Investigation of Optimal Physical Parameters for Precise Proton Irradiation of Orthotopic Tumors in Small Animals.

Abstract

The lack of evidence of biomarkers identifying patients who would benefit from proton therapy has driven the emergence of preclinical proton irradiation platforms using advanced small-animal models to mimic clinical therapeutic conditions. This study aimed to determine the optimal physical parameters of the proton beam with a high radiation targeting accuracy, considering small-animal tumors can reach millimetric dimensions at a maximum depth of about 2 cm. Several treatment plans, simulated using Geant4, were generated with different proton beam features to assess the optimal physical parameters for small-volume irradiations. The quality of each treatment plan was estimated by dose-volume histograms and gamma index maps. Because of its low-energy straggling, low-energy proton (<50 MeV) single-field irradiation can generate homogeneous spread-out Bragg peaks to deliver a uniform dose in millimeter-sized tumors, while sparing healthy tissues located within or near the target volume. However, multifield irradiation can limit the dose delivered in critical structures surrounding the target for attenuated high-energy beams (E > 160 MeV). Low-energy proton beam platforms are suitable for precision irradiation for translational radiobiology studies.