PROJECT SUMMARY Oral cavity and oropharyngeal (OC/OPC) cancers afflict more than 53,000 individuals in the United States annually. Despite advancements in oncologic therapies, the majority of patients will experience significant toxicity burden during and after therapy, including moderate-severe xerostomia, reduced mouth opening (i.e. trismus), periodontal disease, and osteoradionecrosis. To date, acute and chronic orodental complications are largely managed by clinicians and dentists based on empirical knowledge, with wide inter-provider management variability influenced by provider experience and available clinical information which is often incomplete, incorrect, or nonexistent. To further complicate long-term care of OC/OPC survivors, there is no standardized method for communicating with dentists the extent and intensity of radiation doses delivered to tooth bearing areas which is vital information for accurate assessment of risks related to dental procedures. Therefore, development of a standardized radiotherapy dental information tool and data-driven, algorithmic toxicity risk prediction models for enhanced communication and personalized medicine for OC/OPC survivors remains an unmet public health need. In response to NIDCR’s NOT-DE-20-006, we herein propose a rigorous and reproducible application of informatics and computational methods and approaches for the development of machine learning “ML/AI based optimization of clinical procedures for precision dental care”, “novel and robust data analysis algorithms to tackle causal mechanisms of action for onset and progression of disease” related to posttherapy orodental complications, and “computational modeling for treatment planning and assessment of treatment outcomes.” In Specific Aim 1, we will train and validate a deep learning contouring (DLC) neural network for automatic delineation of tooth-bearing regions. Our collaborator, Dr. van Dijk, has previous experience with DLC design and application for auto- delineation of non-dental head and neck organs at risk (OAR). Her research, published in a peer- reviewed journal showing an equal or significantly improved OAR automatic delineation using DLC over atlas-based contouring, will serve as a reproducible model for our proposed project. Using DLC-based mandibular and dental OAR delineation (SA 1), we will develop a novel “radiation odontogram” which will generate automated and accurate summative radiotherapy dose distribution mapping reports for effective data transmission and communication among providers (SA 2). Accurate prognosis and management of high-morbidity high-prevalence post- therapy orodental sequelae will be enabled through the development of a statistically robust machine-learning based model of toxicity risk predictions that incorporates patient- and provide- generated data (Aim 3). In summary, the RADMAP proposal fosters innovative informatics and computational modeling approaches to address existing challenges in multidisci...