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

Abstract

BackgroundFew 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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.

Association between plasma circulating tumor DNA and the prognosis of esophageal cancer patients: a meta-analysis

“… 32 examined GEA. Of these, five studies targeted Western populations 22 , 24 , 27 , 31 , 32 , while the remaining eight focused on Asian populations 23 , 25 , 26 , 28 – 30 . Among the aforementioned investigations, seven were characterized as prospective population studies, and six were identified as retrospective cohort studies.…”

“…Plasma DNA extraction was performed in all studies for subsequent measurement. Several methods were applied in the examination of ctDNA among the studies: (1) next-generation sequencing (NGS) gene panels 22 , 23 , 25 – 28 , 30 , 32 , (2) digital polymerase chain reaction (dPCR) 29 , 30 , (3) droplet digital polymerase chain reaction (ddPCR) 24 , 32 . The clinical endpoint in nearly 77% of the studies (10/13) was OS, followed by PFS in 6/13 studies and DFS/RFS in 4/13 studies.…”

“…The clinical endpoint in nearly 77% of the studies (10/13) was OS, followed by PFS in 6/13 studies and DFS/RFS in 4/13 studies. In addition, several treatment modalities were used among the studies: (1) neoadjuvant therapy followed by surgery 22 , 24 , 26 , 27 , 29 , (2) surgery 23 , 25 , 29 , 31 , (3) chemotherapy 29 , 30 , (4) radiotherapy/chemoradiotherapy with or without surgery 28 . All studies were comparable, reporting the correlation between plasma ctDNA and the outcomes of EC.…”