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Our purpose was to evaluate and compare the clinical utility of simultaneously obtained quantitative ¹⁸F-FDG PET and diffusion-weighted MRI datasets for predicting the histopathologic response of soft-tissue sarcoma (STS) to neoadjuvant isolated limb perfusion (ILP). In total, 37 patients with a confirmed STS of the extremities underwent ¹⁸F-FDG PET/MRI before and after ILP with melphalan and tumor necrosis factor-α. For each patient, the maximum tumor size, metabolic activity (SUV), and diffusion restriction (apparent diffusion coefficient, ADC) were determined in pre- and posttherapeutic examinations, and percentage changes during treatment were calculated. Mann–Whitney U testing and receiver-operating-characteristic analysis were used to compare the results of the different quantitative parameters to predict the histopathologic response to therapy. Results from histopathologic analysis after …