Nuclear interactions in proton therapy: dose and relative biological effect distributions originating from primary and secondary particles.

The dose distribution delivered in charged particle therapy is due to both primary and secondary particles. The secondaries, originating from non-elastic nuclear interactions, are of interest for three reasons. First, if fast Monte Carlo treatment planning is envisaged, the question arises whether all nuclear interaction products deliver a significant contribution to the total dose and, hence, need to be tracked. Second, there could be an enhanced relative biological effectiveness (RBE) due to low energy and/or heavy secondaries. Third, neutrons originating from nuclear interactions may deliver dose outside the target volume. The particle yield from different nuclear interaction channels as a function of proton penetration depth was studied theoretically for different proton beam energies. Three-dimensional dose distributions from primary and secondary particles were simulated for an unmodulated 160 MeV proton beam with and without including a slice of bone material and for a spread-out Bragg peak (SOBP) of 3 x 3 x 3 cm3 in water. Secondary protons deliver up to 10% of the total dose proximal to the Bragg peak of an unmodulated proton beam and they affect the flatness of the SOBP. Furthermore, they cause a dose build-up due to forward emission of secondary particles from nuclear interactions. The dose deposited by d, t, 3He and alpha-particles was found to contribute less than 0.1% of the total dose. The dose distal to the target volume caused by liberated neutrons was studied for four proton beam energies in the range of 160-250 MeV and found to be below 0.05% (2 cm distal to SOBP) of the prescribed target dose for a 3 x 3 x 3 cm3 target. RBE values relative to 60Co were calculated proximal to and within the SOBP. The RBE proximal to the Bragg peak (100% dose) is influenced by secondary particles (mainly protons and a-particles) with a strong dose dependency resulting in RBE values up to 1.2 (2 Gy; inactivation of V79). Depending on the endpoint considered, secondary particles cause a shift in RBE by up to 8% at 2 Gy. In contrast, the RBE in the Bragg peak is almost entirely determined by primary protons due to a decreasing secondary particle fluence with depth. RBE values up to 1.3 (2 Gy; inactivation of V79) at 1 cm distal to the Bragg peak maximum were found. The inactivations of human skin fibroblasts and mouse lymphoma cells were also analysed and reveal a substantial tissue dependency of the total RBE. The outcome of this study shows that elevated RBE values occur not only at the distal edge of the SOBP. Although the variations are modest, and in most cases might have no observable clinical effect, they might have to be considered in certain treatment situations. The biological effect downstream of the target caused by neutrons was analysed using a radiation quality factor of 10. The biological dose was found to be below 0.5% of the prescribed target dose (for a 3 x 3 x 3 cm3 SOBP) but depends on the size of the SOBP. This dose should not be significant with respect to late effects, e.g. cancer induction.