ABSTRACT This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 24-032. American Indian and Alaska Native (AIAN) people experience a disparate burden of cancer than their non-Indigenous counterparts. Critically, substantial differences in cancer burden exist across AIAN groups. Receipt of timely and evidence-based guideline concordant cancer treatment contribute to survival disparities affecting AIAN people. Survival is lower among AIAN people not receiving guideline-concordant cancer care; however, when AIAN people do receive guideline-concordant treatment, cancer-specific survival does not differ from that observed among NHW. Yet, little is known about variation in guideline-concordant care by region among AIAN people, or about differences in receipt of guideline concordant care between people living in Purchased/Referred Care Delivery Areas (i.e., counties that are served by or adjacent to IHS facilities) and those that are not. Our long-term goal is to reduce the burden of cancer among AIAN people by increasing access to timely, guideline-concordant cancer care. Our current objective is to understand variations in and predictors of receipt of timely, guideline-concordant cancer care by IHS region, and between PRCDA/non-PRCDA counties. Our central hypothesis is that there will be substantial variation in receipt of guideline-concordant cancer care among AIAN people. The rationale for this study is that locally relevant information is essential to support local- level intervention development in collaboration with AIAN peoples. To address this objective, this research will pursue two specific aims and one exploratory aim. The first aim will validate a set of healthcare quality metrics that can be used to assess receipt of timely and evidence- based services during diagnosis, staging and first-line treatment among AIAN people using only cancer registry data. We will then use these measures to assess multi-level predictors of timely and guideline-concordant care among AIAN people across IHS regions using national cancer surveillance data.The second aim will examine regional differences in predictors of outcomes for leading cancers (breast, lung, colorectal) among AIAN people, including mediation by receipt of timely and guideline-concordant cancer care. The exploratory aim will investigate how the associations observed in Aims 1 and 2 vary between AIAN between people living in Purchased/Referred Care Delivery Areas (i.e., counties that are served by or adjacent to IHS facilities) and those that are not. This research is innovative because it explores questions about which nothing is known for AIAN people. Upon the successful completion of this research, we will have elucidated differences in guideline- concordant cancer care and its relationship with outcomes by IHS region among AIAN people. This information will provide critical information to understand variation in AIAN cancer dispariti...