Biophysical characterization of collimated and uncollimated fields in pencil beam scanning proton therapy

Objective. The lateral dose fall-off in proton pencil beam scanning (PBS) technique remains the preferred choice for sparing adjacent organs at risk as opposed to the distal edge due to the proton range uncertainties and potentially high relative biological effectiveness. However, because of the substantial spot size along with the scattering in the air and in the patient, the lateral penumbra in PBS can be degraded. Combining PBS with an aperture can result in a sharper dose fall-off, particularly for shallow targets. Approach. The aim of this work was to characterize the radiation fields produced by collimated and uncollimated 100 and 140 MeV proton beams, using Monte Carlo simulations and measurements with a MiniPIX-Timepix detector. The dose and the linear energy transfer (LET) were then coupled with published in silico biophysical models to elucidate the potential biological effects of collimated and uncollimated fields. Main results. Combining an aperture with PBS reduced the absorbed dose in the lateral fall-off and out-of-field by 60%. However, the results also showed that the absolute frequency-averaged LET (LETF) values increased by a maximum of 3.5 keV mu m(-1) in collimated relative to uncollimated fields, while the dose-averaged LET (LETD) increased by a maximum of 7 keV mu m(-1). Despite the higher LET values produced by collimated fields, the predicted DNA damage yields remained lower, owing to the large dose reduction. Significance. This work demonstrated the dosimetric advantages of combining an aperture with PBS coupled with lower DNA damage induction. A methodology for calculating dose in water derived from measurements with a silicon-based detector was also presented. This work is the first to demonstrate experimentally the increase in LET caused by combining PBS with aperture, and to assess the potential DNA damage which is the initial step in the cascade of events leading to the majority of radiation-induced biological effects.