Association Between Treatment Sequencing and Overall Survival in Stage IV NSCLC With Brain Metastases: A National Cancer Database Study.

IF 2.6 3区医学 Q3 ONCOLOGY

Thoracic Cancer Pub Date : 2026-07-01 DOI:10.1111/1759-7714.70359

Anand Shah, Pranav Gwalani, Merry Zhai, Ritik Goyal, Joshua Kra

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引用次数: 0

Abstract

Background: The optimal sequencing of brain-directed radiation and systemic therapy in stage IV non-small cell lung cancer (NSCLC) with brain metastases remains uncertain in the era of CNS-active systemic agents. We evaluated survival outcomes using national real-world data.

Methods: We conducted a retrospective cohort study of adults diagnosed between 2010 and 2022 with stage IV NSCLC and brain metastases in the National Cancer Database who received both brain-directed radiation and systemic therapy. Treatment sequence was classified as radiation-first or systemic-first based on initiation dates. Multivariable Cox proportional hazards models, stratified by treatment era (pre-2015 vs. 2015+), assessed associations with overall survival (OS), adjusting for demographic, clinical, tumor, and treatment factors. Propensity score matching and delayed-entry sensitivity analyses were performed to address confounding and immortal time bias.

Results: Among 45 577 patients, 78.3% received radiation-first and 21.7% received systemic therapy first. Unadjusted Kaplan-Meier analysis showed no significant difference in OS (log-rank p = 0.624). In multivariable analysis, systemic-first sequencing was associated with a modest increase in mortality (adjusted hazard ratio [aHR] 1.06; 95% CI: 1.04-1.09), which was consistent in propensity-matched (HR 1.07; 95% CI: 1.04-1.11) and delayed-entry analyses (aHR 1.09; 95% CI: 1.07-1.12). The use of systemic-first therapy increased over time. Established prognostic factors demonstrated larger effect sizes.

Conclusion: Systemic-first sequencing was associated with a modest increase in adjusted mortality; however, the effect size was small relative to established prognostic factors and likely influenced by residual confounding and selection bias. These findings support individualized, multidisciplinary treatment decisions rather than a uniform sequencing strategy.

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脑转移的IV期非小细胞肺癌治疗顺序与总生存率之间的关系：一项国家癌症数据库研究

背景：在中枢神经系统活性全身药物时代，IV期非小细胞肺癌（NSCLC）脑转移的最佳脑定向放疗和全身治疗的顺序仍不确定。我们使用国家真实数据评估生存结果。方法：我们对2010年至2022年间在国家癌症数据库中诊断为IV期NSCLC和脑转移的成年人进行了一项回顾性队列研究，这些成年人接受了脑定向放疗和全身治疗。治疗顺序根据起始日期分为辐射优先或系统优先。多变量Cox比例风险模型，按治疗时间（2015年前vs 2015年后）分层，评估与总生存率（OS）的相关性，调整人口统计学、临床、肿瘤和治疗因素。倾向得分匹配和延迟输入敏感性分析进行了解决混淆和不朽的时间偏差。结果：45577例患者中，78.3%先接受放疗，21.7%先接受全身治疗。未经校正的Kaplan-Meier分析显示OS无显著差异（log-rank p = 0.624）。在多变量分析中，系统优先测序与死亡率的适度增加相关（校正风险比[aHR] 1.06; 95% CI: 1.04-1.09），这与倾向匹配分析（HR 1.07; 95% CI: 1.04-1.11）和延迟进入分析（aHR 1.09; 95% CI: 1.07-1.12）一致。系统优先治疗的使用随着时间的推移而增加。已确定的预后因素显示出更大的效应值。结论：系统优先测序与调整死亡率的适度增加相关；然而，相对于已确定的预后因素，效应大小较小，可能受到残留混淆和选择偏差的影响。这些发现支持个性化的多学科治疗决策，而不是统一的测序策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Thoracic Cancer ONCOLOGY-RESPIRATORY SYSTEM

CiteScore

5.20

自引率

3.40%

发文量

439

审稿时长

2 months

期刊介绍： Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society. The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.