Small Animal IMRT Using 3D-Printed Compensators

Purpose: Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators. Methods and Materials: Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (similar to 1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx(1)) with boost (Rx(2)) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis. Results: Resolution test-patterns demonstrate practical printer resolution of similar to 0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V-95% = 95%) with organ sparing (organs at risk D-max < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V-95%,(Rx2) = 91.6%, normoxic tumor V-95%,V-Rx1 = 95.7%, normal tissue V-100%,V-Rx1 = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V-95%,V-Rx2 = 90.9%, hypoxic tumor V-95%,V-Rx1 = 62.7%, and normal tissue V-100%,V-Rx2 = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% +/- 2.8%, 96.6% +/- 4.1%, and 90.6% +/- 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes. Conclusions: This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes. (C) 2020 Elsevier Inc. All rights reserved.