Endoscopic Ultrasonography For Predicting The Efficacy Of Neoadjuvant Radiotherapy For Esophageal Squamous Carcinoma

Background: Endoscopic ultrasonography(EUS)-derived maximum tumor thickness(MTT)pre-and post-neoadjuvant chemoradiotherapy(NCRT)for locally advanced esophageal squamous cell carcinoma(LA-ESCC)indicates treatment response.However,the accuracy of predicting treatment response remains uncertain.This study aimed to investigate the association between EUS-derived MTT pre-and post-NCRT and tumor shrinkage rate as well as long-term survival and examine the usefulness of a novel criterion obtained by white light gastroscope(WLE)and EUS-derived tumor shrinkage rate as a tool to evaluate the therapeutic effect of NCRT and to predict pathological complete response(PCR)and major pathological response(MPR)after surgery in patients with LA-ESCC.Methods: We retrospectively enrolled patients with LA-ESCC who underwent EUS from 2017 to 2021.Tumor shrinkage rate was the ratio of the difference between pre-and post-MTT to pre-MTT.The most fitted cut-off values were determined by the receiver operating characteristic(ROC)curve.The best cut-off value of pre-MTT,post-MTT,and tumor shrinkage rates were established at 24 mm,8.8 mm and 52%,respectively.We defined the endoscopic ultrasonography complete clinical response(EUS-CCR)as:(1)Disappearance of endoscopic findings suggesting the presence of a tumor;(2)Entire esophagus can be observed using endoscopy;(3)No endoscopic findings of active esophagitis(e.g.,flat erosive findings,white coating).(4)Tumor shrinkage rate>54%.Univariate and multivariate Cox regression analyses and Kaplan–Meier(KM)curves were used to calculate overall survival(OS)and progression-free survival(PFS).A univariate logistic regression model was fitted to evaluate the association between EUSCCR and MPR and PCR.MPR was defined as residual carcinoma<10%.Data from another center was also used for external validation testing.To test our hypotheses,we prospectively collected data from September 2021 to August 2022.Results:Two hundred and thirty patients were enrolled.For all the patients,the 1-year and 3-year OS rates were 93.9% and 67.9%,and PFS rates were 77.7% and 54.1%,respectively.The median follow-up period was 30.6 months.Post-MTT ≤8.8 mm and EUS-responders were independently associated with better OS.External validation confirmed the prognostic factor of tumor shrinkage rate.The univariate and multivariate logistic regression analyses suggested that the novel criterion of EUS-CCR significantly correlated with MPR(OR,6.86;95%CI,3.13～15.02;P<0.001)and PCR(OR,2.56;95%CI,1.27～5.18;P=0.009).The AUC for diagnosing MPR from LA-ESCC underwent NCRT was 0.72(Sensitivity,80.7%;ppv,83.8%;specificity,62.6%;npv,57.5%);and the AUC for diagnosing PCR from LA-ESCC underwent NCRT was 0.61(Sensitivity,58.9%;ppv,48.5%;specificity,62.0%;npv,71.2%).Internal validation confirmed this accuracy.Conclusion: EUS-derived MTT and tumor shrinkage post-NCRT are independent prognostic factors for long-term survival.The new EUS-based criteria by endoscopic presentations and ultrasound tumor regression are useful for estimating the prognosis of MPR and PCR after NCRT in patients with LA-ESCC.