Abstract / Summary
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard first-line treatment for patients with sensitizing EGFR-mutant lung adenocarcinoma; however, treatment outcomes remain heterogeneous and acquired resistance eventually develops in most patients. Therefore, easily available biomarkers are needed to improve risk stratification in patients treated with EGFR-TKIs. This study evaluated the prognostic value of baseline serum lactate dehydrogenase (LDH) and on-treatment LDH changes in patients receiving first-line EGFR-TKI monotherapy. This retrospective cohort study included 223 patients with EGFR-mutant lung adenocarcinoma treated at Shandong Provincial Hospital between January 2019 and December 2023. Baseline LDH was classified as elevated (> 245 U/L) or normal (≤ 245 U/L), and dynamic LDH changes were evaluated in patients with paired baseline and on-treatment measurements. Progression-free survival (PFS) was assessed using Kaplan–Meier and Cox regression analyses. Exploratory pan-lysine lactylation (pan-Kla) immunohistochemistry was performed in available archival paired tumor and adjacent non-tumor tissues from 18 patients with elevated baseline LDH. Patients with elevated baseline LDH had shorter PFS and a lower disease control rate than those with normal baseline LDH. In multivariate Cox regression analysis, elevated baseline LDH remained independently associated with shorter PFS after adjustment for clinically relevant covariates (HR = 1.75, 95% CI: 1.17–2.60, P = 0.006). In contrast, on-treatment LDH change was not significantly associated with PFS in the overall cohort. Exploratory analyses suggested possible heterogeneity according to EGFR mutation subtype, but the L858R-specific signal was not robust to an alternative definition of LDH change. Exploratory pan-Kla analysis showed a higher pan-Kla-positive area in tumor tissues than in paired adjacent non-tumor tissues ( P = 0.005). Elevated baseline serum LDH was independently associated with shorter PFS in patients with EGFR-mutant lung adenocarcinoma receiving first-line EGFR-TKI monotherapy. On-treatment LDH changes were not significantly associated with PFS in the overall cohort.