A computer-implemented method for determining and evaluating an objective tumor response to an anti-cancer therapy using cross-sectional images can include receiving cross-sectional images of digital medical image data and identifying target lesions within the cross-sectional images. For each of the target lesions, a target lesion type and anatomical location is identified, a segmenting tool is activated for segmenting the target lesions into regions of interest, lesion metrics are automatically extracted from the regions of interest according to tumor response criteria, and conformity of target lesion identification is monitored using rules associated with the tumor response criteria, prompting a user to address any nonconforming target lesion. The method also includes receiving a presence/absence of metastases, determining changes in lesions metrics, and deriving an objective tumor response based on the tumor response criteria.