Modeling the relationship between baseline lactate dehydrogenase and prognosis in patients with extensive-disease small cell lung cancer: a retrospective cohort study

Abstract

Background: Elevated pretreatment lactate dehydrogenase (LDH) has been reported to be associated with poor survival in small cell lung cancer (SCLC). The present study aimed to investigate the continuous relationship between baseline LDH level and survival in patients with extensive-disease SCLC (ED-SCLC). Results: A total of 132 eligible ED-SCLC patients were analyzed. Elevated LDH at baseline was associated with poor survival (HR =1.92; 95% CI,). An increment of LDH would still raise the risk of death even in abnormal range. Among patients with elevated LDH, those who had relatively higher LDH levels (>370 U/L) would have a poorer prognosis than those with moderately elevated LDH levels (245-370 U/L; median survival time, 114 vs. 274 days; P value of log rank test, 0.007).Conclusions: LDH is a significant prognostic biomarker for ED-SCLC patients. The interpretation of continuous relationship between LDH and patients' survival can provide more accurate information for clinical practice. In recent decades, novel approaches of immunotherapy have brought light to cancer treatment (4,5). And trials for investigating the efficacy and safety of immunotherapy with or without chemotherapy in SCLC patients are ongoing (6,7).Predicting prognostic risks of SCLC patients through reliable biomarkers can provide information for disease monitoring and treatment evaluation, which will contribute to the exploration of novel treatments. Lactate dehydrogenase (LDH) is the key enzyme in glycolytic pathway, which is the main source of energy in activities of rapid proliferation and distant metastases for tumor cells. When tissue damage occurs because of tumor activities, LDH will be released from intracellular microenvironment and then lead to an abnormal elevation of serum LDH (8). Therefore, measurements of serum LDH levels can reflect the intensity of tumor activities and thus can be used as a prognostic biomarker. Zhang et al. (9) conducted a metaanalysis involving 4,785 SCLC patients from 28 studies to investigate the prognostic value of baseline LDH for SCLC patients. Their results indicated that patients with an abnormal elevation of serum LDH at baseline would have a 1.45 times higher risk of death than those with normal LDH level (HR =1.45; 95% confidence interval (CI), 1.27-1.66).However, measurements of LDH were all treated as binary outcomes in above studies with a cutoff value at the upper limit of normal range. In that way, it would be impossible to explore the continuous relationship between baseline LDH and survival; namely, different LDH levels within the same group would be regarded as to have the same risk of death.Modeling the relationship between exposure of risk factors and disease outcomes can provide more accurate information for clinical practice. Zhou et al. (10) found nonlinear associations between biomarkers and prognosis in resectable pancreatic ductal adenocarcinoma (PDAC) patients. Their results suggested that a preoperative Carbohydrate antigen 19-9 (CA19-9) level of 100 U/mL and a carcinoembryoni...

Serum Lactate Dehydrogenase Contributes to Prognostic Assessment in Patients With Oligometastatic Cancer and Brain Involvement

“…Sixty percent had brain-only metastases. We found that elevated LDH was associated with significantly shorter survival, in line with our previous results in a larger study of patients who mainly had non-in vivo 33: 229-232 (2019) oligometastatic brain metastases (13) and with other studies in different settings (15)(16)(17).…”

Prognostic Significance of Lactate Dehydrogenase in Patients Undergoing Surgical Resection for Laryngeal Squamous Cell Carcinoma

“…20 Some researchers believe that LDH is an independent prognostic factor of lung cancer and is closely related to the TNM stage, therapeutic effect and survival of lung cancer. 21 , 22 Additionally, serum LDH levels can be used as prognostic indicators for malignant tumors such as colorectal cancer, 23 nasopharyngeal carcinoma, 24 prostate cancer 25 and breast cancer. 26 Our study showed that LDH >132 IU/L was associated with better prognosis in LSCC patients.…”

Central regulation of breast cancer growth and metastasis

“…Indeed, one of the first major breakthroughs in cancer research was the discovery that tumor cells are biased towards aerobic glycolysis rather than oxidative phosphorylation to produce energy (i.e., the Warburg effect [95][96][97] ). Therefore, a common finding in malignant cancers is a strong upregulation of lactate and catalytic enzymes required for lactate production from pyruvate (e.g., lactate dehydrogenase) [98][99][100][101] . Lactate normally acts to aide in glucose sensing and food intake, where it is transported into the brain via monocarboxylate transporters present on endothelial cells lining the blood-brain barrier [102] .…”