Methods, apparatus, and other embodiments predict response to pemetrexed based chemotherapy. One example apparatus includes an image acquisition circuit that acquires a radiological image of a region of tissue demonstrating NSCLC that includes a region of interest (ROI) defining a tumoral volume, a peritumoral volume definition circuit that defines a peritumoral volume based on the boundary of the ROI and a distance, a feature extraction circuit that extracts a set of discriminative tumoral features from the tumoral volume, and a set of discriminative peritumoral features from the peritumoral volume, and a classification circuit that classifies the ROI as a responder or a non-responder using a machine learning classifier based, at least in part, on the set of discriminative tumoral features and the set of discriminative peritumoral features.