Project 2

Project Summary/Abstract FLASH radiotherapy is a promising and potentially transformative innovation in radiation therapy, with the ability to ablate tumors at ultra-high dose rates while minimizing damage to surrounding normal tissues. This approach could be especially impactful for pancreatic cancer, where achieving ablative biologically effective doses (>100 Gy) is currently limited by the radiosensitivity of adjacent organs such as the stomach and bowel. Recent studies suggest that FLASH radiotherapy may also enhance the immunogenicity of the tumor microenvironment. Combining FLASH with immunotherapy may therefore produce both local and systemic anti-tumor responses, potentially regressing both irradiated tumors and distant, unirradiated metastatic sites. In this project, we propose the development of PERFECT (Proton Enhanced Radio-immunotherapy with FLASH Effect in Cancer Treatment), a platform for pancreatic cancer that integrates FLASH proton therapy with sustained immunotherapy delivery using smart radiotherapy biomaterials (SRBs). Our central hypothesis is that the PERFECT approach will significantly improve survival and quality of life for patients with pancreatic cancer, with minimal toxicity or side effects. Project milestones include publishing optimized treatment parameters to maximize therapeutic effect and compiling comprehensive safety and pharmacokinetic data to support future clinical translation. Given the limited therapeutic options and poor prognosis associated with pancreatic cancer, this project has high potential significance. The PERFECT approach may also reduce treatment time and costs, enhancing the scalability of advanced radiotherapy platforms. The project will be conducted collaboratively by faculty from Howard University and Johns Hopkins University, leveraging complementary expertise in proton therapy, radiation biology, biomaterials, and immunotherapy, while providing mentorship and research opportunities for trainees at both institutions.