Abstract 1150: A novel preclinical pancreatic cancer radiation platform: Ptential for high-throughput testing of radiation sensitizers

Abstract

Abstract Introduction Small animal research is integral to the development of preclinical therapies, particularly for terminal diseases such as pancreatic cancer. Unfortunately, application of radiation to such models has been limited to non-conformal, single high dose treatments, which are far removed from the highly conformal, fractionated therapies used in the clinic. To help bridge this translational gap, we have developed a pancreatic cancer small animal radiation research platform (SARRP), which when combined with a mouse orthotopic xenograft model, allows focused, image-guided, fractionated irradiation of pancreatic tumors. We propose that this unique translational mouse model can be used to pre-clinically determine how to optimally combine radiation with novel agents to enhance the treatment of patients with unresectable, resectable, and metastatic pancreatic cancer. Materials and Methods The SARRP uses a constant voltage X-ray source mounted on a gantry. Robotic stages are used to position the animal. Cone-beam computed tomography (CT) is achieved by rotating the animal between the stationary X-ray source and a flat-panel detector. Dosimetry is measured with radiochromic films. Monte Carlo dose calculations are used for treatment planning. The combination of gantry and robotic stage motions facilitate conformal irradiation. Gold fiducials were placed in the mouse pancreas to allow more reliable targeting. Utilizing anesthetized C57BL mice, an incision was made in the left flank and a 1.5 cm film was sewn to a gold fiducial (1.5 mm). Suture was used to attach the film and fiducial to the pancreas and spleen. Mice were placed in the prone position on the SARRP. Five coplanar beams of radiation were delivered to the pancreas. Radiochromic films were removed, scanned and analyzed. Results Cone beam CT planning images with multiple beam arrangement allowed for relative conformality of dose distribution around the pancreas of the C57BL mouse. Spleen and pancreas fiducials were clearly visualized with on-board imaging and analysis of isodose distribution of radiation shows the 70% line (7 Gray) adequately covering the pancreatic fiducial, while effectively sparing the spleen and spinal cord. Analysis of film surrounding the fiducials confirmed that actual dose delivered to pancreas averaged 6.76 Gy (range: 3.91-14.6 Gy, SD 0.40 Gy), while average dose to the spleen was 0.15 Gy (range 0.0-1.39 Gy, SD 0.001 Gy). Mean dose to the pancreas was 21 times greater than that to spleen. Conclusion Our studies confirm the ability to deliver precise, potentially fractionated stereotactic radiation therapy to the mouse pancreas, while avoiding normal tissues. We are hopeful that this platform will allow us to closely mimic contemporary human treatment and test combinations of radiation with novel systemic agents and radiosensitizers, thereby accelerating the transition from bench to bedside. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1150.