Project Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-22-057. The goal of the NOSI is to stimulate or strengthen global cancer health disparities research. One of the major area of global cancer health disparities is in access to radiotherapy, employed in the treatment of over 50% of cancer patients. According to the recent World Health Organization Cancer Report and Lancet Oncology Commission Report for Sub-Saharan Africa, these disparities are particularly alarming for African populations and may underlie the disparities in access to radiotherapy also seen among African American/immigrant populations in the USA. A greater understanding and innovative approaches to reduce these disparities in access to radiotherapy are crucial in addressing the growing global burden of cancer and disparities in cancer deaths. Innovative approaches with potential to significantly reduce disparities in access to radiotherapy include use of evidence-based hypofractionated radiotherapy (HFRT) and smart radiotherapy biomaterials (SRBs), which are being developed under the parent R01 grant. The SRBs can be employed in place of currently used inert radiotherapy biomaterials (fiducials and beacons). Preliminary studies have established that the SRBs can boost both local and metastatic tumor kill when used in conjunction with HFRT. However, a major gap in the scientific literature is the extent of adoption and utilization of HFRT and radiotherapy biomaterials at African country cancer centers and the currently available infrastructure, including human infrastructure for adoption of such an approach with the SRBs. Hence, in this supplement project, we will investigate disparities in the adoption and utilization of evidence-based HFRT and radiotherapy biomaterials in Africa in comparison with the USA, and potential cost savings that could result in use of HFRT with SRBs. Published data resulting from this project will be crucial in informing policy on increasing access to radiotherapy in Africa. The published data will also be highly relevant in planning USA-Africa multi-center clinical trials resulting from the R01-funded project with participation of diverse populations, including Africans and African Americans traditionally underrepresented in clinical trials. Moreover, the significance of this work is even greater now in global health as COVID-19 has further exposed the level of disparities in access to care, with professional societies recommending increased use of evidence-based HFRT.