The CLARO work plan is broken down in 8 Work Packages (WP) addressing the project general objectives. The activities will be carried out at the Università Campus Bio-Medico di Roma, and the University Hospital will be the main site where the patients will be enrolled and treated. The work will involve the following research units: Unit of Radiation Oncology, Unit of Computer Systems and Bioinformatics, Unit of Medical Oncology, Unit of Diagnostic Imaging and Unit of Anatomic Pathology. Furthermore, the Nuclear Medicine team at the Policlinico Universitario Agostino Gemelli in Rome will acquire the PET scans of the patients enrolled at UCBM, composing the discovery set.

Although each work package is led by a specific partner, the overall work plan requires a high degree of interaction among the partners.

WP1: Consortium and project management and coordination. This work package aims at ensuring that the project is carried out respecting the expected timing, cost, and quality levels, satisfying supporting institution requirements and participants’ expectations. All the activities related to the management of the Consortium will be included in this WP. Furthermore, this WP will also develop the IT infrastructure.

WP2: Patient selection and imaging acquisition. The aim of this WP is to select and enroll patients respecting the inclusion criteria in order to provide the raw data for the RPDSS system development.

WP3: Histological image acquisition. For this WP we plan to extract features from ROI in the digitalized histological images taken from lung tissue to develop prognostic and predictive personalized models.

WP4: Patient treatments. This WP focuses on the patients’ medical treatment. In particular, it also aims at building the ground truth for the radiopathomics decision support system.

WP5: Response and outcome evaluation. This WP aims to determine first and long-term response according to RECIST and iRECIST criteria for CT and PET/CT. Also, for stage III patient we will evaluate the pulmonary toxicity according to CTC-AE 4.0. Moreover, PFS will be recorded for all patients.

WP6: Radiopathomics data processing. This WP will result in a predictive model forecasting the outcome of a therapy using a set of significant biomarkers (hereinafter named as descriptors or signature) identified in the discovery phase; it will also have the ability to recognize “non-responder” patients and/or patients in which the therapy could be detrimental. The data collected will be analyzed integrating analytical and multidimensional process and mining imaging features from radiological images (radiomics) and histopathologic images (pathomics).

WP7: System validation. This WP aims at validating on an independent dataset the RP-DSSs developed in WP6. Such a dataset will be provided by two external institutions, i.e. Thoracic Oncology Department, University of Turin, and the Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence which endorses the project.

WP8: Communication, dissemination and exploitation. The overall objective of this WP is to disseminate and exploit the results of this project, addressing the full range of potential users and uses including research, commercial, investment, social, environmental, policy making, setting standards, skills and educational training.