Radiat Oncol J.  2026 Mar;44(1):28-36. 10.3857/roj.2025.00654.

Prognostic significance of the neutrophil-to-lymphocyte ratio in esophageal squamous cell carcinoma treated with proton beam therapy

• Makita K
• Hojo H
• Hirata H
• Dey T
• Nakamura M
• Fujisawa T
• Kotani D
• Wakabayashi M
• Oyoshi H
• Tomizawa K
• Zhou Y
• Koike Y
• Uchida G
• Mishima S
• Kojima T
• Zenda S

• KMID: 2579347
• DOI: http://doi.org/10.3857/roj.2025.00654

Abstract

Purpose
This study evaluated the impact of neutrophil-to-lymphocyte ratio on the survival of patients with esophageal squamous cell carcinoma (ESCC) who underwent proton beam therapy with concurrent chemotherapy.
Materials and Methods
Data of patients with ESCC who received definitive proton beam therapy with concurrent chemotherapy between January 2015 and January 2020 were retrospectively analysed. The 3-year overall and progression-free survival rates were calculated. Prognostic factors, including neutrophil-to-lymphocyte ratio, were examined.
Results
In total, 116 consecutive patients with ESCC (median age, 68 years; range, 45 to 90 years) were included. The median follow-up time was 51.2 months (range, 3.0 to 114.0). Complete clinical response was observed in 75 patients (64.7%). The 3-year overall and progression-free survival rates were 82.4% and 59.4%, respectively. In a multivariate analysis, a Eastern Cooperative Oncology Group performance status ≥1 (hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.00 to 6.34; p = 0.049), clinical stage Ⅳ disease according to the Union for International Cancer Control 8th edition (HR, 3.37; 95% CI, 1.30 to 8.77; p = 0.013), and a neutrophil-to-lymphocyte ratio ≥3.00 (HR, 3.89; 95% CI, 1.36 to 11.19; p = 0.012) were significantly associated with poorer overall survival. Clinical stage Ⅳ disease (HR, 2.86; 95% CI, 1.50 to 5.44; p = 0.003) and neutrophil-to-lymphocyte ratio ≥3.00 (HR, 2.40; 95% CI, 1.32 to 4.39; p = 0.004) were significantly associated with poorer progression-free survival.
Conclusion
In patients with ESCC who received definitive proton beam therapy with concurrent chemotherapy, a high neutrophil-to-lymphocyte ratio was a significant poor prognostic factor for both overall and progression-free survival.

Keyword

Neutrophils; Lymphocytes; Esophageal neoplasms; Squamous cell carcinoma; Proton therapy; Chemoradiotherapy