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

Suguru Kojima¹, Yusuke Inoue¹, Masato Karayama²

¹Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Clinical Lung Cancer

|November 3, 2025

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.

Keywords:

BioAge BioAgeAccel Biological age Chronological age Prognostic factors

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