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Background: Based on the special pattern of recurrence in the excision cavity, secondary computed tomography (CT) can be introduced after hypofractionated whole breast radiotherapy with early breast cancer, aiming for accurate delineation of tumor bed boost and reduced toxicity. This study aimed to assess the volumetric changes in the lumpectomy cavity before and after hypofractionated whole breast radiation therapy (WBRT) and related clinical factors. Method: This prospective study was designed and CT simulation was done for 45 patients from September 2019 to April 2020, two radiotherapy treatment planning were generated for each patient before and after hypofractionated WBRT. The tumor bed is defined using surgical clips, seroma, and postoperative alterations. Based on the original CT and tumor bed boost CT, statistically significant decrease was examined. The relationship between various factors and the volume decrease in the excision cavity was examined. Results: The median value of reduction in the excision cavity was 15.4 cm³with the statistical significance (P < 0.001). In multivariate linear regression, the significant variable, which predict the volume reduction, was the presence of seroma (B = 24.48, confidence interval, 13.09 to 35.87, P < 0.001). Conclusion: our results suggested significant benefit from resimulation before boost planning especially for patients with clinical evident seroma. [ABSTRACT FROM AUTHOR]