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

To demonstrate the difference in biological effectiveness of proton mono-energetic arc therapy (PMAT) compared to intensity modulated proton therapy (IMPT) and conventional 6MV photon therapy and to quantify this difference when exposing cells of different radiosensitivity to the same experimental conditions with 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° over a 180° 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 6MV photons beams in Petri dishes to characterize their radiosensitivity. The relative biological effectiveness of the PMAT plans compared with the 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 the IMPT and photons, δ-H2AX assays were conducted to study the relative number of DNA damage induced by each modality and their repair rate with time. The clonogenic assay revealed similar survival levels to the same dose delivered with IMPT or x-rays. However, a systematic average of 30% increase of effectiveness in PMAT plans was observed when compared with IMPT. Also, the repair kinetic assays proved that PAT 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 photon were similar. Mono-energetic arc beams offer the possibility of taking advantage of the enhanced LET of proton beams to increase TCP.