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: Comparing incidental dose distributions (i.e. images) of patients with different outcomes is a straightforward way to explore dose-response hypotheses in radiotherapy. In this paper, we introduced a permutation test that compares images, such as dose distributions from radiotherapy, while tackling the multiple comparisons problem. A test statistic Tmax was proposed that summarizes the differences between the images into a single value and a permutation procedure was employed to compute the adjusted p-value. We demonstrated the method in two retrospective studies: a prostate study that relates 3D dose distributions to failure, and an esophagus study that relates 2D surface dose distributions of the esophagus to acute esophagus toxicity. As a result, we were able to identify suspicious regions that are significantly associated with failure (prostate study) or toxicity (esophagus study). Permutation testing allows direct comparison of images from different patient categories and is a useful tool for data mining in radiotherapy. [ABSTRACT FROM AUTHOR]