Prognostic Value of Lactate Dehydrogenase in Second-Line Immunotherapy for Advanced Esophageal Squamous Cell Carcinoma

Abstract

Background: Immunotherapy is recommended by the NCCN (National Comprehensive Cancer Network) guidelines as the standard second-line treatment for advanced esophageal squamous cell carcinoma (ESCC). Patients with advanced ESCC can benefit from immunotherapy, but the overall survival time (OS) is still not satisfactory. Therefore, it is of great importance to select effective prognostic indicators. Methods: A retrospective follow-up study was conducted from January 2018 to January 2020 among 44 patients with advanced ESCC treated with second-line immune checkpoint inhibitors (programmed death -1 blocking agents) in our hospital. The cutoff values of baseline lactate dehydrogenase (LDH), LDH level at week 8, serum albumin, hemoglobin, neutrophils, monocytes, and platelets were obtained by receiver operating characteristic (ROC) curves. The Kaplan-Meier method was used to analyze the relationship between LDH at baseline, LDH level at week 8, and LDH changes during treatment with progression-free survival (PFS) and OS time. The Cox proportional hazards model was used for univariate and multivariate analyses to determine the predictors of OS. Results: In univariate analysis, we found patients with lower baseline LDH levels (cutoff value: 200 U/L) had a better median PFS (8 months vs. 3 months; HR = 2.420, 95% CI: 1.178-4.971, p = 0.016) and OS (14 months vs. 6 months; HR = 3.637, 95% CI: 1.638-8.074, p = 0.004). The level of LDH at week 8 and the changes in LDH during treatment were not significantly associated with PFS or OS. The multivariate analyses showed that baseline LDH was an independent predictor of PFS (HR = 2.712, 95% CI: 1.147-6.409, p = 0.023) and OS (HR = 6.260, 95% CI: 2.320-16.888, p < 0.001), and the monocyte count (HR = 0.389, 95% CI: 0.162-0.934, p = 0.035) was significantly associated with OS. Conclusion: Serum LDH is a powerful independent factor for PFS and OS in advanced ESCC patients treated with anti-PD-1 therapy.

Keywords: esophageal squamous cell carcinoma; immunotherapy; lactate dehydrogenase; prognosis; programmed death -1.