1142 - Efficacy of Ultra-high Dose Rate (Flash) Proton Therapy Concomitantly with LIFE Biomaterial in Murine Pancreatic Cancer Treatment
Presenter(s)
M. Moreau1, Z. Feng1, K. Kelly1, G. Wasihun1, I. Basu1, D. K. Ndassi2, A. Narang3, D. Sforza4, D. Miles5, W. Ngwa6, H. Li7, and K. Ding5; 1Johns Hopkins University, Baltimore, MD, 2Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD, 4Department of Radiation Oncology and Molecular Radiation Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, 5Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 6John Hopkins University, Baltimore, MD, 7Johns Hopkins University Department of Radiation Oncology, Washington, DC
Purpose/Objective(s): LIFE Biomaterial has been previously designed as a smart liquid fiducial marker capable of carrying immunoadjuvants to treat tumors such as pancreatic cancer in mice locally, allowing high-precision targeting while optimizing tumor control via concomitant treatment of radiation and immunotherapies. This study focuses on combining LIFE biomaterial-loaded immunoadjuvants to assess the Flash effect of proton therapy by evaluating its efficacy in controlling syngeneic pancreatic tumor growth and mice survival in mice.
Materials/Methods: Transmission-beam proton radiation was delivered using a Hitachi ProBEAT system using a primary energy of 142.4 MeV. For FLASH delivery, a 3x3 spot pattern was used to deliver a nominal 10.02±0.27 Gy to a 1x1cm^2 area within an 84.32 ±7.81 millisecond beam spill (average 120.02 ±13.37 Gy/s). An equivalent conventional field was designed with the same energy and spot pattern (9.85±0.23 Gy, 12.18±0.78 seconds; 0.81±0.05 Gy/s). Syngeneic subcutaneous or orthotopic pancreatic cancer (KPC) tumors of C57BL/6 mice were treated at 10 Gy with CBCT-based image guidance. Mouse survival was evaluated over time. Immunohistochemistry (IHC) was performed for tumors extracted 10-days post-treatment to characterize the tumor microenvironment, immune cell infiltration and tumor proliferation.
Results: Results showed significant (*, p<0.05) subcutaneous tumor growth delay from the conventional proton group compared to Flash and prolonged mice survival in the Flash group compared to the conventional proton. In the orthotopic tumor model, prolonged mice survival was observed for the Flash alone treated group compared to conventional proton and the Flash + LIFE Biomaterial_Anti-CD40 groups. Proton + LIFE Biomaterial_Anti-CD40 group survived 30 days longer compared to all other cohorts. IHC results showed high infiltration of T-cells (CD3, CD4, and CD8), low infiltration of cancer cells proliferation indicated by Ki-67 marker and low levels of angiogenesis formation as indicated by CD31 marker in the combination treatment of either Flash or Proton therapy concomitantly treated with LIFE Biomaterial_Anti-CD40 groups compared to all other cohorts.
Conclusion: This study serves as a catalyst to further investigate the combination treatment of Flash proton therapy concomitantly treated with LIFE Biomaterial loaded with anti-CD40 monoclonal antibody for the orthotopic pancreatic tumor model. In summary, this study showed the feasibility of Synchrotron-based proton therapy systems for preclinical studies of ultra-high dose rate effects in small rodents.