## Materials and Methods
### Patients Selection and Annotation of Regions of Interest (ROIs)  
To carry out this cross-sectional study, the approval of the Research Ethics Committee was obtained. For this study, 47 patients were selected from the databases of the CHUS University hospital (Complexo Hospitalario Universitario de Santiago de Compostela). The inclusion criteria were as follows: (1) patients with colorectal cancer with determination of the KRAS mutation by biopsy between 2016 and 2017 (27 KRAS+ and 20 KRAS- patients, respectively); (2) selection of those patients whose intravenous contrast CT dated before any treatment; (3) obtaining the CT images with a slice thickness of 5 mm. Very thin slice thickness improves spatial resolution but decreases contrast. Therefore, 5 mm is the thickness we estimate best to determine the difference in texture of the tumour pixels. In addition,the patients included in the study already had the CT done, since it is one of the first tests to be performed in tumour staging; the subsequent CTs could not be included in the study, since they are post-treatment and may bias its results. The CT images used must be selected to any treatment applied. Therefore, to obtain the images of each patient, we will resort to the CT performed at the time of diagnosis. From these images, a series of slices are obtained: three slices of the tumour are selected, i.e., the slice in which the tumour presents the largest diameter (central slice) and the slices immediately cranial and immediately caudal to that central slice. The selection of three slices for each tumour is made to encompass the largest possible tumour volume in the analysis, trying to approach a 3D analysis of it. With the three slices we make sure to select the largest amount of tumour that the imaging technique allows. We did not select more slices because in the analysis of some tumours, due to their size and disposition, it was not possible to analyse more than three slices, so it was finally decided to standardize the analysis of all patients' tumours to three slices. Then, with each image of the three slices, the tumour is manually delimited by an expert radiologist, performing the following segmentation sequence:  
* First, an image of tumour is saved without limitation in original size as \"large-original.tiff\" (i.e., Figure 1). The sequence of obtaining the images is very important to speed up the process and ensure that the images have the same focus when they are enlarged. An expert radiologist searches the cut with the largest diameter of the tumour. All images must be saved in \".tiff\" format, as we will explain later. * Secondly, an expert radiologist delimits the tumour, and an image of the delimited tumour is saved in its original size: \"large-delimited.tiff\" (i.e., Figure 2). The delimitation process is carried out manually by an expert, since due to the morphological heterogeneity of the tumour it is impossible to make an automatic delimitation. Figure 1: “Large-original” is the first image to obtain. This image belongs to a KRAS+ patient included in the study. The tumour under study is highlighted with red arrows and can also be seen in greater detail in the adjacent images. Figure 2: “Large-delimited” is the second image to be obtained. In the two adjacent small images, the delimited tumour can be seen in detail. The delimitation line is highlighted between the two red arrows in the most enlarged image. * Third, the screen zoom is adjusted by enlarging the image and an image of the segmented and enlarged tumour is saved: \"small-delimited.tiff\" (i.e., Figure 3). * Finally, without modifying the zoom, the previous delimitation is eliminated, and one image of the tumour is saved without delimiting and enlarged: \"small-original.tiff\" (i.e., Figure 4). This process of obtaining the images is repeated with the slices immediately cranial and immediately caudal. Finally, a set of 12 images is obtained for each patient.