PROJECT SUMMARY The central focus of the Radiation Biology (RB) Program is to increase the effectiveness of radiotherapy (RT) to enhance both tumor control and survival of cancer patients. Program members investigate new agents that can be combined with RT to improve tumor control while minimizing collateral toxicity to normal tissues, develop novel technologies for radiation treatment planning and delivery, and apply new markers to assess treatment response, prognosis, and toxicity. To achieve these goals, basic discoveries, preclinical models, genomics, radiomics, engineering, and deep learning are used to obtain critical supporting data to take these approaches to clinical trials. Thus, the program includes both basic and translational science. The program was co-led by Quynh Le, MD, and Amato Giaccia, PhD, between 2015 and 2019. With Giaccia’s partial retirement in 2019, the program is now led by Quynh-Thu Le, MD, and Maximilian Diehn, MD, PhD. Le provides expertise in hypoxia, the interaction of the immune system with RT, and stem cell-targeted therapies for mitigating RT toxicity, whereas Diehn adds expertise in cancer genomics, liquid biopsies, biomarker technology development, and genetic causes of radiation resistance. The 31 full members of this program represent the School of Medicine, the School of Humanities and Sciences, and the SLAC National Accelerator Laboratory. They are supported by peer-reviewed research totaling $6.2M in direct funding, including 15 R01s, which is higher than the previous cycle of this grant. Peer-reviewed funding consists of $3.9M from the NCI, $1.4M from other NIH Institutes, and $0.8M from other sources. The RB program members are motivated, innovative and collaborative, both within the program and with other research programs across the Stanford Cancer Institute (SCI), in their goal to translate fundamental discoveries made in the laboratory to enhance the safety and efficacy of RT for cancer patients. Since 2015, members of the RB Program have published 561 manuscripts. Of these, 35% represent intra-programmatic collaborations and 37% represent inter-programmatic collaborations. The Stanford Cancer Institute enhances the program’s goals by providing state-of-the-art shared resources, seed grant support for new projects, programmatic funds, retreats, special seminars, support for new recruitments, and facilitates collaboration with other programs through seed funding and retreats. The support from the SCI has been instrumental in promoting both intra- and inter-programmatic collaborations that were essential for the submission of a new P01 application.