LDH and α-HBDH as Prognostic Biomarkers in Extensive-Stage Small Cell Lung Cancer

Key Clinical Summary:

• Design/Population: A retrospective cohort study evaluated 201 patients with extensive-stage small cell lung cancer treated with first line platinum-based chemotherapy plus immune checkpoint inhibitors, assessing serum LDH and α-HBDH at baseline and after 2 treatment cycles.
• Key Outcomes: Elevated baseline LDH (>245 U/L) and α-HBDH (>182 U/L) were independently associated with inferior overall survival (LDH HR 1.80, P = .046; α-HBDH HR 2.27, P = .007). Insufficient early declines after 2 cycles (LDH ≤108.5 U/L; α-HBDH ≤62.5 U/L) strongly predicted worse overall survival (LDH HR 2.56, α-HBDH HR 2.81; both P < .001). Neither biomarker correlated with progression-free survival.
• Clinical Relevance: Baseline and early on-treatment LDH and α-HBDH provide simple, clinically applicable prognostic markers for overall survival in extensive-stage small cell lung cancer receiving chemoimmunotherapy, enabling early risk stratification and potentially informing treatment intensity and monitoring strategies.

According to results from a retrospective cohort study, elevated baseline and early on-treatment serum levels of lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) following first-line chemoimmunotherapy were independently associated with survival outcomes among patients with extensive-stage small cell lung cancer (ES-SCLC). 

“[ES-SCLC] remains a lethal malignancy with limited prognostic biomarkers,” stated Wanjing Li, MD, Shandong University, Jinan, Shandong, China, and coauthors. “We developed [and] validated dynamic thresholds that enhance specificity and uniquely interrogate immunometabolic crosstalk in the ES-SCLC microenvironment.” 

In this study, researchers analyzed data from 201 patients treated with platinum-based chemotherapy combined with immune checkpoint inhibitors, with a median age of 61 years. Optimal cutoffs identified by receiver operating characteristic curve analysis were used to convert continuous variables into categorical variables. Primary end points included overall survival (OS) and progression-free survival (PFS), and associations between biomarker levels and clinical characteristics were explored.

At analysis, elevated baseline LDH levels (> 245 U/L) and elevated α-HBDH levels (> 182 U/L) were each significantly associated with inferior OS. Patients with elevated baseline LDH had a higher risk of death (hazard ratio [HR], 1.798; 95% confidence interval [CI], 1.020 to 3.167; P = 0.046), as did those with elevated baseline α-HBDH (HR, 2.268; 95% CI, 1.288 to 3.994; P = 0.007). 

Insufficient declines in biomarker levels after 2 treatment cycles were also strongly prognostic. Patients with a reduction in LDH of ≤ 108.5 U/L had significantly worse OS (HR, 2.561; 95% CI, 1.291 to 5.080; P < .001), as did those with an α-HBDH reduction of ≤ 62.5 U/L (HR, 2.807; 95% CI, 1.457 to 5.411; P < .001). Neither baseline nor dynamic changes in LDH or α-HBDH were significantly associated with PFS. 

Advanced tumor stage (T4/N3) and age ≥65 years were significantly associated with less favorable biomarker trajectories over time.

 “This study establishes serum LDH and a-HBDH levels as pivotal prognostic biomarkers in ES−SCLC patients receiving first-line chemoimmunotherapy,” concluded Dr Li et al. “We defined clinically applicable thresholds, demonstrating that elevated baseline levels and inadequate reduction after 2 treatment cycles consistently predict poor survival.”

Source:

Li W, Du G, Lu S, et al. 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. Front Oncol. Published online January 11, 2026. doi:10.3389/fonc.2025.1721581