© 2014 by International Society of Gastrointestinal Oncology. Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) are often used to detect the early response of solid tumors to an effective therapy. The early changes in intratumoral physiological parameters measured by DCE-MRI/DWI have been evaluated as surrogate biomarkers allowing a tailored treatment for the individual patient.Methods: Patients with newly diagnosed, biopsy-proven, treatment-naïve gastrointestinal stromal tumor (GIST) or hepatocellular carcinoma (HCC) were enrolled prospectively after institutional review board (IRB)–approved informed consent (5 patients per tumor type). Patients with GIST were treated with sunitinib over 6 weeks. DCE-MRI/DWI was applied before therapy (baseline imaging) and at 2 and 6 weeks after therapy initiation. Patients with HCC were treated with radiation during the first 2 weeks and then with sorafenib for the next 6 weeks. DCE-MRI/DWI was applied in all patients with HCC before and after radiation therapy and at the end of sorafenib therapy. Tumor volume, perfusion parameters (Ktrans, the forward volume-transfer constant, and kep, the reverse reflux-rate constant) and the apparent diffusion coefficient (ADC) were measured.Results: During 2 weeks of sunitinib therapy, GIST volume, Ktrans, and kep decreased 32 ± 13, 45 ± 24, and 42 ± 15%, respectively, whereas ADC increased 76 ± 24%. After 6 weeks of sunitinib therapy, GIST volume, Ktrans, and kep decreased 56 ± 7, 70 ± 7, and 50 ± 12%, respectively, whereas ADC increased 85 ± 33%. After completion of radiation therapy, HCC volume, Ktrans, and kep decreased 34 ± 14, 35 ± 12, and 4 ± 21%, respectively, but ADC increased 21 ± 9%. During the entire 10-week therapeutic period, HCC volume, Ktrans, andkep decreased 65 ± 15, 40 ± 9, and 26 ± 2%, respectively, whereas ADC increased 28 ± 10%.Conclusion: DCE-MRI/DWI can measure the perfusion and diffusion changes in GISTs or HCCs treated with multikinase inhibitors.