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Purpose: The purpose of this study is to assess the correlation between metabolic response with fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and pathological response in patients with locally advanced esophageal cancer treated with neoadjuvant chemoradiotherapy and to study FDG-PET parameters for the prediction of pathological response and outcome., Methods: Twenty-five patients with locally advanced esophageal cancer underwent two FDG-PET/CT scans for initial staging and after neoadjuvant chemoradiotherapy. FDG uptake in the primary tumor was calculated in both scans (SUVmax, SULpeak, and TLG). Metabolic response was assessed according to the reduction of PET parameters: complete response (mCR = 100%), partial response (mPR ≥50%), and no response (mNR ≤50%). Pathological response was also classified as complete (pCR), partial (pPR), or no response (pNR). Patients were followed up (range, 8-99 months) determining free-disease interval (FDI) and overall survival (OS)., Results: Two patients were excluded due to exitus for nonesophageal-related causes. The metabolic response was observed in 18/23 remaining patients (3mCR, 15 mPR), of which 12/18 patients showed a pathological response (3 pCR, 9 pPR). A major discrepancy was observed in 2 mNR patients who achieved pPR. FDI and OS were longer in patients with metabolic response than nonresponders, but no statistical difference was found. No significant correlation was found between PET parameters and pathological response, FDI, and OS., Conclusions: FDG-PET/CT is a useful technique to assess response to neoadjuvant chemoradiotherapy in esophageal cancer. Although in this preliminary study, no correlation between metabolic and pathologic response was found and no statistical differences between responders and nonresponders were observed, a tendency of longer FDI and OS was apparently found in responders patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Nuclear Medicine.)