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Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is a currently widely used strategy for locally advanced esophageal cancer (EC). However, the conventional imaging methods have certain deficiencies in the evaluation and prediction of the efficacy of nCRT. This study aimed to explore the value of functional imaging in predicting the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced esophageal squamous cell carcinoma (ESCC)., Methods: Fifty-four patients diagnosed with locally advanced ESCC from August 2017 to September 2019 and treated with nCRT were retrospectively analyzed. DW-MRI scanning was performed before nCRT, at 10-15 fractions of radiotherapy, and 4-6 weeks after the completion of nCRT. 18 F-FDG PET/CT scans were performed before nCRT and 4-6 weeks after the completion of nCRT. These 18 F-FDG PET/CT and DW-MRI parameters and relative changes were compared between patients with pathological complete response (pCR) and non-pCR., Results: A total of 8 of 54 patients (14.8%) were evaluated as disease progression in the preoperative assessment. The remaining forty-six patients underwent operations, and the pathological assessments of the surgical resection specimens demonstrated pathological complete response (pCR) in 10 patients (21.7%) and complete response of primary tumor (pCR-T) in 16 patients (34.8%). The change of metabolic tumor volume (∆MTV) and change of total lesion glycolysis (∆TLG) were significantly different between patients with pCR and non-pCR. The SUVmax-T post , MTV-T post , and TLG-T post of esophageal tumors in 18 F-FDG PET/CT scans after neoadjuvant chemoradiotherapy and the ∆ SUVmax-T and ∆MTV-T were significantly different between pCR-T versus non-pCR-T patients. The esophageal tumor apparent diffusion coefficient (ADC) increased after nCRT; the ADC during , ADC post and ∆ADC during were significantly different between pCR-T and non-pCR-T groups. ROC analyses showed that the model that combined ADC during with TLG-T post had the highest AUC (0.914) for pCR-T prediction, with 90.0% and 86.4% sensitivity and specificity, respectively., Conclusion: 18 F-FDG PET/CT is useful for re-staging after nCRT and for surgical decision. Integrating parameters of 18 F-FDG PET/CT and DW-MRI can identify pathological response of primary tumor to nCRT more accurately in ESCC., (© 2021. The Author(s).)