Increased Proton Relative Biological Effectiveness at the Very End of a Spread-Out Bragg Peak for Jejunum Irradiated Ex Vivo

Purpose Currently, it is unclear if the variation in proton relative biological effectiveness (RBE) at different positions in the spread-out Bragg peak (SOBP) should be taken into account for medical applications. To date, the majority of studies have examined cells irradiated in vitro. In this work RBE estimates have been made for intact tissue irradiated ex vivo . Materials and Methods Irradiations were performed in the 200 MeV clinical proton beam produced at iThemba LABS (Cape Town, South Africa). The beam was modulated to produce either a 3-cm or a 7-cm SOBP. The number of intestinal crypts regenerated in jejunum sections of mice after single doses of protons was used as the biological end point. For this, a novel ex vivo irradiation technique was implemented to allow measurements at the very end of the SOBP where most variations in proton RBE can be expected. Results The proton RBE at the very end of the 7-cm SOBP increases by 10% compared with the middle of the SOBP; the same 10% increase in RBE is observed between the end and the middle of the 3-cm SOBP. This corresponds to an increase of the proton RBE with reference to cobalt-60 gamma rays from 1.14 at the middle of the 7-cm SOBP to 1.25 at the end. Conclusion The similarity of the RBE increment for the different SOBP's indicates that most of the increase in RBE occurs over the last 15 mm upstream of the fall-off of the beam. Because the corresponding 10% variation of the biologically effective dose exceeds the dose accuracy standards of 3.5% required in radiation therapy , it is highly advisable to allow for it when designing treatment plans.