Radiobiological effectiveness difference of proton arc beams versus conventional proton and photon beams

Abstract

This paper aims to demonstrate the difference in biological effectiveness of proton monoenergetic arc therapy (PMAT) compared to intensity modulated proton therapy (IMPT) and conventional 6 MV photon therapy, and to quantify this difference when exposing cells of different radiosensitivity to the same experimental conditions for each modality. V79, H1299 and H460 cells were cultured in petri dishes placed in the central axis of a cylindrical and homogeneous solid water phantom of 20 cm in diameter. For the PMAT plan, cells were exposed to 13 mono-energetic proton beams separated every 15 degrees over a 180 degrees arc, designed to deliver a uniform dose of higher LET to the petri dishes. For the IMPT plans, 3 fields were used, where each field was modulated to cover the full target. Cells were also exposed to 6 MV photon beams in petri dishes to characterize their radiosensitivity. The relative biological effectiveness of the PMAT plans compared with those of IMPT was measured using clonogenic assays. Similarly, in order to study the quantity and quality of the DNA damage induced by the PMAT plans compared to that of IMPT and photons, gamma-H2AX assays were conducted to study the relative amount of DNA damage induced by each modality, and their repair rate over time. The clonogenic assay revealed similar survival levels to the same dose delivered with IMPT or x-rays. However, a systematic average of up to a 43% increase in effectiveness in PMAT plans was observed when compared with IMPT. In addition, the repair kinetic assays proved that PMAT induces larger and more complex DNA damage (evidenced by a slower repair rate and a larger proportion of unrepaired DNA damage) than IMPT. The repair kinetics of IMPT and 6 MV photon therapy were similar. Mono-energetic arc beams offer the possibility of taking advantage of the enhanced LET of proton beams to increase TCP. This study presents initial results based on exposing cells with different radiosensitivity to other modalities under the same experimental conditions, but more extensive clonogenic andin-vivostudies will be required to confirm the validity of these results.