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Modeling Dose Heterogeneity for Immunological Priming in Murine Studies Using SARRP

F Mourtada1*, H Chen1 , J Keller2 , J Sims Mourtada2 , A Raben1, Y Yu2 (1) Helen F. Graham Cancer Center, Newark, DE, (2) Thomas Jefferson Hospital, Philadelphia, PA


(Sunday, 7/14/2019)  

Room: ePoster Forums

Purpose: The dose regimen needed for radiation-induced immune priming is unclear. Recent studies have indicated that heterogeneous dose distribution (HDD) may provide superior anti-tumor immunity in combination with immunotherapy. Here, We report on a novel small animal radiation method to deliver HDD in murine models.

Methods: HDD concept was validated for the SARRP animal irradiator using high spatial resolution radiochromic film absolute dosimetry for the SARRP 1x1cm² and 0.5x0.5cm² fixed square nozzles. The nozzles size was selected to deliver either a uniform dose of 12-Gy or HDD using two abutted nozzles to deliver low (2-Gy) and high (12-Gy) SBRT-like dose regions within tumor volume. SARRP X-ray output was calibrated with ion chamber in solid water based on AAPM TG-61 protocol worksheet C2. The reference condition (17x17cm², depth at 2cm in solid water) was setup to irradiate film to obtain net optical density to dose calibration curve. This curve was then used to determine the dose rate for the nozzles at 2-5 mm depths in phantom to mimic the murine tumor volume depths. Tumor xenografts of ≤1 cm in diameter were simulated using the SARRP treatment planning software for both a single fraction of 1) uniform dose of 12-Gy using the 1x1cm² nozzle to cover entire tumor and 2) HDD (2-12 Gy) using the 0.5x0.5cm² nozzle.

Results: Based on our film measurements, the dose rate of 17x17cm² field size at 2mm depth is 108% of reference output. For 1x1cm² and 0.5x0.5cm² nozzles, the dose rates at 2mm depth are 79% and 77% of reference output respectively. These output factors will be used to determine the irradiation time for tumor cells on small animals.

Conclusion: HDD in murine tumor models can be delivered, allowing for preclinical characterization of immune responses with both uniform and heterogeneous dose regions within tumor.


Not Applicable / None Entered.


TH- Small Animal RT: Planning

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