Prognostic Impact of Baseline Neutrophil-to-Lymphocyte Ratio and Its On-Treatment Change on Survival Outcomes in Advanced Small-Cell Lung Cancer: A Retrospective Analysis

TL;DR

This study shows that changes in a blood marker called NLR during treatment can help predict survival outcomes in patients with advanced small-cell lung cancer.

Contribution

The study introduces the combined use of baseline and on-treatment neutrophil-to-lymphocyte ratio (NLR) as a novel prognostic tool in extensive-stage small-cell lung cancer.

Findings

Higher baseline NLR and increases in NLR during treatment are significantly associated with shorter survival in patients with ES-SCLC.

Combining baseline NLR and on-treatment changes identifies distinct prognostic groups, with the worst outcomes for those with both high baseline NLR and increased NLR.

Baseline NLR as a continuous variable inversely correlates with time to treatment failure and overall survival.

Abstract

Extensive-stage small-cell lung cancer is an aggressive disease, and predicting patient outcome remains difficult in clinical practice. Simple and widely accessible biomarkers are needed to enable clinicians to better stratify prognosis during the course of treatment. One such marker is the neutrophil-to-lymphocyte ratio (NLR), which can be calculated from routine blood tests and reflects inflammation in the body. In this study, we assessed whether baseline and 6-week NLR were associated with survival in patients with ES-SCLC treated with chemotherapy. We found that patients with higher baseline values and those with increases within six weeks of treatment initiation had poorer survival outcomes. These results suggest that early monitoring of this blood-based marker may help identify patients at higher risk and support treatment decision-making using routinely collected clinical data.

Background: Reliable and readily accessible prognostic biomarkers for extensive-stage small-cell lung cancer (ES-SCLC) are still lacking. The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has shown prognostic relevance in several malignancies; however, its dynamic changes during treatment have not been well characterized in SCLC. Methods: We retrospectively analyzed patients with ES-SCLC who received systemic chemotherapy between January 2010 and December 2024. Baseline NLR was calculated within 7 days before first-line treatment, and on-treatment NLR was assessed at 6 weeks. A predefined NLR cutoff value of 5 was applied, and changes in NLR (ΔNLR) were defined as the difference between 6-week and baseline values. Associations with time to treatment failure (TTF) and overall survival (OS) were evaluated. Results: A total of 176 patients were enrolled. High baseline NLR (≥5) was significantly associated with shorter TTF and OS (both p < 0.01). An increase in NLR during treatment (ΔNLR ≥ 0) was significantly associated with poorer OS. Combined assessment of baseline NLR and ΔNLR identified distinct prognostic groups, with patients exhibiting both high baseline NLR and ΔNLR ≥ 0 demonstrating markedly poor survival. In multivariate analyses, baseline NLR, ΔNLR, performance status, and immune checkpoint inhibitor combination therapy were independent predictors of survival. Baseline NLR analyzed as a continuous variable showed a significant inverse correlation with TTF and OS. Conclusions: Combined evaluation of baseline NLR and its on-treatment change provides improved prognostic stratification in patients with ES-SCLC.

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