A clinical prognostic model for patients with esophageal squamous cell carcinoma based on circulating tumor DNA mutation features.

ABSTRACT

Background: Few predictive models have included circulating tumor DNA (ctDNA) indicators to predict prognosis of esophageal squamous cell carcinoma (ESCC) patients. Here, we aimed to explore whether ctDNA can be used as a predictive biomarker in nomogram models to predict the prognosis of patients with ESCC. Methods: We included 57 patients who underwent surgery and completed a 5-year follow-up. With next-generation sequencing, a 61-gene panel was used to evaluate plasma cell-free DNA and white blood cell genomic DNA from patients with ESCC. We analyzed the relationship between the mutation features of ctDNA and the prognosis of patients with ESCC, identified candidate risk predictors by Cox analysis, and developed nomogram models to predict the 2- and 5-year disease-free survival (DFS) and overall survival (OS). The area under the curve of the receiver operating characteristic (ROC) curve, concordance index (C-index), calibration plot, and integrated discrimination improvement (IDI) were used to evaluate the performance of the nomogram model. The model was compared with the traditional tumor-nodes-metastasis (TNM) staging system. Results: The ROC curve showed that the average mutant allele frequency (MAF) of ctDNA variants and the number of ctDNA variants were potential biomarkers for predicting the prognosis of patients with ESCC. The predictors included in the models were common candidate predictors of ESCC, such as lymph node stage, angiolymphatic invasion, drinking history, and ctDNA characteristics. The calibration curve demonstrated consistency between the observed and predicted results. Moreover, our nomogram models showed clear prognostic superiority over the traditional TNM staging system (based on C-index, 2-year DFS 0.82 vs. 0.64; 5-year DFS 0.78 vs. 0.65; 2-year OS 0.80 vs. 0.66; 5-year OS 0.77 vs. 0.66; based on IDI, 2-year DFS 0.33, p <0.001; 5-year DFS 0.18, p = 0.04; 2-year OS 0.28, p <0.001; 5-year OS 0.15, p = 0.04). The comprehensive scores of the nomogram models could be used to stratify patients with ESCC. Conclusions: The novel nomogram incorporating ctDNA features may help predict the prognosis of patients with resectable ESCC. This model can potentially be used to guide the postoperative management of ESCC patients in the future, such as adjuvant therapy and follow-up.