Although Response Evaluation Criteria in Solid Tumors (RECIST) is the current clinical guideline to assess size change of solid tumors after therapeutic treatment, it has a relatively lower association to the clinical outcome of progression free survival (PFS) of the patients. In this paper, we presented a new approach to assess responses of ovarian cancer patients to new chemotherapy drugs in clinical trials. We first developed and applied a multi-resolution B-spline based deformable image registration method to register two sets of computed tomography (CT) image data acquired pre- and post-treatment. The B-spline difference maps generated from the co-registered CT images highlight the regions related to the volumetric growth or shrinkage of the metastatic tumors, and density changes related to variation of necrosis inside the solid tumors. Using a testing dataset involving 19 ovarian cancer patients, we compared patients' response to the treatment using the new image registration method and RECIST guideline. The results demonstrated that using the image registration method yielded higher association with the six-month PFS outcomes of the patients than using RECIST. The image registration results also provided a solid foundation of developing new computerized quantitative image feature analysis schemes in the future studies.