Lactate dehydrogenase-to-lymphocyte ratio predicts overall and progression-free survival among patients with advanced small-cell lung cancer receiving first-line chemoimmunotherapy: A two-center retrospective observational study.

Authors

Tomofumi Hirose, Shuhei Teranishi, Nobuaki Kobayashi, Anna Tanaka, Yukihito Kajita, Ayami Kaneko, Masaki Yamamoto, Makoto Kudo, Takeshi Kaneko

Published in

Medicine. Volume 105. Issue 33. Pages e50249. Aug 14, 2026.

Abstract

Platinum plus etoposide combined with programmed death-ligand 1 (PD-L1) inhibitors is the standard first-line therapy for patients with advanced small-cell lung cancer (SCLC). However, reliable prognostic biomarkers are yet to be identified. The lactate dehydrogenase-to-lymphocyte ratio (LLR) is a potential indicator of tumor metabolism and host immune response; a high LLR is correlated with a poor prognosis in other carcinomas. The LLR may be a more comprehensive indicator of prognosis than the neutrophil-lymphocyte ratio (NLR) or platelet-lymphocyte ratio (PLR), which mainly reflect host immune status. This study evaluates the prognostic value of the LLR in patients with SCLC receiving first-line chemoimmunotherapy. This retrospective, two-center study was conducted at 2 university hospitals in Japan and analyzed 64 patients with extensive-stage SCLC or post-chemoradiotherapy recurrence of limited-stage SCLC who received platinum-etoposide plus a PD-L1 inhibitor as first-line therapy between August 2019 and December 2023. The LLR, NLR, and PLR were calculated from blood tests immediately before the start of first-line therapy, and cutoff values were set using the X-tile software. The prognostic significance of these markers was assessed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Of the 64 patients included, 10 (16%) had high LLR (>471.5). The median duration of observation was 10.5 months (interquartile range: 6.0-19.0 months); by the time of data cutoff, 56 patients (87.5%) had experienced progressive disease and 36 (56.3%) had died. The high LLR group had significantly shorter overall survival (OS) and progression-free survival (PFS). Multivariate analysis was performed using only those factors (LLR/ECOG PS/bone metastasis regarding OS and LLR/bone metastasis regarding PFS) identified as significant in univariate analyses. A high LLR was an independent predictor of worse OS and PFS. While the NLR was an independent prognostic factor for OS, neither NLR nor PLR was a significant predictor of PFS. The LLR is a novel potential prognostic biomarker that integrates tumor metabolism and host immunity in patients with SCLC receiving first-line chemoimmunotherapy. Because it can be readily calculated from routine blood tests, it may serve as a cost-effective tool for risk stratification. However, further prospective validation in larger cohorts is warranted.

PMID:
42601763
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

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