Lung Cancer最新文献_第4页

Assessing the feasibility and external validity of natural language processing-extracted data for advanced lung cancer patients 评估自然语言处理提取数据对晚期肺癌患者的可行性和外部有效性。

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.lungcan.2025.108080

Yuchen Li , Jennifer Law , Lisa W. Le , Janice J.N. Li , Christopher Pettengell , Patricia Demarco , Michael Duong , David Merritt , Sean Davidson , Mike Sung , Qixuan Li , Sally CM Lau , Sajda Zahir , Ryan Chu , Malcom Ryan , Khizar Karim , Josh Morganstein , Adrian Sacher , Lawson Eng , Frances A. Shepherd , Natasha B. Leighl

Background

Manual extraction of real-world clinical data for research can be time-consuming and prone to error. We assessed the feasibility of using natural language processing (NLP), an AI technique, to automate data extraction for patients with advanced lung cancer (aLC). We assessed the external validity of our NLP-extracted data by comparing our findings to those reported in the literature.

Methods

Patients diagnosed with stage IIIB or IV lung cancer between January 2015 to December 2017 at Princess Margaret Cancer Centre who received at least one dose of systemic therapy were included. Their electronic health records were provided to Pentavere’s NLP platform, DARWEN^TM, in March 2019. Descriptive statistics summarized baseline patient and cancer characteristics, molecular biomarkers, and first-line systemic therapies. Cox multivariate models were used to evaluate prognostic factors for advanced non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) cohort.

Result

NLP extracted clinical information (n = 333 patients) in a total of 8 hours, with only a few missing data for smoking status (n = 2), and Eastern Cooperative Oncology Group (ECOG) status (n = 5). Baseline patient and cancer characteristics summarized from NLP-extracted data were comparable to those in previous studies and population reports. For NSCLC patients, being male (HR 1.44, 95 % CI [1.04, 2.00]), having worse ECOG (1.48 [1.22, 1.81]), and having liver (2.24 [1.45, 3.46]), bone (2.09 [1.48, 2.96]), or lung metastases (2.54 [1.05, 2.26]) were associated with worse survival outcomes. For SCLC patients, having older age (HR 1.70 per 10 years, 95 % CI [1.10, 2.63]) and liver metastases (3.81 [1.61, 9.01]) were associated with worse survival outcomes.

Conclusion

Our study demonstrated that automated data extraction using NLP is feasible and time efficient. Additionally, the NLP-extracted data can be used to identify valid and useful clinical endpoints for research. NLP holds significant potential to accelerate the extraction of real-world data for future observational studies.

背景：人工提取真实世界的临床数据用于研究可能耗时且容易出错。我们评估了使用自然语言处理（NLP）（一种人工智能技术）为晚期肺癌（aLC）患者自动提取数据的可行性。通过将我们的发现与文献报道的结果进行比较，我们评估了nlp提取数据的外部有效性。方法：纳入2015年1月至2017年12月在玛格丽特公主癌症中心诊断为IIIB或IV期肺癌的患者，这些患者接受了至少一剂全身治疗。他们的电子健康记录于2019年3月提供给Pentavere的NLP平台DARWENTM。描述性统计总结了基线患者和癌症特征、分子生物标志物和一线全身治疗。采用Cox多变量模型评价晚期非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）队列的预后因素。结果：NLP共在8小时内提取了临床信息（n = 333例），仅缺失了少量吸烟状态（n = 2）和东部肿瘤合作组（ECOG）状态（n = 5）的数据。从NLP提取的数据中总结的基线患者和癌症特征与既往研究和人群报告相当。对于非小细胞肺癌患者，男性（HR 1.44, 95% CI[1.04, 2.00]）、较差的ECOG（1.48[1.22, 1.81]）、肝脏（2.24[1.45,3.46]）、骨骼（2.09[1.48,2.96]）或肺转移（2.54[1.05,2.26]）与较差的生存结果相关。对于SCLC患者，年龄较大（HR为1.70 / 10年，95% CI[1.10, 2.63]）和肝转移（3.81[1.61,9.01]）与较差的生存结果相关。结论：本研究证明了使用自然语言处理进行数据自动提取是可行且省时的。此外，nlp提取的数据可用于确定有效和有用的临床研究终点。NLP在加速提取现实世界数据以用于未来观察研究方面具有巨大潜力。

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引用次数: 0

Geographic variation in delay to surgical treatment among non-small cell lung cancer patients 非小细胞肺癌患者延迟手术治疗的地理差异。

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.lungcan.2024.108077

Getayeneh Antehunegn Tesema , Rob G. Stirling , Win Wah , Zemenu Tadesse Tessema , Stephane Heritier , Arul Earnest

Objectives

Delayed surgery is significantly associated with an increased risk of disease progression and adverse outcomes in lung cancer. Evidence is available on the variation in delayed surgical treatment among patients with Non-Small Cell Lung Cancer (NSCLC). However, the relative contribution of patient- and area-level risk factors to the geographic patterns of delayed surgery in patients with NSCLC is poorly understood. Therefore, we aimed to explore the geographic variation in delay to surgical treatment among patients with NSCLC.

Materials and Methods

This study utilized data from the Victorian Lung Cancer Registry (VLCR) and the Australian Bureau of Statistics (ABS). A total of 3,088 patients with NSCLC who had undergone surgery were included. We applied a Bayesian spatial multilevel model incorporating spatially structured and unstructured random effects to examine patient and area-level risk factors associated with delays to surgical treatment. Model comparison was conducted using the Deviance Information Criterion (DIC).

Results

Over one-third (40.45 %) of NSCLC patients experienced delayed surgical treatment. Significant geographic variation in delayed surgical treatment among NSCLC patients across Local Government Areas (LGAs) was observed. Factors significantly associated with higher odds of delayed surgical treatment included clinical stage II (AOR = 1.56, 95 % CrI: 1.26–1.92), stage III (AOR = 1.90, 95 % CrI: 1.46–2.47), stage IV (AOR = 2.04, 95 % CrI: 1.15–3.61), treatment at inner regional hospitals (AOR = 2.86, 95 % CrI: 2.17–3.70), presence of comorbidities (AOR = 1.19, 95 % CrI: 1.02–1.40), and diagnosis during the COVID-19 pandemic (AOR = 1.32, 95 % CrI: 1.10–1.57).

Conclusions

This study highlights the need to improve the treatment pathway for patients with NSCLC by reducing the time between diagnosis and surgery. Future targeted initiatives are essential to promote timely surgeries for NSCLC patients, especially in high-need areas.

目的：延迟手术与肺癌疾病进展风险增加和不良结局显著相关。有证据表明非小细胞肺癌（NSCLC）患者延迟手术治疗的差异。然而，患者和区域水平的危险因素对NSCLC患者延迟手术的地理模式的相对贡献尚不清楚。因此，我们旨在探讨非小细胞肺癌患者延迟手术治疗的地理差异。材料和方法：本研究使用了维多利亚州肺癌登记处（VLCR）和澳大利亚统计局（ABS）的数据。共纳入了3,088例接受过手术的非小细胞肺癌患者。我们应用贝叶斯空间多层模型结合空间结构化和非结构化随机效应来检查与延迟手术治疗相关的患者和区域层面的风险因素。采用偏差信息准则（DIC）进行模型比较。结果：超过三分之一（40.45%）的非小细胞肺癌患者经历了延迟手术治疗。观察到不同地方政府区域（LGAs）的非小细胞肺癌患者延迟手术治疗的显著地理差异。与延迟手术治疗几率较高相关的因素包括临床II期（AOR = 1.56, 95% CrI: 1.26-1.92）、III期（AOR = 1.90, 95% CrI: 1.46-2.47）、IV期（AOR = 2.04, 95% CrI: 1.15-3.61）、在区域内医院治疗（AOR = 2.86, 95% CrI: 2.17-3.70）、是否存在合共病（AOR = 1.19, 95% CrI: 1.02-1.40）以及在COVID-19大流行期间诊断（AOR = 1.32, 95% CrI: 1.10-1.57）。结论：本研究强调需要通过缩短诊断和手术之间的时间来改善非小细胞肺癌患者的治疗途径。未来有针对性的举措对于促进NSCLC患者及时手术至关重要，特别是在高需求地区。

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引用次数: 0

Continuing immune checkpoint inhibitors after progression: Real-world patterns of care and outcomes in second-line treatment for extensive-stage small-cell lung cancer 进展后持续免疫检查点抑制剂：广泛期小细胞肺癌二线治疗的现实世界护理模式和结果

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.lungcan.2024.108021

Baishen Zhang , Hejing Bao , Zhanquan Li , Jing Chen , Hui Yu , Meichen Li , Muyan Cai , Likun Chen

Introduction

Small cell lung cancer (SCLC) is a highly malignant tumor with an extremely poor prognosis. In the current era of immunotherapy, the role of immune checkpoint inhibitors (ICIs) in the second-line treatment of patients with extensive-stage SCLC (ES-SCLC) who have progressed to initial chemoimmunotherapy remains unclear.

Methods

A multicenter retrospective study were conducted, involving patients with ES-SCLC who received second-line (2L) therapy after progression to first-line chemoimmunotherapy. Patients were divided into 2L-ICIs group and 2L-non-ICIs group according to whether ICIs were added to the 2L treatment. The efficacy and adverse events of the two groups were analyzed and compared.

Results

A total of 103 patients were included in this study, with 53 in the 2L-ICIs group and 50 in the 2L-non-ICIs group. The 2L-ICIs group demonstrated a longer median progression-free survival (PFS) compared to the 2L-non-ICIs group (4.4 months vs 3.9 months, HR = 0.45, p = 0.001). Similarly, median overall survival was also prolonged in the 2L-ICIs group (10.0 months vs 6.9 months, HR = 0.56, p = 0.015). Cox regression analysis revealed that the addition of ICIs to 2L treatment was an independent prognostic factor for both PFS and OS in ES-SCLC patients. Subgroup analysis indicated that patients with a first-line PFS of ≥6 months could potentially benefit more from 2L ICIs. Furthermore, the occurrence of adverse events in the two groups exhibited a similar pattern.

Conclusion

For ES-SCLC patients who have progressed to first-line chemoimmunotherapy, adding ICIs to second-line treatment may be considered as an option with limited benefit but manageable adverse effects.

简介：小细胞肺癌（SCLC）是一种预后极差的高度恶性肿瘤。在目前的免疫治疗中，免疫检查点抑制剂（ICIs）在已进展到初始化学免疫治疗的大分期SCLC （ES-SCLC）患者的二线治疗中的作用尚不清楚。方法：一项多中心回顾性研究，涉及进展到一线化疗免疫治疗后接受二线（2L）治疗的ES-SCLC患者。根据在2L治疗中是否添加ICIs分为2L-ICIs组和2L-非ICIs组。分析比较两组患者的疗效及不良事件。结果：本研究共纳入103例患者，2L-ICIs组53例，2l -非icis组50例。与非icis组相比，2L-ICIs组的中位无进展生存期（PFS）更长（4.4个月vs 3.9个月，HR = 0.45, p = 0.001）。同样，2L-ICIs组的中位总生存期也延长（10.0个月vs 6.9个月，HR = 0.56, p = 0.015）。Cox回归分析显示，在2L治疗中加入ICIs是ES-SCLC患者PFS和OS的独立预后因素。亚组分析表明，一线PFS≥6个月的患者可能从2L ICIs中获益更多。此外，两组不良事件的发生模式相似。结论：对于进展到一线化疗免疫治疗的ES-SCLC患者，在二线治疗中添加ICIs可能是一种获益有限但不良反应可控的选择。

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引用次数: 0

Impact of locoregional recurrence versus distant metastasis on overall survival in patients with Non-Small cell lung cancer after Surgery: A secondary analysis of PORT-C RCT 局部复发与远处转移对非小细胞肺癌术后患者总生存率的影响：PORT-C RCT的二次分析

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.lungcan.2024.108063

Zeliang Ma , Yunsong Liu , Yongxing Bao , Meiqi Wang , Xu Yang , Yu Men , Jianyang Wang , Lei Deng , Yirui Zhai , Chen Hu , Nan Bi , Luhua Wang , Zhouguang Hui

Purpose

The therapeutic advantage of postoperative radiation therapy (PORT) for non-small cell lung cancer (NSCLC) has not been shown to benefit overall survival (OS) according to two randomized controlled trials (RCTs), albeit an enhancement in locoregional-free survival was observed. We aimed to evaluate the relative influence of locoregional recurrence (LR) and distant metastasis (DM) on OS for patients with NSCLC after surgery.

Methods

This was a secondary analysis of PORT-C RCT. Patients with pN2 NSCLC undergoing complete resection followed by chemotherapy were included. A dynamic prediction model was developed to evaluate the impact of LR and DM on OS. The endpoint was OS. Age, sex, smoking history, histology, Karnofsky Performance Status, tumor side, T stage, and positive lymph node were baseline factors, whereas LR and DM status were time-dependent covariates.

Results

In total, 364 patients were eligible, including 214 and 150 in the non-PORT and PORT groups, respectively. DM significantly decreased OS in both the non-PORT (odds ratio [OR], 4.74; 95 % CI, 2.70–8.30; P < 0.01) and PORT (OR, 5.43; 95 % CI, 2.56–11.48; P < 0.01) groups. LR also significantly impacted OS in the non-PORT (OR, 2.09; 95 % CI, 1.12–3.93; P = 0.02) and the PORT (OR, 3.44; 95 % CI, 1.53–7.75; P < 0.01) groups. Multivariate Cox analysis identified the pT stage, positive lymph nodes, and histology as variables correlated with DM. A nomogram was developed to estimate the risk of DM. PORT did not significantly enhance OS in either the low (HR, 1.42; 95 % CI, 0.63–3.19, P = 0.40) or high-risk (HR, 0.62; 95 % CI, 0.35–1.09, P = 0.10) subgroup but in the medium-risk subgroup (HR, 0.20; 95 % CI, 0.05–0.86, P = 0.02).

Conclusion

DM and LR significantly impacted OS in patients with NSCLC after surgery. DM emerged as the dominant failure pattern, emphasizing more effective control of DM. PORT was beneficial for patients with a medium risk of DM.

目的：根据两项随机对照试验（rct），尽管观察到局部区域无生存期的增强，但未显示非小细胞肺癌（NSCLC）术后放射治疗（PORT）的治疗优势有利于总生存期（OS）。我们旨在评估局部复发（LR）和远处转移（DM）对非小细胞肺癌术后OS的相对影响。方法：这是PORT-C随机对照试验的二次分析。pN2 NSCLC患者接受完全切除和化疗。建立了一个动态预测模型来评估LR和DM对OS的影响。终点为OS。年龄、性别、吸烟史、组织学、Karnofsky Performance Status、肿瘤一侧、T分期和阳性淋巴结是基线因素，而LR和DM状态是随时间变化的协变量。结果：共有364例患者符合条件，其中非PORT组214例，PORT组150例。DM显著降低了非port患者的OS(优势比[OR]， 4.74；95% ci, 2.70-8.30；结论：DM和LR对非小细胞肺癌术后OS有显著影响。糖尿病成为主要的失败模式，强调更有效地控制糖尿病。PORT对糖尿病中度风险的患者是有益的。

{"title":"Impact of locoregional recurrence versus distant metastasis on overall survival in patients with Non-Small cell lung cancer after Surgery: A secondary analysis of PORT-C RCT","authors":"Zeliang Ma , Yunsong Liu , Yongxing Bao , Meiqi Wang , Xu Yang , Yu Men , Jianyang Wang , Lei Deng , Yirui Zhai , Chen Hu , Nan Bi , Luhua Wang , Zhouguang Hui","doi":"10.1016/j.lungcan.2024.108063","DOIUrl":"10.1016/j.lungcan.2024.108063","url":null,"abstract":"<div><h3>Purpose</h3><div>The therapeutic advantage of postoperative radiation therapy (PORT) for non-small cell lung cancer (NSCLC) has not been shown to benefit overall survival (OS) according to two randomized controlled trials (RCTs), albeit an enhancement in locoregional-free survival was observed. We aimed to evaluate the relative influence of locoregional recurrence (LR) and distant metastasis (DM) on OS for patients with NSCLC after surgery.</div></div><div><h3>Methods</h3><div>This was a secondary analysis of PORT-C RCT. Patients with pN2 NSCLC undergoing complete resection followed by chemotherapy were included. A dynamic prediction model was developed to evaluate the impact of LR and DM on OS. The endpoint was OS. Age, sex, smoking history, histology, Karnofsky Performance Status, tumor side, T stage, and positive lymph node were baseline factors, whereas LR and DM status were time-dependent covariates.</div></div><div><h3>Results</h3><div>In total, 364 patients were eligible, including 214 and 150 in the non-PORT and PORT groups, respectively. DM significantly decreased OS in both the non-PORT (odds ratio [OR], 4.74; 95 % CI, 2.70–8.30; P < 0.01) and PORT (OR, 5.43; 95 % CI, 2.56–11.48; P < 0.01) groups. LR also significantly impacted OS in the non-PORT (OR, 2.09; 95 % CI, 1.12–3.93; P = 0.02) and the PORT (OR, 3.44; 95 % CI, 1.53–7.75; P < 0.01) groups. Multivariate Cox analysis identified the pT stage, positive lymph nodes, and histology as variables correlated with DM. A nomogram was developed to estimate the risk of DM. PORT did not significantly enhance OS in either the low (HR, 1.42; 95 % CI, 0.63–3.19, P = 0.40) or high-risk (HR, 0.62; 95 % CI, 0.35–1.09, P = 0.10) subgroup but in the medium-risk subgroup (HR, 0.20; 95 % CI, 0.05–0.86, P = 0.02).</div></div><div><h3>Conclusion</h3><div>DM and LR significantly impacted OS in patients with NSCLC after surgery. DM emerged as the dominant failure pattern, emphasizing more effective control of DM. PORT was beneficial for patients with a medium risk of DM.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108063"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864323","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}

引用次数: 0

Exploring machine learning tools in a retrospective case-study of patients with metastatic non-small cell lung cancer treated with first-line immunotherapy: A feasibility single-centre experience 在接受一线免疫治疗的转移性非小细胞肺癌患者的回顾性病例研究中探索机器学习工具：可行性单中心经验。

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.lungcan.2024.108075

Francesca Rita Ogliari , Alberto Traverso , Simone Barbieri , Marco Montagna , Filippo Chiabrando , Enrico Versino , Antonio Bosco , Alessia Lin , Roberto Ferrara , Sara Oresti , Giuseppe Damiano , Maria Grazia Viganò , Michele Ferrara , Silvia Teresa Riva , Antonio Nuccio , Francesco Maria Venanzi , Davide Vignale , Giuseppe Cicala , Anna Palmisano , Stefano Cascinu , Michele Reni

Background

Artificial intelligence (AI) models are emerging as promising tools to identify predictive features among data coming from health records. Their application in clinical routine is still challenging, due to technical limits and to explainability issues in this specific setting. Response to standard first-line immunotherapy (ICI) in metastatic Non-Small-Cell Lung Cancer (NSCLC) is an interesting population for machine learning (ML), since up to 30% of patients do not benefit.

Methods

We retrospectively collected all consecutive patients with PD-L1 ≥ 50 % metastatic NSCLC treated with first-line ICI at our institution between 2017 and 2021. Demographic, laboratory, molecular and clinical data were retrieved manually or automatically according to data sources. Primary aim was to explore feasibility of ML models in clinical routine setting and to detect problems and solutions for everyday implementation. Early progression was used as preliminary endpoint to test our algorithm.

Results

Out of 123 patients, 106 were included, 52/106 (49 %) had disease progression or died within 3 months of start of ICI. Early progression correlated with increased neutrophil percentage (>80 % of white blood cells), neutrophil/lymphocyte ratio (≥8) and lower-range PD-L1 status (<70 %) at baseline, which was consistent with literature. Automated ML (AutoML) models run on our dataset reached precision scores around 80 %, with Voting Ensemble emerging as best performing model, while white-box models (such as Shapley Additive exPlanations) provided better explainability. In all AutoML models, laboratory features were the top selected features, whilst clinical ones needed more pre-processing before gaining relevance, which was consistent with different data extraction (automatic versus manual) and missing data rates.

Conclusions

ML models’ application is feasible in clinical practice and can trustworthily predict early progression during first-line ICI for metastatic NSCLC. Solving pre-analytical issues is key for future improvement, focusing on automatic tools for data extraction, collection and explainability.

背景：人工智能（AI）模型正在成为识别来自健康记录数据的预测特征的有前途的工具。由于技术限制和在这种特殊情况下的可解释性问题，它们在临床常规中的应用仍然具有挑战性。转移性非小细胞肺癌（NSCLC）对标准一线免疫治疗（ICI）的反应是机器学习（ML）的一个有趣人群，因为高达30%的患者没有受益。方法：回顾性收集2017年至2021年间我院所有连续接受一线ICI治疗的PD-L1≥50%转移性非小细胞肺癌患者。根据数据来源，手动或自动检索人口学、实验室、分子和临床数据。主要目的是探讨ML模型在临床常规设置中的可行性，并发现日常实施中的问题和解决方案。早期进展作为初步终点来测试我们的算法。结果：123例患者中，106例纳入，52/106（49%）在ICI开始的3个月内出现疾病进展或死亡。早期进展与中性粒细胞百分比（白细胞占比≥80%）、中性粒细胞/淋巴细胞比值（≥8）和较低范围PD-L1状态相关(结论：ML模型在临床实践中是可行的，可以可靠地预测转移性NSCLC一线ICI的早期进展。解决分析前的问题是未来改进的关键，重点是数据提取、收集和解释的自动工具。

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引用次数: 0

Genomic analysis of comprehensive next generation sequencing data to explore the criteria for MET amplification as an actionable biomarker in NSCLC 全面的下一代测序数据的基因组分析，探索MET扩增作为非小细胞肺癌可操作的生物标志物的标准。

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.lungcan.2025.108081

David Chun Cheong Tsui , Jessica K. Lee , Candice Francheska B. Tambaoan , Jason Hughes , Bernard Fendler , Brennan Decker , Garrett M. Frampton , Alexa B. Schrock , D. Ross Camidge

Introduction

MET amplification (METamp) can be a de novo or acquired resistance driver; however, the definition of METamp that best captures patients who may respond to targeted therapy remains debated. We explored the genomic landscape of METamp NSCLC including degree of amplification, co-drivers, amplicon size, and outcomes to MET inhibitors.

Methods

Hybrid-capture NGS-based genomic profiling from 88,547 tissue and 12,428 liquid NSCLC samples were queried for METamp (copy number (CN) ≥ ploidy + 4, or amplification ratio (AmpRatio; [CN/sample ploidy] ≥ 3). A nationwide de-identified real-world (rw) clinico-genomic database (CGDB) of NGS results linked to deidentified, electronic health record-derived clinical data was used to assess treatment and outcomes.

Results

Among 10,760 evaluable patients in CGDB, 362 (3.4%) had a METamp. In targeted therapy-naïve cases, MET AmpRatio negatively correlated with non-METex14 co-drivers (median 4.1 vs 2.9, p < 0.0001). MET AmpRatio was not significantly correlated with tumor mutational burden (p = 0.79) but was inversely correlated with amplicon size (p < 0.001). Among paired METamp tissue samples, 8/30 had METamp detected in liquid; higher tumor fraction and AmpRatio were associated with liquid detection. Among 39 METamp patients receiving MET inhibitors, longer median real-world progression free survival was observed with MET AmpRatio ≥ 3 vs < 3 (4.9 vs. 1.7mos, HR 0.53 [95 %CI:0.21–1.3]).

Conclusions

MET AmpRatio positively correlated with focal amplification and absence of co-drivers and trended with increased benefit from MET inhibitors. Further studies evaluating combinatorial data including MET AmpRatio, amplicon size and presence of other potential drivers, as predictive biomarkers for therapies targeting MET amplification in NSCLC are warranted.

简介：MET放大器（METamp）可以是一个新的或获得电阻驱动器；然而，METamp的定义仍然存在争议，该定义最好地捕获了可能对靶向治疗有反应的患者。我们探索了METamp NSCLC的基因组景观，包括扩增程度、共同驱动因素、扩增子大小和MET抑制剂的结果。方法：从88,547例组织和12,428例NSCLC液体样本中查询基于混合捕获ngs的基因组图谱，检测METamp(拷贝数(CN)≥倍体+ 4，或扩增比(AmpRatio；[cn /样本倍性]≥3)。NGS结果的全国去识别现实世界（rw）临床基因组数据库（CGDB）与去识别的电子健康记录衍生临床数据相关联，用于评估治疗和结果。结果：在10760例可评估的CGDB患者中，362例（3.4%）有METamp。在靶向therapy-naïve病例中，MET AmpRatio与非metex14共同驱动因素呈负相关（中位数为4.1 vs 2.9, p）。结论：MET AmpRatio与病灶放大和缺乏共同驱动因素呈正相关，并且MET抑制剂的获益增加。进一步的研究评估组合数据，包括MET扩增比、扩增子大小和其他潜在驱动因素的存在，作为非小细胞肺癌MET扩增治疗的预测性生物标志物是有必要的。

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引用次数: 0

CT-assessed sarcopenia and immune-related adverse events in patients with lung cancer: A competing risk time-to-event analysis ct评估肺癌患者肌肉减少症和免疫相关不良事件：竞争风险-事件分析

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.lungcan.2024.108054

Erick Suazo-Zepeda , Alain R. Viddeleer , Willemijn J. Maas , Douwe Postmus , Marjolein A. Heuvelmans , T. Jeroen N. Hiltermann , Geertruida H. De Bock

Background

Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs). This study investigates the relationship between CT-assessed sarcopenia and irAEs in patients with lung cancer who are receiving ICIs.

Methods

Patients were enrolled if they had lung cancer treated with ICIs at the University Medical Center Groningen (2015–2021) and had undergone low-dose CT scans that included the third lumbar vertebral level (L3). CT-assessed sarcopenia was defined based on reported L3 skeletal muscle mass index (L3SMI) thresholds. Patients were categorized into no, any-grade, and severe irAE groups. The association between CT-assessed sarcopenia and irAEs was assessed by competing risk time-to-event analysis, accounting for the risk of death. Sub-distribution hazard ratios (_SDHR) were calculated using Fine–Gray regression models adjusted for relevant confounders. The association between CT-assessed sarcopenia and overall survival (OS) was evaluated through survival analyses.

Results

We included 363 patients; most were male (60.9 %), had favorable Eastern Cooperative Oncology Group (ECOG) performance statuses (0–1; 90.1 %), had stage IV disease (92.8 %), and received ICI monotherapy (82.9 %). Of these, 45.6 % developed any-grade irAEs and 21 % developed severe irAEs. Endocrine disorders were the most common mild irAEs (24.8 %), while respiratory disorders were the most common severe irAEs (24.7 %). CT-assessed sarcopenia was more prevalent in the no irAE group (87 %) compared with the any-grade (77 %) and severe (79 %) irAE groups. Presence of CT-assessed sarcopenia was associated with a lower risk of developing any irAEs (_SDHR = 0.62 [95 % CI: 0.41–0.92]). No significant association was found between CT-assessed sarcopenia and severe irAEs (fully adjusted model, _SDHR = 0.74 [95 % CI: 0.39–1.4]), or between CT-assessed sarcopenia and OS.

Conclusion

CT-assessed sarcopenia is associated with a reduced risk of any irAEs in patients with lung cancer receiving ICIs, possibly because higher muscle mass enhances the host response to immunological stimulation. Recognizing sarcopenia as a predictive factor for irAEs is relevant for personalizing treatments.

背景：免疫检查点抑制剂（ICIs）可诱导免疫相关不良事件（irAEs）。本研究探讨了接受ICIs的肺癌患者ct评估的肌肉减少症与irae之间的关系。方法：纳入在格罗宁根大学医学中心接受ICIs治疗的肺癌患者（2015-2021），并接受了包括第三腰椎节段（L3）在内的低剂量CT扫描。ct评估的肌肉减少症是根据报告的L3骨骼肌质量指数（L3SMI）阈值来定义的。患者被分为无、任何级别和严重irAE组。ct评估的肌肉减少症和irae之间的关联通过竞争风险时间到事件分析来评估，考虑到死亡风险。子分布风险比（SDHR）采用经相关混杂因素调整的Fine-Gray回归模型计算。通过生存分析评估ct评估的肌肉减少症与总生存（OS）之间的关系。结果：我们纳入了363例患者；大多数为男性（60.9%），具有良好的东部肿瘤合作组（ECOG）绩效状态(0-1；90.1%)， IV期疾病（92.8%），并接受ICI单药治疗（82.9%）。其中45.6%发展为任何级别的irAEs， 21%发展为严重的irAEs。内分泌紊乱是最常见的轻度irAEs(24.8%)，呼吸紊乱是最常见的重度irAEs（24.7%）。ct评估的肌肉减少症在无irAE组（87%）比任何级别（77%）和严重（79%）irAE组更普遍。存在ct评估的肌肉减少症与发生任何irae的风险较低相关（SDHR = 0.62 [95% CI: 0.41-0.92]）。ct评估的肌肉减少症与严重irAEs之间无显著关联（完全调整模型，SDHR = 0.74 [95% CI: 0.39-1.4]），或ct评估的肌肉减少症与OS之间无显著关联。结论：ct评估的肌肉减少症与接受ICIs的肺癌患者发生任何irae的风险降低有关，可能是因为较高的肌肉量增强了宿主对免疫刺激的反应。认识到肌肉减少症是irae的预测因素，与个性化治疗有关。

{"title":"CT-assessed sarcopenia and immune-related adverse events in patients with lung cancer: A competing risk time-to-event analysis","authors":"Erick Suazo-Zepeda , Alain R. Viddeleer , Willemijn J. Maas , Douwe Postmus , Marjolein A. Heuvelmans , T. Jeroen N. Hiltermann , Geertruida H. De Bock","doi":"10.1016/j.lungcan.2024.108054","DOIUrl":"10.1016/j.lungcan.2024.108054","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs). This study investigates the relationship between CT-assessed sarcopenia and irAEs in patients with lung cancer who are receiving ICIs.</div></div><div><h3>Methods</h3><div>Patients were enrolled if they had lung cancer treated with ICIs at the University Medical Center Groningen (2015–2021) and had undergone low-dose CT scans that included the third lumbar vertebral level (L3). CT-assessed sarcopenia was defined based on reported L3 skeletal muscle mass index (L3SMI) thresholds. Patients were categorized into no, any-grade, and severe irAE groups. The association between CT-assessed sarcopenia and irAEs was assessed by competing risk time-to-event analysis, accounting for the risk of death. Sub-distribution hazard ratios (<sub>SD</sub>HR) were calculated using Fine–Gray regression models adjusted for relevant confounders. The association between CT-assessed sarcopenia and overall survival (OS) was evaluated through survival analyses.</div></div><div><h3>Results</h3><div>We included 363 patients; most were male (60.9 %), had favorable Eastern Cooperative Oncology Group (ECOG) performance statuses (0–1; 90.1 %), had stage IV disease (92.8 %), and received ICI monotherapy (82.9 %). Of these, 45.6 % developed any-grade irAEs and 21 % developed severe irAEs. Endocrine disorders were the most common mild irAEs (24.8 %), while respiratory disorders were the most common severe irAEs (24.7 %). CT-assessed sarcopenia was more prevalent in the no irAE group (87 %) compared with the any-grade (77 %) and severe (79 %) irAE groups. Presence of CT-assessed sarcopenia was associated with a lower risk of developing any irAEs (<sub>SD</sub>HR = 0.62 [95 % CI: 0.41–0.92]). No significant association was found between CT-assessed sarcopenia and severe irAEs (fully adjusted model, <sub>SD</sub>HR = 0.74 [95 % CI: 0.39–1.4]), or between CT-assessed sarcopenia and OS.</div></div><div><h3>Conclusion</h3><div>CT-assessed sarcopenia is associated with a reduced risk of any irAEs in patients with lung cancer receiving ICIs, possibly because higher muscle mass enhances the host response to immunological stimulation. Recognizing sarcopenia as a predictive factor for irAEs is relevant for personalizing treatments.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108054"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FURVENT: Phase 3 trial of firmonertinib vs chemotherapy as first-line treatment for advanced NSCLC with EGFR exon 20 insertion mutations (FURMO-004)

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.lungcan.2024.108066

Alexander Spira , Byoung Chul Cho , Enriqueta Felip , Edward B. Garon , Koichi Goto , Melissa Johnson , Natasha Leighl , Antonio Passaro , David Planchard , Sanjay Popat , James Chih-Hsin Yang , Xiaoqian Lu , Yong Jiang , Jack Huang , Morgan Lam , Marcin Kowanetz , Shirley Wang , John Le , Jerry Y. Hsu , Cai-Cun Zhou

引用次数: 0

Efficacy of immune checkpoint inhibitors in pulmonary sarcomatoid carcinoma and predictive potential of mutated TP53 免疫检查点抑制剂在肺肉瘤样癌中的疗效及TP53突变的预测潜力。

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.lungcan.2024.108068

Mingying Wu , Na Zhou , Mei Guan , Yingyi Wang , Yuzhou Wang

Objective

Pulmonary sarcomatoid carcinoma (PSC) is a rare, heterogeneous subgroup of non-small cell lung cancer (NSCLC). Patients with advanced PSCs have poor survival due to resistance to chemotherapy and radiotherapy, and narrow access to targeted therapy. Immune checkpoint inhibitors (ICIs) offer new hope, whereas data on their effectiveness is limited.

Methods

This retrospective study collected medical records of patients with advanced PSCs from January 2010 to March 2024 across two centers in China, analyzing demographic, treatment, and survival data. Sixty cases were included.

Results

In tumors tested for PD-L1 expression, 80 % had PD-L1 positivity, and 60 % exhibited TPS ≥ 50 %. The most frequently mutated genes in PSCs were TP53 (25.9 %), KRAS (22.8 %), MET (7.4 %), BRAF (7.4 %), CDKN2A/B (7.4 % each), and EGFR (6.2 %). Median OS of patients with advanced PSCs receiving anti-PD-1 or anti-PD-L1 antibodies in any line was significantly longer compared to those who did not (NR vs. 11.2 months, p = 0.015). ICI application was an independent favorable factor for the prognosis of patients diagnosed with advanced PSC (HR 0.32, p = 0.008). In the subgroup treated with ICI-based therapies, ORR and DCR were 34.5 % and 82.8 %, respectively. The mPFS and mOS of ICI-based therapies were 12.5 and 16.0 months, respectively. TP53 mutations and PD-L1 TPS ≥ 80 % were associated with prolonged PFS (p = 0.021, p = 0.035) and OS (p = 0.013 and p = 0.018).

Conclusions

Positive or high PD-L1 expression was prevalent in advanced PSCs. Anti-PD-1 or anti-PD-L1 antibodies were associated with favorable prognosis, and should be considered a key treatment option for patients with advanced PSC lacking actionable driver mutations. In addition to PD-L1 expression, TP53 mutations have the potential to predict the efficacy of ICIs in treating patients with advanced PSC and its prognostic significance deserves further validation in larger prospective studies.

目的：肺肉瘤样癌（PSC）是一种罕见的异质性非小细胞肺癌（NSCLC）亚群。晚期PSCs患者由于对化疗和放疗的耐药以及靶向治疗的狭窄，生存期较差。免疫检查点抑制剂（ICIs）提供了新的希望，然而关于其有效性的数据有限。方法：本回顾性研究收集了2010年1月至2024年3月中国两个中心的晚期psc患者的医疗记录，分析了人口统计学、治疗和生存数据。包括60例病例。结果：在PD-L1表达检测中，80%的肿瘤呈PD-L1阳性，60%的肿瘤TPS≥50%。PSCs中最常见的突变基因是TP53（25.9%）、KRAS（22.8%）、MET（7.4%）、BRAF（7.4%）、CDKN2A/B（各7.4%）和EGFR（6.2%）。接受抗pd -1或抗pd - l1抗体治疗的晚期psc患者的中位生存期明显长于未接受抗pd -1或抗pd - l1抗体治疗的患者（NR vs. 11.2个月，p = 0.015）。ICI应用是晚期PSC患者预后的独立有利因素（HR 0.32, p = 0.008）。在以ci为基础的治疗亚组中，ORR和DCR分别为34.5%和82.8%。以ci为基础的治疗的mPFS和mOS分别为12.5和16.0个月。TP53突变和PD-L1 TPS≥80%与PFS延长（p = 0.021, p = 0.035）和OS延长（p = 0.013, p = 0.018）相关。结论：PD-L1阳性或高表达在晚期PSCs中普遍存在。抗pd -1或抗pd - l1抗体与良好的预后相关，应被视为缺乏可操作驱动突变的晚期PSC患者的关键治疗选择。除了PD-L1表达外，TP53突变也有可能预测ICIs治疗晚期PSC患者的疗效，其预后意义值得在更大规模的前瞻性研究中进一步验证。

{"title":"Efficacy of immune checkpoint inhibitors in pulmonary sarcomatoid carcinoma and predictive potential of mutated TP53","authors":"Mingying Wu , Na Zhou , Mei Guan , Yingyi Wang , Yuzhou Wang","doi":"10.1016/j.lungcan.2024.108068","DOIUrl":"10.1016/j.lungcan.2024.108068","url":null,"abstract":"<div><h3>Objective</h3><div>Pulmonary sarcomatoid carcinoma (PSC) is a rare, heterogeneous subgroup of non-small cell lung cancer (NSCLC). Patients with advanced PSCs have poor survival due to resistance to chemotherapy and radiotherapy, and narrow access to targeted therapy. Immune checkpoint inhibitors (ICIs) offer new hope, whereas data on their effectiveness is limited.</div></div><div><h3>Methods</h3><div>This retrospective study collected medical records of patients with advanced PSCs from January 2010 to March 2024 across two centers in China, analyzing demographic, treatment, and survival data. Sixty cases were included.</div></div><div><h3>Results</h3><div>In tumors tested for PD-L1 expression, 80 % had PD-L1 positivity, and 60 % exhibited TPS ≥ 50 %. The most frequently mutated genes in PSCs were <em>TP53</em> (25.9 %), <em>KRAS</em> (22.8 %), <em>MET</em> (7.4 %), <em>BRAF</em> (7.4 %), <em>CDKN2A/B</em> (7.4 % each), and <em>EGFR</em> (6.2 %). Median OS of patients with advanced PSCs receiving anti-PD-1 or anti-PD-L1 antibodies in any line was significantly longer compared to those who did not (NR vs. 11.2 months, p = 0.015). ICI application was an independent favorable factor for the prognosis of patients diagnosed with advanced PSC (HR 0.32, p = 0.008). In the subgroup treated with ICI-based therapies, ORR and DCR were 34.5 % and 82.8 %, respectively. The mPFS and mOS of ICI-based therapies were 12.5 and 16.0 months, respectively. <em>TP53</em> mutations and PD-L1 TPS ≥ 80 % were associated with prolonged PFS (p = 0.021, p = 0.035) and OS (p = 0.013 and p = 0.018).</div></div><div><h3>Conclusions</h3><div>Positive or high PD-L1 expression was prevalent in advanced PSCs. Anti-PD-1 or anti-PD-L1 antibodies were associated with favorable prognosis, and should be considered a key treatment option for patients with advanced PSC lacking actionable driver mutations. In addition to PD-L1 expression, <em>TP53</em> mutations have the potential to predict the efficacy of ICIs in treating patients with advanced PSC and its prognostic significance deserves further validation in larger prospective studies.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108068"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906682","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}

引用次数: 0

STK11 mutations correlate with poor prognosis for advanced NSCLC treated with first-line immunotherapy or chemo-immunotherapy according to KRAS, TP53, KEAP1, and SMARCA4 status 根据KRAS、TP53、KEAP1和SMARCA4状态，STK11突变与一线免疫治疗或化疗免疫治疗的晚期NSCLC预后不良相关。

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.lungcan.2024.108058

Andrea De Giglio , Dario De Biase , Valentina Favorito , Thais Maloberti , Alessandro Di Federico , Federico Zacchini , Giulia Venturi , Claudia Parisi , Filippo Gustavo Dall’Olio , Ilaria Ricciotti , Ambrogio Gagliano , Barbara Melotti , Francesca Sperandi , Annalisa Altimari , Elisa Gruppioni , Giovanni Tallini , Francesco Gelsomino , Lorenzo Montanaro , Andrea Ardizzoni

Background

The upfront treatment of non-oncogene-addicted NSCLC relies on immunotherapy alone (ICI) or in combination with chemotherapy (CT-ICI). Genomic aberrations such as KRAS, TP53, KEAP1, SMARCA4, or STK11 may impact survival outcomes.

Methods

We performed an observational study of 145 patients treated with first-line IO or CT-ICI for advanced non-squamous (nsq) NSCLC at our institution tested with an extensive lab-developed NGS panel. The primary objective was to assess the clinical outcomes of STK11-mutated patients. Then, we performed an external validation through the public OAK/POPLAR dataset, including nsq NSCLC patients treated with single-agent ICI or CT.

Results

Most patients were male (59.7 %), former smokers (61.1 %), with ECOG PS 0–1 (84 %), and received first-line CT-IO (58.6 %). 44.8 % had a mutation in KRAS, 21.4 % in KEAP1, 50.3 % in TP53, 13.1 % in SMARCA4, and 14.4 % in the STK11 gene. The mOS was 8 mo. (95 % CI, 5–16.7) for STK11 mutated pts and 17.3 mo. for STK11 wild-type patients (95 % CI, 8.9–24.4) (p = 0.038). TP53 (8.3 vs 17.3), KRAS (9.2 vs 15.9), and KEAP1 (8.9 vs 15.9) mutated patients evidenced a trend for dismal mOS. SMARCA4 status had no impact on mOS. STK11 mutations were detrimental to OS in the univariate (HR 1.74, p = 0.041) and multivariate model (HR 1.97, p = 0.025) after adjusting for sex, age, ECOG PS, treatment (ICI vs CT-ICI), KRAS, KEAP1, TP53, and SMARCA4 status. Genomic alterations did not impact the mPFS in our cohort. Within the OAK/POPLAR dataset, STK11 mutations (60/818 pts) were significantly associated with increased death risk in the univariate (HR 2.01, p < 0.001) and multivariate model (HR 1.66, p = 0.001) after adjusting for age, sex, treatment (ICI vs CT), KRAS, KEAP1, TP53, and SMARCA4 status.

Conclusion

STK11 aberrations hampered the mOS of nsq NSCLC patients treated with first-line ICI or CT-ICI. The negative prognostic impact seems to be unrelated to ICI administration.

背景：非癌基因成瘾NSCLC的前期治疗依赖于单独免疫治疗（ICI）或联合化疗（CT-ICI）。基因组畸变如KRAS、TP53、KEAP1、SMARCA4或STK11可能影响生存结果。方法：我们对我院145例接受一线IO或CT-ICI治疗晚期非鳞状（nsq） NSCLC的患者进行了一项观察性研究，并采用广泛的实验室开发的NGS面板进行了测试。主要目的是评估stk11突变患者的临床结果。然后，我们通过公共OAK/POPLAR数据集进行了外部验证，包括接受单药ICI或CT治疗的nsq NSCLC患者。结果：大多数患者为男性（59.7%），既往吸烟者（61.1%），ECOG PS 0-1(84%)，接受一线CT-IO（58.6%）。KRAS基因突变占44.8%，KEAP1基因突变占21.4%，TP53基因突变占50.3%，SMARCA4基因突变占13.1%，STK11基因突变占14.4%。STK11突变患者的最大生存期为8个月（95% CI, 5-16.7）， STK11野生型患者的最大生存期为17.3个月（95% CI, 8.9-24.4）（p = 0.038）。TP53 （8.3 vs 17.3）、KRAS （9.2 vs 15.9）和KEAP1 （8.9 vs 15.9）突变患者表现出令人沮丧的mOS趋势。SMARCA4状态对mOS无影响。在调整性别、年龄、ECOG PS、治疗（ICI vs CT-ICI）、KRAS、KEAP1、TP53和SMARCA4状态后，STK11突变在单变量模型（HR 1.74, p = 0.041）和多变量模型（HR 1.97, p = 0.025）中对OS有害。在我们的队列中，基因组改变没有影响mPFS。在OAK/POPLAR数据集中，STK11突变（60/818 pts）与单变量死亡风险增加显著相关（HR 2.01, p）。结论：STK11变异阻碍了一线ICI或CT-ICI治疗的nsq NSCLC患者的生存。负面预后影响似乎与ICI管理无关。

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引用次数: 0