CORE 2 TRANSLATIONAL BIOSPECIMEN AND IMAGING BIOMARKER CORE SUMMARY The Translational Biospecimen and Imaging Biomarker Core Component (Core 2) is a unique, centralized resource to support biospecimen and imaging data collection from radiation-treated patients and will provide sample collection, processing, and sharing. These activities will be carried out for patients enrolled in clinical trials of experimental radiotherapy at the two partnering sites using standardized protocols and procedures. This core will 1) obtain voluntary, informed consent from oncology patients who will undergo or be evaluated for radiation therapy to allow for: (i) identification, storage, and use of patients’ blood, tissue, and clinical information for research purposes, (ii) linkage of clinical information to results from research performed on biospecimens in cooperation with core 1, (iii) sharing and publication of de-identified data generated from scientific study; 2) provide a comprehensive, secure and standardized process for collecting, annotating and storing imaging biomarkers and biological specimens from patients who have undergone, will undergo or be evaluated for radiotherapy at the Massachusetts General Hospital (MGH) and the University of Texas MD Anderson Cancer Centers (UTMDACC); and 3) facilitate the conduct of basic and translational research to further personalize therapy using imaging and blood biomarkers collected during the course of clinical care together with clinical data. Core 2 will support innovative approaches in the projects, such as multiplexed protein analyses and immunophenotyping and new imaging methods. The Core will facilitate translational biomarker studies based on understanding of intrinsic tumor biology and lymphocyte alterations following proton versus photon radiotherapy, which remains largely uncharacterized in the field of particle therapy. Moreover, supporting Project 1, the use of imaging biomarkers to gain information on the effects of proton therapy on normal tissues as a function of both dose and LET is highly innovative, as is the development of AI-based autosegmentation algorithms for MRI and XNAT image analysis pipeline, including the voxel-based analysis of functional imaging for liver, central nervous system and lung. Core 2’s support will enable novel understanding of the interaction of the immune system with proton versus photon radiotherapy in Project 2. Project 3 will rely on Core 2 to provide human tissue specimen for the creation of PDX models and a catalogue of cell lines available for preclinical research across institutions, thereby harnessing the strengths of MGH and UTMDACC. The strength of Core 2 is that it leverages the unique patient population and capabilities at the two Cancer Centers. The MGH site will contribute 20 years of expertise in circulating biomarker studies in over 40 clinical trials, while the UTMDACC site will provide extensive experience in leading nationwide multicenter collaborative p...