CyberKnife radiation therapy as a platform for translational mouse studies

Purpose Radiation therapy (RT) is a common nonsurgical treatment in the management of patients with cancer. While genetically engineered mouse models (GEMM) recapitulate human disease, conventional linear particle accelerator systems are not suited for state-of-the-art, imageguided targeted RT (IGRT) of these murine tumors. We employed the CyberKnife (CK; Accuray) platform for IGRT of GEMM-derived non-small cell lung cancer (NSCLC) lesions. Material and methods GEMM-derived Kras(LSL-G12D/+)/Trp53(fl/fl) -driven NSCLC flank tumors were irradiated using the CK RT platform. We applied IGRT of 2, 4, 6, and 8 Gy using field sizes of 5-12.5 mm to average gross tumor volumes (GTV) of 0.9 cm3 using Xsight Spine Tracking (Accuray). Results We found that 0 mm planning target volume (PTV) margin is sufficient for IGRT of murine tumors using the CK. We observed that higher RT doses (6-8 Gy) decreased absolute cell numbers of tumor infiltrating leukocytes (TIL) by approximately half compared to low doses (2-4 Gy) within 1 h, but even with low dose RT (2 Gy) TIL were found to be reduced after 8-24 h. Conclusion We here demonstrate that the CK RT system allows for targeted IGRT of murine tumors with high precision and constitutes a novel promising platform for translational mouse RT studies