Table2_Influence of adverse effects of neoadjuvant chemoradiotherapy on the prognosis of patients with early-stage esophageal cancer (cT1b-cT2N0M0) based on the SEER database.docx

ObjectiveTo analyze the prognostic impact of neoadjuvant chemoradiotherapy (NCRT) on early-stage (cT1b-cT2N0M0) esophageal cancer (ESCA) and construct a prognostic nomogram for these patients.
MethodsWe extracted the clinical data about patients diagnosed with early-stage esophageal cancer from the 2004–2015 period of the Surveillance, Epidemiology, and End Results (SEER) database. We applied the independent risk factors affecting the prognosis of patients with early-stage esophageal cancer obtained after screening by univariate and multifactorial COX regression analyses to establish the nomogram and performed model calibration using bootstrapping resamples. The optimal cut-off point for continuous variables is determined by applying X-tile software. After balancing the confounding factors by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) method, Kaplan-Meier(K-M) curve, and log-rank test were applied to evaluate the prognostic impact of NCRT on early-stage ESCA patients.
ResultsAmong patients who met the inclusion criteria, patients in the NCRT plus esophagectomy (ES) group had a poorer prognosis for overall survival (OS) and esophageal cancer-specific survival (ECSS) than patients in the ES alone group (p < 0.05), especially in patients who survived longer than 1 year. After PSM, patients in the NCRT + ES group had poorer ECSS than patients in the ES alone group, especially after 6 months, while OS was not significantly different between the two groups. IPTW analysis showed that, prior to 6 months patients in the NCRT + ES group had a better prognosis than patients in the ES group, regardless of OS or ECSS, whereas after 6 months, patients in the NCRT + ES group had a poorer prognosis. Based on multivariate COX analysis, we established a prognostic nomogram which showed areas under the ROC curve (AUC) for 3-, 5-, and 10-year OS 0.707, 0.712, and 0.706, respectively, with the calibration curves showing that the nomogram was well calibrated.
ConclusionsPatients with early-stage ESCA (cT1b-cT2) did not benefit from NCRT, and we established a prognostic nomogram to provide clinical decision aid for the treatment of patients with early-stage ESCA.

**目的** 分析新辅助放化疗（neoadjuvant chemoradiotherapy, NCRT）对早期（cT1b-cT2N0M0）食管癌（esophageal cancer, ESCA）患者的预后影响，并为该类患者构建预后列线图。
**方法** 从监测、流行病学与最终结果（Surveillance, Epidemiology, and End Results, SEER）数据库2004-2015年的数据集里，提取确诊为早期食管癌患者的临床资料。通过单因素及多因素Cox回归分析筛选出影响早期食管癌患者预后的独立危险因素，以此构建预后列线图，并采用Bootstrap重采样法对模型进行校准。使用X-tile软件确定连续变量的最优截断值。通过倾向得分匹配（propensity score matching, PSM）及治疗逆概率加权（inverse probability of treatment weighting, IPTW）法平衡混杂因素后，采用Kaplan-Meier（K-M）曲线及对数秩检验（log-rank test）评估新辅助放化疗对早期食管癌患者的预后影响。
**结果** 在符合纳入标准的患者中，新辅助放化疗联合食管切除术（esophagectomy, ES）组患者的总生存期（overall survival, OS）及食管癌特异性生存期（esophageal cancer-specific survival, ECSS）均差于单纯食管切除术组（p<0.05），尤其在生存期超过1年的患者中更为显著。经倾向得分匹配后，新辅助放化疗联合食管切除术组患者的食管癌特异性生存期仍差于单纯食管切除术组，尤以术后6个月后为甚，而两组总生存期无显著差异。治疗逆概率加权分析显示，术后6个月内，无论总生存期还是食管癌特异性生存期，新辅助放化疗联合食管切除术组患者的预后均优于单纯食管切除术组；但术后6个月后，该组患者的预后则更差。基于多因素Cox回归分析构建的预后列线图，其3年、5年、10年总生存期的受试者工作特征曲线（ROC curve）下面积（AUC）分别为0.707、0.712、0.706，校准曲线显示该列线图校准度良好。
**结论** 早期食管癌（cT1b-cT2N0M0）患者无法从新辅助放化疗中获益，本研究构建的预后列线图可为早期食管癌患者的临床治疗决策提供辅助支持。