.108832
Adam Khorasanchi , Mingjia Li , Songzhu Zhao , Lai Wei , Evelyn Goodyear , Kevin Ho , Hamzah Abu-Sbeih , Austin Secor , Erin M. Bertino , Peter G. Shields , Logan Roof , Jinesh Gheeya , Kai He , Jacob Kaufman , Regan Memmott , Asrar Alahmadi , David P. Carbone , Gregory A. Otterson , Alexa Meara , Carolyn J. Presley , Dwight H. Owen
Background
Patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are at risk for severe immune-related adverse events (irAEs). Limited data exists on the association between severe irAEs requiring hospitalization (irAEh) and overall survival (OS) in patients with NSCLC who received front-line ICIs, as well as risk factors for irAEh.
Methods
Electronic medical records of consecutive patients with metastatic NSCLC treated with front-line pembrolizumab with or without chemotherapy from 2017 to 2022 were assessed retrospectively. An irAEh was defined as any severe irAE requiring hospitalization within 1 year of ICI initiation. Clinical characteristics for the entire cohort were reported descriptively. Kaplan-Meier survival analysis and the Cox proportional hazard model were used to assess the OS and HR between groups.
Results
Among 312 patients, 203 (65 %) were hospitalized for any reason within 1 year of initiating pembrolizumab, including 37 (12 %) for irAEs. irAEh and overall hospitalization rates did not differ for patients treated with pembrolizumab alone compared to pembrolizumab in combination with chemotherapy. The most common reasons for irAEh were pneumonitis and colitis. Patients with irAEh experienced significantly shorter median OS (8.6 months; 95 % CI: 5.0–19.9) compared to those without irAEh (22.7 months; 95 % CI: 18.2–27.4; P = 0.027). Patients who experienced early-onset irAEh (<6 months) had a significantly shorter median OS of 5.4 months (95 % CI: 2.7–8.6) compared to those with late-onset irAEh (≥6 months), median OS not reached (NR); 95 % CI: 8.6-NR; P = 0.003. Patients hospitalized for any reason during the first year of treatment had a shorter median OS (11.2 months; 95 % CI: 9.5–15.2) than those who were not (49.4 months; 95 % CI: 39.5–62.4; P < 0.001).
Conclusions
Severe irAEs requiring hospitalization or hospitalization for any cause within the first year of initiating pembrolizumab among patients with NSCLC was associated with worse survival outcomes.
{"title":"Impact of immune-related and non-immune related hospital admissions on survival of patients with non-small cell lung cancer receiving first-line immunotherapy","authors":"Adam Khorasanchi , Mingjia Li , Songzhu Zhao , Lai Wei , Evelyn Goodyear , Kevin Ho , Hamzah Abu-Sbeih , Austin Secor , Erin M. Bertino , Peter G. Shields , Logan Roof , Jinesh Gheeya , Kai He , Jacob Kaufman , Regan Memmott , Asrar Alahmadi , David P. Carbone , Gregory A. Otterson , Alexa Meara , Carolyn J. Presley , Dwight H. Owen","doi":"10.1016/j.lungcan.2025.108832","DOIUrl":"10.1016/j.lungcan.2025.108832","url":null,"abstract":"<div><h3>Background</h3><div>Patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are at risk for severe immune-related adverse events (irAEs). Limited data exists on the association between severe irAEs requiring hospitalization (irAEh) and overall survival (OS) in patients with NSCLC who received front-line ICIs, as well as risk factors for irAEh.</div></div><div><h3>Methods</h3><div>Electronic medical records of consecutive patients with metastatic NSCLC treated with front-line pembrolizumab with or without chemotherapy from 2017 to 2022 were assessed retrospectively. An irAEh was defined as any severe irAE requiring hospitalization within 1 year of ICI initiation. Clinical characteristics for the entire cohort were reported descriptively. Kaplan-Meier survival analysis and the Cox proportional hazard model were used to assess the OS and HR between groups.</div></div><div><h3>Results</h3><div>Among 312 patients, 203 (65 %) were hospitalized for any reason within 1 year of initiating pembrolizumab, including 37 (12 %) for irAEs. irAEh and overall hospitalization rates did not differ for patients treated with pembrolizumab alone compared to pembrolizumab in combination with chemotherapy. The most common reasons for irAEh were pneumonitis and colitis. Patients with irAEh experienced significantly shorter median OS (8.6 months; 95 % CI: 5.0–19.9) compared to those without irAEh (22.7 months; 95 % CI: 18.2–27.4; <em>P</em> = 0.027). Patients who experienced early-onset irAEh (<6 months) had a significantly shorter median OS of 5.4 months (95 % CI: 2.7–8.6) compared to those with late-onset irAEh (≥6 months), median OS not reached (NR); 95 % CI: 8.6-NR; <em>P</em> = 0.003. Patients hospitalized for any reason during the first year of treatment had a shorter median OS (11.2 months; 95 % CI: 9.5–15.2) than those who were not (49.4 months; 95 % CI: 39.5–62.4; <em>P</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>Severe irAEs requiring hospitalization or hospitalization for any cause within the first year of initiating pembrolizumab among patients with NSCLC was associated with worse survival outcomes.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108832"},"PeriodicalIF":4.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518052","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}
Pembrolizumab is currently used as a first-line therapy for EGFR- and ALK-negative advanced non-small cell lung cancer (NSCLC). However, whether pembrolizumab alone (P-mono) or combined with platinum chemotherapy (P-combo) provides superior long-term benefit remains unclear.
Methods
We retrospectively analyzed 392 patients with PD-L1 TPS ≥ 1 % treated first-line with P-mono (n = 194) or P-combo (n = 198) between 2019 and 2021. Propensity-score matching across 13 baseline variables yielded two well-balanced cohorts of 97 patients each, with a median follow-ups of 42.8 and 44.1 months, respectively.
Results
P-combo prolonged overall survival (OS) (median 31.8 vs 20.7 months; hazard ratio [HR] 0.67, 95 % confidence interval [CI] 0.46–0.96) and progression-free survival (12.5 vs 7.0 months; HR 0.59, 95 %CI 0.43–0.81). The 3- and 4-year OS rates were 49.8 % and 42.7 %, respectively, with P-combo, compared with 28.1 % and 22.3 % with P-mono. The 48-month restricted mean survival time also favored P-combo (p = 0.039). Additionally, greater benefits were observed among patients aged < 75 years, with ECOG performance status 0–1, PD-L1 TPS 1–49 %, and those using proton-pump inhibitors. Grade ≥ 3 treatment-related adverse events (TRAEs) were more frequent with P-combo (35 % vs 20 %, p = 0.024). However, treatment-related deaths (2 % each) and pneumonitis incidence and severity were comparable; cumulative toxicity curves plateaued after 3 years.
Conclusions
These findings suggest that P-combo showed a durable survival advantage over monotherapy and acceptable TRAEs in patients with PD-L1–positive NSCLC, identifying clinical subgroups most likely to benefit. Prospective randomized trials are warranted to validate these observations and guide optimal first-line treatment strategies.
背景：Pembrolizumab目前被用作EGFR和alk阴性晚期非小细胞肺癌（NSCLC）的一线治疗。然而，是否单独使用派姆单抗（P-mono）或联合铂化疗（P-combo）提供更好的长期获益仍不清楚。方法：我们回顾性分析了2019年至2021年间392例PD-L1 TPS≥1%的一线p -单药治疗患者（n = 194）或p -联合治疗患者（n = 198）。13个基线变量的倾向评分匹配产生了两组均衡的队列，每组97例患者，中位随访时间分别为42.8个月和44.1个月。结果：P-combo延长了总生存期（OS）（中位31.8 vs 20.7个月；风险比[HR] 0.67, 95%可信区间[CI] 0.46-0.96）和无进展生存期（12.5 vs 7.0个月；风险比0.59,95%可信区间[CI] 0.43-0.81）。P-combo组3年和4年生存率分别为49.8%和42.7%，而P-mono组分别为28.1%和22.3%。48个月的限制平均生存时间也有利于p组合（p = 0.039）。此外，在老年患者中观察到更大的获益。结论：这些发现表明，在pd - l1阳性非小细胞肺癌患者中，P-combo比单药治疗和可接受的trae具有持久的生存优势，确定了最有可能受益的临床亚组。有必要进行前瞻性随机试验来验证这些观察结果并指导最佳一线治疗策略。
{"title":"Long-term survival comparison of first-line pembrolizumab versus pembrolizumab plus chemotherapy for patients with advanced non-small cell lung cancer: A multicenter propensity-matched cohort study","authors":"Nao Shoshihara , Kinnosuke Matsumoto , Takayuki Shiroyama , Kiyohide Komuta , Akito Miyazaki , Motohiro Tamiya , Akihiro Tsukaguchi , Akihiro Tamiya , Tomoki Kuge , Yasuhiro Mihashi , Masahide Mori , Keijiro Yamauchi , Hidekazu Suzuki , Yuhei Kinehara , Hirotomo Machiyama , Satoshi Tanaka , Toshie Niki , Soichiro Kato , Yuki Nishikawa , Akio Osa , Atsushi Kumanogoh","doi":"10.1016/j.lungcan.2025.108835","DOIUrl":"10.1016/j.lungcan.2025.108835","url":null,"abstract":"<div><h3>Background</h3><div>Pembrolizumab is currently used as a first-line therapy for EGFR- and ALK-negative advanced non-small cell lung cancer (NSCLC). However, whether pembrolizumab alone (P-mono) or combined with platinum chemotherapy (P-combo) provides superior long-term benefit remains unclear.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 392 patients with PD-L1 TPS ≥ 1 % treated first-line with P-mono (n = 194) or P-combo (n = 198) between 2019 and 2021. Propensity-score matching across 13 baseline variables yielded two well-balanced cohorts of 97 patients each, with a median follow-ups of 42.8 and 44.1 months, respectively.</div></div><div><h3>Results</h3><div>P-combo prolonged overall survival (OS) (median 31.8 vs 20.7 months; hazard ratio [HR] 0.67, 95 % confidence interval [CI] 0.46–0.96) and progression-free survival (12.5 vs 7.0 months; HR 0.59, 95 %CI 0.43–0.81). The 3- and 4-year OS rates were 49.8 % and 42.7 %, respectively, with P-combo, compared with 28.1 % and 22.3 % with P-mono. The 48-month restricted mean survival time also favored P-combo (p = 0.039). Additionally, greater benefits were observed among patients aged < 75 years, with ECOG performance status 0–1, PD-L1 TPS 1–49 %, and those using proton-pump inhibitors. Grade ≥ 3 treatment-related adverse events (TRAEs) were more frequent with P-combo (35 % vs 20 %, p = 0.024). However, treatment-related deaths (2 % each) and pneumonitis incidence and severity were comparable; cumulative toxicity curves plateaued after 3 years.</div></div><div><h3>Conclusions</h3><div>These findings suggest that P-combo showed a durable survival advantage over monotherapy and acceptable TRAEs in patients with PD-L1–positive NSCLC, identifying clinical subgroups most likely to benefit. Prospective randomized trials are warranted to validate these observations and guide optimal first-line treatment strategies.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108835"},"PeriodicalIF":4.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495633","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}
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