Program Information
Precision Partial-Tumor Irradiation of Dorsal Rodent Mammary Tumors
J Malcolm1*, K Boss2 , M Dewhirst3 , M Oldham4 , (1) Duke Medical Physics Graduate Program,Durham, NC, (2) Department of Comparative Biomedical Sciences, North Carolina State University, (3) Dpt of Radiation and Cancer Biology, Duke University, Durham, North Carolina, (4) Dpt of Radiation Oncology, Duke University Medical Center, Durham, NC
Presentations
WE-EF-BRA-11 (Wednesday, July 15, 2015) 1:45 PM - 3:45 PM Room: Ballroom A
Purpose:To introduce a pre-clinical treatment technique on a micro-irradiator to treat specific volumes of dorsal mammary tumors in BALB/c mice while sparing lungs and spine. This technique facilitates pre-clinical investigation of tumor response to sub-optimal radiation treatments in which a portion of the tumor is un-irradiated, known as a “marginal miss”. In-vitro data suggests that partial tumor radiations trigger a more aggressive phenotype in non-irradiated, regional tumor cells via bystander effects. . As the lung tissue is spared, the impact of marginal miss on the development of pulmonary metastasis may be assessed.
Methods:End to end test was performed on three BALB/c mice as proof of concept for larger studies. 1Gy was delivered on the micro-irradiator employing previously unexplored lateral parallel-opposed diamond and/or triangle-shaped beams. The margins of the treatment beam were defined using a combination of tumor palpation, barium fiducial markers, and real-time fluoroscopic images. The dose distribution was independently verified with kilovoltage beam Monte Carlo dose calculations with 7% statistical uncertainty and double exposure images. As a final step, the technique was used in a larger pre-clinical study (15Gy, 36 BALB/c mice) and lung metastasis in response to tumor irradiation of 100%, 50% and 0% was quantified.
Results:For the Monte-Carlo dose calculations, the dose volume histograms established a maximum dose within the un-irradiated and radiated portions of the mammary tumor of 0.3Gy and 1.5Gy respectively, with a sharp gradient at the boundary. 100% of the lung volume received less than 0.5Gy. This technique proved suitable for a pre-clinical marginal miss study with 50% more lung metastases in partially-radiated mouse models compared to completely.
Conclusion:We have developed a novel treatment technique for partial or full irradiation of dorsal mammary tumors incorporating lung sparing.The technique will be useful for exploring the phenomena of aggressive tumor phenotype that may arise from miss-irradiation.
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