The Advanced Lung Cancer Inflammation Index (ALI) has shown potential as a prognostic marker in lung cancer, but its role in early-stage non-small cell lung cancer (NSCLC) remains underexplored. This study evaluated the prognostic value of ALI in stage I NSCLC patients.
Methods
This registry-based study enrolled 934 stage I NSCLC patients diagnosed between 2015 and 2020 from the Danish Lung Cancer Registry (DLCR). Data from DLCR were merged with laboratory records. ALI was calculated as body mass index x albumin/neutrophil-to-lymphocyte ratio and dichotomized at the cohort median. Kaplan–Meier analysis (restricted mean survival time truncated at 6 years), Cox proportional hazards model, and C-statistics were used to assess the value of ALI on overall survival (OS) and disease-free survival (DFS).
Results
In patients receiving stereotactic radiation therapy (RT) (n = 301), a significantly longer mean survival was observed in the high ALI group compared with the low ALI group (5.12 vs. 4.81 years; P = .040). Multivariate analysis confirmed ALI as an independent prognostic factor for OS (HR 0.70, 95% CI, 0.51-0.96). No significant association with DFS was observed. In the surgically treated patients (n = 633), ALI was not associated with OS or DFS. C-statistics demonstrated that adding ALI significantly improved prognostic models for OS but not DFS independent of treatment.
Conclusion
ALI is an independent prognostic factor for OS in stage I NSCLC patients treated with stereotactic RT, but not in surgically treated patients. Incorporating ALI into prognostic models improved OS prediction, supporting its role as a simple biomarker in early-stage NSCLC.
{"title":"Advanced Lung Cancer Inflammation Index has Prognostic Impact in Stage I Non-Small Cell Lung Cancer: A Registry-Based Analysis of 934 Patients","authors":"Camilla Højbjerg Gregersen , Ninna Aggerholm-Pedersen , Birgitte Sandfeld-Paulsen , Anne Winther-Larsen","doi":"10.1016/j.cllc.2025.10.013","DOIUrl":"10.1016/j.cllc.2025.10.013","url":null,"abstract":"<div><h3>Background</h3><div>The Advanced Lung Cancer Inflammation Index (ALI) has shown potential as a prognostic marker in lung cancer, but its role in early-stage non-small cell lung cancer (NSCLC) remains underexplored. This study evaluated the prognostic value of ALI in stage I NSCLC patients.</div></div><div><h3>Methods</h3><div>This registry-based study enrolled 934 stage I NSCLC patients diagnosed between 2015 and 2020 from the Danish Lung Cancer Registry (DLCR). Data from DLCR were merged with laboratory records. ALI was calculated as body mass index x albumin/neutrophil-to-lymphocyte ratio and dichotomized at the cohort median. Kaplan–Meier analysis (restricted mean survival time truncated at 6 years), Cox proportional hazards model, and C-statistics were used to assess the value of ALI on overall survival (OS) and disease-free survival (DFS).</div></div><div><h3>Results</h3><div>In patients receiving stereotactic radiation therapy (RT) (<em>n</em> = 301), a significantly longer mean survival was observed in the high ALI group compared with the low ALI group (5.12 vs. 4.81 years; <em>P</em> = .040). Multivariate analysis confirmed ALI as an independent prognostic factor for OS (HR 0.70, 95% CI, 0.51-0.96). No significant association with DFS was observed. In the surgically treated patients (<em>n</em> = 633), ALI was not associated with OS or DFS. C-statistics demonstrated that adding ALI significantly improved prognostic models for OS but not DFS independent of treatment.</div></div><div><h3>Conclusion</h3><div>ALI is an independent prognostic factor for OS in stage I NSCLC patients treated with stereotactic RT, but not in surgically treated patients. Incorporating ALI into prognostic models improved OS prediction, supporting its role as a simple biomarker in early-stage NSCLC.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 1","pages":"Pages 24-33"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578334","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}
Pub Date : 2026-01-01Epub Date: 2025-11-09DOI: 10.1016/j.cllc.2025.11.006
Agostina E. Velo , Jeremy Mudd , Christopher G. Slatore , Raja Flores , Scott Swanson , Cardinale B. Smith , Mark Chidel , Kenneth E. Rosenzweig , Jeffrey A. Kern , Juan P. Wisnivesky
Background
Treatment decision-making for early-stage non–small cell lung cancer (NSCLC) in patients who have high-operative risk is complex. Identifying patient factors that influence physicians’ choices between sublobar resection and stereotactic body radiotherapy (SBRT) is important for guiding cancer care.
Methods
In this multicenter prospective study, patients with stage I NSCLC at high surgical risk were treated with either sublobar resection or SBRT. We collected data on demographics, comorbidities, lung function, functional status, and tumor characteristics. Before treatment, the primary physician rated each patient’s candidacy for SBRT versus sublobar resection on a 0 to 100 scale. Linear regression was used to identify factors influencing treatment recommendations.
Results
Among 331 patients, 62% received SBRT. Older age (mean difference [MD] 0.66 per year; 95% confidence interval [CI], 0.18 to 1.14) and chronic obstructive pulmonary disease (MD 9.77; 95% CI, 0.54 to 18.99) were associated with higher likelihood of SBRT candidacy. In contrast, higher forced expiratory volume (MD −0.23 per % increase; 95% CI, −0.42 to −0.04), larger tumor size (MD −4.13 per cm increase; 95% CI, −8.13 to −0.12), and better functional scores (MD −0.99; 95% CI, −1.64 to −0.35) decreased the likelihood of being considered for SBRT.
Conclusions
In patients with early-stage NSCLC with high-operative risk, treatment decisions are influenced by age, comorbidities, lung function, and tumor features. These findings can guide clinicians in evaluating treatment options and support shared decision-making.
{"title":"Factors Associated With Provider Decision-Making of Early-Stage Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy or Sublobar Resection","authors":"Agostina E. Velo , Jeremy Mudd , Christopher G. Slatore , Raja Flores , Scott Swanson , Cardinale B. Smith , Mark Chidel , Kenneth E. Rosenzweig , Jeffrey A. Kern , Juan P. Wisnivesky","doi":"10.1016/j.cllc.2025.11.006","DOIUrl":"10.1016/j.cllc.2025.11.006","url":null,"abstract":"<div><h3>Background</h3><div>Treatment decision-making for early-stage non–small cell lung cancer (NSCLC) in patients who have high-operative risk is complex. Identifying patient factors that influence physicians’ choices between sublobar resection and stereotactic body radiotherapy (SBRT) is important for guiding cancer care.</div></div><div><h3>Methods</h3><div>In this multicenter prospective study, patients with stage I NSCLC at high surgical risk were treated with either sublobar resection or SBRT. We collected data on demographics, comorbidities, lung function, functional status, and tumor characteristics. Before treatment, the primary physician rated each patient’s candidacy for SBRT versus sublobar resection on a 0 to 100 scale. Linear regression was used to identify factors influencing treatment recommendations.</div></div><div><h3>Results</h3><div>Among 331 patients, 62% received SBRT. Older age (mean difference [MD] 0.66 per year; 95% confidence interval [CI], 0.18 to 1.14) and chronic obstructive pulmonary disease (MD 9.77; 95% CI, 0.54 to 18.99) were associated with higher likelihood of SBRT candidacy. In contrast, higher forced expiratory volume (MD −0.23 per % increase; 95% CI, −0.42 to −0.04), larger tumor size (MD −4.13 per cm increase; 95% CI, −8.13 to −0.12), and better functional scores (MD −0.99; 95% CI, −1.64 to −0.35) decreased the likelihood of being considered for SBRT.</div></div><div><h3>Conclusions</h3><div>In patients with early-stage NSCLC with high-operative risk, treatment decisions are influenced by age, comorbidities, lung function, and tumor features. These findings can guide clinicians in evaluating treatment options and support shared decision-making.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 1","pages":"Pages 59-69"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687120","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}
Background: Immune checkpoint inhibitors (ICIs) with platinum-doublet chemotherapy (Chemo-ICIs) are used as the standard treatment for advanced non-small cell lung cancer (NSCLC) with performance status (PS) 0 to 1. However, patients with PS2 are often excluded from clinical trials, leading to an evidence gap that makes it difficult to select the optimal treatment strategy. The efficacy and safety of first-line Chemo-ICIs in PS2 remain unclear.
Patients and methods: This multicenter retrospective cohort study analyzed real-world data of 2425 patients with stage IV NSCLC and PS0 to 2 without driver oncogenes. Propensity score matching was used to compare outcomes between patients receiving Chemo and those receiving Chemo-ICIs. Primary endpoints included progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), and the incidence of grade ≥ 3 adverse events.
Results: Among 424 patients with PS2 (median age 71 years; 73% men), 56 received Chemo-ICIs and 117 received Chemo. After matching, median PFS was significantly longer in the Chemo-ICIs group (5.7 vs. 2.3 months; hazard ratio [HR] 0.58 [0.36-0.93]; P = .025), and ORR was higher (43% vs. 21%; P = .02). OS showed a non-significant trend toward improvement (8.0 vs. 6.0 months; HR 0.75 [0.47-1.19]; P = .219). Rates of grade ≥ 3 adverse events were comparable (50.0% vs. 43.6%; P = .514).
Conclusions: Chemo-ICIs significantly improved PFS and ORR compared to Chemo in patients with NSCLC with PS2 without higher toxicity. These findings highlight the clinical relevance of chemoimmunotherapy in patients with PS2 and may help bridge the evidence gap in existing treatment guidelines.
背景：免疫检查点抑制剂（ICIs）联合铂双药化疗（Chemo-ICIs）被用作治疗性能状态（PS）为0 - 1的晚期非小细胞肺癌（NSCLC）的标准治疗。然而，PS2患者经常被排除在临床试验之外，导致证据空白，难以选择最佳治疗策略。一线Chemo-ICIs治疗PS2的疗效和安全性尚不清楚。患者和方法：这项多中心回顾性队列研究分析了2425例无驱动癌基因的IV期NSCLC和PS0至2期患者的真实数据。倾向评分匹配用于比较接受化疗的患者和接受化疗- icis的患者之间的结果。主要终点包括无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）和≥3级不良事件发生率。结果：在424例PS2患者中（中位年龄71岁，73%为男性），56例接受了Chemo- icis， 117例接受了Chemo。匹配后，化疗- icis组的中位PFS明显更长（5.7 vs 2.3个月；风险比[HR] 0.58 [0.36-0.93]; P = 0.025）， ORR更高（43% vs 21%; P = 0.02）。OS无明显改善趋势（8.0 vs. 6.0个月；HR 0.75 [0.47-1.19]; P = 0.219）。≥3级不良事件发生率具有可比性（50.0% vs 43.6%; P = .514）。结论：与化疗相比，化疗icis显著改善了NSCLC伴PS2患者的PFS和ORR，且没有更高的毒性。这些发现强调了化疗免疫治疗在PS2患者中的临床相关性，并可能有助于弥补现有治疗指南中的证据差距。
{"title":"Multicenter Real-World Data on First-Line Chemoimmunotherapy in Patients With Advanced Non-Small Cell Lung Cancer and Performance Status 2: WJOG18424L.","authors":"Shunichi Kataoka, Takehito Shukuya, Hiroshi Ohtsu, Taichi Miyawaki, Daichi Fujimoto, Hidetoshi Hayashi, Yukihiro Toi, Toshihide Yokoyama, Teruhumi Kato, Teppei Yamaguchi, Kaoru Tanaka, Satoru Miura, Motohiro Tamiya, Motoko Tachihara, Kohei Otsubo, Yuki Sato, Satoshi Ikeda, Shinya Sakata, Takeshi Masuda, Shinnosuke Takemoto, Nobuyuki Yamamoto, Isamu Okamoto, Kazuhisa Takahashi","doi":"10.1016/j.cllc.2025.12.002","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.12.002","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) with platinum-doublet chemotherapy (Chemo-ICIs) are used as the standard treatment for advanced non-small cell lung cancer (NSCLC) with performance status (PS) 0 to 1. However, patients with PS2 are often excluded from clinical trials, leading to an evidence gap that makes it difficult to select the optimal treatment strategy. The efficacy and safety of first-line Chemo-ICIs in PS2 remain unclear.</p><p><strong>Patients and methods: </strong>This multicenter retrospective cohort study analyzed real-world data of 2425 patients with stage IV NSCLC and PS0 to 2 without driver oncogenes. Propensity score matching was used to compare outcomes between patients receiving Chemo and those receiving Chemo-ICIs. Primary endpoints included progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), and the incidence of grade ≥ 3 adverse events.</p><p><strong>Results: </strong>Among 424 patients with PS2 (median age 71 years; 73% men), 56 received Chemo-ICIs and 117 received Chemo. After matching, median PFS was significantly longer in the Chemo-ICIs group (5.7 vs. 2.3 months; hazard ratio [HR] 0.58 [0.36-0.93]; P = .025), and ORR was higher (43% vs. 21%; P = .02). OS showed a non-significant trend toward improvement (8.0 vs. 6.0 months; HR 0.75 [0.47-1.19]; P = .219). Rates of grade ≥ 3 adverse events were comparable (50.0% vs. 43.6%; P = .514).</p><p><strong>Conclusions: </strong>Chemo-ICIs significantly improved PFS and ORR compared to Chemo in patients with NSCLC with PS2 without higher toxicity. These findings highlight the clinical relevance of chemoimmunotherapy in patients with PS2 and may help bridge the evidence gap in existing treatment guidelines.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896420","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}
Pub Date : 2025-12-01Epub Date: 2025-07-19DOI: 10.1016/j.cllc.2025.07.011
Yuanze Sun , Dan Yang , Zhe Huang , Huan Yan , Liang Zeng , Qinqin Xu , Lianxi Song , Chunhua Zhou , Ling Peng , Jiwen Xiao , Shaoding Lin , Zhiqing Zhou , Siqi Xiang , Zhaohui Ruan , Nong Yang , Yongchang Zhang
Background
DNA-based next-generation sequencing (NGS) has identified ALK rearrangements in lung squamous cell carcinoma (LUSC), a subset of nonsmall cell lung cancer traditionally lacking effective targeted therapies. While ALK tyrosine kinase inhibitors (TKIs) like crizotinib and alectinib are effective in ALK-rearranged lung adenocarcinoma, their efficacy in LUSC remains poorly defined due to limited subtype-specific data.
Methods
We presented a case of ALK-rearranged LUSC and established a patient-derived xenograft (PDX) model to validate the tumor-inhibitory effects of various ALK-TKIs on ALK-positive LUSC. Additionally, we conducted a retrospective study that included 28 patients diagnosed with stage IIIC-IV LUSC who received treatment at Hunan Cancer Hospital between June 2014 and May 2024 to evaluate the clinical characteristics and therapeutic outcomes of ALK-rearranged LUSC in a real-world cohort.
Results
We report a patient with LUSC harboring a novel CSNK1G3-ALK fusion, who demonstrated treatment response and durable disease control with first-line alectinib for over 30 months. PDX-based in vivo studies demonstrated significant tumor shrinkage with crizotinib, alectinib, and lorlatinib compared to vehicle control. In the retrospective cohort (n = 28), first-line ALK-TKI treatment was associated with improved progression-free survival (median PFS: 16.0 months vs. 3.0 months, P < .01), overall survival (median OS: 30.0 months vs. 18.5 months, P = .039), and objective response rates (ORR: 75% vs. 25%, P = .021), compared to first-line chemotherapy.
Conclusions
This study provides real-world evidence supporting the therapeutic benefit of ALK-TKIs in ALK-rearranged LUSC, highlighting their potential as a viable therapeutic strategy for this rare nonsmall cell lung cancer subtype.
背景：基于dna的新一代测序（NGS）已经在肺鳞状细胞癌（LUSC）中发现了ALK重排，LUSC是传统上缺乏有效靶向治疗的非小细胞肺癌的一个亚群。虽然ALK酪氨酸激酶抑制剂（TKIs）如克里唑替尼和阿勒替尼对ALK重排肺腺癌有效，但由于亚型特异性数据有限，它们对LUSC的疗效仍不明确。方法：我们提出了一例alk重排LUSC，并建立了患者来源的异种移植（PDX）模型，以验证各种ALK-TKIs对alk阳性LUSC的肿瘤抑制作用。此外，我们进行了一项回顾性研究，纳入了2014年6月至2024年5月在湖南省肿瘤医院接受治疗的28例IIIC-IV期LUSC患者，以评估真实世界队列中alk重排LUSC的临床特征和治疗结果。结果：我们报告了一名具有新型CSNK1G3-ALK融合的LUSC患者，该患者在一线alectinib治疗反应和持久的疾病控制超过30个月。基于pdx的体内研究表明，与对照相比，克唑替尼、阿勒替尼和氯拉替尼的肿瘤缩小显著。在回顾性队列（n = 28）中，与一线化疗相比，一线ALK-TKI治疗改善了无进展生存期（中位PFS: 16.0个月vs. 3.0个月，P < 0.01）、总生存期（中位OS: 30.0个月vs. 18.5个月，P = 0.039）和客观缓解率（ORR: 75% vs. 25%, P = 0.021）。结论：本研究提供了真实世界的证据，支持ALK-TKIs在alk重排LUSC中的治疗益处，突出了它们作为这种罕见的非小细胞肺癌亚型的可行治疗策略的潜力。
{"title":"Clinical Outcomes of Patients With Advanced ALK-Rearranged Lung Squamous Cell Carcinoma Treated With ALK Tyrosine Kinase Inhibitors","authors":"Yuanze Sun , Dan Yang , Zhe Huang , Huan Yan , Liang Zeng , Qinqin Xu , Lianxi Song , Chunhua Zhou , Ling Peng , Jiwen Xiao , Shaoding Lin , Zhiqing Zhou , Siqi Xiang , Zhaohui Ruan , Nong Yang , Yongchang Zhang","doi":"10.1016/j.cllc.2025.07.011","DOIUrl":"10.1016/j.cllc.2025.07.011","url":null,"abstract":"<div><h3>Background</h3><div>DNA-based next-generation sequencing (NGS) has identified <em>ALK</em> rearrangements in lung squamous cell carcinoma (LUSC), a subset of nonsmall cell lung cancer traditionally lacking effective targeted therapies. While ALK tyrosine kinase inhibitors (TKIs) like crizotinib and alectinib are effective in <em>ALK</em>-rearranged lung adenocarcinoma, their efficacy in LUSC remains poorly defined due to limited subtype-specific data.</div></div><div><h3>Methods</h3><div>We presented a case of <em>ALK</em>-rearranged LUSC and established a patient-derived xenograft (PDX) model to validate the tumor-inhibitory effects of various ALK-TKIs on ALK-positive LUSC. Additionally, we conducted a retrospective study that included 28 patients diagnosed with stage IIIC-IV LUSC who received treatment at Hunan Cancer Hospital between June 2014 and May 2024 to evaluate the clinical characteristics and therapeutic outcomes of <em>ALK</em>-rearranged LUSC in a real-world cohort.</div></div><div><h3>Results</h3><div>We report a patient with LUSC harboring a novel <em>CSNK1G3-ALK</em> fusion, who demonstrated treatment response and durable disease control with first-line alectinib for over 30 months. PDX-based <em>in vivo</em> studies demonstrated significant tumor shrinkage with crizotinib, alectinib, and lorlatinib compared to vehicle control. In the retrospective cohort (<em>n</em> = 28), first-line ALK-TKI treatment was associated with improved progression-free survival (median PFS: 16.0 months vs. 3.0 months, <em>P</em> < .01), overall survival (median OS: 30.0 months vs. 18.5 months, <em>P</em> = .039), and objective response rates (ORR: 75% vs. 25%, <em>P</em> = .021), compared to first-line chemotherapy.</div></div><div><h3>Conclusions</h3><div>This study provides real-world evidence supporting the therapeutic benefit of ALK-TKIs in <em>ALK</em>-rearranged LUSC, highlighting their potential as a viable therapeutic strategy for this rare nonsmall cell lung cancer subtype.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages 617-625.e6"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811893","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}
Pub Date : 2025-12-01Epub Date: 2025-07-22DOI: 10.1016/j.cllc.2025.07.015
Tuğba Akın Telli , Ali Murat Tatlı , Özkan Alan , Gülsema Yıldıran Keskin , Nuri Karadurmuş , Serdar Karakaya , Muhammet Ali Kaplan , Özgür Açıkgöz , Ahmet Bilici , Eda Eylemer Mocan , Ahmet Demirkazık , Seda Kahraman , Mehmet AN. Şendur , Mutlu Doğan , Meltem Topalgökçeli Selam , Özlem Er , Oktay Ünsal , Ozan Yazıcı , Erkan Özcan , Ayşegül Kargı , Perran Fulden Yumuk
Background
Real-world data on BRAF-mutant non-small cell lung cancer (NSCLC) remain limited, particularly regarding outcomes with dabrafenib plus trametinib (D + T).
Methods
This multicenter retrospective study included 88 patients with advanced BRAF-mutant NSCLC treated across 30 centers. Clinicopathologic characteristics, treatment outcomes, and safety data were collected and analyzed. Patients received either chemotherapy or dabrafenib plus trametinib in the first-line or subsequent settings. Progression-free survival (PFS), overall survival (OS), and objective response rates (ORR) were compared across treatment groups.
Results
Among 88 patients (78 V600E, 10 non-V600E), median age was 64 years. Co-mutations were more frequent in non-V600E cases (40% vs. 10%). Brain metastases were more frequent in non-V600E cases (60% vs. 15%, p = .001). First-line D + T was associated with superior ORR (67% vs. 39%, p = .02), DCR (81% vs. 51%, p = .009), and PFS (median 13.1 vs. 6.1 months, p = .007) compared to chemotherapy, while OS was similar between groups. Among chemotherapy regimens, platinum-pemetrexed outperformed platinum-taxane in terms of ORR (77% vs. 33%, p = .006) and PFS (median 14.7 vs. 3.2 months, p = .002). No significant differences in efficacy were observed between first-line and later-line use of D + T. Co-mutations were associated with shorter OS (median 8.7 vs. 20.2 months, p = .009). PD-L1 status and BRAF subtype did not impact OS. Median treatment duration with D + T was 10.6 months, with treatment-related adverse events occurring in 61% of patients, most commonly fatigue and pyrexia.
Conclusions
In this real-world cohort, dabrafenib plus trametinib was associated with superior response rates and PFS compared to chemotherapy in the first-line setting. Presence of co-mutations was associated with poorer outcomes.
背景：braf突变的非小细胞肺癌（NSCLC）的实际数据仍然有限，特别是关于达非尼加曲美替尼（D + T）的结果。方法：这项多中心回顾性研究包括在30个中心接受治疗的88例晚期braf突变NSCLC患者。收集和分析临床病理特征、治疗结果和安全性数据。患者在一线或后续环境中接受化疗或达非尼加曲美替尼。比较各治疗组的无进展生存期（PFS）、总生存期（OS）和客观缓解率（ORR）。结果：88例患者（V600E 78例，非V600E 10例），中位年龄64岁。在非v600e病例中，共突变更为频繁（40%比10%）。脑转移在非v600e病例中更常见（60%比15%，p = 0.001）。与化疗相比，一线D + T与更高的ORR （67% vs. 39%, p = 0.02）、DCR （81% vs. 51%, p = 0.009）和PFS（中位13.1 vs. 6.1个月，p = 0.009）相关，而组间OS相似。在化疗方案中，铂-培美曲塞在ORR （77% vs. 33%, p = 0.006）和PFS（中位14.7 vs. 3.2个月，p = 0.002）方面优于铂-紫杉烷。一线和后期使用D + t的疗效无显著差异，共突变与较短的OS相关（中位8.7个月vs. 20.2个月，p = 0.009）。PD-L1状态和BRAF亚型对OS无影响。D + T治疗的中位持续时间为10.6个月，61%的患者发生治疗相关不良事件，最常见的是疲劳和发热。结论：在这个真实世界的队列中，与一线化疗相比，达非尼加曲美替尼与更高的缓解率和PFS相关。共突变的存在与较差的预后相关。
{"title":"Real-World Outcomes in BRAF-Mutant Non-small Cell Lung Cancer: A Multicenter Analysis From the Turkish Oncology Group","authors":"Tuğba Akın Telli , Ali Murat Tatlı , Özkan Alan , Gülsema Yıldıran Keskin , Nuri Karadurmuş , Serdar Karakaya , Muhammet Ali Kaplan , Özgür Açıkgöz , Ahmet Bilici , Eda Eylemer Mocan , Ahmet Demirkazık , Seda Kahraman , Mehmet AN. Şendur , Mutlu Doğan , Meltem Topalgökçeli Selam , Özlem Er , Oktay Ünsal , Ozan Yazıcı , Erkan Özcan , Ayşegül Kargı , Perran Fulden Yumuk","doi":"10.1016/j.cllc.2025.07.015","DOIUrl":"10.1016/j.cllc.2025.07.015","url":null,"abstract":"<div><h3>Background</h3><div>Real-world data on BRAF-mutant non-small cell lung cancer (NSCLC) remain limited, particularly regarding outcomes with dabrafenib plus trametinib (<em>D</em> + <em>T</em>).</div></div><div><h3>Methods</h3><div>This multicenter retrospective study included 88 patients with advanced BRAF-mutant NSCLC treated across 30 centers. Clinicopathologic characteristics, treatment outcomes, and safety data were collected and analyzed. Patients received either chemotherapy or dabrafenib plus trametinib in the first-line or subsequent settings. Progression-free survival (PFS), overall survival (OS), and objective response rates (ORR) were compared across treatment groups.</div></div><div><h3>Results</h3><div>Among 88 patients (78 V600E, 10 non-V600E), median age was 64 years. Co-mutations were more frequent in non-V600E cases (40% vs. 10%). Brain metastases were more frequent in non-V600E cases (60% vs. 15%, <em>p</em> = .001). First-line <em>D</em> + <em>T</em> was associated with superior ORR (67% vs. 39%, <em>p</em> = .02), DCR (81% vs. 51%, <em>p</em> = .009), and PFS (median 13.1 vs. 6.1 months, <em>p</em> = .007) compared to chemotherapy, while OS was similar between groups. Among chemotherapy regimens, platinum-pemetrexed outperformed platinum-taxane in terms of ORR (77% vs. 33%, <em>p</em> = .006) and PFS (median 14.7 vs. 3.2 months, <em>p</em> = .002). No significant differences in efficacy were observed between first-line and later-line use of <em>D</em> + <em>T</em>. Co-mutations were associated with shorter OS (median 8.7 vs. 20.2 months, <em>p</em> = .009). PD-L1 status and BRAF subtype did not impact OS. Median treatment duration with <em>D</em> + <em>T</em> was 10.6 months, with treatment-related adverse events occurring in 61% of patients, most commonly fatigue and pyrexia.</div></div><div><h3>Conclusions</h3><div>In this real-world cohort, dabrafenib plus trametinib was associated with superior response rates and PFS compared to chemotherapy in the first-line setting. Presence of co-mutations was associated with poorer outcomes.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages e649-e659"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854796","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}
Pub Date : 2025-12-01Epub Date: 2025-08-26DOI: 10.1016/j.cllc.2025.08.015
Noah H Richardson , Alexander S Watson , Tejas Patil , David Ross Camidge , Nasser H Hanna , Misty D Shields
•
Lorlatinib, a potent CNS penetrant oral ALK tyrosine kinase inhibitor, is approved in multiple countries for the treatment of advanced/metastatic ALK-positive NSCLC. However, data on dose-escalated strategy in patients with isolated CNS progression and prior lorlatinib exposure is lacking.
•
We report the feasibility of using escalated dose of lorlatinib (125-150 mg daily) in 2 patients with metastatic ALK-positive NSCLC and progressive brain metastasis with previous lorlatinib exposure who obtained disease control with multimodality therapies incorporating dose-escalated lorlatinib.
•
Use of dose-escalated lorlatinib was well tolerated, further investigation of dose-escalated lorlatinib for isolated CNS progression in patients on lorlatinib exposure is suggested.
{"title":"Management of Central Nervous System Progression With Dose-Escalated Lorlatinib in ALK-Positive NSCLC: A Report of 2 Cases and Literature Review","authors":"Noah H Richardson , Alexander S Watson , Tejas Patil , David Ross Camidge , Nasser H Hanna , Misty D Shields","doi":"10.1016/j.cllc.2025.08.015","DOIUrl":"10.1016/j.cllc.2025.08.015","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Lorlatinib, a potent CNS penetrant oral ALK tyrosine kinase inhibitor, is approved in multiple countries for the treatment of advanced/metastatic ALK-positive NSCLC. However, data on dose-escalated strategy in patients with isolated CNS progression and prior lorlatinib exposure is lacking.</div></span></li><li><span>•</span><span><div>We report the feasibility of using escalated dose of lorlatinib (125-150 mg daily) in 2 patients with metastatic ALK-positive NSCLC and progressive brain metastasis with previous lorlatinib exposure who obtained disease control with multimodality therapies incorporating dose-escalated lorlatinib.</div></span></li><li><span>•</span><span><div>Use of dose-escalated lorlatinib was well tolerated, further investigation of dose-escalated lorlatinib for isolated CNS progression in patients on lorlatinib exposure is suggested.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages 680-684"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074648","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}
Pub Date : 2025-12-01Epub Date: 2025-08-26DOI: 10.1016/j.cllc.2025.08.013
Aakash Desai, Ellen McNeeley, Sanad Alhushki, Mia Haught, Juan Xavier Masjoan Juncos, Dhartiben Patel, Jeffery Brand, Leigh McManus, Sejong Bae, Maya Khalil, Yanis Boumber
Background
Immune checkpoint inhibitors (ICIs) have improved outcomes in metastatic non–small cell lung cancer (NSCLC), but benefit in tumors lacking PD-L1 expression remains limited. Dual checkpoint blockade may enhance antitumor immunity by overcoming an immunologically “cold” tumor microenvironment. Circulating tumor DNA (ctDNA) is an emerging early response biomarker.
Patients and Methods
The DISCERN study (UAB 2432) is a single-center, randomized, open-label pilot trial comparing dual immune checkpoint blockade (nivolumab + ipilimumab) plus chemotherapy (Arm A) versus single ICI (pembrolizumab) plus chemotherapy (Arm B) in patients with PD-L1-negative, stage IV NSCLC. The study plans to enroll 24 patients. ctDNA positivity is required at baseline. ctDNA response is evaluated at Cycle 3 Day 1 using Guardant Infinity NGS platform. Primary endpoint is ctDNA molecular response. Secondary endpoints include RECIST-based response rates, progression-free survival (PFS), and overall survival (OS).
Conclusion
DISCERN will provide novel insight into the comparative impact of dual versus single ICI regimens in PD-L1-negative NSCLC and the potential role of ctDNA clearance as an early marker of treatment efficacy in this subset of NSCLC.
{"title":"DISCERN: A Randomized Pilot Study Comparing Dual Versus Single Immune Checkpoint Blockade Plus Chemotherapy in PD-L1 Negative Advanced Non-Small Cell Lung Cancer","authors":"Aakash Desai, Ellen McNeeley, Sanad Alhushki, Mia Haught, Juan Xavier Masjoan Juncos, Dhartiben Patel, Jeffery Brand, Leigh McManus, Sejong Bae, Maya Khalil, Yanis Boumber","doi":"10.1016/j.cllc.2025.08.013","DOIUrl":"10.1016/j.cllc.2025.08.013","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs) have improved outcomes in metastatic non–small cell lung cancer (NSCLC), but benefit in tumors lacking PD-L1 expression remains limited. Dual checkpoint blockade may enhance antitumor immunity by overcoming an immunologically “cold” tumor microenvironment. Circulating tumor DNA (ctDNA) is an emerging early response biomarker.</div></div><div><h3>Patients and Methods</h3><div>The DISCERN study (UAB 2432) is a single-center, randomized, open-label pilot trial comparing dual immune checkpoint blockade (nivolumab + ipilimumab) plus chemotherapy (Arm A) versus single ICI (pembrolizumab) plus chemotherapy (Arm B) in patients with PD-L1-negative, stage IV NSCLC. The study plans to enroll 24 patients. ctDNA positivity is required at baseline. ctDNA response is evaluated at Cycle 3 Day 1 using Guardant Infinity NGS platform. Primary endpoint is ctDNA molecular response. Secondary endpoints include RECIST-based response rates, progression-free survival (PFS), and overall survival (OS).</div></div><div><h3>Conclusion</h3><div>DISCERN will provide novel insight into the comparative impact of dual versus single ICI regimens in PD-L1-negative NSCLC and the potential role of ctDNA clearance as an early marker of treatment efficacy in this subset of NSCLC.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages e743-e744"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063330","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}
Pub Date : 2025-12-01Epub Date: 2025-09-18DOI: 10.1016/j.cllc.2025.09.004
Hanbo Pan , Weiyang Huang , Wanlin Yang , Ling Li , Zhen Ge , Weicheng Kong , Hang Chen , Yu Tian , Wanyu Li , Junwei Ning , Liang Fang , Zhongjie Chen , Guomo Ruan , Zhizhuo Dai , Min Zheng , Ming Zhang , Hui Wang , Xiaomin Niu , Jia Huang , Hui Yin , Qingquan Luo
Background
The role of adjuvant chemotherapy (ACT) for stage IA lung adenocarcinoma (LUAD) with tumor spread through air spaces (STAS) remains inconclusive. This study aimed to evaluate the efficacy of ACT in stage IA STAS+ LUAD patients and to identify subpopulations that might derive clinically significant benefits from ACT.
Methods
Consecutive pathological stage IA (T1a-cN0M0) STAS+ LUAD patients who underwent surgery, with or without ACT, between 2012 and 2020 across 6 high-volume centers were retrospectively reviewed. Propensity-score matching (PSM) was performed to minimize selection bias. The primary endpoint was overall survival. Clinically significant survival benefits were predefined as a hazard ratio (HR) < 0.70, or HR < 0.75 with an absolute 5-year survival improvement > 5%.
Results
Among 3026 eligible cases, 2619 patients (873 ACT and 1746 no ACT) were matched by PSM, achieving well-balanced clinicopathological characteristics. Over a median follow-up of 6.88 years, ACT did not confer clinically significant improvements in overall survival (hazard ratio = 0.795, P = .010) in the overall cohort. Cox regression analyses identified age, histology subtype, lymphovascular invasion (LVI), resection extent, and pathological stage as independent prognostic factors. Interaction analyses further revealed that histology subtype, LVI, and resection extent, but not age or pathological stage, modified ACT’s effect on survival. Exploratory stratified analyses demonstrated that ACT may be associated with clinically significant survival benefits among patients undergoing sub-lobectomy, those with LVI+ tumors, and those with solid/micropapillary-predominant histology.
Conclusions
Although ACT demonstrated limited clinical survival benefit for the overall stage IA STAS+ LUAD population, it may be necessary for selected high-risk subgroups, specifically those undergoing sub-lobectomy, with LVI+ tumors, or with solid/micropapillary-predominant histology.
{"title":"Efficacy of Adjuvant Chemotherapy in Stage IA Lung Adenocarcinoma with Tumor Spread Through Air Spaces: A Multi-Center Real-World Study","authors":"Hanbo Pan , Weiyang Huang , Wanlin Yang , Ling Li , Zhen Ge , Weicheng Kong , Hang Chen , Yu Tian , Wanyu Li , Junwei Ning , Liang Fang , Zhongjie Chen , Guomo Ruan , Zhizhuo Dai , Min Zheng , Ming Zhang , Hui Wang , Xiaomin Niu , Jia Huang , Hui Yin , Qingquan Luo","doi":"10.1016/j.cllc.2025.09.004","DOIUrl":"10.1016/j.cllc.2025.09.004","url":null,"abstract":"<div><h3>Background</h3><div>The role of adjuvant chemotherapy (ACT) for stage IA lung adenocarcinoma (LUAD) with tumor spread through air spaces (STAS) remains inconclusive. This study aimed to evaluate the efficacy of ACT in stage IA STAS<sup>+</sup> LUAD patients and to identify subpopulations that might derive clinically significant benefits from ACT.</div></div><div><h3>Methods</h3><div>Consecutive pathological stage IA (T1a-cN0M0) STAS<sup>+</sup> LUAD patients who underwent surgery, with or without ACT, between 2012 and 2020 across 6 high-volume centers were retrospectively reviewed. Propensity-score matching (PSM) was performed to minimize selection bias. The primary endpoint was overall survival. Clinically significant survival benefits were predefined as a hazard ratio (HR) < 0.70, or HR < 0.75 with an absolute 5-year survival improvement > 5%.</div></div><div><h3>Results</h3><div>Among 3026 eligible cases, 2619 patients (873 ACT and 1746 no ACT) were matched by PSM, achieving well-balanced clinicopathological characteristics. Over a median follow-up of 6.88 years, ACT did not confer clinically significant improvements in overall survival (hazard ratio = 0.795, <em>P</em> = .010) in the overall cohort. Cox regression analyses identified age, histology subtype, lymphovascular invasion (LVI), resection extent, and pathological stage as independent prognostic factors. Interaction analyses further revealed that histology subtype, LVI, and resection extent, but not age or pathological stage, modified ACT’s effect on survival. Exploratory stratified analyses demonstrated that ACT may be associated with clinically significant survival benefits among patients undergoing sub-lobectomy, those with LVI<sup>+</sup> tumors, and those with solid/micropapillary-predominant histology.</div></div><div><h3>Conclusions</h3><div>Although ACT demonstrated limited clinical survival benefit for the overall stage IA STAS<sup>+</sup> LUAD population, it may be necessary for selected high-risk subgroups, specifically those undergoing sub-lobectomy, with LVI<sup>+</sup> tumors, or with solid/micropapillary-predominant histology.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages 659-670.e7"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291373","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}
This study aimed to evaluate whether pretreatment circulating tumor DNA (ctDNA) is a predictive biomarker for recurrence in patients with early-stage non-small cell lung cancer (ES-NSCLC), including those with pathologically unproven (PU) who received ablative radiotherapy.
Materials and methods
Patients clinically diagnosed with cT1-2N0M0 NSCLC treated with radiotherapy alone at a single institute were included. Pretreatment plasma and matched white blood cell samples were subjected to targeted sequencing to detect ctDNA. The association between ctDNA detection and prognosis was evaluated. Integrated analysis including non-squamous cell carcinoma (SQ) cohort and enhancement of recurrence prediction with radiographic features were also evaluated.
Results
Of the 19 patients (10 SQ, and 9 PU) who met the sequence quality criteria, ctDNA was detected in 6. At the median follow-up of 60 months, detectable ctDNA was significantly associated with inferior progression-free survival (PFS) in both the SQ and PU cohorts (P = .01 and .02). In an analysis of 62 patients combined with the non-SQ cohort, ctDNA detection was the only significant factor for PFS. The combination of ctDNA and a high positron emission tomography maximum standardized uptake value provided a better recurrence risk model than ctDNA alone (the C-index improved from 0.63 to 0.72).
Conclusion
These results suggest that pretreatment ctDNA detection can predict recurrence in patients with cT1-2N0M0 NSCLC, including those with PU tumors treated with ablative radiotherapy.
{"title":"Tumor-Agnostic Circulating Tumor DNA Analysis as a Comprehensive Predictive Biomarker of Recurrence after Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer","authors":"Masaki Nakamura , Shun-Ichiro Kageyama , Hidenari Hirata , Masaki Ohira , Shunsuke A. Sakai , Yumi Hakozaki , Hidehiro Hojo , Takeshi Fujisawa , Riu Yamashita , Hiroshi Haeno , Akinori Kanai , Yutaka Suzuki , Masayuki Yamaguchi , Katsuya Tsuchihara , Sadamoto Zenda","doi":"10.1016/j.cllc.2025.09.013","DOIUrl":"10.1016/j.cllc.2025.09.013","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to evaluate whether pretreatment circulating tumor DNA (ctDNA) is a predictive biomarker for recurrence in patients with early-stage non-small cell lung cancer (ES-NSCLC), including those with pathologically unproven (PU) who received ablative radiotherapy.</div></div><div><h3>Materials and methods</h3><div>Patients clinically diagnosed with cT1-2N0M0 NSCLC treated with radiotherapy alone at a single institute were included. Pretreatment plasma and matched white blood cell samples were subjected to targeted sequencing to detect ctDNA. The association between ctDNA detection and prognosis was evaluated. Integrated analysis including non-squamous cell carcinoma (SQ) cohort and enhancement of recurrence prediction with radiographic features were also evaluated.</div></div><div><h3>Results</h3><div>Of the 19 patients (10 SQ, and 9 PU) who met the sequence quality criteria, ctDNA was detected in 6. At the median follow-up of 60 months, detectable ctDNA was significantly associated with inferior progression-free survival (PFS) in both the SQ and PU cohorts (<em>P</em> = .01 and .02). In an analysis of 62 patients combined with the non-SQ cohort, ctDNA detection was the only significant factor for PFS. The combination of ctDNA and a high positron emission tomography maximum standardized uptake value provided a better recurrence risk model than ctDNA alone (the C-index improved from 0.63 to 0.72).</div></div><div><h3>Conclusion</h3><div>These results suggest that pretreatment ctDNA detection can predict recurrence in patients with cT1-2N0M0 NSCLC, including those with PU tumors treated with ablative radiotherapy.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages 671-679.e2"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353991","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}
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