Background: An appropriate strategy is needed to determine the therapeutic effect of chemotherapy on primary lesions in esophageal cancer. This multicenter cohort study aimed to examine the usefulness of a novel criterion obtained by multiplying the lengths of the major and minor esophageal axes from helical computed tomography as a tool to evaluate the therapeutic effect of neoadjuvant chemotherapy and to predict prognosis after surgery in locally advanced esophageal cancer. Materials and Methods: A first investigation evaluated the reproducibility of the new criterion between two independent examiners. In a second investigation, we examined the association of the novel criterion with pathological tumor regression grade and long-term outcomes. Pretreatment primary lesions less than 20 mm on computed tomography were excluded. Results: In an initial cohort of 81 patients, the intraclass correlation coefficient for the novel criterion was higher than that for the tumor major axis both before and after neoadjuvant chemotherapy. In the second cohort of 255 patients, the novel criterion significantly correlated with tumor regression grade (p = 0.0003), overall survival (p < 0.0001), and disease-free survival (p < 0.0001). It was also an independent predictor for overall survival (p = 0.0023), along with age, tumor regression grade, and pathological stage. Conclusions: The measurement derived by multiplying the esophageal major and minor axes on computed tomography is easy to obtain and has better objectivity and reproducibility for tumors of any shape. This novel criterion may be clinically useful because it can estimate therapeutic effect, tumor regression grade, and prognosis after neoadjuvant chemotherapy followed by surgery for esophageal cancer.
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