Johns Hopkins Radiation Oncology Kimmel Cancer Center Millersville, MD
K. Aziz1, D. Sforza2, E. Tajik-Mansoury2, M. Rezaee2, and L. R. Kleinberg3; 1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, 2Department of Radiation Oncology and Molecular Radiation Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, 3Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
Purpose/Objective(s): Radiation induced lymphopenia has an inverse correlation with treatment response in several disease sites including brain. The mechanism of this well-established clinical phenomenon remains poorly understood. The volume of blood flowing through a radiation field could in fact play a crucial role in death of radiosensitive lymphocytes. We hypothesize FLASH RT reduces lymphocyte killing due to the significantly shorter treatment time and therefore smaller volume of blood transiting through treatment field while radiation dose is being delivered. Particularly in the poorly immunogenic brain microenvironment, improved sustenance of lymphocyte counts may provoke a more robust immune response and therefore superior tumor cell clearance. Materials/
Methods: The Department of Radiation Oncology at Johns Hopkins Physics division developed and built a novel irradiation system, named FLASH kV x-ray cabinet system for preclinical laboratory research (FLASH-SARRP). The system is able to deliver ultra-high dose rates from greater than 100 Gy/s as well as conventional dose rates of 1.0 Gy/s. A custom designed docking system was developed to reproducibly position and immobilize mouse for stereotactic radiation of the brain using parallel opposed x-ray sources. Dose and dose rate measurements were performed with calibrated radiographic film in solid water with 0.025 mm additional copper filter. Healthy 8 weeks old C57BL6J mice were then irradiated with either single fraction of 16 ± 0.8 Gy or 4 Gy x 10 fractions at dose rates of 80 ± 4.0 Gy/s. Peripheral blood was collected at various time points to assess nadir of specific populations of immune cells utilizing routine CBC as well as flow cytometry. Serum was collected for immune cytokine profiling. At necropsy, histopathological changes will be assessed through H&E staining of harvested brain (n = 6 per arm). Conventional radiation was delivered using identical set up on conventional SARRP platform at the dose rate of 0.05 Gy/s. Results: We describe the technology and implementation of small animal partial brain x-ray FLASH radiotherapy. FLASH-SARRP system provides kV x-rays at FLASH dose rates to the entire target volume in the mouse brain. Average dose-rate in the irradiated volume was 79.2±2.1Gy/s corresponding to the 10 mm depth in the immobilized mouse brain. Average delivered dose at the depth was comparable to the SARRP platform. Total treatment durations were 344 s and 0.2 s for conventional and FLASH RT, respectively. Characterization of lymphopenia and cytokine profiling is currently in progress. Conclusion: We have successfully designed a high-precision platform to study partial brain x-ray FLASH effects in mice.
