A new risk score model based on lactate dehydrogenase for predicting prognosis in esophageal squamous cell carcinoma treated with chemoradiotherapy

Abstract

Background: The prognostic role of lactate dehydrogenase (LDH) has been confirmed in many malignant tumors, but it has not been widely discussed in esophageal squamous cell cancer (ESCC). This study aimed to assess the prognostic value of LDH in patients with ESCC and to generate a risk score model to predict prognosis in patients who were treated with chemoradiotherapy.

Methods: A total of 614 patients with ESCC who received chemoradiotherapy from 2012 to 2016 were examined in this single-center retrospective study. The optimal cutoff points for age, cytokeratin 19 fragment antigen 21-1 (Cyfra21-1), carcinoembryonic antigen (CEA), tumor length, total dose, and LDH were calculated by the X-tile software. We analyzed the association between the level of LDH and clinicopathological characteristics, and a 1:3 propensity score matching analysis was used to compensate for differences in baseline characteristics. Kaplan-Meier and Cox regression models were used to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). Based on the results, we developed a corresponding risk score model and established a nomogram to assess its predictive capacity.

Results: The optimal cutoff point of LDH was 134 U/L. Patients in the high-LDH group had significantly shorter PFS and worse OS than did those in the low-LDH group (all P values <0.05). Multivariate survival analysis indicated that pretreatment serum LDH level (P=0.039), Cyfra21-1 level (P=0.003), tumor length (P=0.013), clinical N stage (P=0.047), and clinical M stage (P=0.011) were independent predictors for OS in patients with ESCC who underwent chemoradiotherapy. Furthermore, a risk score model based on these 5 prognostic factors was established to divide patients into 3 prognostic groups to identify those patients with ESCC who were most likely to benefit from chemoradiotherapy (χ²=20.53; P<0.0001). However, the prediction nomogram that integrated the significant independent factors for OS is not performed very well in predicting survival (C-index =0.599).

Conclusions: Pretreatment serum LDH level may be a reliable factor in predicting the therapeutic effect of chemoradiotherapy in ESCC. Further validation is needed before this model can be widely used in clinical practice.

Keywords: Lactate dehydrogenase; chemoradiotherapy; esophageal squamous cell carcinoma; prognosis.

Figure 1

X-tile analyses. The optimum cutoff point for LDH was 134 U/L according to the X-tile program. LDH, lactate dehydrogenase.

Figure 2

Kaplan-Meier survival curves of OS and PFS grouped by LDH for 256 patients in the matched cohort. (A) The OS curve of patients with ESCC who underwent chemoradiotherapy classified by LDH. (B) The PFS curve of patients with ESCC who underwent chemoradiotherapy classified by LDH. OS, overall survival; PFS, progression-free survival; LDH, lactate dehydrogenase.

Figure 3

Kaplan-Meier survival curves of OS for patients with ESCC who underwent chemoradiotherapy classified according to the different prognostic factors. (A) Patients classified by Cyfra21-1 (Cyfra21-1 ≤6.4 ng/mL vs. Cyfra21-1 >6.4 ng/mL). (B) Patients classified by tumor length (tumor length ≤6.5 cm vs. tumor length >6.5 cm). (C) Patients classified by cN stage (N0 vs. N+ stage). (D) Patients classified by cM stage (M0 vs. M1a stage). OS, overall survival; ESCC, esophageal squamous cell carcinoma; Cyfra21-1, cytokeratin 19 fragment antigen 21-1. cN, clinical N stage; cM, clinical M stage.

Figure 4

Kaplan-Maier survival curves of overall survival for patients with ESCC who underwent chemoradiotherapy stratified according to the new risk score model. ESCC, esophageal squamous cell carcinoma.

Figure 5

Prediction nomogram for OS. OS, overall survival; ECOG PS, Eastern Cooperative Oncology Group Performance Status; LDH, lactate dehydrogenase.

Figure 6

The calibration plot for the probability of survival. (A) The calibration plot for the probability of 1-year survival. (B) The calibration plot for the probability of 3-year survival.