Compensator-based small animal IMRT enables conformal preclinical dose painting: application to tumor hypoxia

Techniques for preclinical intensity modulated radiation therapy are being developed to improve translation by replicating the clinical paradigm. This study presents the first treatment planning comparison between small animal IMRT (SA-IMRT) and three-dimensional conformal radiotherapy (CRT) in a model application, oxygen-guided dose painting of tumor hypoxia, using actual mouse data. A novel compensator-based platform was employed to generate SA-IMRT and CRT plans with 2-15 beam angles for seventeen mice with fibrosarcoma tumors. The whole tumor received a dose of 22.5 Gy, with a simultaneous integrated boost of 13 Gy to hypoxic voxels identified via electron paramagnetic resonance imaging. Plan quality was assessed using the Paddick conformity index (CI), uniformity, and dose volume histograms. For 3-angles, SA-IMRT yielded significantly improved dose conformity (median hypoxic CI = 0.45 vs. 0.17), tumor dose uniformity (11.0% vs. 14.3%), and dosimetric spread between boost and non-boost targets (D50% difference = 13.0 Gy [ideal], 13.1 Gy [SA-IMRT], 7. 3 Gy [CRT]). No significant improvement in CI was associated with > 3 beam angles (Wilcoxon signed-rank test, p < 0.05). This study demonstrates that SA-IMRT provides significant improvements in radiation plan quality and yields dose distributions that more closely mimic the clinical setting relative to current CRT approaches.