Functional Avoidance Liver Stereotactic Body Radiation Therapy Guided by MR Multitasking-driven Abdominal Integrated Imaging (MT-AI2)

Radiation plays an important role in treating primary and secondary liver tumors. Stereotactic body radiation therapy (SBRT) has become a standard treatment in the model era. However, toxicity-inducing doses to the normal liver often accompany the high biologically effective dose to the tumor, so radiation-induced liver disease (RILD) is a common complication that can be fatal to patients. As patient survival rates rise and therapeutic options expand, SBRT aims not only to ablate tumors but also to reduce radiation exposure to functional liver voxels, thereby decreasing treatment-related toxicities to maintain hepatic function and support future interventions, such as liver transplantation. Functional Avoidance SBRT (FA-SBRT) has been proposed. Researchers have created FA-SBRT plans using commercial planning systems. However, it was concluded there was insufficient data to confirm efficacy. The inability to establish the efficacy can be attributed to the following reasons: the lack of clinically accessible methods to assess voxel-level liver function, the lack of quantifiable liver function metrics for treatment planning, and the severe limitations of commercial planning systems in achieving a more significant level of functional liver sparing. We pioneered the development of a Multi-Tasking (MT) MR imaging sequence and advanced non-coplanar 4π planning method. The convergence of cutting-edge imaging and plan optimization strategies presents an unparalleled opportunity to optimize treatment delivery, reduce radiation-induced liver toxicity, and augment therapeutic outcomes. The proposal directly responds to PAR-25- 145, Clinical Characterization of Cancer Therapy-induced Adverse Sequelae and Mechanism-based Interventional Strategies. The three proposed aims are 1. To develop and optimize the MR multi-tasking abdominal integrated imaging (MT-AI2); 2. To create a functional avoidance SBRT planning strategy using advanced 4π optimization; 3. To conduct a phase II clinical trial to test efficacy. The project’s success will demonstrate the effectiveness of integrating cutting-edge imaging and therapeutic methods to maximally preserve liver function for future treatment options. Project Number: 1R01CA301509-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Wensha Yang (+3 co-PIs) | Institution: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, SAN FRANCISCO, CA | Award Amount: $700,838 | Activity Code: R01 | Study Section: Radiation Therapeutics and Biology Study Section[RTB] View on NIH RePORTER: https://reporter.nih.gov/project-details/11317977