Biological Aging and Survival Outcomes in Patients With Advanced Non–Small Cell Lung Cancer Receiving Systemic Therapy

IF 3.9 3区医学 Q2 ONCOLOGY

Clinical lung cancer Pub Date : 2026-04-01 Epub Date: 2025-10-13 DOI:10.1016/j.cllc.2025.10.009

Suguru Kojima , Yusuke Inoue , Masato Karayama , Dai Hashimoto , Kazuhiro Asada , Shun Matsuura , Shiro Imokawa , Takashi Matsui , Hiroyuki Matsuda , Nao Inami , Yusuke Kaida , Jun Sato , Yasuhiro Ito , Masato Fujii , Mikio Toyoshima , Hideki Yasui , Yuzo Suzuki , Hironao Hozumi , Kazuki Furuhashi , Noriyuki Enomoto , Takafumi Suda

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Abstract

Background

Chronological age alone does not adequately capture inter-individual variability in the health status and treatment outcomes of patients with advanced non–small cell lung cancer (NSCLC). Biological age, calculated using routine clinical biomarkers (BioAge), may offer superior prognostic value.

Patients and Methods

A retrospective analysis was conducted on 138 patients treated with immune checkpoint inhibitors (ICIs; ICI cohort) and 154 ICI-naïve patients treated with chemotherapy (chemotherapy cohort). BioAge was calculated using chronological age and seven clinical biomarkers. BioAge acceleration (BioAgeAccel) was defined as the residual derived from the linear regression of BioAge on chronological age. The Kaplan–Meier method and Cox proportional hazards model were used for survival analyses. In the ICI cohort, associations with immune-related adverse events (irAEs) development were evaluated using competing risk regression.

Results

Higher BioAge (≥79.1 years) was independently associated with shorter overall survival (OS) in both cohorts, whereas chronological age (≥75 years) was not. In the ICI cohort, biologically older patients demonstrated significantly worse OS than biologically younger patients, and BioAgeAccel was an independent prognostic factor. However, the BioAgeAccel was not associated with OS in the chemotherapy cohort. No significant associations were observed between BioAge, BioAgeAccel, or chronological age and the risk of irAEs.

Conclusion

Biological age is a robust prognostic factor for advanced NSCLC. BioAgeAccel has additional prognostic value, particularly in the context of immunotherapy. Incorporating biological age metrics into clinical practice may improve patient stratification and support individualized treatment decisions.

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接受全身治疗的晚期非小细胞肺癌患者的生物学老化和生存结局。

背景：单独的实足年龄并不能充分反映晚期非小细胞肺癌（NSCLC）患者健康状况和治疗结果的个体间差异。使用常规临床生物标志物（BioAge）计算的生物年龄可能具有更好的预后价值。患者和方法：回顾性分析138例接受免疫检查点抑制剂治疗的患者（ICI队列）和154例接受化疗（化疗队列）的患者（ICI-naïve）。生物年龄是通过实足年龄和7项临床生物标志物来计算的。生物年龄加速（BioAgeAccel）定义为生物年龄对实足年龄线性回归的残差。生存率分析采用Kaplan-Meier法和Cox比例风险模型。在ICI队列中，使用竞争风险回归评估与免疫相关不良事件（irAEs）发展的关联。结果：在两个队列中，较高的生物年龄（≥79.1岁）与较短的总生存期（OS）独立相关，而实足年龄（≥75岁）与此无关。在ICI队列中，生理年龄较大的患者比生理年龄较小的患者表现出明显更差的OS， BioAgeAccel是一个独立的预后因素。然而，在化疗队列中，BioAgeAccel与OS无关。未观察到BioAge、BioAgeAccel或实足年龄与irae风险之间的显著关联。结论：生物学年龄是晚期非小细胞肺癌的重要预后因素。BioAgeAccel具有额外的预后价值，特别是在免疫治疗的背景下。将生物学年龄指标纳入临床实践可以改善患者分层和支持个体化治疗决策。

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

Clinical lung cancer 医学-肿瘤学

CiteScore

7.00

自引率

2.80%

发文量

159

审稿时长

24 days

期刊介绍： Clinical Lung Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of lung cancer. Clinical Lung Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of lung cancer. The main emphasis is on recent scientific developments in all areas related to lung cancer. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.