One embodiment include an image acquisition circuit that accesses a pre-treatment and a post-treatment image of a region of tissue demonstrating non-small cell lung cancer (NSCLC), a segmentation and registration circuit that annotates the tumor represented in the images, and that registers the pre-treatment image with the post-treatment image; a feature extraction circuit that selects a set of pre-treatment and a set of post-treatment radiomic features from the registered image; a delta radiomics circuit that generates a set of delta radiomic features by computing a difference between the set of post-treatment radiomic features and the set of pre-treatment radiomic features; and a classification circuit that generates a probability that the region of tissue will respond to immunotherapy based on the difference, and that classifies the region of tissue as a responder or non-responder. Embodiments may generate an immunotherapy treatment plan based, at least in part, on the classification.