Prognostic Value of LDH and α-HBDH Dynamic Levels for 1-Year Overall Survival and Progression-Free Survival in Patients with Extensive-Stage Small-Cell Lung Cancer Treated with Chemoimmunotherapy

Wanjing Li^1,2Guochang Du¹Shuangqing Lu¹Hui Zhu¹Ke Zhao¹Jinming Yu^1,2*Yanqin Yang^1*

• ¹Affiliated Cancer Hospital of Shandong First Medical University Department of Radiation Oncology, Jinan, China
• ²Shandong University Cheeloo College of Medicine, Jinan, China

Abstract Background Extensive-stage small cell lung cancer (ES-SCLC) remains a lethal malignancy with limited prognostic biomarkers. This study evaluated the prognostic utility of lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) levels at baseline and after 2 cycles of treatment in ES-SCLC patients receiving first-line chemoimmunotherapy. Methods Continuous variables were converted into categorical ones based on optimal cutoffs identified by ROC curve analysis (maximizing Youden's index). Overall survival (OS) and progression-free survival (PFS) were calculated via the Kaplan‒ Meier method and compared via the log-rank test. In addition, the Cox regression model was used to analyze prognostic factors. Associations between LDH and α-HBDH levels and clinical parameters (T/N stage, age, and immune-related toxicity) were analyzed using the Mann–Whitney U test and binary logistic regression. Results A cohort of 201 ES-SCLC patients treated with chemotherapy and immune checkpoint inhibitors was analyzed retrospectively. Elevated baseline serum LDH >245 U/L and α-HBDH >182 U/L levels predicted poor OS (p = 0.046, HR = 1.798, 95% CI: 1.020–3.167; p = 0.007, HR = 2.268, 95% CI: 1.288–3.994); inadequate 2-cycle reductions (ΔLDH≤108.5U/L; Δα-HBDH≤62.5U/L) further predicted poor OS (p<0.001, HR = 2.561, 95% CI: 1.291–5.080; p<0.001, HR =2.807, 95% CI: 1.457– 5.411). For progression-free survival, no significant difference was observed between patients with elevated baseline serum LDH >245 U/L or α-HBDH >182 U/L and those with normal levels; similarly, there was no significant difference between patients with an on-treatment increase (ΔLDH>12.5 U/L or Δα-HBDH>0.5 U/L from baseline) and those with a lesser increase or decrease. (P = 0.768, HR = 1.055, 95% CI: 0.739–1.507 for baseline LDH; P = 0.529, HR =1.121, 95% CI: 0.785–1.601 for baseline α-HBDH; P = 0.115, HR =0.719, 95% CI: 0.457–1.131 for ΔLDH; P = 0.094, HR =0.730, 95% CI: 0.494–1.080 for Δα-HBDH). Advanced T4/N3 stage and age ≥65 years significantly modulated biomarker trajectories (p<0.05). Conclusion LDH and α-HBDH serve as key prognostic biomarkers in ES-SCLC patients undergoing first-line chemoimmunotherapy. We established clinically validated thresholds, which can guide treatment by identifying patients with elevated or insufficiently declining levels as high-risk, thereby supporting early and targeted therapeutic intervention.