## 3 Materials  
This work studies 97 patients with NSCLC stage III that were treated with definitive concurrent chemoradiotherapy. The enrollment protocol was approved by Ethical Committee of Campus Bio-Medico University on 30 October 2012 and registered at ClinicalTrials.gov on 12 July 2018 with Identifier NCT03583723 after an initial exploratory phase. The Institutional review board approved this analysis, and a written informed consent was collected from all the patients. For each patient, the simulation CT images were acquired before the treatment using a Siemens Somatom Emotion, with 140 Kv, 80 mAs, and 3 mm for slice thickness. Subsequently all of the images were preprocessed using a lung filter (kernel B70) and a mediastinum filter (kernel B31). The patients were then clinically followed, for a median follow-up of 18.55 months after that it was possible to divide patient into two classes: 53 dead (class 0) and 44 alive (class 1). The patients had a mean Overall Survival (OS) time of \(28.7\pm 26.4\) months (min 4.8 months, max 142.6 months).  
In this study we consider three different VOIs for each patient, the Gross Tumour Volume (GTV), the Clinical Target Volume (CTV), and the Planning Target Volume (PTV) segmented by radiation oncologists, as already introduced in Sections 1 and 2. For GTV, the expert radiation oncologists included all the macroscopic disease defined at CT or PET-CT and nodes PET positive and/or larger than 1 cm in the short axis at CT imaging. Starting from GTV, the other volumes can be segmented: CTV former contains GTV plus a margin for sub-clinical disease spread, which therefore cannot be fully imaged, and it represents the volume that must be adequately treated to achieve cure [43]. PTV is a geometric concept that is designed to ensure that the radiotherapy dose is actually delivered to CTV. It is determined expanding CTV with a safety margin, which is necessary to manage internal motion and set-up reproducibility [44].  
It is worth noting that the ability to segment tumour mass and the surrounding tissue involved with the tumour to a certain extent is an important professional skill for a medical speciality that is radiation oncology. Several methods are proposed in the literature to reduce interpersonal variability [45; 46]. This is why, in our work, the same radiation oncologist segmented all the images in our repository, and then another lung cancer expert radiation oncologist proofread the segmentations. Furthermore, to mitigate the inter-reader variability the segmentations were performed according to the international guidelines [47].  
Figure 1 shows an example of these VOIs: the GTV is drawn in red, and it is the smallest segmentation that precisely delineates the visible tumour; CTV is represented in yellow and it includes areas, where, in the image, there is no evidence of tumour, but where sub-clinical disease may be. PTV, in blu, is the largest segmentation.  
Figure 1: Example of a CT image of a patient suffering from Non-Small Cell Lung Cancer (NSCLC), where we highlight the segmentations corresponding to Gross Tumour Volume (GTV) (red), Clinical Target Volume (CTV) (yellow), and Planning Target Volume (PTV) (blue).