Project Summary Metastatic prostate cancer (PCa) is a debilitating and often deadly disease affecting tens of thousands of men in the U.S. and worldwide. Effective therapeutic options exist for symptom relief and control of the cancer, with others in the pipeline for testing. It is even thought that some patients might be cured if we could detect metastatic disease when it is limited to only a small number of locations. However, both treatment and testing of novel therapies require accurate imaging of the metastases. Unfortunately, most PCa metastases are in bones, where imaging quality is poor, and metastases are considered unmeasurable with conventional techniques. The broad goal of this project is to optimize and test innovative approaches to quantitative imaging, radiation targeting, and response assessment of PCa. The proposal centers on distortion correction and advanced diffusion MRI models, which are effective for detection of PCa lesions and have shown promising association with clinical outcomes. The first specific aim of the proposal is to implement distortion-corrected diffusion MRI into a radiotherapy treatment planning system and measure the impact of distortion correction on precise and accurate tumor delineation in bone metastases. The second aim is to evaluate the prognostic value of diffusion MRI metrics as predictors of clinical outcomes after radiotherapy for bone metastases, a treatment with evidence of a survival benefit in some oligometastatic patients and important for quality of life in patients with painful bone lesions. The third aim is to evaluate the reliability of diffusion MRI for quantitative treatment response assessment of individual bone metastases, an unmet need for clinical practice and clinical trials. Dr. Seibert, assistant professor of Radiation Medicine and Bioengineering, seeks to advance patient care with this proposal and to improve the ability of other investigators to more efficiently test experimental treatments for PCa. Simultaneously, Dr. Seibert will gain mentored experience as a principal investigator and build on his engineering, clinical, and imaging backgrounds with specific expertise in the development of quantitative tools for PCa assessment. UC San Diego and the Center for Multimodal Imaging and Genetics— directed by K08 proposal mentor, Dr. Dale—provide the ideal environment for this project and career development, with a veteran team of mentors and an abundance of resources and skilled personnel to facilitate successful completion of the specific aims and to launch Dr. Seibert’s career as a physician-scientist in radiation oncology and biomedical imaging.

Project Narrative The proposed work directly addresses an international research priority by seeking improved, accurate, quantitative imaging of prostate cancer bone metastases. Reliable measurement of tumor changes in response to therapy would allow physicians to make rapid, personalized treatment adjustments for individual patients— and would also accelerate evaluation of novel therapies in clinical trials. Moreover, advanced diffusion MRI could provide useful prognostic information and help radiation oncologists deliver precision radiotherapy for bone metastases, a strategy proven to alleviate pain and now thought to possibly extend survival in select patients with only a few bone metastases.